PRECISE PHARMAClJLlJ PRECISE lilJ!

JjlM~~lJLlJGY
TABLE OF CONTENTS Sulphonamides and trimethoprim ...............................co 90
Preface Quinolones c., . 95
Contributors and Acknolwledgements Oxazolidinones , 108
Table of contents Lincosamides . 109
'",
Amphenicols . 112
CHAPTER ONE
Carbapenems . 114
Introduction to Pharmacology
Nitrofurans . 116
Definition of terms used in Pharmacology . I
Other antibacterials . 118
Pharmacokinetics ~o, o . 1
Drugs used in the treatment of tuberculosis .. 128
Pharmacodynamics . 4
Drugs used in the treatment of leprosy .. 136
CHAPTER TWO
CHAPTER FIVE
Drug administration
Drug dosage forms .. 7
Drugs used in the treatment of fungal infections
Description of common dosage forms 0. 7 Polyene antifungals 142
Routes of drug administration . 7 Imidazole antifungals 145
Drug administration in special cases . 15 Triazole antifungals 147
Common abbreviations used in drug administraion .. 17 Allylamine derivatives 151
Other antifungals.............................................................. 153
CHAPTER THREE
CHAPTER SIX
Understanding drugs
Antiprotozoal Drugs
Drug nomenclature , , . 20
Sources of drugs . Antimalarial drugs 155
20
Classification of drugs .. 20 Nitroimidazoles 170
Schedules of controlled substances/ drugs .. 21 Anthelmintics 177
Drug storage . 22
CHAPTER SEVEN
Essential drugs ; .. 23
Drugs used in the Treatment of Viral infections
Rational use of medicines .. 27
Prescription writing .. 28 Guanine analogues .:........................................................ 190
Antiretrovirals 195
CHAPTER FOUR
Antibacterial Drugs j CHAPTER EIGHT
Drugs acting on Gastro- Intestinal system
Introduction to antibacterial .. 32
Penicillins ; c ••• 36 Drug for peptic ulcer disease 202
Cephalosporins . 55 Drugs for nausea and vomiting 227
Macrolides . 77 Drugs for haemorrhoids and Piles ,........................ 240
Tetracyclines . 83 Drugs for inflammatory bowel disease 243
Aminoglycosides . 8~ Drugs for constipation 215

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ECLLllISE Pl1ID\1AC~1J!ID'J

Antidiarrhoeal drugs :k.................................... 252 Drugs for scabies and pediculosis 436
Prokinetic drugs 261 Antipruritic drugs 438
Drugs for obesity.............................. 261 Drugs for alopecia "...................................... 439

CHAPTER NINE
., CHAPTER FOURTEEN
Drugs for Respiratory Tract Disorders Drugs for the eye
Drugs for asthma . 263 Antibacterial eye preparations .. 442
Drugs for allergic rhinitis .. 280 Antiviral drugs ' . 447
Drugs used in the treatment of cough 0
302 Drugs used in allergic conjunctivitis .. 448
Non-steridal antinflammatory eye preparations .. 452
CHAPTER TEN Drugs for glaucoma . 452
Drugs for Cardiovascular Disorders
Drugs used in the treatment of hypertension . 306 CHAPTER FIFTEEN
Drugs used in the treatment of angina pectoris .. 34 Drugs used in the management of CNS disorders
Drugs for heart failure 0 00 ..
345 Drugs used in the treatment of depression .. 459
Drugs for hyperlipidaemia .. 355 Drugs used in the treatment of epilepsy .. 475
Anxiolytic , sedatives and hypnotics .. 490
CHAPTER ELEVEN Drugs used in the treatment of parkinsonism .. 501
Blood and blood forming organs Antipsychotic drugs . 507
Anticoagulants . 365
370 CHAPTER SIXTEEN
Antiplatlet drugs 0 ••••••••• .. •••••••••• ..

Analgesics
Thrombolytic drugs .. 373
375 Non-opiod analgesics . 521
Antifibrinolytic drugs .
376 Opiod analgesics 0. 525
Drugs used in the treatment of anaemia ..
Drugs used in the treatment of migraine . 532
Skeletal muscle relaxants .. 535
CHAPTER TWELVE
Endocrine and Metabolic Drugs CHAPTER SEVENTEEN
Drugs for Diabetes mellitus .. 381 Obstetric and gynaecological drugs
Drugs for thyroid disorders 0
397 Drugs used in the treatment of menstrual disorders .. 541
Drugs used in treatment of infertility : . 546
CHAPTER THIRTEEN Drugs used in treatment of pre-eclampsia
Dermatological Drugs and eclampsia . 550
Drugs for eczema .. 400 Drugs used during labour . 552
Drugs for psoriasis . 408 Drugs affecting lactation . 560
Drugs for acne , 413 Drugs used in the treatment of endometriosis .. 562
Topical Anti-infectives . 419 Drugs for contraception " .. 56'1
Drugs for warts 0 • • .. •••
434 )

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 PRECISE PHARMACOLOGY PRECI~i'Q:!)1i!MilQI!IHijl
CHAPTER EIGHTEEN COMMON ABBREVIATIONS
Drugs for urologic disorders ACE Angiotensin-Converting Enzyme
Drugs for benign prostatic hyperplasia.......................... 570 ADH Antidiuretic Hormone
Drugs for Erectile dysfunction 575 ADR Adverse Drug Reaction
AAFB Alcohol Acid-Fast Bacillus
CHAPTER NINETEEN Ag Antigen
Drugs for muscular skeletal disorders AIDS Acquired Immune Deficiency Syndrome
Drugs for gout 0 00.00................ 579 BP Blood Pressure
Drugs used in the treatment of rheumatoid arthritis 582 Ca Carcinoma
Non steroidal anti-inflammatory drugs............ 585 CHF Congestive Heart Failure
CI Contra -Indication
CHAPTER TWENTY CMV Cytomegalovirus
Drugs used in the treatment of cancer 60 I CNS Central Nervous System
I.
COC Combined Oral Contraceptives
CHAPTER TWENTY ONE COPD Chronic Obstructive Pulmonary Disease
Drugs used in anaesthesia COX Cyclo Oxygenase
Local anaesthetics 612 CSF Cerebrospinal Fluid
General anaethetics 612 CT Computerised Tomography
Depolarizing neuromuscular blocking drugs 622 CxR Chest X-ray
DM Diabetes Mellitus
CHAPTER TWENTY TWO DMARD Disease Modifying Antirheumatic Drugs
Vaccines and immunoglobulins 625 DU Duodenal Ulcers
DVT Deep Vein Thrombosis
Index ,· c. 640 E/C Enteric Coated
ECG Electro Cardio Gram
ECT Electro Convulsive Therapy
EEG Electro Encephalogram
ENT Ear, Nose and Throat
FBC Full Blood Count
g Gram
G6PD Glucose 6-Phosphate Dehydrogenase
GA General Anaesthetic
GI Gastro Intestinal
GTN Glyceryl trinitrate
HAART Highly Active Antiretroviral Therapy
HAV Hepatitis A Virus
Hb Haemoglobin
i

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_1111111 R£ PRECiSE PHARMACOLOGY ] "I ~PHARMACOLOGY

HBV Hepatitis B Virus MMOL Millimole

HCV Hepatitis C Virus MRI Magnetic Resonance Imaging
HDL High Density Lipoprotein NNRTls Non Nucleoside Reverse Transcriptase Inhibitors
HDV Hepatitis D Virus NRTls Nucleoside Reverse Transcriptase Inhibitors
Hg Mercury .' NSAID Non Steroidal Anti Inflammatory Drugs
HIV Human Immunodeficiency Virus OA Osteoarthritis
HRT Hormone Replacement Therapy OC Oral Contraceptives
HSV Herpes Simplex Virus PI Protease Inhibitors
IDDM Insulin Dependent Diabetes Mellitus PID Pelvic Inflammatory Disease
i.e. That is to say PMS Premenstrual Syndrome
1M Intramuscular PPI Proton Pump Inhibitor
INF Infusion RA Rheumatoid Arthritis
INH Isoniazid RTI Respiratory Tract Infection
inj 5\" Injection SC Subcutaneous
lOP !IlW Intraoccular Pressure SPP Species
SSRI Selective Serotonin Reuptake Inhibitor
IU ,1" International Units
IV Intravenous STD Sexually Transmitted Disease
Kg Kilogram STI Sexually Transmitted Infection
L Litre TB Tuberculosis
LDL Low Density Lipoproteins UC Ulcerative Colitis
LFT Liver Function Test USP United States Pharmacopoeia
LH Luteinising Hormone UTI Urinary Tract Infection
LMWH Low Molecular Weight Heparins VDRL Venereal Diseases Research Laboratory
LVF Left Ventricular Failure VLDL Very Low Density Lipoprotein
LVH Left Ventricular Hypertrophy WHO World Health Organization
m2 Metres Squared Z Pyrazinamide
MAOls Monamine Oxidase Inhibitors.
MAX Maximum
MCG Microgram
MDI Metered Dose Inhaler
mEq Milliequivalent
MG Milligram
mg/kg Milligram per Kilogram body weight.
MI Myocardial Infarction
Min Minutes.
ml Millilitre
mmHg Millimetres of Mercury

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en 'I PRECISE PHARMAciII!n!t. PRECISE IiHAftMACOLOD
Drug absorption
Before a drug can exert a pharmacological effect in tissues, it has to be
CHAPTER ONE taken into the blood stream. Absorption is the movement of a drug from
INTRODUCTION TO PHARMACOLOGY the site of administration into the blood stream (general circulation).
Drugs are absorbed from the gastro intestinal tract mainly by passive
Pharmacology is thest~dy of drugs and their intei"action with the diffusion or active transport.
living system. The term phil:rmacology comes from the Greek words
pharmakon meaning medicine and the suffix -ology meaning study Factors affecting absorption
of. .:. Rate of dissolution of a drug
Since a drug has to be dissolved before it is absorbed, drugs
1.1.1 Definition of terms used in Pharmacology present in formulations that allow rapid dissolution will be
absorbed faster.
Therapeutics •:. Blood flow:
Therapeutics is a branch of medicine that deals with different methods Absorption of the drug is fastest from sites where blood flow
of treatment especially the use of drugs in the cure of diseases. is high.
•:. Lipid solubility of a drug
Toxicology Highly lipid soluble drugs can readily cross the membrane
This is the study of the adverse effect of the drugs on the living compared to those with low lipid solubility.
system.
Bioavailability
Chemotherapy Bioavailability is the extent to and the rate at which the active moiety
Chemotherapy is the use of chemical agents or drugs to treat cancer or (drug or metabolite) enters systemic circulation, thereby accessing the
~other diseases caused by bacteria, fungi, viruses or parasites.
site of action.
Factors affecting Bioavailability.
Classfication of Pharmacology.
Pharmacology is divided into two:- First pass metabolism: If a drug is rapidly metabolized on its first
.:. Pharmacokinetics entry into the liver, the amount of unchanged drug that reaches system's
.:. Pharmacodynamics circulation is decreased.
-
1.1.2 PHARMACOKINETICS Solubility of the drug: Drugs that are very hydrophilic are
Pharmacokinetics is the study of what the body does to the drug. poorly absorbed because of their inability to cross the lipid-rich cell
It includes:- membranes.
.:. Absorption
.:. Distribution Chemical instability: Some drugs such as penillin G are unstable to
.:. Metabolism the PH of gastric juice contents.
•:. Excretion

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PRErm)PHARMAClllOGY PRECISE IQ:m;!M'~OLOGY

Nature of the drug formulation: The size of the particles, salt form 1.1.3 PHARMACODYNAMICS
and excipients such as binders, disintergrants can influence the ease of Pharmacodynamics is the study of what the drug does to the body.
dissolution and affect the rate of absorption of the drug.
Common Terms Used In Pharmacodynamics
Drug Distribution .. Efficacy
After a drug enters the systemic circulation, it is distributed to This is the ability of the drug to produce maximal response.
the body's tissues. Distribution is the movement of a drug from
the general circulation into different organs and fluids of the body. Potency
Distribution is generally uneven and is influenced by the following Potency is a measure of how much drug is required to elicit a
factors:- response.
•:. Blood flow to the tissues
.:. Capillary permeability (ability of a drug to exit the vasc~lar Drug receptor
system). It is a specialized cell component that combines with a drug or hormone
.:. liAbility of a drug to enter cells to alter cellular functions or mediate its pharmacological action.
•:. Regional pH
Halflife
Drug Metabolism This is the time taken to reduce the amount of the drug in the body by
Metabolism is the enzymatic alteration of a drug structure. This normally one half during elimination
takes place in the liver. Metabolism may result into the following:-
.:. Promotion of renal excretion of the drug Therapeutic dose
.:. Activation of inactive drugs (Pro-drugs) This is a dose between the minimum effective and the maximum doses
.:. Enhancement of therapeutic action of the drug which provides the desired effect without toxic effects.-
.:. Alteration of toxicity of the drug
Factors influencing individual drug metabolism rates include; Therapeutic index
.:. Genetics This is the ratio of the dose that produces toxicity to the dose which
.:. Co-existing disorders e.g. chronic liver disorders produces clinical response. Therapeutic index is thus a measure of
.:. Drug interaction. the drug'S safety since the higher the therapeutic index, the safer the
drug.
Excretion
Excretion is the removal of drugs from the body. Drugs may be excreted Toxicity
through any of the following:- ::\1:\ , This is an adverse drug reaction caused by excess drug in the body. This
.:.
Urine "';' may be due to excessive dosing or accumulation of the drug.
.:.
Bile
.:.
Feaces Agonist
.:.
Breast milk An agonist is a substance that binds to the receptor and causes a
II .:.
Sweat
response.
I
.:.
Saliva
.:.
Expired air

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lm"'"--'--PHARMACdI PRECISE PHARMACOLOGY I
Antagonist Psychological dependence
An antagonist is a substance that binds to a receptor and prevents a This is the emotional state of craving for a drug whose presence has a
response. desired effect on mind or whose absence has an undesired effect.
..,
Partial agonist Allergic reaction
Partial agonist is a substance that binds to a receptor and cause effects This is an immunologically mediated adverse response to a drug
similar to but less than that of a pure agonist. requiring previous sensitization.

Side effects Anaphylaxis

These are expected, well known, undesirable effects of a drug that This is a state of immediate hypersensitivity following sensitization to
occur at doses normally used for therapy. a foreigh protein or a drug. It is characterized by itching, swelling of
the mouth: wheezing, sudden drop in blood pressure and sometimes
Adverse efffects death.
These are any noxious, undesirable and unintended effects that occur
at normal drug doses. Idiosyncratic drug reaction
This is an unusual and unpredictable response to a drug based on a
Drug interaction genetic predisposition.
This is the alteration of one drug by another. It occurs when two
or more drugs are administered to a patient simultaneously. Drug Teratogenic effect
Illteraction may result into either negative effects or positive effects. This is a drug-induced birth defect

Synergism Carcinogenic effect

It 1\ it drug interaction in which two drugs combine to give a therapeutic This a drug-induced cancer
(.lIcKt which exceeds the sum of their separate effect e.g. gentamycin
I Jlclflldilins have synergistic effect in the treatment of bacterial
Illf•• (lIon5,

Tolc'r.1ncc'
lolt',.lIu" II .1 p,rlldual decrease in response to a drug as a result of
re'pt•. IIMd dilly' .\lhllinistration. Tolerance may occur through a decrease
111 II It' CO"Cl:lIlII.lt Ion of drug at the receptor or through decrease in
le~poll"l' of I"" !'''coptor to the same concentration of a drug.
Drug dc\pc'ndcmc'(\
This is Iht· (Olllp"I.. IVt. lise of a substance resulting in physical,
psychologlcll 01 \OC 1.11 11.11111 to the user with continued use despite
the harm.

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 " ' ", ~~PHAftMACOLOGY
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PRECISE PHARMACOLOGY I

Types of tablets
CHAPTER TWO
Tablets are formulated as coated or uncoated.
DRUG ADMINISTRATION
Coated tablets include enteric coated, sugar coated, film coated and
slow-release coated tablets.
2.1.1 DRUG DOSAGE FORMS
This is a form in which a medicine is prescribed for use by the patient
Enteric coated tablets: These tablets are covered with a special
such as injections, tablets, capsules or syrups.
coating which resists break down in the stomach but dissolves in the
Dosage forms do not contain just the active ingredient but also contain alkaline environment in the small intestine where the drug is absorbed.
other components called excipients or additives. These make the dosage The coating is inteded to avoid irritating the stomach.
form suitable for handling, administration and enable it to release the
active medicaments in the appropriate manner to make it efficacious Slow-release tablets: These tablets are manufactured to provide a
for treatment of diseases or conditions. continuous, sustained release of certain drugs. These tablets names are
accompanied by abbreviations such as S.R (slow release)or L.A (long
Dosage forms can be in solid, semisolid, liquid or gaseous form. acting) e.g Nifelat R®, Olfen S.R ® or Adalat LA ®

Common dosage forms and their routes of administration

Sugar coated tablets: These are formulated with a sugar coating to
disguise the bitter taste of the active ingredient.
Route of administration Dosag•
I

,
Oral Tablets, capsules, solutions, syrups, elix- Film coated tablets
irs, suspensions, emulsions, gel, powder, These tablets are covered with a very thin layer of coating materi~L
III
-----_.~-~---~-------_."-
granules.
Rectal Suppositories, ointments, creams and Scored tablets: These tablets have an indented line running across
.... solutions the top of the tablet. Scored tabletes can easly be broken down into 2
------_._----
Topical Ointment, creams, pastes, lotions, gels, pieces.
---------_.
solutions, topical aerosols (sprays)
Parenteral Injections (solutions, suspensions, Caplets.
.. I emulsion) These are easy-to-swallow coated tablets in forms of capsules e.g.
Lung Aerosols, inhalation sprays panadol®
liasal ,!l:m!L. Solutions, inhalations and gases
.....•.. Effervescent tablets
.~ye Solutions, ointments and creams
Ear
...........
·m:H~i!!. Solutions, suspensions, ointments These are uncoated tablets containing acidic substances and either
carbonates or bicarbonates which react rapidly in the presence of
2.1.2 Description of common dosage forms water to release carbondioxide. They are intended to be dissolved in
water before administration. e.g. dispersible tablets
Tablets
Tablets arc solid dosage forms containing one or more dried compressed
active drug as WI·II as binders.

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 PRECISE PHARMACOLOGY] PREC I~ PHARMACOLOGY
Capsules Pessaries
Capsules are cylindrically shaped solid unit dosage form containing one These are solid preparations containing one or more active ingredients
or more substance enclosed within a hard or soft gelatin shell. intended to be inserted into the vagina.

Types of capsules: Suspension

Slow release capsules: These capsules contain pellets that dissolve This is a liquid preparation containing fine, undissolved particles of a
in the GIT releasing the drug slowly thereby producing sustained drug drug suspended in it.
action. e.g. Olfen S.R ®
Aerosol
Soft gelatin capsules: These capsules contain the drug in liquid form This is a pressurized preparation that when activated releases a fine
inside the shell e.g. vitamin A capsules dispersion of liquid or solid materials in a gaseous medium.

Hard shell capsules: These are manufactured in two pieces which fit Enema
together and hold the powder. A liquid intended to be injected into the rectum.

A cream Inhalation
This is a semisolid emulsion of an oil and water (with the main ingredient Drug droplets, vapour, or gas administered by the oral or nasal
being oil). respiratory route via an aerosol or nebuliser.

Lotions Injection
These are liquid or semi-liquid preparations containing one or more A sterile, pyrogen-free preparation intended to be administered using a
active ingredients in a suitable vehicle. They are intended to be applied needle and syringe (parenterally).
to the unbroken skin without friction. e.g. calamine lotion.
Lozenges (troches)
Emulsion Disk-shaped solid preparations intended to slowly dissolve in the oral
An emulsion is a suspension in which fat particles are mixed with cavity for localized effects.
water.

Suppository Mouthwashes
It is a solid dosage form containing a solid base of glycerin or cocoa These are aqueous solutions containing one or more active ingredients.
butter intended for insertion into the body orifices where it melts, They are intended for use in contact with the mucous membrane of
dissolves and exerts a systemic or localised effect. the oral cavity.

Ointment
A semisolid preparation intended for external application to the skin or
mucous membranes.
. 1

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 ",'" :' , ",'" ~ECISE PHARMACl!I!!I!DI
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PRI3Q~'f PHARMACOLOGY I

Pellet (Implant) Parenteral route is the fastest route by which a drug can be absorbed.
A sterile, small, rod or ovoid-shaped mass intended to be implanted It includes:-
under the skin for the purpose of providing the slow release of .:. Intraveneous
medication over an extended period of time. .:. Intramuscular
.:. Subcutaneous
Powder .:. Intradermal
A mixture of finely divided drug particles or chemical substances. .:. Intrathecal
.:. Intra-articular
Solution
A liquid preparation containing soluble chemical substances usually Intravenous (IV) injection
dissolved in water. Drugs are injected /administered directly into the blood stream via a
vein where it is distributed in blood all over the body.
Spray
A liquid minutely divided or nebulised as by a jet of air or a stream. Advantages
,ffi1 Disadvantages,
• A quick onset of action is achieved • The drug has to be administered
Syrup
by a trained person
A concentrated sugar solution in water that may contain a flavoring
agent or drug. • The entire dose ofthe drug is • In cases oftoxicity, retrieval of
administered the drug is not possible
Eye drops • A lower dose is given compared • It requires strict sterility
These are sterile aqueous or oily solutions or suspensions of one or to oral route
more active ingredients intended for instillation into the eye. • Administration is useful for • It is painful
drugs that are irritant when
2.1.3 ROUTES OF DRUG ADMINISTRATION administered.
These are various ways in which drugs are administered into the body.
Drugs can be administered by several different routes as determined Intramuscular (1M) Injection
by the intended site of action, rapidity and duration of effect desired, The drug is injected in one of the large skeletal muscles e.g. deltoid.
chemical and physical properties of the drug.
•:. Parenteral route Advantages Disadvantages
.:. Topical route • Drugs that give depot effect such • It requires a trained personnel
~. Enteral route Benzathine penicillin can be given to administer the drug
.:. Inhalational route by this route

• It is generally faster than • Absorption of the drug is

Parenteral route
subcutaneous route sometimes variable depending
Drugs given by this route are in form of solutions, suspensions, and on which muscle is used
emulsions.

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 PRECisE PHARMACOLOGY I III PRECISE PHARMACOLOGY I

• Relatively irritating substances • Some drugs given 1M can be • Wastage of drugs is possible
may be given. painful e.g. Ceftriaxone injection since there is no measurable
dose
Its less painful compared to IV • Self administration of the drug is
injection not possible.
Enteral route
This includes; rectal, oral, sublingual, and buccal routes.
Subcutaneous (sc) Injection
The drug is injected into the subcutaneous tissue, the fatty layer of Rectal route
tissue underneath the dermis. It is commonly used in administering Drugs are administered via the rectum in form of suppositories or
vaccines and insulin. This route of administration, like the intramuscular, enema
provides absorption that is slower than the IV route.
Advantages ,lIl1111 II' Disadvantages Advantages lUll IlIlUi Disadvantages
Absorption is slower than 1M • Can be painful • Provides a safe route • May be uncomfortable and a
injection .i<liill::lH for a patient who is embarrassing for the patient
The patient can self administer the • Irritating drugs may result in vomiting, unconscious or
drug severe pain and local tissue unable to swallow
necrosis • Provides an effective • Drugs may result in irregular or
• Care has to be taken not to route to treat vomiting incomplete drug absorption depending
inject IV on whether faeces are present.
'--------- • It is faster than oral • May stimulate the patient'svagal nerve
route by stretching the anal sphincters
Topical route
Drugs are applied directly to the skin or the mucuos membrane of • It avoids destruction of
the eye, ear or nose. Drugs given by this route are in form of creams, medication by digestive
ointments, lotions, gels etc. enzymes in stomach and
small intestine
• Drugs may be given
'I
Disadvantages for local effects e.g.
Advanta es
haemorrhoids
Self administration of the drug is • Some drugs like Dithranol
possible ointment stain the skin and
clothe
Oral route
The oral route is the most convenient and safest route of drug
Its less expensive compared to • Adverse skin reactions are
parenteral route. possible administration. Drugs are given by oral route in form of tablets, capsules,
syrups, suspension or powders.
Its easy to monitor the ) • Some drugs like topical steroids
treatment bleach and cause thining of the
skin

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PRECISE P1:Ji1;IMMol!II!f1 ,PRECISE PHARMACOLOGY I
Advantages Disadvantages oxygen to the fetus. This results in under development or
• It is cheap for the patient • Has a delayed action and hence under weight babies.
not suitable for emergencies Can cause contraction of the uterine muscles injuring the fetus or
• It does not require a skilled • It requires patient commitment causing preterm labor.
person to administer the drug to improve on compliance
• Self administration of the drug • Oral route can not be used by a Examples of drugs contra-indicated in pregnancy;
is possible patient in coma
• Some drugs can only be given • Psychiatric patients and children
Drug Effect
by the oral route e.g. nifedipine may refuse to take the drug by
oral route ACEls Cause fetal and neonatal mortal-
. In case of drug toxicity. it can be • Some drugs can be destroyed ity and morbidity
retrieved by the GIT enzymes e.g. insulin Phenytoin Minor cranio-facial defects
Streptomycin Damage to the fetus's ears re-
• It is not suitable for a patient
sulting into deafness.
I" who is vomiting
• A higher dose is required Tetracycline Permanent yellowing of the
compared to parenteral route teeth.

Sublingual route Paediatrics

The drug, usually in form of a tablet, is placed under the tongue and A number of drugs are not used during childhood because they are
allowed to dissolve slowly. e.g. Nitroglycerin. associated with serious adverse reactions.
The drug is absorbed qUickly through the oral mucous membrane into
the blood stream. It provides a faster therapeutic response than the Drug Effect
oral route.
Aspirin Reye's syndrome

2,1.4 DRUG ADMINISTRATION IN SPECIAL CASES Tetracyclines Permanent discoloration of teeth

Drugs should be administered with special attention in the following Quinolones Arthropathy(cartilage break-
cases; pregnancy, lactating mothers, paediatrics, and geriatrics. down)
Pregnancy

Generally drug therapy during pregnancy is not needed unless

Classification of paediatric age groups
absolutely necessary as many of them cross the placenta and harm the
Premature infants < 36weeks of gestation
fetus. Drugs can affect the fetus in any of the following ways;
Full term infants 36-40weeks gestation age
By directly causing damage, abnormal development leading to
Neonates less than 4 postanatal weeks
birth defects or death.
Infants 5-52 weeks
Altering the physiological function of the placenta causing
Children 1-12years
vasoconstriction thus reducing supply of nutrients and
Adolescents I 2-16years

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 •
PRECISE p@liJMtdolll1il'1 illll'

Lactating mothers
iv Intravenous
If a drug enters breast milk in pharmacologically significant quantities,
sc Subcutaneous
therapeutic doses in the mother may cause toxic effects in the infant.
Mist Mixture
In addition, some drugs suppress lactation such as combined oral
... Inj Injection
contraceptives while others may inhibit the infant's sucking reflex.
Aq Water
With the above challenge, a proper decision should be made when
caps Capsules
drugs are prescribed to a breastfeeding mother.
Tab Tablet
SUDD SU ppository
Geriatrics
Dess , A pessary
A geriatric patient is a person who is 65years of age and above.
Syr Syrup
The prescription and use of drugs in the elderly must be carefully
planned and monitored. Ung Ointment
Inf Infusion
Enem Enema
This is because elderly patients are at a high risk of experiencing
Gut Drops
problems with drug therapy due to decline in organ function and the
risks of polypharmacy. g Gram
During prescribing, attention should be focused on drug interactions, mg Milligram
liver and renal function and a simple treatment plan. ml Milliliter
JJg Micrograms
2.1.5 COMMON ABBREVIATIONS USED IN DRUG
ADMINISTRATION

Abbt~viation ' ,
I M~aning
od Once daily
bd Twice daily
tds Three time daily
....
q.i.d Four times daily
q.h Every hour
p.r.n When needed
stat Irrmediately
o.m Each morning
o.n .'m. Each night
a.c
1---",--"
Before meals
p.c i l '/!!" After meals
----

--po ... By mouth

im Intramuscular
-----

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Common examples of generic and brand names

CHAPTER THREE Generic name Brand name

UNDERSTANDING DRUGS Amoxicillin Amoxil®, Duramox®, Amoxapen®
Propranolol Inderal®
'.. A drug is any chemical substance administered in the body or a biological
Paracetamol Panadol®, Kamadol®, Cetamol®
system that affects the structure or functioning of a living organism.
Salbutamol Ventolin®, Vental®
Drugs are used for prevention, diagnosis, treatment of diseases and
relief of symptoms. Diazepam Valium® , Slitizem®

3.1.1 DRUG NOMENCLATURE

A drug may have three categori.es of names namely:-
3.1.2 SOURCES OF DRUGS
.:. Chemical name
Drugs for medical use can be obtained from any of the following
.:. Generic name
sources:-
.:. Brand name
.:. Plants e.g. digoxin, morphine, quinine.
•:. Animals e.g. insulin, adrenaline.
Che~ical name: .:. Microorganisms e.g. penicillins, streptomycin .
The chemical name describes the drug's chemical composition and •:. Chemical substances (made from factories) e.g. ampicillin,
molecular structure. It's not normally used during prescribing because
diazepam.
it is cumbersome.
.:. Minerals e.g. iron.

Generic name (non proprietary name): 3.1.3 CLASSIFICATIONS OF DRUGS

The generic name is the name approved by a competent drug body
Drugs may be classified in the following ways:-
e.g. food and drug administration (FDA). It is much simpler than the
,.:. Prescription classification.
chemical name and is commonly used in prescribing.
.:. Pharmacological classification.
•:. According to drug legislation.
Brand name (Trade or proprietary name):
The brand name is the copyrighted name that is given by the company
Prescription classification
manufacturing and selling the drug.
In this classification, drugs are classified basing on whether they are
obtained using a prescription (prescription only medicine) or they can
Example
be obtained without a prescription (Over The Counter drugs).
Chemical name (+/-)-2-(p-isobutylphenyl) propionic acid
Generic name ibuprofen. PrescriptioJlt drugs: These drugs can only be obtained when a patient
Brand name Brufen®
presents a valid prescription to a pharmacy. Examples of pre~cri~t~on
drugs include: - Amoxicillin, Ciprofloxacin, Diclofenac and Nlfedlpme
among others.

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 OLlJGY • • PRECI~1~ PHARMACOLOGY _
Non prescription drugs (over the counter drugs). These drugs can be They have less abuse potential than drugs in schedule I and II and have
obtained from either a pharmacy or a drug shop without a prescription. accepted medical uses.
Examples of over the counter drugs include:- Panadol®, Hedex®,
Vitamins and Goodmorning syrup® among others. Schedule IV drugs
Drugs from schedule IV include:- diazepam, lorazepam.
Pharmacological classification They have lower abuse potential than drugs in schedule 1- III and have
Drugs can be classified using this system basing on:- accepted medical uses.
Target body system such as cardiovascular drugs il41it*,
Activity on microorganisms such as Antibiotics, Antivirals and Schedule V drugs "
Antifungal among others. Drugs from schedule V include those drugs that are generally for relief
of cough or diarrhoea that contain limited quantities of certain opioid
Legal classification controlled substances e.g. Loperamide, piritex with codeine syrup,
Legal classification divides the drugs as follows:- kaolin etc. p
.
..
Class A drugs: morphine, pethidine, cocaine (schedule I and 2) They have lower abuse potential because of their low strength and
Class B drugs: phenobarbitone, ciprofloxacin, amoxycillin, diazepam, have accepted medical uses.
codeine, griseofulvin, metformin etc (Schedule 3, 4, and 5 and)
Class C drugs: over the counter drugs 3.1.5 DRUG STORAGE
Stability of drugs depends on factors such as
3.1.4 SCHEDULE OF CONTROLLED SUBSTANCES. .:. Temperature
.:. Air
Schedule I drugs .:. Light
Drugs from this schedule includes:- heroin, Iysergide (LSD) etc .:. Humidity
These drugs have a high abuse potential and are not currently used .:. Dosage form
medically. .:. Active ingredient
.:. Manufacturing process
Schedule II drugs
Drugs from schedule II include:- morphine, codeine, pethidine, In general, drugs should be stored according to the manufacturer's
methadone, cocaine among others. recommendations. Most of the drugs shuld be stored in a cool, dry
place out of reach of children.
They have high abuse potential and acceptable medical uses.
They may lead to severe physical and psychological dependence. Some drugs need to be stored in a refrigerator for example Insulin,
vaccines, amphotericin B among others.
Schedule III drugs Other drugs are sensitive to light therefore should be kept in a dark
Drugs from schedule III include:- phenobarbitone, preparations place.
containing limited opioid quantities, preparations combined with one Class A drugs like pethidine are stored according to legal requirement
or more active ingredients that are non controlled substances e.g. I.e. they are kept in a lock and key box.
Paracetalllol with codeine (co-codamol)

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 PRECISE PHARMACOLOGY
• • • • • • • • • •1II11111m.mCISE PHARMACOLOGY I
2.1.6 ESSENTIAL DRUGS AND RATIONAL MEDICINE USE Antibacterials Amoxicillin
Essential drugs (medicines) are those which satisfy the health needs of
Amoxicillin + c1avulanic acid
the majority of the population. These drugs should therefore always be
Benzathine penicillin
available in adequate quantities and appropriate dosage forms. Benzylpenicillin
Ceftriaxone
Criteria for selection of essential drugs Cefuroxime
The selection of essential drugs is based on the following factors:- Flucloxacillin
.:. Pattern of disease prevalence in the country. Cloxacillin
.:. Available treatment facilities. Chloramphenicol
.:. Training and experience of available personnel. Ciprofloxacin
.:. Available financial resources. Cotrimoxazole
.:. Genetic, demographic and environmental factors. Doxycycline
Gentamycin
.:. Efficacy and safety proven from clinical data.
Erythromycin
.:. Assured quality and bioavailability.
Antituberculosis Ethambutol
.:. Stability under normal conditions of use and storage. drugs Isoniazid
.:. Cost/ benefit ratio .
Pyrazinamide
•:. Formulation as single compounds. Rifampicin
.:. Combination products evaluated on the basis of therapeutic Streptomycin
effect, Antifungal drugs Amphotericin B
.:. Safety and patient compliance. C1otrimazole
Fluconazole
Examples of essential drugs in Uganda Griseofulvin
Ketoconazole
CLASS Miconazole
Nystatin
Antimalarials Artemether ..
.~-------

Antileprosy drugs Clofazimine

Artemether/ lumefantrine
Dihydroartemesinin/piperaquine Dapsone
Quinine Rifampicin
Primaquine Thalidomide
I r:-A-.::rt-.::e=s:..::u~n~at::..::e;.../a:..::m_o:..::d_i_aq...!.u_i_ne _
Antiamoebic Metronidazole
Tinidazole

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 ElF PRECISE PHARMACOLOGY I Qi!#B~f PHARMACOLOGY I

Antiepileptics and Carbamazepine Dermatological drugs Benzoic acid + salicylic acid

anticonvulsants C10nazepam Miconazole
Diazepam C1otrimazole
Ethosuximide Benzyl peroxide
Magnesium sulphate injection
Phenobarbitone
'" Coal tar
Dithranol
Phenytoin Podophyllum resin
Valproic acid Salicylic acid 2%, 5%
Anthelmintics Mebendazole Silver nitrate pencil 40%
Albendazole Betamethasone cream
Ivermectin Calamine lotion 15%
Praziquantel Hydrocortisone cream/ ointment 1%
Diethylcarbamazine Malathion lotion 0.5%
Analgesics and Acetylsalicylic acid Benzyl benzoate lotion 25%
antipyreties Diclofenac Silver sulphadiazine cream I %
I~t', Paracetamol Neomycin + bacitracin ointment
---
Antigout drugs Allopurinol Chlorhexidine cream 5%
Colchicine Antiulcer drugs Cimetidine
Indomethacin Omeprazole
Probenecid -----_.. ...
~
Ranitidine
Opioid analgesics Codeine Magnesium trisilicate compound
Morphine Antiemetics Domperidone
Pethidine Promethazine
Dihydrocodeine Metoclopramide
Antiviral drugs Acyclovir Cyclizine
Ganciclovir Laxatives Bisacodyl
Cardiovascular drugs Atenolol Senna I
Isosorbide dinitrate Antidiabetic drugs I
Insulin
Nifedipine Glibenclamide
Propranolol Metformin
Verapamil Tolbutamide
Captopril
Hydralazine
Methyldopa
I
Lisinopril
I
Digoxin -----~---

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 p' • I!: IJ! I I L PRECISE PHARMACOLOGY I

Cytotoxic drugs Asparaginase .:. Inconsistent drug supply in health centres

Calcium folinate .•:. Lack of medicine formulary in hospitals
Cyclophosphamide .:. Promotional misleading claims by drug companies
Cytarabine
.:. Inadequate drug regulation
Dacarbazine
Dactinomycin .:. Bribing of prescribers / Dispensers by drug companies
Fluorouracil .:. Poor attitude towards continuing medical education
Doxorubicin
Hydroxyurea Consquences of irrational use of medicines
Mercaptopurine .:. Over use of antibiotics leads to development of
Methotrexate
resistance
Methotrexate
Mustine .:. Leads to wastage of scarce resources
Stilboestrol .:. Leads to increased costs of drugs to the patient
~ 'II
Thioguanine .:. Increases adverse drug reactions (especially with poly-
\~ .
Vincristine pharmacy)
.:. May lead to loss of patient confidence in the health
3.1.7 RATIONAL USE OF MEDICINES
system
Rational use of medicine means that patients receive medicines
appropriate to their clinical needs, in appropriate doses and for .:. May lead to poor patient outcome
an adequate period of time and at costs affordable to them and the
community.
3.1.8 PRESCRIPTION WRITING
Irrational use of medicines
Definition:
Irrational use of medicines involves use of too many medicines per
patient, wrong choice of drugs for particular condition, inadequate
.
A prescription is a written instruction from a prescriber (doctor,
dosages and unnecessary use of injections where oral dosage form can dinical officer, a midwife or a nurse.) to a dispenser (pharmacist,
be applicable, indiscriminate use of antibiotics in the treatment of viral pharmacy technician or nurse) on medicines to be administered to a
infections such as cough, diarrhoea among others. patient.
rile prescriber has a duty of care to provide a prescription that is
Factors underlying irrational medicine use; I.'gible in order to minimize the potential for errors in treatment.
•:. Heavy patient load (most prescribers target clearing the line)
.:. Poor communication skills among the medical personnels Generally a good prescription should contain essential information as
.:. I ;lek of ethics among the medical personnels outlined below.
•:. Ii l.lppropriate interpretation of lab tests
.:. Poor attitude towards work
.:. Mi\lo,Hlillg beliefs by the patient (some patients believe they
can oilly be cured by injections)

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 gil!tISE PHAQMACOLOW

It should:- below:-
.:. Be written legibly in ink .:. Define the problem of the patient
.:. Be dated and indelible .:. Specify the therapeutic objective
.:. State the full name and address of the patient .:. Choose the treatment basing on efficacy, safety, compliance
.:. Specify the age and weight of the patient (especially Children) ... and co-existing conditions of the patient.
.:. State the diagnosis •:. Write an accurate prescription
.:. Have the name of drugs written in full .:. Give the patient clear information about the condition and its
.:. State the form, dose and strength of the drug prescribed treatment
.:. State the quantity of drug to be supplied and duration of .:. Review the patient
treatment .:. Decide whether to stop, continue or change treatment.
.:. State the frequency of administration of the drug prescribed Not~:
.:. Have clear instruction for the patient Over prescribing is wasteful, can cause unnecessary adverse effects,
.:. Be signed in ink by the prescriber increase the chances for overdoses, can cause addiction and increases
.:. Have ~he address and telephone contact of the prescriber. the patient's expense on drugs.
.:. Have <lddrcss of the health facility Under prescribing is also wasteful and potentially harmful as it results in
ineffective treatment, resistance and more expensive for the patient as
Qmllitles of a good prescriber more expensive drugs may be prescribed on the next visit after failing
A good prescriber:- to respond to the previous one.
.:. Prescribes medications when necessary
.:. Chooses a treatment regimen that is appropriate to the The Dispensing process
disease and the patient The process of dispensing is undertaken by the dispenser.
.:. Continues therapy for an appropriate time and alters A dispenser is anyone who gives out the medicine / treatment to the
doses of therapy when necessary patient or client. He may be a pharmacist, pharmacy technician, nurse
.:. Prescribes the right medicines according to the diagnosis or a midwife.
•:. Gives a clear explanation to the patient about his/her
condition Roles of a dispenser:-
.:. Explains the effect of the drug and why Its needed .:. Dispenses drugs to patients and wards
.:. Gives information about possible adverse effects of the drug .:. Gives drug information to the patient or client
and what to do if they occur .:. Keeps drug records
.:. Monitors the patient's prognosis and advises the patient when .:. Ensures proper storage of drugs
to return for review .:. Advises the prescriber about drugs
.:. Sometimes procures drugs
The process of rational treatment
Good prescribing is achieved with time through development of The process of dispensing
the necessary skills and a clear understanding of the importance of The procedure of dispensing a prescription involves:-
prescribing appropriately and the processes involved as outlined .:. Receiving a prescription
.:. Interpreting a prescription

-29- -30-
 PRECISE PHARMIDl!l!OGVI PRE]ISE PHARMACOLOGY I
Retrieving medication
Making a proper explanation to the patient and ensure
CHAPTER FOUR
that he/she has understood and will comply to the
ANTIBACTERIAL DRUGS
medication
Ensuring that drugs are packaged well.
.,
4.1.1 INTRODUCTION TO ANTIBIOTICS
Ensuring proper record keeping
Antibiotics are substances produced by or derived from micro-
Supplying of medicine or drugs
organisms which inhibit the growth of or kill other microorganisms.
The dispensing process requires a person to have sufficient knowledge
They are divided into two:-
about the following:-
.:. Bacteriostatic antibiotics.
•:. Formulation of drugs
.:. Bactericidal antibiotics.
•:. Dosage
.:. Indications
•:. Pre.::autions
Bacteriostatic antibiotics
These are antibiotics that inhibit the growth of susceptible bacteria.
•:. Contraindications
They do not kill them immediaely but eventually lead to bacterial deat~ .
.:. Adverse effects
These antibiotics rely on the immune system to eliminate the bactena
.:. Packaging and labeling procedures
Examples;
.:. Storage of the medicine
.:. Tetracyclines.
•:. Legal requirements regarding supply, storage, records and
.:. Chloramphenicol.
labeling of controlled drugs
.:. Erythromycin .
•:. Medicine administration
.:. Azithromycin.
•:. Disease process

Bacteriostatic antibiotics may become bactericidal depending on the

concentration or type of bacteria.

Limitations of bacteriostatic antibiotics

.:. They are less effective for immuno-compromised patients.
•:. They are less effective when organisms are not growing or
dormant.
Bactericidal antibiotics
These are antibiotics that kill bacteria at safe plasma concentrations.
They do not rely on the immune system of the patient.
Examples;
.:. Penicillins (Amoxicillin, ampicillin, Cloxacillin).
•:. Cephalosporins (Cephalexin, Cefaclor, Ceftriaxone) .
•:. Aminoglycosides (Gentamycin, Amikacin).

31- -32-
 , PREC~ PRI$e~13 PHARMACOLOGY I

Key issues to note: Chemical Structure

.:. Bactericidal antibiotics are highly recommended in immuno- Antibiotics sharing the same structure generally have;
compromised patients .:. Similar pattern of antibacterial activity (indications)
.:. Some bactericidal antibiotics are more effective when cells are .:. Effectiveness
.:. Toxicity
actively dividing therefore bacteriostatic drugs reduce their ..,
.:. Same side effects and contraindications
effectiveness when given together.
Chemical Structure Classification of Antibiotics
Classification of antibiotics Class hemical structure) . Examples
Antibiotics can be classified basing on:
Beta Lactams Penicillins
.:. Spectrum of activity
Penicillin G
.:. Mechanism of action Amoxicillin
.:. Chemical Structure Flucloxacillin
Cephalosporins
Spectrum of activity: Cephalexin
Antibiotics can be classified as either narrow spectrum or broad Ceftriaxone
"pO(:.tnllll. Cefuroxime
Nl,rrow spectrum antibiotics Carbapenem
rhose antibiotics are effective against a limited range of bacteria. Mero enem
Thoy are not recommended in mixed infections unless combined with Macrolides Erythromycin
another antibiotic to widen the spectrum of activity. Azithromycin
Examples; C1arithrom cin
.:. Isoniazid Tetracyclines Tetracycline
.:. Cloxacillin Doxycycline
.:. Clindamycin Minoc cline
.:. Flucloxacillin Quinolones Norfloxacin
Broad spectrum antibiotics Ciprofloxacin
These antibiotics are effective against a wide range of bacteria (Gram Ofloxacin
negative and Gram positive bacteria). Pefloxacin
Examples; Aminoglycosides Gentamycin
.:. Tetracycline Amikacin
.:. Chloramphenicol Nitroimidazoles Metronidazole
.:. Ciprofloxacin Tinidazole
Secnidazole
Mechanism of action Sulphonamides Co- Trimoxazole
Antibiotics may be classified as either bacteriostatic or bactericidal. Sui hadoxine
Lincosamides Clindam cin

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 PR~HARMACOlOGY • • • • • •I:---==-=======:JP~RruECISEPHARMACOLOGY I

Principles of antibiotic Therapy Disadvantages of combination therapy

Before an antibiotic is prescribed, the following should be considered; .:. Increased risk of toxicity
.:. Evidence supporting an infection e.g. fever, leukocytosis .:. Selection of multiple drug resistant microorganisms
.:. Establish severity of the infection .:. Eradication of normal host flora leading to super-infection
Ih
.:. Determine the pathogens commonly associated with the'" .:. Increased cost of the drugs to the patient
infected site
.:. Attempt to identify pathogens by carrying out culture and Prophylaxis
sensitivity, Gram stain This is the use of drugs for prevention of disease or infection. It is of
.:. Select an antibiotic basing on clinical efficacy and side effect two types i.e non-surgical and surgical prophylaxis.
profile.
.:. The route of administration of an antibiotic i.e parenteral for 4.1.2 -PENICILLINS
severe infections and oral for mild infections Penicillins are bactericidal antibiotics that Include natural and semi-
.:. Duration of therapy (depends on nature of infection and synthetic derivatives. They are the most widely used antibacterial drugs
response to treatment) because of their availability, low cost and safety profile.
.:. The dose of an antibiotic to be used i.e depends on age, weight
Penicillins are mainly effective against infections caused by gram positive
of the patient, severity of infection, hepatic and renal function
cocci such as Streptococcus pneumoniae, Streptococcus pyogenes and
some gram negative bacteria such as N. meningitidis and N. gonorrhoeae
Empirical therapy
although resistance has emerged.
This is treatment of an infection before culture and sensitivity or
laboratory results are reported. Empirical therapy is based on
Mode of action
knowledge of local patterns of likely pathogens and local susceptibility
Penicillins act by inhibiting cell wall synthesis in susceptible organisms.
data. It can be achieved with the use of a broad spectrum antibiotic or
They are inactive against cell wall deficient organisms (bacteria which
combination therapy.
do not have cell wall) such as Mycoplasma. Legionella species.
Combination therapy
Classification of Penicillins
It involves use of two or more antibiotics to treat mixed bacterial
infections, where the required spectrum of cover cannot be provided Natural penicillins
with a single drug. Combination therapy is used in the treatment of They are hig~ly effective against Gram positive cocci but are uneffective
pelvic inflammatory disease and tuberclosis against most strains of Staphylococcus aureus. They are readily destroyed
by penicillinase (beta lactamase enzyme).
Advantages of combination therapy Examples:
.:. It prevents development of resistance "' .:. Benzyl penicillin (Penicillin G.)
.:. It J'<'Cluces the side effects of the individual drugs .:. Phenoxymethyl penicillin (penicillin V) .
•:. II t'llhilllCes antimicrobial activity (synergism)
.:. M.lY btl lIsed in mixed infections in which the cause is Repository forms of penicillin
111I1<1I0Wll Benzathine benzyl Penicillin.
.
Procaine Penicillin .

··~35- -36-
 , ' 'PRECISE PHARMACOIim , III' PREC~MACOlOGY

Penicillinase resistant penicillins Contraindications

They have a narrow spectrum of activity and are resistant to degradation Known hypersensitivity to penicillins or cephalosporins
by penicillinase enzyme. These drugs are useful for treating S. aureus Severe acute infections
infections.
Dose
Examples:
Adult:
.:. Cloxacillin.
SOOmg 6 hourly increased up to Ig 6 hourly in severe infections
.:. Flucloxacillin.

Broad-spectrum penicillins (Aminopenicillins) Children:

These penicillins have a wide spectrum of activity against gram negative 12.Smg Ikg 6 hourly, OR
and gram positive bacteria. 6-12years: 2S0mg 6 hourly
Aminopenicillins are susceptible to beta lactamase and cannot be used 1-5years: 12Smg 6 hourly
in conditions caused by S. aureus except in combination with beta Imonth - Iyear: 62.Smg 6 hourly
lactamase inhibitors such as c1avulanic acid or salbactam
Examples: Rheumatic fever prophylaxis:
.:. Ampicillin. Adult 2S0mg twice daily
.:. Amoxicillin . Children > 2 years 12Smg twice daily
•:. Amoxicillin plus Clavulanic acid.
Side effects
.:. Urticaria
PENICILLIN V (Phenoxymethylpenicillin) .:. Fever
Available preparations: Tablets 2S0mg
.:. Joint pains
powder for oral suspension 12Smg/Sml
.:. Serum sickness like reactions
Available brand: Pen-V®, unipen®, kam-pen®
.:. Diarrhoea
.:. Skin rashes
Pharmacokinetics
.:. Anaphylaxis
Penicillin V is acid stable and is well absorbed, widely distributed to
.:. Nausea
kidneys, tonsils, liver and it apears in breast milk. It is excreted in urine
and breast milk.
Drug interactions
Probenecid may increase penicillin V blood concentration and risk of
Indications toxicity.
•:. Pharyngitis
Penicilin-V decreases immunological response to live typhoid vaccine.
•:. Tonsillitis
Penicillin-V may reduce the excretion of methotrexate (increased
.:. Gingival infections and periodontitis
toxicity
.:. Tooth abscesses
Key issue to note
.:. Otitis media
.:. Penicillin V should be given on empty stomach atleast I hour
.:. Cellulitis
before or 3 hours after meals to improve on absorption .
•:. Erysipelas
.:. Food or milk may decrease absorption of penicillin-V
.:. Prophylaxis of rheumatic fever

-37- -38-
 \.

'," PRECISDiARMACOLOGV PRE'CISE·PHARIVIA1';OLOGvl

.:. Instruct the patient to complete the prescribed course of Contraindications
treatment even though symptoms may abate before the full Known hypersensitivity to penicillins
course is over. Infectious mononucleosis
.:. Instruct the patient to report any sign of allergic response eg Dose
Skin rush, itching or hives. ., Adult
•:. For streptococcal infections, treatment is given for 10 days Oral: 500mg 4 times daily, doubled in severe infections.
to ensure eradication of S. pyogenes and reduce the risk of 1M: 500mg-1 g 6hourly.
rheumatic fever. Intravenous infusion: over 30-60minutes 500mg 4 times daily
up-to 12g daily for severe infection.
AMPICILLIN
Ampicillin is a semi-synthetic penicillin with a broad spectrum of activity Children:
against gram negative and gram positive bacteria. It is destroyed by 5-12years: 250mg 4 times daily doubled in severe infections.
beta-Iactamase enzymes. 1-5 years: I 25mg 4 times daily doubled in severe infections.
11 I month - I years: 62.5mg 4 times daily doubled in severe
Available preparation: Capsules 250mg infections.
\1 powder for oral suspension I 25mg/ 5ml Neonates:
Powder for Injection 500mg under 7 days 30mg/kg twice daily
14-21 days 30mg/kg 3 times daily
Available brands: Camicil®, Ampiren®, Kam ampi®, 21-28 days 30mg/kg 4 times daily
Pembritin®, Dynacil®, medampi®,
Other conditions
Pharmacokinetics Typhoid: 1-2g 6 hourly for 2 weeks.
Ampicillin is poorly absorbed (40%) and its absorption is reduced by Gonorrhoea: 2g with probenecid Ig as a single oral dose.
the presence of food in the GIT. It is widely distributed in the body, Acute cholecystitis: Adult 1-2g IV / 1M, 6 hourly with gentamycin
small amount is metabolized in the liver and also excreted unchanged 5-7mg/kg IV daily in divided doses.
by the kidneys. Meningitis: Injection I V, 2 -3 g 6hourly for 14days.
Infants and Children: 50-1 OOmg/kg (max 3g) every 4-6 hours.
Indications Neonates: .
.:. Bronchitis .:. Pneumonia Under I week of age 50mg/kg every 12 hours)
.:. Septicaemia .:. Typhoid Older neonates 50mg /kg every 8 hours.
.:. Urinary tract infections .:. Meningitis
.:. Endocarditis .:. Sinusitis Side effects
.:. Gonorrhoea .:. Otitis media .:. Nausea and vomiting .:. Serum sickness -like reaction
.:. Peritonitis .:. Acute cholecystitis .:. Antibiotic associated colitis .:. Rash
.:. Fever .:. Urticaria
.:. Diarrhoea .:. Pain at 1M injection site

-39- -40-
 PRECISE IQlti1;lMMrI!l1if1 PRECI
Drug interactions Pharmacokinetics
.:. Probenecid decreases renal excretion of ampicillin, thereby in- Amoxicillin is well absorbed when taken orally, distributed into lungs,
reasing its blood concentration. prostate, ear, tonsils and sputum, partially metabolized in the liver and
•:. Allopurinol increases the frequency of skin rashes in patients excreted in urine.
receiving ampicillin. ?,

.:. Ampicillin decreases the effectiveness of oral contraceptives Indications

.:. Ampicillin reduces excretion of methotrexate leading to .:. Pneumonia
increased risk of toxicity. .:. Exacerbation of chronic bronchitis
.:. Ampicillin may increase the bleeding effect of anticoagulants. .:. Urinary tract infections
.:. Decreased effectiveness with tetracyclines and .:. Otitis media
chloramphenicol. .:. Dental abscess
.:. Sinusitis
Key issues to note: .:. Lyme disease
.:. Use of ampicillin is limited by the development of bacterial .:. H.pylori eradication
resistance. .:. Billiary tract infections
•:. Food decreases rate and extent of absorption of ampicillin, .:. Acute cholecystitis
therefore, take the oral drug atleast 30minutes before food. .:. Prophylaxis of bacterial endocarditis
.:. Oral suspension is stable for 14 days under refrigeration .
•:. Avoid rapid IV administration of large doses as it may result in Contraindications
seizures. .:. known hypersensitivity to penicillins
•:. Ampicillin is physically incompatible with aminoglycosides .:. Infectious mononucleosis
therefore separate in terms of IV administration by I hour to .:. Penicillin associated jaundice
avoid inactivation of the aminoglycoside by the penicillin.
Dose
AMOXICILLIN Adult: 2S0-S00mg 8 hourly.
AlTloxiciliin is a hydroxylated derivative of ampicillin with similar Ig 8 hourly may be used in severe cases like Pneumonia
spectrum of activity but well absorbed compared to ampicillin. It is
preferred to oral ampicillin because of lower incidence of diarrhoea. Children
5-12years: 2S0mg 3 times daily doubled in severe infections.
Available preparation: Capsules 2S0mg, SOOmg. 1-5years: 12Smg 3times daily doubled in severe infections.
Powder for oral suspension2S0mg/Srnl, I month-I year: 62.Smg 3 times daily doubled in severe infections.
12Smg/ Sml \, Neonates:
Powder for Injection SOOmg/vial. under 7 days 30mg/kg twice daily (max 62.Smg 2 times daily)
7-28 days 30mg/kg 3 times daily (max 62.Smg 3 times daily)
Available brands: Amoxydar®, Amoxil®, Amoxapen®, Duramox®
Penamox®, Amoxiren®, Promox®, Miloxy®
Pulmoxyl®

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 n ' , " "" " , ,PREC~PHARMAC[iJ{l • PREC PHARMACOLOGY

Pneumonia CLOXACILLIN
Adult: 500mg to Ig every 8 hours. Cloxacillin is a semisynthetic derivative of penicillin that is resistant
Dental Abscess to destruction by the penicillinase enzyme. It is therefore effective
Adult: 3 g repeated once after 8 hours. aganist Beta lactamase-producing Staphylocccus aureus.
..:
Available preparation: Capsules250mg
Eradication of H-Pylori: Ig twice daily in combination with Powder for oral suspension I25mg/ 5 ml
c1arithromycin or metronidazole and a proton pump inhibitor.
J Powder for Injection 500mg vial

Otitis media Available brands: Kam c1oxa®, Mediclox®, C1oxispa®, Cloxil®

Imonth-18years 40mg/kg daily in3 divided doses Cloxaren®, Alclox®, Asclox®, Ceclox®,
C1oxcip®
Side effects
.:. Nausea and vomiting Pharmacokinetics
•:. Diarrhoea Cloxacilin is poorly absorbed (50%) and food reduces its absorption.
.:. Skin rash \ It's partially metabolized in the liver and also excreted unchanged in
\

•:. Hepatitis urine.

.:. Serum sickness-like syndrome
.:. Haemolytic anaemia Indications
.:. Urticaria .:. Septicaemia .:. Impetigo
.:. Staphylococcal endocarditis .:. Cellulitis
Drug interactions .:. Pyomyostis .:. Pneumonia
•:. Allopurinol may increase the incidence of skin rash. .:. Septic arthritis .:• Osteomyelitis
.:. AmoxicillJn may decrease effectiveness of oral contraceptives. .:. prophylaxis in bone and joint surgery
•:. Probenecid may increase amoxicillin blood concentration and
risk of toxicity. Contraindications
.:. Amoxicillin reduces excretion of methotrexate thus increasing known hypersensitivity to penicillins
risk of toxicity. Dose.
Adult:
KC'y Issues to note Oral 500mg 6hourly
-t. Inform the patient that amoxicillin may be taken without regard 1M: 250mg 6hourly
to meals. IV: 500mg 6houriy by slow injection or infusion
.:. Instruct the patient to complete the prescribed course of
treatment even if he or she feels better before the full course
Children:
is over. 2-IOyears: 1/2 adult dose
Less than 2years: 1f4 adult dose

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 , ,', ," ",,,", ":! ,I /':,:" ':' " , ' "'''''', PRECISE PHARMACOLOl!i'l

Side effects Pharmacokinetics

.:. Serum-like sickness reaction .:. Diarrhoea Flucloxacillin is well absorbed when taken orally, partially metabolized
.:. Antibiotic associated colitis .:. Skin rashes and excreted in urine.
.:. Joint pains .:. Nausea and vomiting
Urticaria -, Indications
.:.
.:. Haemolytic anaemia .:.
•:. Candidiasis .:. Hepatitis Endocarditis .:. Cellulitis
•:. Pain and inflammation at injection site .:. Osteomyelitis .:. Pneumonia
.:. Impetigo .:. Infected scabies
Drug interactions .:. .:.
Otitis externa Septicaemia
.:. Concomitant use with aminoglycosides produces synergistic .:. Septic arthritis .:. Mastitis
bactericidal effect .:. .:.
Folliculitis and boils Surgical prophylaxis
.:. Probenecid decreases renal excretion of cloxacillin. .:. Infected bums .:. Abscesses
•:. Cloxacillin increases risk of bleeding when given concurrently
with Warfarin. Contraindications
•:. Cloxacillin decreases the immunologic response to live typhoid .:. Known hypersensitivity to penicillins.
VllIccine. Therefore, allow 24 hours or more to elapse between •:. History of f1ucloxacillin associated jaundince
the last dose of cloxacillin and the administration of oral typhoid .:. Ocular administration
vaccine.
.:. The effectiveness of oral contraceptives may be reduced by Dose
cloxacillin. Oral
Adult: 2S0-S00mg every 6 hours. maxAg daily
Key issues to note
'IV 1-2g every after 6 hours. Max 12g daily.
•:. Oral cloxacillin should be taken on an empty stomach, I hour
before meals, because the presence of food decreases its
Children:
absorption.
Oral
.:. Oral cloxacillin is not optimal for the treatment of severe
I O-18years: 2S0-S00mg 4 times daily.
infections, therefore use the injectable form.
2-IOyears: 12S-2S0mg 4 times daily.
•:. Instruct the patient to complete the prescribed course of
I month -2 years: 62.S-12Smg 4 times daily.
treatment to avoid relapse of the infection.
IV SOmg / kg every after 6 hours.

FLUCLOXACILLIN Side effects:

Flucloxacillin has the same spectrum of activity as .cloxacillin but it is .:. Nausea and vomiting .:. Joint pains
well absorbed compared to Cloxacillin. .:. Urticaria .:. Fever
Available preparations: Capsules 2S0mg .:. Skin rash .:. Chills
Powder for oral suspension 12Smg/Sml .:. Diarrhoea .:. Headache

Available brands: Ramaxir®, Floxapen®

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 IDRECISE PHARMAC:!lED

Drug interactions Side effects

.:. probenecid delays the renal excretion of flucloxacillin. .:. Gastrointestinal upset
.:. Flucloxacillin may affect the gut flora leading to lower oestrogen .:. Urticaria
re-arbsoption and reduced efficacy of combined oral
contraceptives.
., .:.
.:.
Skin rash
Phlebitis with IV injection
.:. Diarrhoea
Key issues to note .:. Indigestion
.:. Flucloxacillin, if prescribed together with aminoglycosides,
. should not be mixed in the same syringe or giving set. Drug interactions
Precipitation may occur. .:. Probenecid decreases renal excretion of flucloxacillin
•:. Instruct the patient to complete the prescribed course of
flucloxacillin to avoid relapse. AMPICILLIN + CLOXACILLIN H'

.:. Flucloxacillin is best absorbed if taken on an empty stomach, Available preparations: Capsule sOOmg.
atleast 30minutes before food or 2 hours after. Powder for oral Suspension 2s0mg/sml
l.i .,
Powder for Injection sOOmg
FLUCLOXACILLIN + AMOXICILLIN
Available preparations: Capsules sOOmg Available brands: Ampiclox®, Pen-A-c1ox®, Azuclox®,
Powder for oral suspension 2s0mg/sml Reiclox®, Spamclox®, C1oxap®, Elyclox®,
Powder for Injection Ig
Indications
Available brands: Flucamox®, Flamox® .:.
.:. Pneumonia Bronchitis
Indications .:. Tonsillitis .:. Septic abortion
.:. Pneumonia .:. Chronic bronchitis .:. Post operative wound .:. Boils
.:. Sinusitis .:. Otitis media infections .:. Abscesses
.:. Pharyngitis .:. Tonsillitis .:. Endocarditis .:. Osteomyelitis
.:. Wound infections .:. Osteomyelitis .:. Meningitis .:. Sinusitis
.:. Gonorrhoea .:. Urinary tract infection .:.
.:.
Otitis media .:. Surgical prophylaxis
.:. Boils .:. Cellulitis Urinary tract infections .:. Septicaemia
.:. Abscesses .:. Septicaemia
Contraindications
Contraindications Known allergy to penicillins.
•:. Known hypersensitivity to penicillins
Dose Dose:
Adult: Adult: 500-1 OOOmg 6 hourly.
500 -I OOOmg every 6-8 hours. Children:
Children: 2-IOyears: 2s0-s00mg 6 hourly.
2-12years: 2s0-s00mg every 6-8 hours. I month -2 years: 12s-2s0mg 6 hourly.
I lIlonth-2 years: 12s-2s0mg every 6-8 hours.

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 I I, ' I': " PRECISE PHARMACOLOGY

Side effects Dose

.:. Gastrointestinal disturbances .:. Urticaria Adult Oral: 625mg twice daily or 375mg 3 times a day for 7 days
:ilid:',,
.:. Haemolytic anaemia .:. Skin rash 1:'!!liiP:': Severe infection: Ig twice daily/ for 7-10 days.
.:. Joint pains .:. Fever !l11111!!!:!;:; Dental infection: 375mg 3 times a day for 5 days
.:. Serum sickness I I! Injection: IV 1.2g 6-8 hourly over 2 minutes or infusion over
'" . ,: 30minutes
Key issues to note
.:. Instruct the patient to take ampicillin/ cloxacillin on empty Children:
stomach, because presence of food decreases its absorption. Over 6years: 3 12mg 3 times daily
•:. Instruct the patient to complete the prescribed course. 1-6years: 156mg 3 times daily.
Under I year: 25-50mg/kg /day of amoxicillin in divided doses
AMOXICILLIN + CLAVULANIC ACID every 8 hours.
The above combination acts synergistically because c1avulanic acid
Side effects
binds to beta- lactamases thereby protecting amoxicillin from being
.:. Diarrhoea .:. Nausea
destroyed by beta-Iactamase producing strains of bacteria.
.:. Vomiting .:. Skin rashes
Available preparations: Tablet 375mg, 625 mg, and IOOOmg.
.:. Urticaria .:. Indigestion
Powder for oral suspension I 56mg/5ml,
.:. Gastritis .:. Abdominal discomfort
228mg/ 5ml.
.:. Vaginitis .:. Anorexia
Powder for Injection 600mg
.:. Antibiotic associated colitis

Available brands: Augmentin®, Clavulin®, Fleming®, Clavam®,

Drug interactions
_Enhancin®, C1avomid®, Co-Amox®, Myclav®,
.:. Probenecid decreases the renal excretion of amoxicillin
resulting into increased and prolonged blood levels
Indications
ill .:., Effectiveness of oral contraceptives is reduced byamoxicillin/
.:. Pneumonia .:. Otitis media
c1avu lanate
.:. Sinusitis .:. Tonsillitis
.:. Allopurinol may increase the incidence of skin rash
.:. Urinary tract infections .:. Urethritis
.:. Wound infections .:. Boils
Key issues to note
.:. Cellulitis .:. Osteomyelitis
.:. Advise the patient to take the drug with meals to minimise
.:. Dental infections .:. Intra abdominal sepsis
gastrointestinal disturbances.
•:. Animal bite .:. Septic abortion
.:. The patient should maintain adequate hydration especially
.:. Acute exacerbation of chronic bronchitis
when using high doses of the drug to prevent risk of
Contraindications crystalluria.
•:. Known hypersensitivity to penicillins .:. Clavulanic acid degrades rapidly therefore parenteral solution
.:. History of penicillin or amoxicillin with c1avulanic acid- associated should be used immediately after mixing and the tablet
jaundince or hepatic dysfunction. should be stored in air tight containers.

-49- -50-
 .:. Dosage should be reduced in moderate to severe renal
impairement.
.:.
.:.
.... ! :',,':

Serum sickness like reactions

Antibiotic associated colitis
.:.
.:.
Diarrhoea
Nausea
,
PftECIS PHARMACOJiIiVI

.:. Coagulation disorders

BENZYL PENICILLIN
Available preparations: Powder for Injection 600mg Drug interactions
(I,OOO,OOOunits). .:. Probenecid decreases renal excretion of benzyl penicillin
Indications .:. Benzyl penicillin may interact with bacteriostatic drugs such as
.:. Community aquired pneumonia .:. Septicaemia chloramphenicol and tetracycline
.:. Meningitis .:. Anthrax .:. Oral contraceptive effectiveness may be reduced by
.:. Syphilis .:. Gas gangrene Benzylpenicillin
.:. Lyme disease
.:. Pharyngitis /tonsillitis Key issues to note
.:. Necrotizing fasciitis .:. Inform the patient that intramascular benzyl penicillin injection
.:. Aspiration pneumonia is painful.
.:. Infective endocarditis .:. IV benzyl penicillin is physically incompatible with
aminoglycosides therefore give them separately.
Contraindications .:. Avoid rapid IV administration of large dozes of benzyl
.:. Known hypersensitivity to penicillins. penicillin, it may result in convulsions.
•:. Intrathecal route. .:. The intravenous route is prefered for ne.onates and infants.

Dose BENZATHINE PENICILLIN

Adult: 600mg 6 hourly. Benzathine penicillin is a repository preparation that slowly releases
Severe infection: I .2g every 4 hours IV usually with an benzylpenicillin after intramuscular injection, by hydrolysis. of the
aminogiycoside. benzathine - penicillin complex. Low serum levels may be detected
Neurosyphilis in adults: by slow IV injection 1.8 -2.4g every 4 for up to 30 days. Distribution and elimination are similar to
hours for 2 weeks. benzylpenicillin.
Children:
I month -12 years: I OOmg /kg daily in 4 divided doses. Available preparations: Powder for Injection 2.4MU (million units)
Infants: 1-4weeks: 75mg/kg daily in 3 divided doses.
Neonates: SOmg/kg daily in 2 divided doses. Indications•
•:. Syphilis
Side effects .:. Streptococcal pharyngitis
.:. Urticaria .:. Fever .:. Acute cervical adenitis
.:. Joint pains .:. Skin rashes .:. Diphtheria
.:. Haemolytic anaemia •••.. Convulsions .:. Primary prevention of rheumatic fever
.:. Pain and inflammation at .:. Coma
injection site .:. Angioedema

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 " ,,' \DREC ~ EPHARMACOLQG't'1
,
Contraindications
.:. Known hypersensitivity to penicillins. Available preparations: powder for injection-4MU .
•:. Neurosyphilis.
•:. Intravascular injection. Indications
.:. Congenital Syphilis .:. Cellulitis
Dose .:. Cutaneous anthrax .:. Childhood pneumonia
Early syphilis: 2.4MU by deep 1M injection as a single dose divided .:. Erysipelas .:. Bites
between two sites. .:. Diphtheria .:. Mouth infections
Late syphilis: 2.4MU deep 1M divided between two sites once weekly
for 3 consecutive weeks. Contraindications
Pharyngitis and rheumatic fever: 1M 1.2MU as a single dose. .:. Known hypersensitivity to penicillins
Children under 30kg: 600,000 units deep 1M as a single dose. .:. Neuro syphilis
.:. Intravascular injection
Side effects Dose
.:. Joint pain .:. Fever Adults: 1M 600,000 units-I.2MU daily
•:. Urticaria .:. Skin rashes Syphillis: 1M °1 million units daily for 10-14 days.
.:. Serum sickness like reaction .:. Neutropenia Infants and Children:
.:. H<lernolytic anaemia .:. Thrombocytopenia Pneumonia: Deep 1M SOmg/kg (max. 1.2g) daily for 10 days
.:. Pain and inflammation at injection site Congenital syphillis:
Children upto 2years: SOmg/kg daily for 10 days
Drug interactions
.:. Probenecid decreases renal excretion of benzathine penicillin
Side effects
.:. Oral contraceptive effectiveness may be reduced by .:. .:.
Urticaria Fever
benzathine penicillin. .:. Joint pains .:. Skin rashes
•:. Benzathine penicillin may reduce excretion of methotrexate .:. .:.
Serum sickness like reaction Haemolytic anaemia
leading to increased toxicity. .:. .:.
Angioedema Thrombocytopenia
Key Issues to note .:. Diarrhoea .:. Nausea
.:. Give doses> 900mg( I .2MU) as two injections at separate .:. Pain at injection site
sites.
.:. Give Benzathine Penicillin with caution in renal failure. Drug interactions
.:. Do not give by intravenous injection. Probenecid decreases renal excretion of procaine benzyl penicillin

PROCAINE PENICILLIN Key issues to note

Procaine penicillin is a relatively insoluble suspension of complexed .:. Never administer procaine penicillin intravenously
procaine and benzyl penicillin which releases benzyl penicillin slowly .:. Give Procaine penicillin with caution in infectious
after intramuscular injection. Peak serum levels are achieved within mononucleosis because of high incidence of rash.
1-4 hours in adults and decline steadily over 24 hours.

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4.1.3 CEPHALOSPORINS Second generation cephalosporins

;'I' Cephalosporins are semi synthetic beta lactam antibiotics closely related This group includes:-
both structurally and functionally to penicillins. They have an advantage .:. Cefuroxime
over the penicillins in that they are less susceptible to inactivation by .:. Cefaclor
beta lactamase enzyme and have a broader spectrum of activity. Hence Second generation cephalosporins have similar coverage against
are often used when penicillin treatment has proved ineffective gram positive organisms as the first generation but with enhanced
gram negative coverage. However, they are less active against gram
Mode of action +ve bacteria than the first generation and have no activity against
Cephalosporins are bactericidal in action and inhibit the synthesis of the enterococci or P. aeruginosa.
bacterial cell wall.
Classification of cephalosporins. Cefuroxime, has good activity against S. aureus and beta-Iactamase
Cephalosporins are classified into generations basing on bacterial producing H. influenzae. It is the only second generation drug with
susceptibility patterns and resistance to beta lactamases, as follows:- good penetration of the central nervous system.
•:. First generation Cephalosporins Spectrum of activity of Second generation
.:. Second generation cephalosporins .:. Streptococcus pneumoniae
.:. Third generation cephalosporins .:. Escherichia coli
.:. Fourth generation cephalosporins .:. Anaerobic streptococci
.:. Streptococcus pyogenes
First generation Cephalosporins. .:. Neisseria gonorrhoeae
This group includes:- .:. Proteus mirabilis
.:. Cephalexin .:. Klebsiella pneumoniae
.:. CefadroxiI .:. Haemophilus influenzae
.:. Cephradine
.:. Cefazolin Third generation cephalosporins
First generation cephalosporins are mainly active against gram positive This class includes:-
bacteria and have limited activity against gram negative bacteria like H. .:. Ceftriaxone .:. Cefotaxime
influenzae. .:. Ceftazidime .:. Cefixime'
Spectrum of activity of first generation .:. Cefpodoxime .:. Cefdinir
••• Streptococcus pyogenes Third generation cephalosporins are less active than the first and
•
•:. Streptococcus pneumoniae second generation drugs agaim'tgram +ve bacteria, but are more
.:. Staphylococcus aureus active against gram -YJvbacteria. including those resistant to the first
.:. Staphylococcus epidermidis and second generatiOn. They are less active against S. aureus than the
.:. Klebsiella pneumoniae first generation drugs.
•:. Proteus mirabilis
.:. Escherichia coli w Spectrum of activity
.:. Anaerobic cocci (e.g. peptococcus, peptostreptococcus) .:. Escherichia coli
.:. Klebsiella pneumoniae

-55- -56-
 , II) , I ,

I:' 'I " I , "" PRECI~i1PHARMACOLOGY

.:. Proteus mirabi/is .:. Haemophilus influenzae Contraindications
.:. Pseudomonas aeruginosa .:. Neisseria gonorrhoeae .:. known allergy to cephalosporins
.:. Enterobacter aerogenes .:. Providencia
.:. Serratia .:. B. fragi/is Dose
Adult: 250 mg every 6 hours or 500mg every 8-12 hours increased up
Fourth generation cephalosporins I • to Ig every after 6-8 hours for severe infection. Max 4g per day
These drugs include:- Celluitis and erysipelas: 500mg 6 hourly for 7-10 days following intial
•:. Cefepime. therapy with cefazolin .
Fourth generation drugs, like the third generation, have an extended Osteomyelitis: 1-2g every 6 hours to complete the course of 4- 6
spectrum of activity against gram -ve bacteria compared to the 15t weeks following intial therapy with cefazolin.
and 2nd generation. Cefepime is active against gram positive and gram Children: 25mg/kg daily in divided doses, doubled in severe infection
negative infections including Pseudomonas aeruginosa. OR
12 years: 250mg every 8 hours
CEPHALEXIN I - 5 years: 125mg every 8 hours
Available preparations: Capsules 2S0mg, SOOmg Under I year: 125mg every 12 hours
Powder for oral suspension 12Smg/ 5ml, Otitis media: 75 - I OOmg / kg / day in 4 divided doses
250mg/5ml. Prophylaxis of recurrent UTI
Adult: 125mg at night.
Available brands: Cephadar®, Keflex®, Sporidex®, Cefamor®,
Felexin®, Oriphex®, Cephoxin®, Cefex® Side effects
.:. Nausea .:. Diarrhoea
Pharmacokinetics .:.Vomiting .:. Abdominal pain
Cephalexin is absorbed rapidly from the GIT after oral administration, .:. Dyspepsia .:. Loss of appetite
distributed widely into most body tissues including the gall bladder, .:. Headache .:. Urticaria
sputum, bone, synovial fluid. It is not metabolized and is excreted in .:. Rash .:. Angioedema
unchanged in urine. .:. Pruritus .:. Vaginal candidiasis
.:. Fatigue
Indications
.:. Otitis media Pneumonia Drug interactions
.:. Impetigo Erysipelas .:. Probenecid decreases renal excretion of cephalexin, increasing
.:. Cellulitis Pyomyositis its blood levels.
.:. Osteomyelitis .:. Septic arthritis .:. Oral contraceptives effectiveness may be reduced by
.:. Urinary tract infections .:. Pharyngitis cephalexin
.:. Dental infections .:. Tonsillitis .:. Aminoglycosides and loop diuretics may increase the
•:. Bronchitis nephrotoxicity caused by cephalexin.
.:. Prevention of bacterial endocarditis
----~

-57- -58-
 'II' iI"II
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I EPHAR ACOLOGY ISE PHARMACOLOIWJ

Key Issues to note Side effects

.:. Administer cephalexin on an empty stomach, atleast one hour .:. Nausea .:. Oral candidiasis
prior to meals or 2 hours after meals. .:. Vomiting .:. Vaginal candidiasis
.:. Shake the suspession well before use. .:. Headache .:. Skin rash
.:. Instruct the patient to complete the prescribed course to avoid .:. Diarrhoea .:. Pruritus
relapse of infection. .:. Abdominal pain .:. Urticaria

CEFADROXIL Drug interactions

Available preparations: Tablets 2S0mg,sOOmg .:. Probenecid decreases renal excretion of cefadroxil
Powder for oral suspension 12smg / sml, .:. Loop diuretics may increase nephrotoxicity of cefadroxil
2s0mg/Sml .:. Concomitant use with bacteriostatic agents like tetracyclines,
erythromycin may interfere with bactericidal activity.
Available brands:
Key Issues to note:
Pharmacokinetics .:. Cefadroxil may be administered with or without meals.
Cefadroxil is absorbed rapidly and completely from the GI tract after .:. Shake the suspession well before use.
oral administration and is distributed widely into most body tissues. It .:. Administration with food may decrease nause~ or vomitting.
is not metabolized and is excreted unchanged in urine.
CEPHRADINE
Indications Available preparations: Capsules sOOmg, 2S0mg
.:. Pneumonia .:. Pharyngitis Powder for oral suspen~jon 12smg/Sml.
.:. Mastitis .:. Chronic bronchitis 1/
.:. Tonsillitis .:. Osteomyelitis Available brands: Velosef®, Valodin®', Bactocef ®
.:. Urinary tract infections .:. Otitis media
.:. Septic arthritis .:. Sinusitis Pharmacokinetics
.:. Cellulitis .:. Skin and soft tissue infection Cephradine is well absorbed from the GIT and is distributed widely
into body tissues like bone, kidneys, sputum, gall bladder, synovial
Contraindications fluids. CSF penetration is poor but the drug crosses the placenta. It is
.:. known hypersensitivity to cephalosporins not metabolized and is excreted unchanged in urine.

Dose Indications
Adult: 500 - 1000 mg twice daily .:. Pneumonia
Children: .:. Osteomyelitis
Over 6 years: 12.Smg/kg once or twice daily or sOOmg twice daily .:. Urinary tract infections
I - 6 years: 2s0mg twice daily " .:. Prostatitis
Under I year: 12Smg twice daily .:. Otitis media

-59- -60-
 , , ~PHARMACOLOGY

.:. Prophylaxis in surgery .:. Oral suspension is stable for 7 days at room temperature or If

.:. Tonsillitis 14 days at 2-8°C after reconstitution

.:. Pharyngitis
.:. Skin and Soft tissue infections CEFUROXIME
,..
Available preparations: Tablets 250mg, 500mg.
Cont'raindications Powder for oral suspension 125mg / 5ml
.:. known hypersensitivity to cephalosporins Powder for Injection 750mg, 1.5g

Dose Available brands: Zinnat®, Axetine®, Kefstar®

Adult: 250-500mg every 6 hours or 500mg every 12hours, up to Ig Zamur®, Zinacef®,
every 6hours for severe infection. Proximexa®, Pulmocef®,
Pharmacoldnetics
Children: Cefuroxime axetil is absorbed from the GIT and its absorption is
I month-12 years: 25-50mg /kg daily in 2-4 divided doses. enhanced by food. It penetrates well into most fluid spaces and tissues.
Otitis media: 75- IOOmg/kg daily in equally divided doses It is not metabolized and is excreted primarily in urine.
every 6 hours.
Indications
Side effects .:. Acute and chronic bronchitis .:. Pneumonia
.:. Abdominal Pain .:. Anorexia .:. Acute otitis media .:. Gonorrhoea
.:. Diarrhoea .:. Glossitis .:. Sinusitis .:. Bacterial Meningitis
.:. Nausea and Vomitting .:. Vaginitis .:. Tonsillitis and Pharyngitis .:. Surgical prophylaxis
.:. Pseudomembranous Colitis .:. Rash .:. Impetigo and pyoderma .:. Pelvic inflammatory
.:. Urticaria disease
Contraindications
Drug interactions .:. known allergy to cephalosporins
.:. Concomitant use with nephrotoxic drugs like vancomycin ,loop Dose
diuretics, and aminoglycosides increases the risk of Adult: Oral
nephrotoxicity Pneumonia 500mg 12 hourly for 7-10 days.
.:. Concomitant use with bacteriostaticdrugs like tetracyclines, Pharyngitis and tonsillitis 250mg 12 hourly for 10 days.
erythromycin may interfere with bactericidal activity of Otitis media 250mg 12 hourly for 10 days.
cephradine Otitis media (Children over 2 years) 250mg twice daily for 10
days.
Key Issues to note Gonorrhoea Ig single dose.
.:. Cephradine may be administered with or without meals. Urinary tract infection 125mg twice daily doubled in
Le. food may decrease the rate but not the extent of oral pyelonephritis.
absorption 1M/IV 750mg 8 hourly,.Severe infection IV 1.5g 6-8 hourly
.:. Shake the suspession well before use
/
-61- -62-
 , , ',1,' , 'I '" ",," ,': , PRECISE PHARMACl I
", , , ' , , PRE
Children: Available brands: ceclor®, vercef®
Oral 12Smg twice daily r
1M/IV 30-1 OOmg/day in 3-4 divided doses. Pharmacokinetics
Cefaclor is well absorbed from the GIT. Food delays but does not
Side effects '1',

.:. Skin rash .:. prevent complete absorption. It is well distributed into most body
Headache
.:. Urticaria .:. tissues and fluids but CSF penetration is poor. It is not metabolized and
Fever
Is excreted primarily in urine.
.:. Nausea and vomiting .:. Anorexia
.:. Diarrhoea .:. Abdominal pain Indications
.:. Pseudomembraneous colitis .:. Nephrotoxicity +:. Pneumonia
.:. Vaginal candidiasis .:. Sinusitis
.:. Pharyngitis .:. Tonsillitis
Drug interactions .:. Otitis media .:. Bronchitis
.:. Efficacy of oral contraceptives may be reduced .:. Urinary tract infections .:. Gonococcal urethritis
.:. Nephrotoxic drugs such as gentamycin, vancomycin may .:. Skin and soft tissue infections
increase the potential for nephrotoxicity Contraindications
.:. Probenecid inhibits the tubular secretion of cefuroxime .:. Known hypersensitivity to cephalosporins
resulting into prolonged high serum concentrations .:. Infants less than one month
.:. A disulfiram-like reaction may occur when alcohol is given
concurrently with cefuroxime Dose '11

Key issues to note Adult: 2S0-S00mg every 8 hours, or 37S-7S0mg every 12 hours using
((,tntrolled release. jt
.:. Cefuroxime axetil is well absorbed after a light meal, therefore
Children:
it should be administered with food
•:. Shake suspension well before use ',', Over 5 years: 2S0mg every 8 hours.
•:. The tablet should not be broken before swallowing I - 5 years: 12Smg every 8 hours.
•:. Reconstituted injectable solution is stable for, 24 hours at room I month - I year: 62.Smg every 8 hours.
temperature and 48hours when refrigerated
Side effects
.:. Reconstituted oral suspension may be stored at room
.:. Diarrhoea .:. Pruritus
temperature or refrigerator and discarded after 10 days
.:. Vomiting .:. Nausea
.:. Oral candidiasis .:. Rashes
CEFACLOR
.:. Fever .:. Headache
Available preparations: Capsules /tablets 37Smg
Powder for oral suspension; 12Smg / Sml, .:. Pseudo membranous colitis .:. Urticaria
.:. Abdominal discomfort .:. Serum sickness syndrome
2S0mg/Sml
suspension bd I87mg/Sml

-63- -64-
 " I '11'11""
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Drug interactions Dose
.:. Probenecid decreases renal excretion of cefaclor Adult and Children over 10 years: 200 - 400mg daily in I - 2 divided
•:. Cefaclot may enhance the anticoagulant effect of warfarin doses.
.:. Contraceptive effect of oestrogens may be reduced
., Gonorrhoea: 400mg or 800mg as a single dose
Children:
Key Issues to note: 6 • 10 years: 200mg daily in 1-2 •
.:. Advise the patient to take entire course of medication even If I - 5 years: I OOmg daily
she/he feels better early in the course 6months· Iyear: 7Smg daily
.:. Store the capsules / tablets and any unreconstituted powder
for oral suspension at room temperature Side effects
.:. Food or milk delays and decreases plasma concentration of the .:. Diarrhoea .:. Flatulence
drug .:. Nausea .:. Vomiting
.:. Swallow the tablets whole. Do not crush or chew them .:. Abdominal pain .:. Loose stool
.:. Dyspepsia .:. Headache
CEFIXIME .:. Rashes .:. Dizziness
Available preparations: Tablets IOOmg, 200mg, 400mg .:. Urticaria .:. Pruritus
Powder for oral suspension IOOmg/Sml, .:. Vaginal candidiasis
7Smg/Sml.
Drug interactions
.:. Cefixime may increase carbamazepine serum concentrations
Available brands: Gramocef-O®, Cefim®, Topcef®, Ixime®,
.:. Probenecid increases serum concentration of cefixime
Spaxime®, Cefix®, Maxpan®, Taxim-O®
.:. Increased bleeding with anticoagulants
Pharmacokinetics .:. Antacids
Cefixime is well absorbed from the GIT. Presence of food delays its Key Issues to note
absorption but total amount absorbed is not affected. It is partially .:. Reconstituted suspension may be stored for 14 days
metabolized and is excreted primarily in urine. at room temperature or under refrigeration .
•:. Cefixime may be administered with or without food although
Indications
food delays the time to reach peak concetration .
.:. Acute bronchitis •:. Typhoid
.:. Shake suspension well before use.
.:. Pharyngitis and tonsillitis •:. Otitis media
.:. Gonorrhoea (
.:. Pneumonia
CEFPODOXIME ,.",
.:. Acute exacerbations of chronic b~onchitis
Available preparations: Tablets 200mg
.:. Uncomplicated urinary tract infections ~
Powder for oral suspension IOOmg/Sml
Contraindications
Available brands: Orelox®, Tambac®, Cefodox®'
.:. History of anaphylactic reaction to penicillins
.:. Known hypersensitivity to cephalosporins

-65- -66-
,
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,I', 'II i ' ': " : PRECISE PHARMACOLOGY , . ' ." , PREflSE PHARMA~QL.1~YJ

Pharmacokinetics Drug interactions

Cefpodoxime proxetil is a pro-drug that is metabolized to the active +:. Concomitant administration with high doses of antacids or H 2
metabolite cefpodoxime. It is rapidly absorbed after oral administration, blockers reduces plasma concentration of cefpodoxime
widely distributed to most body tissues, undergoes minimal metabolism +:. Renal excretion of cefpodoxime is inhibited by probenecid
and is excreted unchanged in urine. to,
Kc.~y Issues to note
Indications .:. Food increases oral bioavaibility of cefpodoxime therefore give
.:. Acute bronchitis .:. Cellulitis the tablet with food
.:. Chronic bronchitis .:. Pneumonia .:. After reconstitution, suspension may be stored in a refrigerator
.:. Acute Sinusitis .:. Tonsillitis for 14 days
.:. Pharyngitis .:. Infected wounds
.:. Urinary tract infections .:. Abscesses CEFDINIR 1I.
.:. Otitis media .:. Gonorrhoea AVllilable preparation: Capsules 300mg

Contraindications AVltilable brand: Adci®

.:. Known hyp~rsensitivityto cephalosporins
I·h.. rmacokinetics
Dose C:tllfdlnir is absorbed from the gastrointestinal tract following oral
Adults: ~d,ninistration, widely distributed into tissues and is 60 to 70% bound
Pharyngitis and tonsillitis: 100mg 12 hourly for 5-10 days 10 plasma proteins. It is not appreciably metabolised and is excreted in
Gonorrhoea: 200mg Single dose. thCllurine.
Pneumonia and Bronchitis: 200mg 12 hourly for 10-14 days
Skin and soft tissue infections: 400mg 12 hourly for 7-14 days Indications
Uncomplicated urinary tract infections 100mg 12 hourly for .:. Tonsillitis .:. Pneumonia
7 days. .:. Acute otitis media .:. Pharyngitis
Children: .:. Skin and Soft tissue infections .:. Acute Sinusitis
Over 9 years: I OOmg every 12 hours .:. Acute exacerbation of chronic bronchitis
3-8 years: 80mg every 12 hours
2months - 2 years: 40mg every 12 hours or 8mg/kg/day in 2 • Contraindications
·, Ii
divided doses. .:. Known hypersensitivity to cephalosporins
I
Side effects
Dose • -/
.:. Diarrhoea .:. Pruritus
Adult: 300mg 12 hourly for 5-10 days Or 600mg once daily for 10
.:. Vomiting .:. Nausea
d~ys. ,
.:. Headache .:. Abdominal pain
.:. Tinnitus .:. Skin rashes
51cln and Soft tissue infection: 300mg 12 hourly for 10 days.
Children: 6months -12 years; 7mg/kg 12 hourly for 5- 10 days.
.:. Malaise

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 a.JIIIIDII.IIIIII.II.I_._II.IIII_I.J.I
•• '7.IEJp~RE~CI~SEJiPmHARMACOLOGYI Ii PRECISE

Surgical prophylaxis .:. Septicaemia

Side effects
.:. Dtarrhoea Constipation Syphilis .:. Acute peritonitis
.:. Pruritus Insomnia Typhoid fever
.:. Vaginal candidiasis Dizziness Osteomyelitis and septic arthritis
?,

.:. Nausea Flatulence Pelvic inflammatory disease

.:. Abdominal pain Anorexia Skin and soft tissue infections
.:. Headache
Contraindications
Drug interactions .:. Neonates with jaundice
.:. Preparations containing iron may interfere with absorption of .:. Acidosis
cefdnir .:. Known hypersensitivity to cephalosporins
.:. Concomitant administration of antacids containing aluminium Dose
. (' or magnesium interfere with absorption of oral cefdnir A~u~t: I.-2g once daily or in two divided doses given as deep 1M or slow
~ .:. Probenecid reduces renal elimination of cefdnir IV injection over 2-4 min. or as infusion over at least 30 min. increased
to 4g daily in severe infections
Key Issues to note Uncomplicated gonorrhoea: 2S0mg 1M as a single dose.
•:. Cefdinir may be administered with or without food,
~urgi~al prophylaxis: 1M or IV inj~ction over at least 2-4minutes Igat
administer with food If stomach upset occurs
induction, colorectal surgery 2g at induction.
•:. Administer cefdinir atleast 2 hours before or after
Children:
antiacids or Iron supplements ~ess ~han SOkg: 2S-S0mg/kg once daily increased to 80mg/kg iii severe
infections.
CEFTRIAXONE Neonates: SOmg/kg/day.
Available preparations: Powder for Injection 1M / IV
SOOmg, I g, 2g
Side effects
.:. Skin reaction , .:. Phlebitis at injection site
Available brands: Medaxonum®, Rocephin®, Mesoporin®, .:. .:.
Superinfection Fever
Powercef®, Axone®, Oframax® .:. Loose stool .:. Diarrhoea
,I',
.:. Nausea and vomiting .:. Headache
Pharmacokinetics .:. Dizziness .:. Pancreatitis
Ceftriaxone is widely distributed into body tissues and fluids after
parenteral administration. It penetrates well into the CSF, especially
Drug intractions
when the meninges are inflamed and it's excreted unchanged in urine.
.:. Ceftriaxone may reduce the effectiveness of oral
contraceptives
Indications .:. Concomitant use with aminoglycosides produces synergistic
.:. Pneumonia .:. Otitis media
antimicrobial activity against Pseudomonas aeruginosa
.:. Gonorrhoea .:. Chancroid
and some strains of Enterobacteriaceae
.:. Meningitis .:. Urinary tract infection

-69- -70-
 -IFCIV' sI' _. P,REIB~i~ PHARM}CO !IID

Key Issues to note: Children: 100 - I SOmg/kg daily in 2 - 4 divided doses increased up to
.:. Reconstituted solution is stable for 24 hours at room 200mg/kg daily in severe infections
temperature or 3 days when refrigerated
.:. Ceftriaxone is incompatitable with calcium, therefore do not Neonates:
give with calcium containing solution ., 0-1 week old SOmg/kg I 2 hourly
.:. Intramascular doses over Ig should be divided between 1-4weeks old SOmg/kg 8 hourly
more than one site
Side effects
.:. Pseudomembranous colitis .:. Skin rash
CEFOTAXIME .:.
.:. Headache Vomiting
Available preparations: Powder for injection SOOmg, I g
.:. Diarrhoea .:. Nausea
.:. Pain and inflamation at injection site .:. Candidiasis
Available brands: Valoran® ,C1aforan®, Cefotim®, Oritaxim®
.:. Pain at injection site .:. Malaise

Pharmacokinetics Drug interactions

... Cefotax~e is not absorbed from the GIT and must be given by injection. .:. Probenecid decreases renal excretion of cefotaxime
It is distributed widely into most body tissues such as liver, kidney, and prolong its half life
bone, sputum and also has adequate CSF penetration when meninges .:. Concomitant use with aminoglycosides results in
are inflamed. It is metabolized partially to an active metabolite and synergistic activity
excreted in urine and to some extent in breast milk. .:. Chloramphenicol inhibits anti bacterial activity of
Indications cefotaxime
.:. Typhoid fever .:. Pneumonia
.:. Acute and chronic bronchitis .:. Bacterial meningitis Key Issue to note
.:. Septicaemia .:. Cellulitis .:. Use cefotaxime instead of ceftriaxone for gram-negative
.:. Osteomyelitis .:. Acute peritonitis septicaemia in neonates
.:. Pelvic inflammatory disease .:. Brain abscess .:. Rapid IV administration of large doses may result in seizures
.:. Gonorrhoea .:. Surgical prophylaxis
.:. Neonatal gonococcal conjunctivitis CEFTAZIDIME
.:. Septic arthritis Available preparations: Powder for Injection Ig, SOOmg
Available brands: Fortum®
Contraindications
.:. Known hypersensitivity to:cephalosporins Pharmacokinetics
.:. History of anaphylactic re~ction to penicillins Ceftazidime is well absorbed when given parenterally, distributed
widely into body tissues and is not metabolized. It is excreted primarily
Dose
in urine and small amount in breast milk.
Adult: IV 11M or by intravenous infusion Ig every 12 hours ,increased
in severe infection like meningitis to 2g every 6 hours.
Gonorrhoea, Ig 1M as a single dose.
(
-71- -72-
/
 " ",,' " " PREC s(PHARMACOrmg

Indications .:. Abdominal cramps ~:. Pain at injection site

.:. Bone and joint infections .:. Urinary tract infections .:. Hypersensitivity ~:. Antibiotic associated colitis
.:. Abdominal infections .:. Surgical prophylaxis .:. Pruritus <.:. Serum sickness like reaction
.:. Neutropenic patients .:. Pneumonia .:. Phlebitis .:. Fever
.:. Skin infections including burns .:. Septicaemia ¥,
.:. Arthralgia
.:. Sinusitis .:. Biliary tract infections
.:. Meningitis .:. Osteomyelitis Drug interactions
.:. Concomitant use with aminoglycosides results in synergistic
Contraindications activity against pseudomonas aeruginosa
.:. Allergy to penicillin or cephalosporins .:. Concomitant use with c1avulanic acid results in synergistic
activity against some strains of Bacteroides fragilis
Dose .:. Probenecid decreases renal clearance of ceftazidime
Adult: .:. Loop diuretics may increase nephrotoxicity caused by
Deep 1M, Intravenous injection or infusion ,Ig every 8 hours or 2g every ceftazidime
12 hours, 2gevery 8-12hours in severe infections. .:. The effectiveness of oral contraceptives may be reduced by
Urinary trah infection; sOOmg-12 hourly ceftazidime.
Bone and Joint infections: 2g IV 12hourly
Meningitis: 2g IV 8 hourly Key Issues to note
Pneumonia: 500 - I OOOmg 8 hourly .:. Reconstituted solution may be stable for 24 hours at room
Surgical prophylaxis: I OOOmg at induction of anaesthesia temperature or 10 days when left refrigerated
Children: .:. Ceftazidime is incompatable with sodium bicarbonate
By intravenous injection or infusion .:. IV Ceftazidime is physically incompartible with many
I month -18 years: 2smg/kg every 8 hours doubled in severe substances, avoid mixing with other drugs
infections, febrile neutropenia and meningitis (max 6g daily).
Neonates 21-28 days: 2smg/kg every 8 hours doubled in severe CEFEPIME
infections including meningitis. Available preparations: Powder for injection Ig, 2g
Neonates 7-2 I days: 2smg/kg every 12 hours, double in severe
infection including meningitis. Available brands: Maxipime®
Neonates under 7 days: 2smg/kg every 24 hours, double the dose in
severe infection including meningitis. Pharmacokinetics .,
Cefepime is rapidly and almost completely absorbed following
Side effects Intramuscular injection. It is widely distributed in body tissues and fluid
.:. Headache .:. Dizziness and is excreted unchanged in urine.
.:. Urticaria .:. Nausea
.:. Vomiting .:. Diarrhoea Indications
.:. Urinary tract infection
.:. Skin and skin structure infection

-73- -74-
 "
I
' , " : ,,' ,
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' I PRECISE PHARMA I I 7' PRECISE PHARMAcoull/fl
.:. Nosocomial pneumonia Key Issues to note
.:. Surgical prophylaxis .:. Store the drug at room temperature and protect from light
.:. Intra abdominal infections .:. Cefepime is incompatible with metronidazole, aminoglycoside
.:. Febrile neutropenia and aminophylline
Contraindications
.:. History of anaphylactic reaction to penicillins
C:I:FAZOLIN
.:. Known hypersensitivity to cephalosporins Available preparation: Powder for injection 500mg, Ig
Dose Available brands: Zepilen®
Adult:
Pharmacokinetics
1"2 g every 12 hours for mild to moderate infections, increased to 4 g
CCbfazolin is poorly absorbed from the GIT, therefore it must be
daily in 2 divided doses in severe infections, up to 6 g daily in 3 divided
Il lvcm by parental route. It crosses the placenta, penetrates bones
doses has been given for febrile neutropenia.
/llld synovial fluid well but CSF penetration is poor. It is excreted
Urinary tract infection: 500mg every 12 hours for 7 - 10 days
1l11(:hanged in urine.
Nosocorplal pneumonia: I - 2g every 12 hours for 10 days.
Febrile n~tropenia: 2g every 8 hours Indications:
Surgical prophylaxis: 2g as a single IV infusion dose starting 60 minutes .:. Pneumonia .:. Cellulitis
1\
before operation. .:. Erysipelas .:. Osteomyelitis
Children: .:. Septicaemia .:. septic arthritis
>2 months and weighing up to 40 kg: .:. Urinary tract infection .:. Pyomyositis
50 mg/kg twice daily; or 3 times daily for febrile neutropenia for 7 - 10 .:. Surgical prophylaxis
days .:. Bacterial endocarditis prophylaxis
Side effects
.:. Skin Rashes .:. Thrombophlebitis C:ontraindications
.:. Urticaria .:. Fever .:. Known hypersensitivity to cephalosporins
•:. Vaginal candidiasis
•:. Headache
.:.
.:.
Anaphylaxis
Vomiting
l)ose. ,.
Adult. I -2g every 8 hours for 5 - 10 days.
,'--'.

•:. Diarrhoea .:. Pseudomembraneous colitis

()'teomyelitis 1-2g every 8 hours for 4-6 weeks.
•:. Abdominal pain .:. Pain at injection site
'.'ptic arthritis.I-2g every 8 hours for 2-3 weeks
Drug interactions
\urgical prophylaxis Ig IV at induction of anaesthesia.
.:. Aminoglycosides and frusemide may increase the risk of
''''"nts and Children: 25mg/kg every 8 hours
nephrotoxicity and ototoxicity with cefepime
.:. Probenecid decreases renal excretion of cefepime 'Ide effects
.:. Nausea .:. Vomiting
.:. Skin rashes .:. Diarrhoea
.:. Oral candidiasis .:. Urticaria
.:. Bronchospasm .:. Fever
.:. Pseudomembranous colitis

-75- -76-
 , I I 1 I j I , I II I I
, ' :: i.' ", , I" " ' " 1il:I:{~ PHARMACOLOGY
Drug interactions Available brands: Ero®, Erybon®, Erymed®, Erocos®, Erocin®
.:. Probenecid decreases renal excretion of cefazolin
Pharmacokinetics
Key issues to note Erythro~Ycin is adequately absorbed from the gut and food may delay
.:. Powder for injection should be stored intact at room absorption of other preparations. It is widely distributed in the tissues
temperature and protect from light ~rosse~ the placenta and gets into breast milk. The drug is metabolized
In the liver and excreted in bile.
•:. Reconstituted solution is stable for 24 hours at room
temperature or 10 days when refrigerated Indications
.:. Pneumonia .:. Whooping cough
4.1.4 MACROLIDES .:. Campylobacter enteritis .:. Lymphogranuloma venereum
Macrolides are a group of antibacterials derived from Streptomyces .:. Acne vulgaris .:. Skin and soft tissue infection
spp. .:. Chancroid .:. Non gonococcal urethritis
.:. Prostatitis .:. Bronchitis
Macrolides include:- .:. Acute otitis media .:. Neonatal conjunctivitis
.:. ~hromycin .:. Sinusitis .:. Pharyngitis and tonsillitis
.:. Azithromycin Contraindications
.:. C1arithromycin
.:. Patients allergic to erythromycin or other macrolides
.:. Roxithromycin .:. Porphyria
They have antibacterial spectrum similar but not identical to penicillins .:. Severe hepatic impairment
but with additional activity against atypical bacteria. Dose
They are bacteriostatic but in high enough concentrations, they may.be Adul~ a~d Child~en over 8 years: 250 ;- 500mg every 6 hours up to
4g dally In severe Infection for 10 days
bactericidal against some bacteria.
Lymphogran~~oma venereum: 500mg every 6 hours for 14 days.
Clarithromycin is an erythromycin derivative with slightly greater Early syphilis: 500mg 4 times daily for 14 days.
activity than erythromycin. Acne: 500mg twice daily for 2 - 3 months.
Azithromycin has slightly less activity than erythromycin against Non gonococcal urethritis: 500mg twice daily for 14 days
gram positive bacteria, but has enhanced activity against some gram Children: "
negative organisms, including H. influenzae. I month - 2 years, 125mg 4 times daily
Mode of action 2 - 8 years: 250mg 4 times daily.
Bacteriostatic, inhibit bacterial protein synthesis by binding to the 50S Whooping cough: IOmg/kg / dose every 6 hours for 14 days.
ribosomal sub unit Side effects
.:. Nausea Vomiting
ERYTHROMYCIN
Available preparation: Tablets 250 mg .:. Abdominal discomfort Diarrhoea
.:. Urticaria Skin Rashes
Powder for oral suspension 125mg / 5ml
Eye ointment .:. Reversible hearing loss Pancreatitis

-77- -78-
 , ,": ',: ,: ,'" " ii, ,,: : PREC~PHARMACOLOGY " : ' , ' : I,,"
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II [
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1111111,!lll I,I! hili,'!
':',;,'1' ":', ',:'
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~

Drug interactions .:. Mycobacterium avium complex(MAC) infections

.:. Erythromycin increases plasma carbamazepine concentration . .:. Non gonococcal urethritis
•:. Erythromycin possibly inhibits metabolism of
Contraindications
dexamethasone,hydrocortisone and prednisolone.
.:. Known hypersensitivity to azithromycin or other macrolides
.:. Erythromycin enhances anticoagulant effect of warfarin.
.:. Severe hepatic impairement

Key issues to note Dose

.:. Do not crush enteric coated tablets. They should be Adult: SOOmg once daily for 3 days.
swallowed wholly. Non gonococcal Urethritis Ig single dose
•:. Erythromycin is best absorbed one hour before or 2 hours Typhoid SOOmg once daily for 7 days
after meals. Incase of stomach upsets, take the medicine with Children over 6 months IOmg / kg once daily for 3 days
food . OR
•:. Warn the patient that erythromycin interacts with many drugs 15 - 2Skg 200mg once daily for 3 days
therefore he or she should not take additional 26 - 3Skg 300mg once daily for 3 days
~ication without doctor's recommendation 36 - 4Skg 400mg once daily for 3 days
.:. Stop Erythromycin if severe hepatic dysfunction develops Over 4Skg SOOmg once daily for 3 days
Side effects
AZITHROMYCIN .:.
Anorexia .:. Vertigo
Available preparations: Capsules/ tablets 2S0mg, SOOmg .:.
Nausea .:. Flatulence
Powder for oral suspension 200mg / Sml .:.
Vomiting .:. Urticaria
.:.
Dyspepsia .:. Abdominal discomfort
Available brands: Zithromax®, Zocin®, Azilide®, Zithrox®, .:.
Constipation .:. Convulsion
Aziwok®, Azicure®, Zithromed®, Azifast®, .:.
Headache .:. Somnolence
.:.
Dizziness .:. Skin rash
Pharmacokinetics .:.
Taste disturbances
AZithromycin is rapidly absorbed from GI tract but food reduces its
absorption. It is widely distributed in the body tissues, small amounts Drug interactions
are demethylated in the liver and is excreted in bile as unchanged drug .:. Concurrent administration of antacids containing aluminium
and metabolites. or magnesium salts can reduce the rate but not the extent of
absorption of azithromycin
.:. Avoid concomitant use of lumefantrine and artemether with
Indications
.:. Pneumonia .:. Bronchitis
azithromycin
.:. Skin and soft tissue infections. .:. Pertussis
.:. Plasma concentration of azithromycin is increased by ritonavir
.:. Azithromycin enhances anticoagulant effect of warfarin
.:. Typhoid. .:. Sinusitis
.:. Azithromycin increases the plasma concentration of digoxin
.:. Pharyngitis / tonsillitis .:. Otitis media .:. The effectiveness of oral contraceptives may be reduced by
.:. Trachoma .:. Traveller's diarrhoea azithromycin
.:. Pelvic inflammatory disease

-79"- -80-
 ,, , " : i,' """':':: :'" ,,', ',[,'" :,:,: , ' PREC PHARMACOL
R' -*71 &£££&1£ 4i!#nil~:r;ljlM:tQI!!rIijl
Key issues to note
Eradication of H. Pylori: 500mg twice daily for 7 days in combination
.:. Shake the suspension well before use with amoxicillin and proton pump Inhibitors
.:. Administer azithromycin on an empty stomach i.e I hour
before or 2 hours after a meal Children:
.:. Azithromycin has a long tissue half-life and once daily dosage 7.5mg /kg twice daily for 5-10 days. OR
is recommended 1-2years 62.5mg twice daily
3-6 yearsl25mg twice daily
CLARITHROMYCIN '7-9 years 187.Smg twice daily
Available preparations: Tablets 2S0mg, SOOmg 10-12 years 2S0mg twice daily
Powder for oral suspension 12Smg / Sml,
2S0mg/Sml Side effects
-:- Diarrhoea .:. Nausea
Available brands: Klerimed®, Clarix®, Claranta®, C1arem® -:- Abnormal taste .:. Dyspepsia
.:. Abdominal pain .:. Headache
Pharm~kinetics . . .:. Stomatitis
C1arithromycin is rapidly absorbed from the gastrointestinal tract, and .:. Glossitis
-:- Arthralgia .:. Myalgia
undergoes first-pass metabolism. The extent of absorption is relatively .:. Dizziness
unaffected by the presence of food. It is widely distributed, metabolized .:. Vertigo
.:. Insomnia
in the liver and excreted in urine. .:. Anxiety
.:. Pseudomembranous colitis
Indications I)n.g interactions
-:. Pneumonia. .:. Bronchitis
.:- Clarithromycin may increase blood concentration and toxicity
.:. Pharyngitis and .:. Acute otitis media
of carbamazepine, digoxin and theophylline
.:. Eradication of H. pylori .:. MAC infections
.:. Rifampicin may decrease c1arithromycin blood concentration
.:. Skin and Soft tissue infection .:. Whooping cough
.:. Prophylaxis of endocarditis Tonsillitis ""V Issues to note
.:. Acute and chronic sinusitis .:. Administer tablets or oral suspension with or without meals
.:- Shake suspension well before use
Contraindications .:. The drug interacts with many drugs. Advise the patient not to
.:. known hypersensitivity to macrolides use it without doctor's advice

Dose "OXITHROMYCIN
Adult: -,,,..liable preparations: Tablets ISOmg
250mg every 12 hours for 7 days. Increased to SOOmg 12 hourly in
severe infection for 14 days AVltll''lble brands: Roxid®
Mycobacterium Avium Complex treatment: SOOmg twice daily rhitnnacokinetics
with ethambutol.
~,11l1I "romycin is well absorbed when taken orally with a bioavailability
Mycobacterium Avium Complex Prophylaxis: SOOmg twice daily
"', IIhollt 50%. Absorption is reduced when taken after a meal. It is

-81-
-82-
 , PRECISE PH
ZIT
th~ urine, but doxycycline is excreted by other routes and can be used
widely distributed in tissues and body fluids, a small amount of the drug
without dosage adjustment in patients with renal failure.
is metabolized in the liver and the majority is excreted in faeces.
Due to wide spread bacterial resistance, tetracyclines are no longer
drugs of choice in most infections.
Indications ",
.:. Acute Pharyngitis Mode of action
.:. Tonsillitis Bacteriostatic, inhibit bacterial protein synthesis by reversibly binding
.:. Skin and soft tissue infections to 30S sub unit of the ribosome
.:. Community acquired pneumonia
TETRACYCLINE
Contraindications Available preparations: Capsules 2S0mg
.:. Hypersensitivity to roxithromycin Eye ointment 1%
Skin ointment 3%
Dose Available brands: Intacycline®, Teracin® Agotetra®
Adult: ISOmg 12 hourly or 300mg once daily Pharmacokinetics
Childr~ Less than 40kg S-8mg/kg body weight daily lCtltracyclin~is v:ell abs.or~ed but, absorption is reduc~d by the presence
1.)1 lood. It IS widely distributed to most body tissues and fluids. Small
Side effects 1'lI1o~nt is metabolized in the liver atld most of it is excreted unchanged
.:. Nausea
.:. Vomiting
.:. hI urine
Diarrhoea
.:. Abdominal pain
.:. Flatulence ItICllcations
.:. Constipation
.:. ..:. Brucellosis .:.
Headache Gonorrhoea
.:. Dyspepsia
.:. tt:. Acne vulgaris .:.
Loss of appetite Shigellosis
.:. Dizziness
-Co Trachoma .:.
.:. Weakness Rosacea
.:. Lymphogranuloma venereum .:. Cholera
Key issues to note .:. Bronchitis .:. Pharyngitis
.:. Roxithromycin is best absorbed if taken atleast 15 minutes .:.
before a meal. Incase of stomach upsets, take it with food
<. Non-gonococcal urethritis Sinusitis
.> Malaria .:. Periodontal disease

4.1.5 TETRACYCLINES Conl.raindications

-Co Children below 12 years
Tetracyclines include:- ':0 Pregnant mothers
.:. Tetracycline .:. Doxycycline
.:. Minocycline .:. Oxytetracycline
.> Breast feeding mothers
.> Patients with known hypersensitivity to any tetracycline
Tetracyclines are broad spectarum antibacterial drugs derived from
Streptomyces spp. They are effective against gram positive and gram
I.,.....
A.'ult 250 - 500mg 6 hourly
negative bacteria. They are also active against mycoplasmas, Chlamydiae
Nil" Konococcal urethritis 500mg every 6 hours for 7 - 14 days
spirochetes and ricketsiae. Most tetracyclines are excreted primarily in A. lilt IjOOmg every 12 hours for 3 months

-84-
-83-
 • I a--~EpRECISEPHARMACOLOO , , SE~8L8GY

Syphilis: SOOmg every 6 hours for 14 days. .:. Exacerbation of chronic bronchitis
.:. Acute bacterial sinusitis
Side effects .:. Pelvic inflammatory disease (PID)
.:. Anorexia .:. Epigastric distress .:. Non gonococcal urethritis
.:. Nause .:. Vomiting ", .:. Malaria treatment and prevention
.:. Diarrhoea .:. Stomatitis .:. Recurrent aphthous ulcer
.:. Sore throat .:. Headache
.:. Photosensitivity .:. Hypersensitivity reaction Contraindications
.:. Children less than 8 years (causes staining and occasionally
Drug interactions dental hypoplasia)
.:. Tetracycline absorption may be decreased by antacids .:. Pregnant mothers
containing aluminium, calcium .:. Breast feeding mothers
.:. Oral iron, diary products and food may reduce absorption of .:. Hypersensitivity to tetracyclines
tetracycline .:. Porphyria
Key i~ues to note
.:. J"etracycline should be taken whole with plenty of water Dose
2hours before a meal Brucellosis: 200mg daily for 6weeks with rifampicin 600-900mg daily
.:. Avoid prolonged exposure to light during the course of Malaria I OOmg every 12 hours for 7 days with quinine
treatment PID 100mg every 12 hours for 14 days with other antibiotics
.:. Prolonged use of tetracycline may result into Malaria prophylaxis I OOmg once daily starting 2 days before entering
superinfections <tnd continue for 2 - 4 weeks after leaving malaria area
.:. Avoid taking antacids, iron, dairy products or milk Acne: I OOmg once daily
formula within 3 hours of tetracycline administration Early syphilis I OOmg twice daily for 14 days
DOXYCYCLINE latent syphilis I OOmg twice daily for 30 days
Available preparations: Capsules 100mg Non gonococcal urethritis I OOmg twice daily for 7 days
Tablets 100mg Lyme disease. I OOmg twice daily for 14-21 days

Available brands: Remycin®, Doxyren®, Agodox®, Microdox® Side effects

.:. Nausea Flushing
Pharmacokinetics .:. Vomiting Diarrhoea
Doxycycline is well absorbed when taken orally (90-100%), presence .:. Loss of appetite Dyspepsia
of food does not significantly affect its absorption. Itis well distributed .:. Oesophageal irritation Headache
to body tissues and fluids and excreted in faeces. .:. Permanent staining of teeth Tinnitus
Indications .:. Vaginal candidiasis Photosensitivity
.:. Acne vulgaris .:. Rosacea Drug interactions
.:. Anthrax .:. Brucellosis .:. Antacids and preparations containing iron, calcium or
•:. Syphilis .:. Chronic prostatitis magnesium may impair absorption of doxycycline.

-85- -86-
 , PRECI
iilSE PHARMAC(ollnif' , I" ,'.' ' PRECISE PHARMACOLOGY

.:. Doxycycline may increase the anticoagulant action of oral GENTAMICIN

Available preparations: Injection 80mg/2ml
anticoagulant drugs.
.:. Doxycycline may decrease therapeutric effect of penicillins. Eye drop 0.3%
.:. Doxycycline may decrease the effect of oral contraceptives. • Skin ointment O. I %
Pharmacokinetics
Key issues to note 0 • • 0
Gentamicin is completely absorbed from 1M injection site and is
.:. To reduce the risk of esophageal Irritation and ulceration, distributed to body tissues and fluids including urine. Penetration into
do cyeline should be taken with adequate amount of water the CSF is poor even when the meninges are inflamed. It is excreted
.:. Do~ot administer doxycycline to children below 12 years of unchanged in urine and accumulation occurs in renal impairment.
~e ,
.:. Photosensitivity may occur on prolonged exposure to sun light Indications
.:.Urinary tract infections .:. Brucellosis
4.1.6 AMINOGLYCOSIDES .:.Bacterial endocarditis .:. Pneumonia

Aminogly~sidesinclude:-
.:.Pelvic inflammatory disease .:. Septicaemia
.:. C;~tarnicin .:. Am ikacin .:.Skin infections (burns or ulcers) .:. Cystic fibrosis
Neomycin .:.Surgical prophylaxis .:. Peritonitis
.:. Streptomycin
Kanamycin .:.Biliary tract infections .:. Neonatal sepsis
.:. Tobrarnycin .:.Otitis Externa
.:. paramomycin
' I 'deS are agroup of antibacterial drugs derived from bacteria Contraindications
A mlnogycosl
actinomycetes (streptomyces and micromonospora). .:. Known hypersensitivity to gentamicin or other
rly absorbed from the gut, therefore can only be
Th ey are po O .. . aminoglycosides
o t d by in)'ection for the treatment of systemic infection. There .:. Myasthenia gravis
ad miniS ere
0

'nolstered topically to treat infections of the skin, mucous

are asoI ad ml Dose
membranes, and ocular tissues.
Multiple dose regimen
Ok O' ore stable than gentamicin to aminoglycoside-inactivating Adult: 1M/IV slow intravenous injection 3 - Smg /kg daily in 3 divided
A ml aCIn IS m
enzymes and is used where gentamicin has failed. doses.
Children:
I month-I 2 years: 2.5mg / kg every 8 hours
Mode of action
Bactericidal, inhibit protein synthesis by irreversibly binding to the 30S 12-18years: 2mg/kg every 8 hours
'b I sub unit and also cause cell membrane damage. Once daily regimen.
rI osoma
IV infusion, S-7mg/kg/day
Urinary tract infections: 1M 160mg once daily
N~~ . Patients < SOkg 3mg/kg once daily
enicillins which act on the cell wall of bacteria enhance
D rugs such aSP 0 . ' 0 0

'oo of the aminoglycoslde Into bacterial cells resulting In a Surgical prophylaxis: IV injection Smg /kg as a single dose at
t he penet rat I
synergistic bactericidal effect. induction with c1indamycin

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PREC~PHARMACOLOGY

Side effects Indications

.:. Nephrotoxicity .:. Ototoxicity .:. Skin and soft tissue infections .:. Pneumonia
.:. Headache .:. Diarrhoea .:. Bone and joint infections .:. Infected burns
.:. Nausea .:. Vomiting .:. Urinary tract infections .:. Peritonitis
ilt'
.:. Rash .:. Blood disorders .:. Infections in neutropenic patients .:. Endometritis
.:. Antibiotic associated colitis .:. Neonatal sepsis

C::ontraindications
Drug interactions
.:. Hypersensitivity to amikacin
.:. Concurrent use with amphotericin B increases the risk of
.:. Myasthenia gravis
nephrotoxicity
.:. Concurrent use with frusemide increases risk of ototoxicity r)("IC.~
.:. Concurrent use with vancomycin increases the risk of Iy 1M or slow intravenous injection or by infusion: 7.Smg/kg
nephrotoxicity and ototoxicity I ).hourly
C. ••• Concurrent use with suxamethonium increases muscle U,'lnary tract infection: 2S0mg twice daily for 7-10 days.
) ·fi\l
relaxant effects Nlilw born and premature babies: Initially 10mg/kg loading dose
Inllowed by 7.Smg/kg every 12 hours.
Key issues to note
.:. Gentamicin is incompatible with penicillins and cephalosporins "Udc~ effects
therefore, administer penicillins or cephalosporins atleast .:. Ototoxicity .:. Nephrotoxicity
I hour before or after gentamicin .> Nausea .:. Vomiting
.:. Adjust the dosage of gentamicin in renal impairment .:- Headache .:. Hypotension
.:. Use gentamicin cautiously in elderly patients as they are more .... Tremor .:. Skin rash
likely to have pre-existing renal and hearing impairment
1)"Llif interactions
AMIKACIN ~. Concurrent use of amikacin with frusemide increases risk of
Available preparations: Injection SOOmg ototoxicity
'C. Concurrent use with vancomycin increases the risk of
Available brands: Lanomycin®, Amikin® nephrotoxicity and ototoxicity

Pharmacokinetics 04. 1.7 SULPHONAMIDES AND TRIMETHOPRIM

Amikacin is rapidly absorbed from the 1M injection site, distributed All ilva/lable sulphonamides are structurally related to Para-aminobenzoic
primarily into extracellular fluid, a small percentage penetrates into tt. It I (PABA). The therapeutic importance of sulphonamides has declined
bronchial secretions but, penetration into the blood-brain barrier hllc:llllse of emergence of resistance.
is poor even when the meninges are inflamed. It is mainly excreted
unchanged in urine.

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 " :,,:: " """," " PRECISE PHARMACOLOGY
"" I
CEIIIZ.'E I L PRECISEI~:miMWOLOGY
Classification of Sulphonamides (::c:mtraindications
Sulphonamides may be classified on the basis of the rapidity with .:. Hypersensitivity to sulphonamides or trimethoprim
which they are absorbed and excreted as follows; -:. Severe renal and hepatic failure
~. Neonates
Class Examples l:)Of'l!!

Absorbed and excreted Sulphamethoxazole ~c:lult: By mouth 960mg every 12 hours

rapidly Sulphadiazine
(;,hlldren:
Poorly absorbed, active in bowel Sulphasalazine lit weeks - 5 months: 120mg 12 hourly
lumen jfI months - 5 years: 240mg 12 hourly
lit .... 12 years: 480mg 12 hourly
Topically used sulphonamides Silver sulphadiazine
~~r,.)"hylaxis of PCP: 960mg once daily
Long-acting Sulphadoxine
'~'lIJltment of PCP by mouth or intravenous infusion
M~ofaction Adult and Children over 4 weeks: 120mg/kg daily in 4 divided doses
Sulphhnamides are bacteriostatic. They arrest bacterial cell growth by 1"1 ~ I days.
inhibiting bacterial folic acid synthesis. Trimethoprim acts by blocking
the action of bacterial dihydrofolate reductase enzyme which leads to Illld~ effects
inhibition of folate synthesis in bacteria. -:. Nausea .:. Diarrhoea
<- Headache .:. Itching
CO-TRIMOXAZOLE (> Skin rash .:. Renal failure
Available preparation: Tablets 480mg, 960mg .> Urticaria .:. Hyperkalaemia
.~
Oral suspension 240mg/Sml Anorexia .:. Stomatitis
Injection for infusion 960mg/3ml .> Photosensitivity reactions
Available brands: Septrin®, Unitrim®, Cotrim®, O"UIt Interactions
Cotreich®,Metrim®, renetrim®, cosatrim®,
(. Digoxin levels may be in~reased by co-trimoxazole
Pharmacokinetics .:- Ef~icacy of oral contraceptives may be reduced by co-
Co-trimoxazole is well absorbed after oral administration and widely tnmoxazole
distributed to body tissues and fluids. It is excreted in urine. t) Co-trimoxazole may increase the anticoagulant effect of
warfarin
Indications .> Co-trimoxazole may increase the blood glucose lowering
.:. Urinary tract infections Pneumonia effects of oral antidiabetic drugs
.:. Granuloma inguinale Bronchitis I(,tr I,sues to note
.:. Toxoplasmosis Otitis media .> A high fluid intake to maintain urinary flow is recommended
.:. Brucellosis Traveller's diarrhoea in patients receiving co-trimoxazole to reduce the risk of
.:. Shigellosis cry~ta"uria and damage to the kidney
.:. Pneumocystis carinii pneumonia (PCP) '¢' PatIents should be monitored for life threatening reactions
and the drug discontinued at the first sign of such a reaction
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~I.
,fg.
SULPHADIAZINE SULFASALAZINE
Available preparations: Tablets SOOmg Available preparations: Tablets SOOmg
Indications
.:. Toxoplasmosis Available brands: Salazopyrin®
.:. Prophylaxis of rheumatic fever
Indications
Contraindications .:. Ulcerative colitis
·:·Renal failure .:. Liver failure .:. Rheumatoid arthritis
·:·Porphyria .:. Infants less than 2months
.:. Active crohn's disease
.:. Pregnancy .:. Lactation
·:·Hypersensitivity to sulphonamides Contraindications
Dose .:. Children less than 2 years
Tox~lasmosis.4-6g daily in 4 divided doses in combination with .:. Severe hepatic impairment
pyri~thamine 2Smg and folinic acid 5-1 Omg every 3 days. .:. Severe renal dysfunction
Rheumatic fever: > 30kg Ig daily .:. Known hypersensitivity to sulphonamides
< 30 kg SOOmg daily .:. Pregnancy at term
Side effects
.
:. Nausea .
.: Vomiting Dose
.
:. Diarrhoea .
.: Headache Ulcerative colitis:
.
:. Skin rash ..
: Pruritus Adult: Ig 3-4 times daily.
.
:. Oliguria .
.: Anuria Ma.intenance: SOOmg 4 times daily, max. 6g daily
.
:. Aplastic anaemia .
.: Photosensitivity reactions Chl.ldren over 2years: 40-60mg/kg/day in divided doses 6 houri
.:. Exfoliative dermatitis Mamtenance: 20-30mg/kg/day in divided doses y
Drug interactions Itheumatoid arthritis: 500 -I OOOmg/day for I week increased by
.:. Sulphadiazine potentiates antidiabetic effects of sulphonylureas SOOmg/ week up to max. of 3g/day given in 2-4 divided doses
.:. Sulphadiazine enhances the anticoagulant effect of warfarin
Side effects
.:. concurrent use with phenytoin increases plasma concentration .:. Anorexia .:. Nausea
of phenytoin .:. Vomiting .:. Headache
.:. Sulphadoxine and pyrimethamine increase antifolate effect of .:. Oligospermia .:. Abdominal discomfort
sulphadiazine .:. Skin rash .:. Fever
.:. Sulphadiazine increases the risk of toxicity of methotrexate
Key issues to note Drug interactions
.:. Administer with water on an empty stomach .:. Sulfasalazine increases the effect of oral anticoagulants,
.:. Supplemental folinic acid should be administered to reverse methotrexate and oral hypoglycaemic drugs
or prevent problems due to folic acid deficiency .:. Sulfasalazine decreases the effect of iron, digoxin and folic
.:. Avoid large quantities of vitamin C to prevent crystalluria acid

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, , " , PR
Key issuses to note NALIDIXIC ACID
.:. Sulfasalazine may be administered after meals or with food
Available preparation: Tablets 500mg
.:. Maintain adequate fluid intake
.:. Sulfasalazine may cause photosensitivity reactions, therefore, Available brands:
advise the patient to wear protective clothing or use sun QUinoneg®, Uriseptic®, Gramofil®,
Nalacid®, Dawaseptic®
screen
Pharmacokinetics
4.1.8 QUINOLONES ~alidixic acid is well absorbed from GI tract, concentrates in renal
Quinolones are a group of synthetic antibacterials with original member tissues an~ seminal fluids but does not penetrate prostatic tissues. It
as nalidixic acid. Successive modifications of the structure of nalidixic 1$ metabolized to a more active form in the liver and excreted via the
acid resulted into the f1uoroquinolones. The modification improved kidney.
antimicrobial activity and pharmacokinetic properties. Indications
.:. Urinary tract infections
CiasSWcation of Quinolones .:. Shigellosis
Generation Examples Comments
First generation Nalidixic acid Effective against gram negative Contraindications
'ill
bacteria but not pseudomonas. .:. Known hypersensitivity to nalidixic acid
Use limited to UTI because .:. History of epilepsy
ofthe minimal serum levels .:. CNS lesions
.. ii, achieved in other tissues. I;)OllC
Second Ciprofloxacin, Have excellent activity against
generation Norfloxacin, a wide range of gram negative
Udn~ry tract infections: I g every 6 hours for 7 days for acute
h,f"ct:lon and for chronic infection, SOOmg every 6 hours
Ofloxacin, bacteria ncluding pseudomonas,
Pefloxacin and
(,:hildren Over 3 months: SOmg/kg daily in 4 divided doses reduced
but limited activity against gram
Itl Iu'olonged treatment to 30mg/kg daily. ,
Lomefloxacin positives and atypical pathogen. III h1art'llosis:
Note: Have poor activity against
Adult: Ig every 6 hours for 5 days
streptococcus pneumoniae
Thirdllli,"i!{li;::;:1 ''Levofloxacin, f :hlldren over 3 months: ISmg/kg every 6 hours for 5 days
Have good activity against
generation
Pi

Sparfloxacin, gram negative bacteria but '."11 c~rrects

Gatifloxacin and with expanded spectrum <- Nausea
Headache
Moxifloxacin against gram positives including + Dizziness
Drowsiness
streptococcus pneumoniae + Confusion
Cranial nerve palsy
and atypical pathogen + Vomiting
Diarrhoea
+ Vertigo
.:. Visual disturbances
Mode of action + Weakness
.:. Abdominal pain
Quinolones are bactericidal and act by inhibiting DNA gyrase enzyml' • Skin rash
~II_;;' • Urticaria Convulsion
thereby interfering with synthesis of bacterial DNA.

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, I ( I h I, i I I" I

.:. Allergy to ciprofloxacin

Drug interactions
.:. Probenecid prolongs the half life of nalidixic acid .:. Children below 18 years
.:. Nalidixic acid may increase the risk of bleeding when given with
l)ose
oral anticoagulants
Adult:
'bulpiratory tract infections: 2S0-7S0mg twice daily
Key issues to note
.:. Advise the patient to take nalidixic acid on an empty stomach 'Jl"lnary tract infections: 2S0-S00mg twice daily
••one and Joint infections: 750mg twice daily
preferably I hour before meals
(:hronic Prostatitis: SOOmg twice daily for 28 days
Iyphoid: SOOmg twice daily for 14 days
CIPROFLOXACIN
rlonorrhoea, chancroid, shigellosis, cholera: SOOmg single dose
Available preparations: Tablets SOOmg, Ig
Injection 200mg! IOOml "llu'gical prophylaxis: 7S0mg 60-90min before procedure
Eye drops 0.3%w/v 'U.h~ effects
I~ .:. Headache Dizziness
Available brands: Ciprobay®, Ladinin®, Bactiflox®, Cipfil®, -:. Restlessness Light headedness
Cipro-denk®, Ciprobid®, Cifran®, Ciplox®, -:. Palpitation Skin rash
.:. Diarrhoea Convulsion
Pharmacokinetics
Ciprofloxacin is rapidly and well absorbed when taken orally with <. Drowsiness Dyspepsia
bioavailability of 70-80%. It is widely distributed throughout the body. <. Depression .:. Tremors
with good penetration of tissues and bones. It is metabolized in the .c. Nausea and vomiting .:. Abdominal discomfort
liver and excreted in urine and faeces.
.c. Urticaria Insomnia
.c. Anorexia

Indications hWtl interactions

.:. U~inary tract infections .:. Septicaemia .:. Antacids containing aluminium and magnesium interfere with
.:. Surgical prophylaxis .:. Typhoid absorption of ciprofloxacin
.:. Chronic prostatitis .:. Chancroid .:. Concomitant administration with probenecid results into
.:. Travellers' Diarrhoea .:. Cholera higher plasma level of ciprofloxacin
.:. Shigellosis .:. Otitis externa <. Phenytoin, theophylline and anti coagulant blood levels may
.:. Peritonitis .:. Bone and joint infections Ii
" be increased by ciprofloxacin
.:. Gonorrhoea .:. Anthrax
I

<. Therapeutic effect of ciprofloxacin may be decreased by iron

.:. Respiratory tract infections salts and sucralfate
.:. Prophylaxis of meningococcal meningitis <0 Ciprofloxacin may increase the effects of oral anticoagulants
ttl.~ IllSues to note
Contraindications
<0 Ciprofloxacin is absorbed well if taken I hour before, or 2
.:. Breast feeding
hours after meals
.:. Pregnancy

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 , ' ' "' "1":,' ,.. " , 'II ~~PHARMACOLlJGY , 1 ," I" " ~ISE PHARMAClJLOGY
I " <I, ,I II I

.:. Drink alot of fluids while using ciprofloxacin Chronic relapsing urinary tract infections: 400mg twice daily up
•:. Advise the patient not to take dairy foods, antacids, iron, zinc to 12weeks.
or calcium supplements with ciprofloxacin. Gastroenteritis: 400mg twice daily for 5 days.
.:. Ciprofloxacin may increase the effects of caffeine in some .., Gonorrhoea: 800mg as a single dose plus doxycycline I OOmg twice
people, therefore, advise the patient to reduce amount of daily for 7 days.
Travelers' diarrhoea: 400mg twice daily for 3 days.
caffeine used
.:. Ciprofloxacin may worsen seizures in epileptic patients. Side effects
.:. Nausea and vomiting Headache
NORFLOXACIN .:. Dry mouth Heart burn
Available preparations: Tablets 400mg .:. Seizures Tinnitus
.:. Anxiety Insomnia
Available brands: Negaflox®, Loxone®, Uriflox®, Nor 400® .:. Skin rash Diarrhoea
Norfen®, Noxacin®, Surflox® .:. Photosensitivity abdominal pain
Phafmacokinetics .:. Anorexia Flatulence
Norfloxaciniis absorbed well from the GIT but presence of food can .:. Fatigue
delay ab~~rption. Norfloxacin penetrates well into tissues of the genito-
Drug interactions
urinary tract, crosses the placenta and is excreted unchanged in urine
.:. Antacids reduce absorption of norfloxacin
within 24 hours.
.:. Probenecid reduces urinary excretion of norfloxacin
.:. Norfloxacin may increase the effect of oral anticoagulants
Indications
.:. Norfloxacin may increase the serum levels and toxic effects of
.:. Gonorrhoea
theophyllines and cyclosporine
.:. Urinary tract infections
.:. Chronic prostatitis Key issues to note
.:. Chronic relapsing urinary tract infections .:. Administer norfloxacin on an empty stomach, I hour before
.:. Gastroenteritis or 2 hours after meals
.:. Travelers' diarrhoea .:. Drink alot of fuids while taking the drug
.:. Do not use dairy products, antiacids , iron, zinc, or calcium
Contraindications supplements within 2 hours of norfloxacin dose.
.:. Children younger than 12 years OFLOXACIN
.:. Known hypersensitivity to quinolones Available preparations: Tablets 200mg
.:. Pregnancy
Available brands: Flamocin®, Oflox®, Oflin®,Kiroll®
.:. Lactation

Dose Pharmacokinetics
Urinary tract infections: 400mg twice daily for 7-10 days (3 days in Ofloxacin is rapidly and well absorbed from the GIT, presence of food
uncomplicated lower urinary tract infections). may delay the absorption but, the extent of absorption is not substantially
Chronic prostatitis: 400mg twice daily for 28 days. affected. It is widely distributed in body fluids and tissue penetration is

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 PRECISE PHARMACOLOGY , I" ,,' ",'," " , "ii' " " II ,i:,I, ' I' ,i PRECISE PHARMACOLOGY

good. It crosses the placenta and is distributed into breast milk. It is .:. Fatigue
.:. Pruritus
metabolized in the liver and excreted in urine.

Drug interactions
Indications
.:. Antacids may decrease absorption and the effect of ofloxacin
.:. Gonorrhoea
.:. Ofloxacin may increase the effect of oral anticoagulants
.:. Urinary tract infection
.:. Typhoid
.:. Community acquired pneumonia Key issues to note
.:. Administer Ofloxacin on an empty stomach I hour before or
.:. Chronic bacterial prostatitis
2 hours after meals
.:. Pelvic inflammatory disease
.:. Drink alot of fuids while taking the drug
.:. Infected diabetic foot
.:. Avoid prolonged exposure to sunlight
.:. Skin and soft tissue infections
.:. Non-gonococcal urethritis
r
)
~ LEVOFLOXACIN
Available preparations: Tablets 2S0mg, SOOmg.
Contraindications
Injection SOOmg/ I OOml
.:. Hypersensitivity to quinolones
.:. Pregnancy
Available brands: Glevo®, Levobact®, Levomac®, Qure®,
.:. Lactation
Levobay®, Levotop®, Metador®
.:. Children under 12 years
Pharmacokinetics
Dose Levofloxacin is rapidly and almost completely absorbed following oral
Urinary tract infections: 200mg twice daily for 3 days or 10 days in lise. It is distributed into body tissues including the bronchial mucosa
complicated UTls. and lungs but, penetration into CSF is relatively poor. Levofloxacin is
Chronic bacterial prostatitis: 200mg twice daily for 28 days excreted largely unchanged primarily in the urine.
Sldn and soft tissue Infections: 400mg twice daily for 10 days Indications
Pelvic inflammatory disease 400mg twice daily for 14days with .:. Community acquired pneumonia
metronidazole .:. Acute sinusitis
Gonorrhoea: 400mg single dose plus doxycycline I OOmg twice daily .:. Chronic prostatitis
Pneumonia: 400mg twice daily for IOdays .:. Skin and soft tissue infections
Non-gonococcal urethritis 300mg twice daily for 7 days .:. Exacerbation of chronic bronchitis
.:. Urinary tract infections
Side effects
.:. Vomiting Contraindications
.:. Nausea
.:. Dry mouth .:. Known hypersensitivity to levofloxacin or fluoroquinolones
.:. Diarrhoea
.:. Skin rash .:. Pregnant mothers
.:. Dizziness
.:. Insomnia .:. Lactating mothers
.:. Headache
.:. Flatulence .:. Children less than 12years
.:. Abdominal pain

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 ·' ' " ,' " PRECISE~I{IINg

Dose Indications
Chronic Prostatitis: 500mg once daily for 28days .:. Acute bronchitis
Skin and soft tissue infections: 250mg daily or 500mg once or twice .:. Community acquired pneumonia
daily for 7-14 days .:. Urinary tract infections
Urinary tract infections: 250mg daily for 7-1 Odays (3 days in .:. Skin and soft tissue infections
uncomplicated UTI) .:. Non gonococcal urethritis
Pneumonia: 500mg once daily for 7-14 days .:. Uncomplicated gonorrhoeae
Side effects
.:. Diarrhoea Dizziness Contraindications
.:. Headache .:. Anxiety .:. Hypersensitivity to quinolones
.:. Nausea .:. Abdominal pain .:. Lactation
.:. Sleep disorders .:. History or any episode of an epileptic fit
.:. Hypotension .:. Children under 12 years

~rug interactions Dose

.:. Antacids and minerals reduce absorption of levofloxacin .400mg initially, followed by 200mg once daily after meals for 5-10
.:. Concurrent use of levofloxacin with NSAIDs increases risk of days
seizures
.:. Cimetidine, famotidine, lansoprazole, omeprazole and Side effects
ranitidine reduce absorption of levofloxacin
.:. Diarrhoea .:. Abdominal pain
.:. Convulsions .:. Flushing
Key issues to note .:. Itching .:. Nausea
.:. Advise the patient to drink plenty of fluids .:. Vomiting .:. Headache
.:. Advise the patient to avoid direct exposure to sun light .:. Insomnia
.:. The drug may be taken without regard to meals but, do not
take antacids within 2 hours of levofloxacin administration Drug interactions
.:. Erythromycin reduces efficacy of sparfloxacin
SPARFLOXACIN .:. Antacids and minerals reduce absorption of sparfloxacin
Available preparations: Tablets 200mg .:. Sparfloxacin inhibits metabolism of phenytoin, increasing
plasma phenytoin level
Available brands: Sparx®, Sparflo® , Spardac®
Key issues to note
Pharmacokinetics .:. Patient should avoid direct exposure to sunlight
Sparfloxacin is well absorbed from the GIT with bioavailability of about .:. Advise the patient to drink alot of fluids
90%. It is widely distributed into body tissues and fluids, including
respiratory tissues. It is metabolized in the liver and excreted in faeces PEFLOXACIN
and urine. Available preparations: Tablets 400mg
Injection 400mg/ I OOml

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 d PRECmPHARMACOlOGY

Available brands: Pelox®. Peflobid®. Peflox®, Indications

Agoflox®, Unikpef®
.:. Acute exacerbation of chronic bronchitis
.:. Acute sinusitis
Indications
.:. Intra abdominal infections
.:. Acute bronchitis .:. Urinary tract infections
.:. Community acquired pneumonia
.:. Surgical prophylaxis .:. Typhoid
.:. Skin and soft tissue infections
-:- Septicaemia .:. Bone and joint infections
.:. Gonorrhoea Contraindications
.:- Acute exacerbation of chronic bronchitis
.:. Known hypersensitivity to quin%nes
Contraindications .:. Severe hepatic impairment
.:- Known hypersensitivity to qUinolones .:. History of symptomatic arrhythmias
.:. Children under 12 years .:. Electrolyte imbalances
j)-:. Pregnancy -:. Lactation
.:. Lactation -:- Children below 12years
-:- Pregnancy
Dose
Adult: 400mg twice daily
Side effects
.:. Nausea and vomiting .:.
•
Gastric pain
Dose
Communi~ acquired Pneumonia: 400mg once daily for 10 days
Exacerbation of Chronic bronchitis: 400mg once d'l r
5~ IOdays al y ,or
.:. Diarrhoea .:. Anorexia
.:. Confusion .:. Abdominal distension
.:. Insomnia .:. Skin rash Si~usitis: 400mg once daily for 7 days
.:. Convulsions .:. Urticaria Skin and soft tissue infection: 400mg once daily for 7 days
.:. Tendon rupture .:. Disorientation Side effects
Drug interactions ~I .:. Nausea
Vomiting
.:. Products containing aluminium, calcium and magnesium may .:. Headache
Super infections
reduce absorption of pefloxacin .:. Diarrhoea
Dizziness
-:. Chest pain
MOXIFLOXACIN Backache
.:. Dyspepsia
Available preparations: Tablets 400mg Malaise
-:. Abdominal pain
Injection 400mg/250ml
Available brands: Avelon® Drug interactions
Pharmacokinetics .:. Antacids and iron preparations may decrease the absorption
Moxifloxacin is well absorbed from the GI tract after oral of moxifloxacin
administration. It is widely distributed throughout the body. Moxifl~xacin inhibits metabolism of warfarin and phenytoin
.~.
metabolised in the liver and excreted in urine and feaces. Morphme reduces absorption of moxifloxacin

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 SE IQ:@#rMnknOCI pRl#a~1IQ:t;';J6fjBI)!fld

Drug interactions
Key issues to note b f .:. Antacids, digoxin, iron preparations may decrease gatifloxacin
.:. Moxifloxacin should be taken atl~ast 4 hours e ore plasma concentration and half life
multivitamins containing zinc or Iron .:. Probenecid may increase gatifloxacin plasma concentration and
.:. The drug can be taken with or without food half life
lH GATIFLOXACIN
Available preparations: Tablets 200mg, 400mg Key issues to note
.:. Gatifloxacin may be taken with or without meals
Available brands: Microgat®, Gatiquin®, Gatt 400®, .:. Gatifloxacinshould be taken at least 4 hours before or 8 hours
Zyquin® after multvitamins containing iron and zinc

Indications .. 4.1.90XAZOLIDINONES
.:. Acute exacerbation of chronic ~ronchltls The oxazolindinones are a group of drugs active against non replicating
.:. Community acquired pneumoma bacteria.
y .:. Uncomplicated skin infection They include:-
.:. Acute sinusitis L1nezolid
.:. Gonorrhoea
.:. Urinary tract infections tf Mode of action
Contraindications They inhibit protein synthesis by binding to the 50S ribosomal subunit
.:. Known hypersensitivity to quinolones ltnd preventing the formation of a functional 70S initiation complex.
•:. Children less than 12 years
.:. Pregnancy LlNEZOLID
.:. Lactation Available preparations: Tablets 600mg

~~::nic bronchitis, UTI and skin infections: 400mg once daily for Available brands: Lizolid®

7- lOdays I'harmacokinetics
Sinusitis: 400mg once daily for 10 days I..Inezolid is rapidly and completely absorbed following oral
Pneumonia: 400mg once daily for 7-14 days
ndrninistration, distributed into bone, fat, lungs, muscle, skin blister,
Gonorrhoea: 400mg single dose /lulds and into CSF. It is metabolized mainly by oxidation to inactive
Side effects Illetabolites and excreted in urine and small amount in faeces.
Mental confusion
.:. Rapid heart beat
Insomnia Indications
.:. Headache
Dizziness .:. Nosocomial pneumonia
.:. Diarrhoea
Nausea .:. Community acquired pneumonia
.:. Photophobia
Depression .:. Skin and soft tissue infections (including diabetic foot
.:. Abdominal pain
Bradycardia
.:. Abnormal vision infection)
.:. Hypertension
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 Wi@ISE PHARMACOLOGY I , PRECJ.tlPHARMACOLOGY

Contraindications Mode of action

.:. Breast feeding They inhibit protein synthesis by binding to the 50S ribosomal sub
•:. Hypersensitivity to linezolid unit.
"

Dose CLiNDAMYCIN
Adult: 600mg 12 hourly for I 0-14days (max. duration of treatment
Available preparations: Capsules ISOmg, 300mg
28 days)
Injection ISOmg Iml,
Children Iweel< - 12 years; IOmg/ kg 8 hourly for 10-14 days
Powder for suspension 7Smg/Sml
Side effects Topical solution 1%
.:. Diarrhoea Nausea Vaginal cream 2%
.:. Vomiting Metallic taste
.:. Skin rashes Headache Available brands: Dalacin-C ®, C-mycin®, Clindacin ®
.:. Vaginal candidiasis Fever
Pharmacol<inetics
.:. Fatigue Dizziness
Clindamycin is nearly completely absorbed from the gastrointestinal
.:. Insomnia Abdominal pain
tract and is widely distributed in most tissues (including bone) and
~. Constipation
body fluids. Some of the drug is metabolised in the liver and is
excreted in bile and urine.
Drug interactions
.:. Linezolid reduces contraceptive effect of estrogft, Indications
.:. Linezolid may decrease the effects of MAOls .:. Pneumonia .:. Endocarditis
Key issues to note .:. Endometritis .:. Gas gangrene
.:. Advise the patient to complete the entire course of therapy .:. Dental infections .:. Bacterial vaginosis
even if symptoms improve .:. Osteomyelitis .:. Septic arthritis
.:. Avoid alcohol and tyramine-containing foods e.g cheese, red .:. Wound infections
wine while taking linezolid .:. Surgical prophylaxis
.:. Peritonitis and abdominal abscess
4.1.10 LlNCOSAMIDES .:. Pelvic inflammatory disease
.:. Septicaemia and endocarditis
Lincosamides include:- .:. Pneumocystis carinii pneumonia
.:. C1indamycin .:. Acne
.:. Lincomycin
Contraindications
.:. Known hypersensitivity to c1indamycin or lincomycin
They are bacteriostatic or bactericidal, depending on the concentration, .:. Diarrhoeal states
and are active mainly against gram-positive bacteria and many anaerobic .:. History of antibiotic··associated colitis
bacteria such as Bacteroides spp. They also appear to have some .:. Severe hepatic impairment
antiprotozoal activity. Clindamycin is associated with a higher incidence .:. Ulcerative colitis
of pseudomembranous colitis than other antibiotics.

-109- -110-
 aJECISE PHARMACOLOGY I QinB SE PHARMACOlOGrJ
4-1.11 AMPHENICOLS
Dose
Adult orally: 150- 300mg 6 hourly (max. 450mg 6 hourly in severe This class includes:-
.:. Chloramphenicol
Infection)
Dental infection: 300- 450mg 8 hourly for 5-7 days .:. Thiamphenicol
Bacterial vaginosis: 300mg twice daily for 7 days CHLORAMPHENICOL
PCP: In combination with primaquine 300- 450mg every 6 hours Chloramphenicol is a broad-spectrum antibioitc that is active against
Children: 3-6mglkg 6 hourly. pneumococci, meningococci, H. influenzae, salmonella spp, Bacteroides.

By deep intramuscular injection or intravenous infusion The use of chloramphenicol has declined because of the presence of
Adult: 0.6-2.7g daily in 2-4 divided doses (450-900mg every 8 hours); effective and less toxic antibiotics
max. 4.8g daily Available preparations: Capsule 250mg
Children I month-12years: 3.75-6.25mglkg 4 times daily; increased Powder for Injection I g
lip to I Omglkg 4 times daily in severe infections Powder for oral suspension I 25mgl 5ml
Eye or ear drops
Side effects
.:. Diarrhoea Abdominal discomfort Available brands: Chlorocide®,Medicol®, Agophenol®
.:. J'Nausea .:. Vomiting Elycetin®, Kamchlor®, Renechlor®
.:. Jaundice Skin Rash
Urticaria Pharmacokinetics
.:. Pruritus
Chloramphenicol is rapidly and completely absorbed when given
.:. Leucopenia
orally with bioavailability of 80%. It is widely distributed into tissues,
.:. Thrombophlebitis after intravenous injection
body fluids and cavities achieving high levels in the brain and CSF. It is
.:. Pseudomembranous colitis
metabolized in the liver and excreted in urine.
Drug interactions Indications
.:. C1indamycin may reduce the efficacy of oral contraceptives .:. Bacterial meningitis Brain abscess
.:. C1indamycin may enhance the effects of suxamethonium .:. Septicaemia Typhoid
.:. Gas gangrene Ricketsial diseases
Key issues to note
.:. Discontinue therapy and investigate if significant diarrhoea Contraindications
.:. Pregnancy .:. Porphyria
occurs
.:. Clindamycin may be taken with food when there is .:. Blood dyscrasias .:. Bone marrow depression
gastro-intestinal intolerance, it may delay but not decrease .:. Previous allergy to chloramphenicol
absorption Dose
.:. Oesophageal irritation can be avoided by taking c1indamycin Adult: Oral/IV: 500mg 6 hourly
with adequate amount of fluid Children: 12.5-25mglkg every 6 hours
Infants less than 2weeks: 25mglkglday in 4 divided doses

-111- -112-
 , PREcmPHARMACOlOGY PREC~PHARMACOlO~

Dose
Side effects
.:. Anaemia .:. Fever Adult: 2S0-S00mg 3 times daiiy
.:. Thrombocytopenia .:. Peripheral neuritis Children: 30-1 OOmglkg daily in divided doses
.:. Optic neuritis .:. Nausea and vomiting Side effects
.:. Diarrhoea .:. Stomatitis .:. Dry mouth
.:. Glossitis .:. Skin rash .:. Visual disturbances
.:. Bone-marrow depression .:. Grey baby syndrome .:. GI upset
.:. Skin rash
Drug Interactions
.:. Phenytoin levels may be increased by chloramphenicol .:. Severe blood dyscrasias (aplastic anaemia)
.:. Warfarin anticoagulant effects may be enhanced by .:. Grey baby syndrome
chloramphenicol
.:. Rifampicin, phenobarbitone may reduce the efficacy of Drug interactions
.:. Thiamphenicol may enhance the anticoagulant effect of
chloramphenicol
.:. Oral !:c'ontraceptives eficacy may be reduced by warfarin
.:. Thiamphenicol may increase the hypoglycaemic effects of
chloramphenicol
.:. ~aematologic response to iron salts and vitamin B 12 is reduced sulphonylureas
J,y chloramphenicol 4.1. 12 CARBAPENEMS
Carbapenems include:-
Key issues to note 1>11
.:. Meropenem
.:. Due to its toxicity, chloramphenicol use is not recomended for
.:. Imipenem
less serious infections
They are active against a wide range of bacteria including many
THIAMPHENICOL tltrains resistant to other antibiotics.

Available preparations: Tablets 2S0mg, SOOmg MEROPENEM

Available preparations: Powder for injection SOOmg, Ig
Available brands: Thiobactin®
Available brands: Meronem®, Ronem®, Monan®
Indications
.:. Acute respiratory infections Pharmacokinetics
.:. Gastrointestinal infections Meropenem is administered IV and distributes to all body fluids and
.:. Urinary tract infections tissues. It is excreted unchanged in urine.
•:. Typhoid
Indications
Contraindications
.:. Meningitis .:. Septicaemia
.:. Known hypersensitivity to thiamphenicol
.:. Cystic fibrosis .:. Melioidosis
.:. Nosocomial pneumonia .:. Urinary tract infections
.:. Skin and soft tissue infection .:. Gynecological infections

-113- -114-
 , ' II:"','" II '",":" ,,' I,,'
'IL j l l l i l l I I
PRECI~'iJPHARMACOLOGY

.:. Community acquired pneumonia 4.1.13 NITROFURANS

.:. Intra-abdominal infections Nltrofurans includes:-
.:. Infections in immunocompromised patients .:. Nitrofurantoin
Nltrofuratoin is also called urinary tract antiseptic because its activity
Contraindications III localised to the urinary bladder. It is bactericidal against gram-
.:. History of sizures or CNS abnormality I)ositive and gram-negative bacteria that commonly cause urinary tract
.:. Known hypersensitivity to penicillins Infections, including E. coli, Enterococcus faecalis, K. Pneumoniae, and
S/'aphylococcus saprophyticus but is not active against Proteus species,
Dose tlild P. aeruginosa.
Adult:
By IV injection over 5 minutes or by intravenous infusi~n over. 15- NITROFURANTOIN
30minutes, 0.5-1 g every 8 hours double the dose in hospital acqUlre.d Available preparations: Tablets 50mg, 100mg
pneumonia, peritonitis, septicaemia and infections in neutropenic
patients Av.\lIable brands: Furadantin®, Agotoin®
Meningitis, cystic fibrosis: 2g every 8 hours "harmacokinetics
Children: Nitrofurantoin is readily absorbed from the GIT btu food may increase
\l 3months -12 years: I 0-20mg /kg every 8 hours 11M bioavailability. It is distributed to body tissues, but only in small
J Meningitis, cystic fibrosis: 40mg /kg every 8 hours iIItllOunts. Therapeutic concentrations are only reached in the urinary
~e~~ j .1'I\(:t. The drug is excreted in urine.
.:. Skin reaction .:. Pruritus
•
••• U' .
rtlcana •••• Angioedema Indications •
•
••• C onvu Islon
. •••• Abdominal pain .:. Uncomplicated lower urinary tract infections
•
••• N ausea •••• \'omiting
v' .:. Prophylaxis of urinary tract infection
.:. Diarrhoea .:. Candidiasis C::ontraindications
.:. Headache .:. Renal impairment
.:. Disturbance in liver function tests .:. Infants less than 3 months
.:. Pseudomembranous colitis .:. Pregnancy
.:. Thrombophlebitis and pain at injection site .:. Lactation
Drug interactions .:. Hypersensitivity to nitrofurantoin
.:. Meropenem may reduce the serum levels of sodium valproate .:. Porphyria
.:. Probenecid inhibits renal excretion of meropenem .:. G6PD-deficiency

nOlle
Key issues to note A. ute uncomplicated infections
.:. Prolonged use of meropenem may result in superinfections Adult: 50mg 6 hourly or 100mg 12 hourly for 7days
.:. Safety and efficacy in children below 3 months is not yet C~hlldren over 3 months: 3mg/kg daily in 4 divided doses
documented

-115- -116-
 PREC , :' " ' '",,:1 PRECISE PHARil'J.f:IIiOLOGY
Severe recurrent urinary tract infections 4.1.14 OTHER ANTIBACTERIALS DRUGS
Adult: I OOmg 6hourly for 7 days SPECTINOMYCIN
Children: 3mg Ikg daily in 4 divided doses
Prophylaxis of urinary tract infections $pectinomycin is an antibacterial that acts by binding to the 30S subunit
Adult: 50-1 OOmg at night 1:,1 the bacterial ribosome and inhibiting protein synthesis.
Children over 3 months: I mg/kg at night
Available preparations: Powder for injection 2g
Side effects
.:.Anorexia .:. Nausea Available brands: Togamycin®
.:.Vomiting .:. Diarrhoea
.:.Hepatitis .:. Pancreatitis
.:.Arthralgia .:. Blood disorders
Indications

.:. Pulmonary reactions .:. Peripheral neuropathy

.:. Uncomplicated gonorrhoea
+:+ Disseminated gonorrhoea
.:. Hypersensitivity reaction +:. Chancroid
+:. Neonatal gonococcal conjunctivitis
Drug interactions
.:. Absorption of nitrofurantoin is reduced by oral magnesium Contraindications
trisci@:ate .:. Known hypersensitivity to spectinomycin
.:. Excretion of nitrofurantoin is reduced by probenecid Dose
.:. Concurrent use of nifrofurantion with folic acid may result in Uncomplicated gonococcal infections and chancroid: Deep 1M 2g
decreased folic serum levels /lM il single dose; may be increased to 4g as a single dose, divided into
.:. Nifrofurantion may result in antagonism of the antibacterial 2 Injection sites
effect of norfloxacin Disseminated gonococcal infections: Adult Deep 1M 2g twice daily
for 7days
Key issues to note Neonatal gonococcal conjunctivitis: Deep 1M injection 25mglkg as
.:. Administer the drug with food or milk to minimise nausea .\ ~ingle dose (max 75mg)
vomiting. Food also improve absorption of the drug. Side effects
.:. Nitrofurantoin may cause brown discoloration of urine .:. Nausea Vomiting
.:. Periodic liver function tests during prolonged therapy may be .:. Dizziness Fever
required .:. Urticaria Pain at injection site
.:. Advise the patient to avoid alcohol during therapy :'1
Key issues to note
.:. In the treatement of gonorrhoea, spectinomycin is followed
by doxycycline 100mg bid for 7 days or erythromycin if
pregnant or allergic to doxycycline.
•:. Spectinomycin is ineffective aganist syphilis and may mask
symptoms

-117- -118-
 PftECI PHARMACOLOGY
...
DRUGS OF CHOICE FOR COMMON BACTERIAL INFECTIONS Bacterial S. aureus Initially topical If severe, use
,
conjunctivitis S. pneumoniae chloramphenicol neomycin +
RUGS
I
S. pyogenes polymyxin or
COMMON • \,~Ci/)Mllitla~T
f;FECTION OF CHOICE , I H. inf/uenzae Ciprofloxacin or
PATHOGENS
.. , gentamycin or
..
Mcnil1.gitis Ampicillin may be erythromycin.
E. coli and Cefotaxime
Neonates added if Listeria Treat for 7days
other or Ceftriaxone
monocytogenes is and use ointment
Gram negative
suspected at night and
organisms
...... Alternative; drops during day
H. influenzae Cefotaxime
Children: chloramphenicol
N. Meningitidis or Ceftriaxone
I month-
or Benzyl penicillin Blepharitis S. aureus Erythromycin Treatment
6years
S. epidermidis Bacitracin should be for
S. pneumoniae Cefotaxime or Ceftriaxone Empirically use polymyxin 1-2weeks
Adults a 3rd generation
N. Meningitidis or Neomycin
Benzyl penicillin cephalosporin
Gentamicin
Tobramycin
Benzylpenicillin + Prompt
Brain Mixed
metronidazole or neurosurgical
abscess organisms Trachoma Chlamydia Newborn Single dose
chloramphenicol attention is
essential
trachomatis Erythromycin aZithromycin for

Substitute
Adults mass treatment
Tetracycline
a 3rd gen.
Doxycycline
cephalosporin
Azithromycin
for penicillin
if there is
contiguous r ar, nose and throat infections
middle ear Dental attention is
Dental Mixed organisms Phenoxymethylpenicillin
infection with metronidazole or required for abscess
Infections
c1indamycin Treat for Sdays and
Eye
start with parenteral
infections
antibiotics
\llIllSitis S.pneumoniae Amoxycillin
Awte H. in(1uenzae
Chronic Mixed organisms Co-amoxiclav
or amoxycillin +
metronidazole

-120-
-119-
 III PRECISE I LlJGY
7 7 _pn-_QiJ~8tiilQ:r;'iJMt~'ll'IifI
Diphtheria C. diphtheriae Penicillin or Antitoxin ----------,-------.
.... erythromycin required <60years S. pneumoniae Benzylpenicillin or
Pharyngitis, Group A beta Phenoxymethylpencillin Add macrolide
and no co- C pneumoniae amoxicillin or tetracycline if
tonsillitis haemolytic or Benzathine penicillin morbidity M pneumoniae
streptococci Azithromycin response is poor.
Cefaclor Treat for IOdays
>6Oyears or
Cefpodoxime co-morbidity
Cefuroxime
S. pneumoniae Co-amoxiclav or
Clarithromycin Severe
Erythromycin
L. pneumophila cefuroxime plus a
pneumonia
K pneumoniae macrolide pnE~unnorliae is
S. aUreus
Epiglottitis H. in(luenzae 3ed generation Alternative
cephalosporins chloramphenicol

_.....
Cardiovascular infections
Acute otitis Often viral Amoxicillin Treat for 7- I Odays
media S. pneumoniae Cefuroxime Use cefuroxime
Infective Viridans
H. in(luenzae Cefaclor or Cefaclor in Benzylpenicillin + an Usually 4weeks
~!I,docarditis streptococci
B. catarrhalis Amoxicillin + penicillin allergy aminoglycoside (1/2 therapy IV is
c1avulanic acid dose) needed for
~.?wer respiratory tract infections endocarditis
E. faecalis Ampicillin + an
Chronic H. in(luenzae Amoxicillin or Mucolytic
bronchitis S. pneumoniae Cotrimoxazole expectorant aminoglycoside
or tetracycline or may be added 1/2 dose
amoxicillin +c1avulanic to promote S. aureus
Cloxacillin or Optional to add

IWlpSls ---t:~:;;:==::____--t~f1~u~c~lo~x;a~c!.!iill~in~-___:_:___J_!a~n~am~in~o~l}"c~o~s~id~e~
acid or azithromycin expectoration -
or N '
. menmgitis Penicillin + cloxacillin
("ndetermined streptococci
.. _- Clarith romycin
fir/Kin) S. aureus
c:ommunity acquired pneumonia
. 60years Gram negative 2nd generation
""d 110 co- streptococci cephalosporin or co-
111I)l'bidity
amoxiclav
·I\Oyears or
IIIl c'o~.morbidity

I ..'MtrClintestinal Tract Infections

-121-
-122-
_sma_I? 11111111• . - . . . . . . . . . . . PREC~1IQ:rMMMI!!HIfI

Acute E. coli, Ampicillin + Follow with oral I'IYr1hc)id fever S. typhi Ciprofloxacin Alternative
amoxicillin with ceftriaxone chloramphenicol
Cholecystitis Klebsiella spp aminoglycoside I
c1avulanic acid if Ofloxacin
or Ceftriaxone or
necessary Azithromycin
cefotaxime
Add 9~rli~?r urinary tract
metronidazole C::yMtltis E. coli and other Norfloxacin or Treat
if there is biliary Coliforms Ciprofloxacin or uncomplicated
obstruction co-amoxiclav cystitis for 3 days.
Alternative. Single
Co/iforms Ampicillin + gentamycin Surgical is I
Peritonitis dose qUinolones
bacteriods spp + metronidazole or generally
or urinary
E. faecaf/is Ceftriaxone + IV necessary
antiseptics
clostridia metronidazole or co-
I~YC1lonephritis E. coli Norfloxacin or Culture and
amoxiclav
Rehydration is S. saprophyticus Ciprofloxacin or sensitivity test
Campylobacter Campy- Erythromycin
Ciprofloxacin essential Treat Proteus co-amoxiclav, but recommended
enteritis W lobacter jejuni with erythromycin
'I·' Klebsiella continue for 10-
for 7-1 Odays or
...- 14days
norfloxacin for 5days "

"mstatitis N. gonorrhoeae Ciprofloxacin single

At:lJte C. trachomatis dose + tetracycline
C. difficile Chronic for 7days
Clostridium C. difficile Oral metronidazole
infections range Coliforms Ciprofloxacin Prolonged
difficile Oral Vancomycin
from mild to Norfloxacin therapy (up to
Bacitracin i
severe diarrhoea Ofloxacin 6weeks)
....
Stop antibacterial Partner
therapy if possible Vllglnal N. gonorrhoeae Ciprofloxacin single notification and
Treat for 7-1 Odays dl$charge C. trachomatis dose + doxycycline treatment is
E. coli Norfloxacin or Treat for 3days, T. vaginalis for 7days + essential.
Travellers'
Ciprofloxacin or Fluid replacement metronidazole single Promote use of
diarrhoea
Cotrimoxazole or may be necessary. dose condoms and safe
Bismuth subsalicylate or Loperamide !
sex practices.
Azithromycin( children & use is not Counsel and
pregnant mothers) recommended in educate about
dysentery cases the risk of HIV
Tetracycline or Rehydration infection
Cholera V. cho/erae
Ciprofloxacin or is first line
Doxycycline treatment

-123- --124-
 "1

Q;!~~~1'4:rMMMOLOGY I '~' " PREC111PHARMACIILOGY

........
,
.-..
Doxycycline for Treate the sexual Puerperal Mixed aerobes and Metronidazole +
urethritis C. trachomatis
partner. Hepsis and anaerobes benzylpenicillin +
no n 7days
Erythromycin for Heptic gentamycin
Gollococcal abortion
7days
Azithromycin single SClptlc arthritis/ S. aureus Cloxacillin Treat for at/east 4
Urethritis N. gonorrhoeae ()5teomyelitis weeks.
Flucloxacillin
Gonococcal dose Culture and sensitivity
Ciprofloxacin tests strongly
Cefazolin recommended
Cefixime
Ceftriaxona Skin..-infed:i~r;ls
"'" '" . ,II, "

Ofloxain Erysipelas S. pyogenes Benzylpenicillin,

Spectinomycin tu..
azithromycin
.. _-.-
Benzathine penicillin Impetigo S. pyogenes mupirocin 2% ,
Genital ulcer H. ducreyi
(1M) Erythromycin cream flucloxacillin
(Chancroid)
Ciprofloxacin Cloxacillin
Azithromycin azithromycin
Ceftriaxone Erythromycin
......•
Ciprofloxacin or Hospitalized Amoxicillinl
pcivic N. gonorrhoeae
ceftriaxone or patients should c1avulanate
nflammatory C. trachomatis
Cefotaxime single start with Cephalexin
lisease anaerobes
dose + doxycycline parenteral Cephradine
for 14days + therapy :~ I. q,,,'
C1arithromvcin
metronidazole for Clindamycin + C:(~lIulitjs S. pyogenes Cloxacillin Addition of an
14days Gentamicin. S. aureus Flucloxacillin aminoglycoside
Erythromycin may be needed in
Levofloxacin diabetic patients
Syphilis I pallidum Primary, Benzathine penicillin Erythromycin or
(1M) once a week tetracycline for Cephalexin Treatfor 5- 10
secondary or early
for 3 weeks ISdays days
latent
f )I.-betic foot Anaerobes Oral metronidazole and If severe, use
Erythromycin
Late syphilis IIllct<:tion Gram cephalexin or c1indamycin +
or tetracycline
positive and Amoxicillin + c1avulanic oral ciprofloxacin.
for 30days (late
gram negative acid Cleansing
syphilis) aerobes debridement,
...• _-
Benzylpenicillin IV
Neuro
syphilis
I pallidum
for I 0 days followed I' wound dressing,
glycaemic control
by Benzathine ... also important.
penicillin (1M)
weekly for 3 weeks
..

-125- -126-
n
,- ....
Boils.
folliculitis,
2-
S. aureus Flucloxacillin
Cephalexin
QMJlISE PHAllh1ACOLmd
Treat for 5-7days
Drainage may be
required
, ,.

4.1.15 DRUGS USED IN TREATMENT OF TUBERCULOSIS

PRECISE PHARMACOLOGY

Tuberculosis is a chronic infectious disease caused by Mycobacterium

Clindamycin
carbuncles Treat for 5-7days tuberculosis or sometimes M.bovis. M.tuberculosis infection is spread
Flucloxacillin or
Start with by the inhalation of infected droplet nuclei and the lungs are the first
S. aureus Cephalexin or
Mastitis Cefazolin organs to be affected.
Clindamycin
injection if severe.
Amoxicillin + clavulanic Clean, irrigate Signs and symptoms
Bites human S. aureus
with sodium .:. Cough for more than 3 weeks
and animal Streptococci acid
Cefuroxime or chloride 0.9% .:. Loss of weight
Anaerobes and debride
Metronidazole + .:. Fever
Pasteurella
doxycycline or wound .:. Night sweating
ciprofloxacin + thoroughly
Treat for 5-1 Odays
clindamycin Drugs use in the treatment of tuberculosis are classified as first line and
~, Check tetanus
"
.~(:ond line drugs. Second line drugs are reserved for cases that are
immunisation
1'1!l",I"'tant to the first line drugs.
status.
IUlIlll': IHIII.u ---,

.-- Clindamycin solution or Use oral Examples

4'
Acne prop;on;-
antibiotics for
bacterium Doxycycline or 'llr.t.!ine drugs
Erythromycin 3months and
acne Nirllmpicin (R)
topical antibiotics
l"l~ptomycin (S)
for 3 months
.. Treat for 6weeks
'It\mnbutol (E)
Doxycycline +
.-,

Brucellosis Brucella spp "¥I .1linamide (Z)

rifampicin or 1.~'IIl;,zid (H) or (INH)
Doxycycline + ..._----------------..,..,---..,.",-..,..,---,-j
streptomycin ' ••:ondline drugs 1;!I',iii .,;
Alternative
Tick bite fever R. conar;;
Doxycycline
chloramphenicol ~I Itlk"cin.
~ "futmycin
t y' loscrine

~l .... t ment of tuberculosis:

1"I'tI' CIllosis is treated in 2 phases; i.e.
'nltlal (intensive) Phase; 2-3 months
Continuation phase; 4-6 months

-128-
---127 -
 , , PREC PHARMACOLOGY

lj-eatment regimens are usually expressed in standard form as:-

.:. 2EHRZ/6EH (new cases)
.:. 2SEHRZ/1 EHRZ/SEHR (re-treatment regimen)
- Dose
:'" ,,' RE ISE PHARMACOLOGY

Tuberculosis: I Omg/kg daily in combination with other drugs

Brucellosis : 600 -1200mg daily in 2-4 divided doses, in combination
I

.:. 2HRZ/4HR (children regimen) with other drugs like doxycycline

Prophylaxis against meningitis due to Haemophilus influenzae:
From the above treatment regimens, the letters represent abbreviated Adult: 600mg daily for 4days
drug names and the numbers show the duration of treatment in months Infants and children: 20mg /kg/day in 2 divided doses for 4 days
and the division between the treatment phases. Prophylaxis against meningococcal meningitis and the treatment
of meningococcal carriers:
RIFAMPICIN Adult: 600 mg twice daily for 2days
Rifampicin is bactericidal for intra- and extra cellular bacteria and is one Infants and children: 20mg /kg/day in 2 divided doses for 2 days
of the most effective antituberculosis drugs.
Side effects
Available preparations: Capsules ISOmg, 300mg .:. Anorexia Nausea and vomiting
.:. Headache Facial flushing
Available brands: Rifadin®, Rifacos®
.:. Itching Rash
Mode of action .:. Influenza like syndrome Fever
Rifampicin suppresses initiation of chain formation for RNA synthesis by .:. Heart burn Bone pain
inhibiting DNA-dependent RNA polymerase enzyme. .:. Malaise Diarrhoea
.:. Hepatoxicity
Pharmacol<inetics
Drug interactions
Rifampicin is well absorbed from the GI tract. Food delays and reduces
the amount of drug absorbed; well distributed into most body tissues Rifampicin is an enzyme inducer and may reduce the effectiveness of
and fluids, including CSF. It undergoes enterohepatic recycling; is II wide variety of drugs which include:-
metabolized in the liver and is excreted principally in faeces and also .:. Oral contraceptives Phenytoin
in urine. .:. Corticosteroids Oral antidiabetics
.:. Oral anticoagulants Verapamil
Indications
.:. Fluconazole Digoxin
.:. Tuberculosis in combination with other drugs
.:. Chloramphenicol .:. Alcohol
.:. Leprosy in combination with other drugs
.:. Prophylaxis of meningococcal meningitis .:. Ritonavir and saquinavir
Key issues to note
.:. Brucellosis
Contraindications .:. Advise the patient tb take the drug on an empty stomach, at
.:. Acute hepatic disease least I hour before or 2 hours after meals
.:. Treatment with combined saquinavir and ritonavir .:. Inform the patient that rifampicin may cause discoloration of
.:. Hypersensitivity to rifamycins urine, tears or sweat and it is harmless
.:. Lactation .:. Rifampicin may permanently stain soft contact lenses

-129- --130-
',;,

.J~It,,'lj
 PRECISE PHARMACOLOGY 1 PRE~PHARMACOlOGY

STREPTOMYCIN Ihlel effects

Streptomycin is effective against rapidly growing extracellular .:- Paraesthesia
mycobacteria. .> Optic neuritis
.:. Fever
Available preparations: Powder for injection Ig ..
'
.:. High frequency range hearing impairment
.:. Pain and abscess at injection site
Mode of action O¢. Bone marrow suppression
Streptomycin is bactericidal in action and inhibits protein synthesis by O¢. Nephrotoxicity
binding to the 30S unit of the bacterial ribosome. <. Peripheral neuropathies

Pharmacoldnetics I),'ug interactions

Streptomycin is not absorbed when taken orally. It is widely .:. Nephrotoxic drugs such as amphotericin B, Cephalosporins.
distributed into most body tissues and fluids, except the brain and acyclovir increase the nephrotoxicity caused by
following 1M administration. It is excreted unchanged in urine. streptomycin
.:. H 2 receptor blockers may mask the early signs of toxicity
Indications caused by streptomycin
.:. Tuberculosis in combination with other drugs .:. Streptomycin may potentiate the effect of neuromuscular-
.:. Brucellosis blocking drugs used during anaesthesia
.:. Plague .:. Penicillins and extended-spectrum antibiotics may inactivate
streptomycin
Contraindications .:. Streptomycin may enhance the effects of anticoagulants
.:. Hearing disorders
.:. Pregnancy k.. y issues to note
.:. Known hypersensitivity to streptomycin .:. Use with caution in patients with pre-existing vertigo, tinnitus,
.:. Renal impairment and hearing loss
.:. Myasthenia gravis .:. Reconstituted solution retains its potency for 2days at room
temperature and for 14 days when refrigerated
Dose
Tuberculosis t· rHAMBUTOL
Adults: ISmg/kg daily, max. I g daily ~ thambutol is effective against M tuberculosis and other mycobacteria
Children: IS-20mg/kg daily, max. I g daily lllduding M avium.
Brucellosis
Adults and children >8years: I g 1M once daily for 2 weeks, together AVflilable preparations: Tablets 400mg
with doxycycline I OOmg twice daily for 6 weeks
Plague: Available brands: Etham®, Ecox®
Adult: Ig 1M twice daily for 7-IOdays

-131- -132-
 ,,, ,,' PRECISE PHA
En I
PYRAZINAMIDE
Mode of action
Ethambutol is bacteriostatic. It impairs synthesis of Mycobacteria cell Available preparations: Tablets 500mg
wall resulting into suppression of multiplication.
Available brands: PZA-ciba®
Pharmacokinetics ~
Ethambutol is readily absorbed from the GIT; widely distributed to most
Pharmacokinetics
tissues and body fluids, including the lungs and kidneys. It is partially
Pyr~inamid.e is well absorbed orally (unaffected by food), widely
metabolized in the liver and excreted primarily in urine.
dlstnbut~d In body fluids and tissues and diffuses into the CSF. It is

Indications l'l1et,abo!lzed primarily in the liver by hydrolysis to the major active

.:. Tuberculosis in combination with other drugs metabolite and excreted through the kidneys (urine) .
•:. Mycobacterium avium complex (MAC) infections
Indications
Contraindications .:. Treatment of tuberculosis in combination with other drugs
.:. Hypersensitivity to ethambutol
.:. Sever'e renal failure Contraindications
.:. Optic neuritis .:. Severe hepatic impairment
.:. Children under 5years .:. Acute gout
.:. Hypersensitivity to pyrazinamide
Dose
ISmglkg as a single daily dose Dose
Adults: 15-30mglkg daily
Side effects Children: 20 -40mgl kg daily, Max. 3g1day
.:. Gout
.:. Optic neuritis
.:. Skin Rash Side effects
.:. Urticaria
.:. Peripheral neuritis .:. Hyperuricaemia .:. Anorexia
.:. Reduced visual acuity
.:. Thrombocytopenia .:. Arthralgia Skin rash
.:. Pruritus
.:. Nausea and vomiting .:. Jaundice Nausea and vomiting
.:. Abdominal distress
.:. anorexia .:. Malaise Fever
.:. Confusion
.:. Sideroblastic anaemia Dysuria
Drug interactions .:. Liver failure .:. Acne
.:. Antacids containing aluminium salts may decrease levels of
.:. Urticaria
ethambutol and should be taken at least 2 hours before or after
ethambutol administration. Drug interactions
.:. Pyraz:i~amide may decrease the effect of allopurinol,
Key issues to note colchicine and probenecid
.:. The drug may be administered with meals to reduce GI
symptoms kt.ly issues to note
.:. The drug should be taken regularly .:. Pyrazinam~de may cause photosensitivity reactions, patient
should avoid exposure to sunlight or artificial light sources

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 , :'"'''''' I,', ," ',' , PRECISE~OL9GY

Drug interactions
ISONIAZID . d' 'd'ng organisms but bacteriostatic on .:. Isoniazid may inhibit the hepatic metabolism of carbamazepine,
Isoniazid is bactericidal against IVI I phenytoin, ketoconazole, theophylline and diazepam
resting organisms .:. Absorption of isoniazid is reduced by aluminum antacids
Available preparations: Tablets I OOmg, 300mg .:. Alcohol increases the incidence of isoniazid-related hepatitis
.:. Acetaminophen and rifampicin may increase the risk of
Available brands: S0 Ionex ® , Agozid®· hepatotoxicity if given concurrently with isoniazid
.:. Corticosteriods may reduce plasma concentrations of
Mode of action . . , nd nucleic acid biosynthesis in growing isoniazid
Rifampicin interferes :'It~ hPd~d a f n of the bacterial cell wall.
tubercle bacilli, resulting In Isrup 10
I(Cfty issues to note
Pharmacokinetics I lIy It is widely distributed to .:. Absorption is optimal when isoniazid is taken on an empty
II b orbed when ta <en ora . d
Isoniazid is we a s . b r d by acetylation in the liver an stomach
tissues and body fluids. It IS meta 0 Ize .:- Warn the patient to avoid alcohol when taking the drug
excreted in urine .> Pyridoxine therapy may be necessary in pregnant women,
alcoholics and malnourished patients
Indications , . . combination with other drugs 1.11'
••• Treatment of tubercu OSIS In ~ Inform the patient to report any of the following symptoms;
.;. Prophylaxis of tuberculosis burning sensation, tingling or numbness in the extremities ~!
Contraindications . . III
" I, 16 DRUGS USED IN THE TREATMENT OF LEPROSY
.:. H ersensitivity to isomazld . .
.:. A~~te liver disease /drug-induced hepatic dls~as~ .
11:
1"IItW05y is a chronic, granulomatous infectious disease caused by
.:. Previous history of isoniazid-associated hepatic inJury I"", u/wcterium leprae. It affects the peripheral nervous system and the
'~IH It is transmitted from person to person when bacilli are shed from
Dose • Iii
Treatment of tuberculosIs . ~ltll Hose and skin lesions of an infected person. The clinical form of
Adults: 5mg/kg/day OR 300mg dally . ,II. cllM~ase is determined by the degree of cell-mediated immunity
Children: 5mg/kg daily max 300mg dally IIII11'U lI\llcd by the individual towards M. leprae.
Tuberculosis Prophylaxis ~"l'ln~y may be classified as either multibacillary or paucibacillary. II
Adult: 300mg daily for a: least 6 ~o~t~smonths max 300mg daily
Children: 5-1 Omg/kg dally for at eas MII'IIlMcillary Leprosy
" D4ll~ I IH~ when cellular immunity is largely deficient. It is sub divided as
Side effects .:. Nausea ad vomiting li!l!i __ tw,
.:. Peripheral neuritis
.:. Convulsions , + I (!promatous (LL)
.:. Rashes .:. Fever l' Borderline lepromatous (BL)
.:. Diarrhoea 01> Mid borderline leprosy (BB)
.:. Optic neuritis
.:. Fatigue Ii
.:. Visual disturbances 'II
II
.:. Epigastric distress
.:. HepatotoxicitX '-
.:. Pyridoxine deficiency

-136-
-135-
 gj13Q~13 PHARMACOLOGY I
Mil
DAPSONE
Paucibacillary Leprosy Dapsone is similar to sulphonamides and is the most active drug against
It occurs when cellular immunity is only partially deficient. It includes:-
M.leprae .
•:. Borderline Tuberculoid (BT)
.:. Tuberculoid (TT)
Available preparations: Tablets IOOmg
.:. Indeterminate Leprosy (I)
Note: In this case, the skin smear is negative and lepromine test is Pharmacokinetics
D~pson~ is ~Imost completely absorbed from the gastrointestinal tract,
positive.
Widely distributed to all body tissues and flUids including the skin and is
WHO classification of leprosy patients excreted slowly in urine as unchanged drug and metabolites.
Multibacillary (patients with more than 5 skin lesions)
Paucibacillary (patients with 1-5 skin lesions) Indications
.:. Leprosy
The medical complications of leprosy are due to nerve damage,
.:. Pneumocystis carinii pneumonia (prophylaxis)
immunological reactions and bacilliary infiltration. .:. Dermatitis herpetiformis
.:. :rimary prevention of toxoplasmosis with pyrimethamine,
Drugs used in the treatment of Leprosy are divided into two:-
In people unable to tolerate trimethoprim with
.:. Drugs used to treat leprosy sulfamethoxazole
.:. Drugs used to treat lepra reactions

Drugs used to treat leprosy include:- Contraindications

.:. Rifampicin .:. Known hypersensitivity to dapsone
.:. Dapsone .:. Severe anaemia
.:. Clofazimine
Oose
Drugs used for lepra reactions include:-
".mcibacillary Leprosy; I OOmg daily in combination with other
.:. Chloroquine drugs
.:. Cortcosteroids (:hlldren IO-14years: 50mg daily, continue treatment for 6months
.:. Thalidomide Multibacillary leprosy in combination with rifampicin and
Key issues to note flnfilZimine:
.:. Abrupt changes in clinical stability leads to complicating Adult: I OOmg daily
inflammatory conditions known as lepra reactions which result Children IO-14years: SOmg daily, continue treatment for 12months
in significant morbidity and disability due to nerve damage I).. rrnatitis Herpetiformis: SOmg daily, gradually increased to 300mg
.:. Prompt treatment of lepra reactions is essential to minimize Itltlly or more if required
nerve damage and prevent disability ttlophylaxis of pneumocystis carinii pneumonia; IOOmg once
.:. Leprosy therapy should continue as reactions are being ," ,l"lly
managed
.:. Treatment of leprosy is long term ranging from several month-, ,.'
to years.

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-137-
 IIIRI PRECISE PHARMACOLOGY I III PRECISE~LIJGY

Side effects Contraindications

.:. Anaemia .:. Peripheral neuropathy .:. Hypersensitivity to C10fazimine
.:. Insomnia .:. Allergic dermatitis skin rash .:. Lactation
.:. Anorexia .:. Nausea and vomiting
Dose
.:. Headache .:. Tachycardia
loprosy
.:. fever
Adult: 300mg once each month, then SOmg once daily
Children < IOyears: IOOmg once each month then I mg/kg once
Drug interactions
dilily. (
.:. Serum concentrations of dapsone are increased when given
Children> IOyears ISOmg once each month then I mg/kg once daily
together with probenecid
Chronic type 2 lepra reactions: 300mg daily for not more than 3
.:. Rifampicin reduces serum concentration of dapsone
II\onths
.:. Pyrimethamine increas,es risk of haematological disorders
.:. Didanosine may inhibit dissolution of dapsone in the stomach Side effects
.:. Concurrent use of trimethoprim and dapsone results in .:. Nausea .:. Vomiting
increased plasma concentrations of both drugs .:. Abdominal pain Headache
.:. Photosensitivity .:. Acne-like eruptions
Key issues to note
.:. Anorexia
.:. Dapsone distributes into breast milk and may harm the baby,
.:. Red to brown discoloration of the skin
therefore the decision to discontinue breastfeeding or the
.:. Discoloration of hair, tears and sweat
drug has to be made
.:. Advise the patient to avoid exposure to sun light by wearing Drug interactions
protective c10things and lip sunscreen .:. Anti- inflammatory action of c10fazimine in type 2 lepra
.:. The drug may be used in conjuction with either rifampin or reactions may be reduced by dapsone
c10fazimine to prevent development of drug resistance and
KClY issues to note
reduce infectiousness of the patient quickly
.:. C10fazimine is absorbed well when taken with food
.:. Inform the patient that the skin may become pink to brownish-
CLOFAZIMINE
black during treatment but slowly normalises on completion
Available preparations: Capsules IOOmg
of the treatment
.:. Advise the patient to wear protective c10things and use of
Pharmacokinetics
sun screen to avoid exposure to sun light which worsens skin
C10fazimine is incompletely absorbed when taken orally, bioavailability
discolouration
being increased when taken with food. It accumulates in tissues such as
fats, skin, liver and kidney and is eliminated in bile and faeces. fHALIDOMIDE
Available preparations: Tablets SOmg
Indications
.:. Leprosy (multibacillary)
Pharmacokinetics
.:. Chronic type 2 lepra reactions
I h"lidomide is slowly absorbed from the gastrointestinal tract, crosses
thC' placenta and is distributed into semen. The exact metabolic fate of

-139- -140-
 , PRECIf;iljjHARMAClJLlIGY rt 7
thalidomide is unknown however, it appears to undergo non-enzymatic
hydrolysis in plasma and is excreted in urine.
CHAPTERS
Indications
.:. Kaposis sarcoma DRUGS USED IN THE TREATMENT OF FUNGAL
".:. Primary brain malignancies INFECTIONS
.:. Crohn's disease
•:. Multiple myeloma Antifungals are drugs used in the treatment of fungal infections.
.:. HIV associated wasting syndrome rhey may be classified as follows:-
.:. Severe type 2 lepra reaction in combination with .:. Polyene antifungals
corticosteroids .:. Imidazole antifungals
.:. Recurrent aphthous stomatitis in immunocompromised .:. Triazole antifungals
patients .:. Allylamine antifungals
Contraindications .:. Other antifungals
.:. Women of Child bearing age '·OlYENE ANTIFUNGALS
•:. Pregnancy
I'tllyene antifungals are produced by streptomyces species.
Dose I hillY include:
Type 2 lepra reactions: I 00-300mg once daily preferably at bed time .:. Nystatin

~!
The dose should be reduced gradually by 50mg every 2-4weeks once a
.:. Amphotericin B
satisfactory response has been achieved.
Side effects I It~y are not absorbed from the GIT when taken orally and can either
.:. Constipation .:. Dizziness lill ~Iven topically or by injection
.:. Peripheral neuropathy .:. Orthostatic hypotension Model of action
.:. Drowsiness .:. Hypersensitivity reaction
I'qlycmes irreversibly bind to ergosterol in the cell wall of fungi, causing
.:. Loss of libido .:. Premature ejaculation
dlftltlh by promoting leakage of intracellular ions and disruption of
.:. Malformation of limbs and defects of the ears and eyes tlltlillbrane active transport mechanisms.
Drug interactions NVSTATIN
.:. The sedative effects of barbiturates, alcohol, chlorpromazine,
-'v"lIabie preparations: Tablets 500000 iu
may be enhanced by thalidomide
Suspension 100000 iu
Key issues to note Lozenges 100000iu
.:. The drug is teratogenic, whether taken by male or female Pessaries 100000 iu
patients. Care should be taken especially in those considering AliAII'lble brands: Mycostat®, Nystasha®, Mycoren®
pregnancy
"h~rlllacokinetics
.:. Advise the patient to take the drug at bedtime as it is
associated with sedation ,iiI,:, Nylll.llin is not absorbed from GI tract when take orally, and it is
.4lt IIft'ledalmost entirely in faeces as unchanged drug.

-141- -142-
 2&1_ _ Qi!$e~1'Q:Mjl~!rM'I'IIi\1 'i " ,,'::,'" , ' : I'" ", PHARMAClIUIGY

Contraindications
Indications
.:. Vaginal candidiasis .:. Known hypersensitivity to amphotericin B
.:. Skin candidiasis
.:. Oesophageal candidiasis .:. Breast feeding
.:. Intestinal candidiasis
.:. Patients receiving anti-neoplastics
Contraindications
.:. Known hypersensitivity to nystatin [)ose

Dose
ny intravenous infusion: Initially, test dose'of I mg infused over
Intestinal candidiasis: 500,000 units every 6 hours, doubled in severe '2,O·30minutes, then 250mcg/kg daily increased gradually over 2-4 days
If tolerated to I mg/kg daily
infection
IClvere infection: 1.5mg/kg daily or alternate days
Children: I OO,OOOunits 4 times daily
Vaginal candidiasis: Insert I pessary into the vagina at night for 14 r!'l(! daily dose is infused over 2-4 hours at a concentration of 100mcg
11111 In glucose 5%.
days.
$Iower infusion over up to 6 hours may be necessary to reduce the
Side effects Il\ddence of acute toxic effects.
.:. Nausea Vomiting
Diarrhoea
.:. Skin rash 1~lde effects
.:. Oral irritation .:. Fever Headache
.:. Anorexia Nausea and vomiting
Key issues to note
.:. Liquid Nystatin should be held in the mouth for several .:. Malaise Muscle and joint pains
minutes before swallowing .:. Epigastric pain Diarrhoea
.:. Nystatin suspension or tablets are effective for minor oral .:. Abnormal liver function Blood disorders
.:. Renal function disturbance
fungal infections,
.:. Shake suspension well before use .:. .Peripheral neuropathy
.:. Pain and thrombophlebitis at injection site
AMPHOTERICIN-B
Available preparations: Injection 50mg/ml 1).. \llt interactions

Fungizone®, Amphotret®
.c. Amphotericin B may increase the toxicity of digoxin
Available brands: .c. Corticosteroids may increase loss of potassium from the body
caused by amphotericin B
Indications
.:. Cryptococcal meningitis .c. Aminoglycoside antibiotics when given together with
.:. Histoplasmosis amphotericin B increase the likelihood of kidney damage
.:. Coccidiodomycosis .c. Amphotericin B may prolong the muscle relaxing effect of
.:. Candidiasis neuromuscular blocking agents, due to hypokalaemia
.:. Aspergillosis .c. Concurrent use with frusemide incr~ases the risk of
hypokalemia caused by amphoteri~
' ' ' -',-

--143 - -144-
 , PRECISE PHARMACOLOGY

Key isses to note Gontraindications

.:. Use an antihistamine, paracetamol or hydrocortisone to .:. Hepatic impairment
prevent or treat infusion reactions .:. Breast feeding
.:. Monitor renal function and electrolytes at least 3 times a .:. Known hypersensitivity to ketoconazole
week
.:. Amphotericin B. should be protected from light 1)()lIC

IMIDAZOLE ANTIFUNGALS C:hronic vaginal candidiasis: 400mg once daily for 5 days
Imidazole antifungals have a broad spectrum of activity against C)ther conditions: 200mg once daily increased to 400mg once daily if
dermatophytes and candida spp. Most of the members in this class IHt ildequate response is not obtained

are available in topical form only except ketoconazole. C::hlldren:

15~30kg IOOmg once daily
Examples: C)vllIr 30kg 200mg once daily OR
.:. Ketoconazole .:. Miconazole ~,,12years I OOmg once daily for a period of 2-3 weeks
.:. Bifonazole .:. Econazole
I ,,4 years SOmg once daily
.:. Tioconazole .:. Isoconazole
,llll'
Mode of action tilde effects
Imidazoles suppress cell membrane synthesis of ergosterol leading to .:. Nausea and vomiting .:. Abdominal pain
II .:- Pruritus .:. Headache
their breakdown, cell leakage and death.
.:. Dizziness .:. Urticaria
KETOCONAZOLE .:. .:.
Paraesthesia Photophobia
Available preparations: Tablets 200mg .:. Liver damage .:. Thrombocytopenia
Cream 2% .:. Gynaecomastia .:. Skin rash
Shampoo 2%
Available brands: Nizoral®, Ketrozol®, Keto®, I;)rug Interactions
Fungral®, 'Fungicide® .:. Antacids, cimetidine, ranitidine and omeprazole may decrease lit
Pharmakonetics ketoconazole absorption
Absorption of ketoconazole when taken orally is ¥ariable and increases .:. Rifampicin, isoniazid and Phenytoin may decrease blood
when the PH in the stomach is acidic. It is metabolized in the liver to concentration of ketoconazole
inactive metabolites and excreted both as metabolites and unchanged .:. Ketoconazole may enhance the anticoagulant effect of
drug in faeces and urine. warfarin
Indications .:. Alcohol may increase hepatotoxicity of ketoconazole
.:. Oral candidiasis .:. Vaginal candidiasis
.:. Histoplasmosis .:. Tinae versicolar I(IIY issues to note
.:.
.:.
Tinae capitis
Tinae unguium
.:. Seborrheic dermatitis
.:. Dandruff
t'" Do not use oral ketoconazole to treat superficial fungal
infections unless there is no alternative, because of the
.:. Athletes foot .:. Ring worm
.:. Prophylaxis of fungal infections in immunocompromised associated toxicities
patients

-145- -146-
 ,
j I I
' ; ' '1',' ", " ' ,
"I I
PRECISE PHARMACOLOGY " '," :," ':,:,,": " ' PRECISE~Y

.:. Wait for at least I month before starting ketoconazole after C:ontraindications
stopping griseofulvin treatment .:. Known hypersensitivity to fluconazole or triazole compounds
.:. Acidic enviroment in the stomach favours absorption of .:. Co-administration with cisapride
ketoconazole, therefore administer the drug with orange ~mH!,:
juice or food Dose
Oral: Vaginal candidiasis and candida balanitis: 150mg single
5.1.3 TRIAZOLE ANTIFUNGALS llr,)se
This class of antifungals are used in the treatment of systemic infections Oral candidiasis; 50-1 OOmg once daily for 7 -14 days
because of their safety and effectiveness. 'f1nae pedis, corporis, cruris, skin candidiasis and Tinae versicolar:
Examples;- ~Orng once daily for 2-4weeks up to 6 weeks in tinae pedis OR 150mg
.:. Fluconazole t:lflce a week for 4 weeks
.:. Itraconazole ()nychomycosis: I50-300mg once weekly for 3-12 months
Children 1-18 years: 3mg/kg daily max 50mg
Mode of action Cryptococcal meningitis following amphotericin B induction
They inhibit cytochrome P-450 dependant enzymes resulting in
•.hc~rapy; oral/parenteral:
impairment,of ergosterol synthesis in fungal cell membranes.
Adult: 800mg daily for 2 days then 400mg daily for 8 weeks
FLUCONAZOLE Children: 6-12mg/kg daily
Available preparations: Tablets 50mg, I50mg, 200mg, Prevention of relapse of cryptococcal meningitis in AIDS patients
Capsules 100mg, 200mg "ter completion of primary therapy
Injection 200mg/ IOOml Adult: I00-200mg daily
Diflucan®, Forcan®, Stabilanol® Prophylaxis in immunocompromised patients 50-400mg once
Available brands:
dully
Pharmacokinetics Children
Oral absorption of fluconazole is rapid and almost complete, widely 1·4 weeks 3-12mg /kg once daily every 48 hours
distributed with good penetration into CSF. About 80% is excreted Under 2 weeks: 3-12mg/kg once daily every 72 hours. Max dose
unchanged in urine and small amount of metabolites are excreted in ,h()uld not exceed 400mg daily
faeces. !lUde effects
Indications .:. Abdominal pain Nausea and vomiting
.:. Oral candidiasis .:. Vaginal candidiasis .:. Flatulence Skin rash
.:. Cryptococcal meningitis .:. Coccidiodomycosis .:. Thrombocytopenia Diarrhoea
.:. Body ring worm .:. Tinae versicolar .:. Taste disturbance Headache
.:. Histoplasmosis .:. Skin candidiasis .:. Hepatic disorders .:. Angioedema
.:. Tinae pedis (athletes' foot) .:. Hypersensitivity reaction
.:. Prevention of fungal infection in immunocompromised Drug interactions
patients .:. The effect of fluconazole may be reduced by rifampicin
.:. Fluconazole may increase the risk of hypoglycaemia with oral
sulphonylureas

-147- -148-
 ,

.:.

.:.
" PRECISE PHARMACOl

Fluconazole may increase the blood levels of phenytoin,

atorvastatin, caffeine, cyclosporin, diazepam etc
Fluconazole may increase the effect of oral anticoagulants
117
- MW#tISE PHARMACmmrI
Children Imonth-12 years: 3-smg/kg once daily max. 100mg daily
for Isdays
VUlvovaginal candidiasis: 200mg twice daily for I day
Key issues to note Pityriasis versicolar: 200mg once daily for 7 days
.:. Fluconazole is not a first line drug for the treatment of Children Imonth-12 years: 3-smg/kg once daily max. 100mg daily
superficial dermatophyte infections, therefore use topical for 15 days
antfungals first and reserve fluconazole for resistant cases Tlnae corporis and cruris: 100mg once daily for 15 days or 200mg
.:. Monitor liver function tests with prolonged therapy once daily for 7days
Children Imonth-12 years: 3-smg/kg once daily, max. 100mg once
ITRACONAZOLE daily for 15 days
Available preparations: Tablets 100mg
Tlnae pedis and tinae manuum: 200mg twice daily for 7 days or
Capsules IOOmg IOOmg once daily for 30 days I

Available brands: Canditral®, Sporanox® Children Imonth-12 years: 3-smg/kg once daily max 100mg daily
Ic)," 30 days
Pharmacokinetics
Onychomycosis: 200mg once daily for 3 months
Itraconazole is absorbed from the GIT when administered orally,
Alllpergillosis: 200mg once daily, increased to 200mg twice daily in
Absorption from the capsule formulation is enhanced by an acidic .~jI\i6eminated disease
gastric environment and is greatest when doses are tak~n wi~h food; 'flnae versicolar: 200mg once daily for 7 days
Itraconazole is widely distributed but only small amounts diffuse into thl'
CSF. Itraconazole is metabolized in the liver and excreted in faeces. 1lllde effects
.:. Dyspepsia .:. Abdominal pain
Indications .:. Nausea
.:. Oral candidiasis .:. Vaginal candidiasis .:. Vomiting
.:. Diarrhoea
.:. Pityriasis versicolar .:. Aspergillosis Constipation
.:. Urticaria
.:. Blastomycosis .:. Histoplasmosis Heart failure
.:. Headache
.:. Tinae corporis .:. Tinae pedis Dizziness
.:. Pruritus
.:. Tinae manuum .:. Onychomycosis Skin rash
.:.. Hepatitis
.:. Prophylaxis of fungal infectious in immunocompromised Peripheral neuropathy
.:. Menstrual disorders .:. Alopecia
patients .:. Jaundice
Contraindications l:)t'ug interactions
.:. Hypersensitivity to Itraconazole or other azoles
.:. Rifampicin and phenytoin reduce the oral bioavailability of
.:. Pregnancy itraconazole
.:. Itraconazole can inhibit the metabolism of drugs such as
Dose
midazolam, felodipine, simvastatin
Oral candidiasis: 100mg (200mg in AIDS patients or neutropeni;l)
.:. Clarithromycin, erythromycin may increase plasma
once daily for 15 days concentration of Itraconazole

-149- -150-
 " ', " ' PRECISE PHARMACOLOGY 911.r SF'·wcls£ t:JlMil&MQIJ!IIij"
.:. Drugs that reduce stomach acidity such as antacids, proton .:. Tinae cruris
pump inhibitors and H2 receptor antagonists may reduce .:. Onychomycosis
absorption of Itraconazole .:. Tinea versicolor ( cream)
Contraindications
Key issues to note
.:. Itraconazole capsules should be taken with food, but not rice .:. Known hypersensitivity to terbinafine
.:. Severe hepatic disease
meal for best absorption
.:. Do not take antacids within 2 hours of Itraconazole capsule as Dose
it will interfere with its absorption Adult:
.:. Itraconazole is better tolerated and more effective than Athletes' foot: 250mg daily for 2-6 weeks
griseofulvin and ketoconazole in the treatment of superficial Tinae ~ruris: 250mg once daily for 2-4 weeks
infectons Body ringworm: 250mg once daily for 4 weeks
On.ychomycosis: 250mg once daily for 6 weeks - 3month
5.1.4 ALLYLAMINE DERIVATIVES Children: s
Allylamine antifungals are the newest and have a broad spectrum of 'r1nae capitis:
activity against the dermatophytes. They are fungicidal in action ~ver 40kg: 250 mg once daily for 2 weeks
Examples: lO.40kg: I25mg once daily for 2 weeks
.:. Terbinafine. IO.20kg: 62.5mg once daily for 2 weeks
•:. Butenafine IIUde effects
.:. Nausea
Mode of action .:. Diarrhoea
.:. Anorexia
Terbinafine acts by inhibiting fungal sterol biosynthesis, causing .:. Skin rash
.:. Dizziness
accumulation of squalene within the fungal cell and cell death. .:. Myalgia
.:. Photosensitivity
.:. Headache .:. Visual disturbance
.:. Dyspepsia
TERBINAFINE .:. Mild abdominal pain .:. Urticaria
Available preparations: Tablets I25mg, 250mg .:. Malaise
.:. Arthralgia
Cream 1% .:. Taste disturbance
.:. Flatulence
O"ug interactions
Available brands: Exifine®, Lamisil® Fungisafe®
.:. Break thro~gh bleeding may OCcur when oral contraceptives
are ta l<en with terbinafine
Pharmacokinetics
.:. ~imeti?i,ne may increase blood levels of terbinafl'ne
Terbinafine is well absorbed from the gastrointestinal tract, distributed .:. Rrf:
into the stratum corneum ofthe skin, nail plate, and hair. It is metabolizc( I amp,lcln, may reduce the blood levels and therapeutic effect
of terblnaflne
in the liver to inactive metabolites which are excreted mainly in urine M.. y Issues to note
Indications
.:. Athlete's foot
<. Tabl.ets may be administered without regard to meals
.:. Body ringworm -:. ~dvlse the patient to complete the course of treatment even if
t e symptoms appear to be resolved

-151- -152-
 PREG~ilPHARMAGDLDGY ", ' , PREGI~PHARMAGDLDGY
.:. Terbinafine may be used for other forms of tinea where 1:)~lI'lltion of treatment depends on the site, ie
griseofulin is ineffective and treatment usually takes 4 - 6 weeks corporis 4 weeks.
1"ll1llt'1
I~Ilnm~l capitis 4-6 weeks
OTHER ANTIFUNGALS 11'lnCla pedis 4-8 weeks.
NI.lllnfections 4- 6 months or longer.
GRISEOFULVIN
Griseofulvin is antibiotic derived from Penicillium griseofulvum. It is *Idc~ effects
effective against wide range of dermatophytes but not effective against (. Headache Skin rashes
Candida. It is used in treatment of extensive dermatophyte infections (. Insomnia Fatigue
which are unresponsive to topical therapy and those affecting nail and .:. Urticaria Dry mouth
scalp. (+ Angular stomatitis Diarrhoea
+:+ Dizziness .:. Altered sensation of taste
Available preparations: Tablets SOOmg
+:+ Nausea and vomiting
Available brands: Fulcin®, Griso®, Creafulvine
C)l'ug interactions
Mode of action +:+ Griseofulvin may decrease the effect of oral contraceptives and
Griseofulvin inhibits fungal cell mitosis at metaphase by disrupting the warfarin
cell's microtubule function; it binds to human keratin making it resistant +> Phenobarbitone may decrease the gastro intestinal absorption
to fungal invasion of griseofulvin
Pharmacokinetics +:. Griseofulvin may increase the effects of alcohol
Griseofulvin is fairly absorbed from the GIT, but fatty meal or I(.y issues to note
micronization improves its absorption. It is metabolised in the liver and -:. Advise the patient to take griseofulvin with a fatty meal to
excreted in urine. increase its absorption.
Indications (. Advise the patient not to take alcohol during therapy.
.:. Tinae cruris (+ Advise the patient to avoid exposure to sun light or use
.:. Onychomycosis (nail infections) protective clothes
.:. Tinae pedis (Athlete's foot) +:+ Inform the patient with nail infections that treatment is long
.:. Tinea corporis (Ringworm) term since the infected nail has to grow out
Contraindications
+:. Advise women to use additional non hormal contraceptives
such as condoms since the effectiveness of oral contraceptives
.:. Severe liver disease .:. Porphyria is reduced
.:. Pregnancy .:. Breast feeding .:. Advise men not to father a child during and 6 months after
.:. Known hypersensitivity to Griseofulvin treatment since it affects s p e r m s '
Dose
Adult:
Tinea of skin, hair, groin: SOOmg once daily
Tinea of feet, nails: I OOOmg daily
Children: I Omglkg daily in single or divided doses

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rri'l
 r:
• 22
I I II T II II O( II

,I'" ",'", I, , I' PRECI

Exceptional cases wh ere ACT.,s are not recomendered as first line
CHAPTER SIX drugs
ANTI PROTOZOAL DRUGS Children below 4months Or less than 5kg
QUinine 10mg/kg 8hourly for 7days
6.1.1 ANTIMALARIAL DRUGS Pregnant mothers in first trimester
Oral quinine 600mg 8hourly for 7days
MALARIA
Malaria is an acute ilness characterized by fever (and other clinical Second line drugs
features) which is caused by infection with the malaria parasites of the Oral quinine
genus plasmodium. Adult: 600mg 8hourly for 7days
The four species of plasmodium include:- Children: IOmg/kg 8hourly for 7days
.:. P. falciparum
.:. P.malariae
Complicated malaria
.:. R vivax A pati~nt v:ith complicated malaria may present with some of the
follOWing signs and symptoms;
.:. Rova/e I"~
Plasl110dium falciparum is the most common in Uganda (contributes 90- .:. Convulsions
95% of malaria cases) and it causes the commonest and most severe .:. Inability to drink or breast feed
.:. Altered mental state
II
form of malaria.
Malaria is transmitted from person to person by a bite of an infected .:. Extreme weakness
female anopheles mosquito. .:. Severe anaemia Ilf
.:. Severe dehydration IJI
Classification of Malaria .:. Severe vomiting Ii
.:. Uncomplicated malaria
.:. Complicated malaria Treatment
Patients ~ith complicated malaria normally require admission parenteral I"
Uncomplicated malaria
A patient with uncomplicated malaria may present with any of the
.lIltmalanals are used which include: .~!
Quinine IV: I::
following signs and symptoms
Fatigue
I Omg/kg ~ hourly in dextrose 5%. Change to oral quinine as soon .~ I: IIII1
.:. Fever 11$ the patient can swallow and continue to complete the 7 d f "

.:. Malaise
Loss of appetite ll'~latment. ays 0
'II,
I"

.:. Vomiting Sweating

Muscle aches IV Quinine is administered in 5% Dextrose to counteract the
.:. Joint pains hypoglcaemic effect of quinine.
•:. Rigors and chills
.:. Headache OR II

Artemisinin derivative
Treatment for malaria Inj. artemether: 3.2mg/kg start, then 1.6mg/kg daily for the next 4 '1,,1
IIi
Uncomplicated malaria dnys, 24hours apart for each dose.
First line Drugs
Artemether + lumefantrine Or Artesunate + amodiaquine
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!
I
I '
rJi/i.i,J
 PRECISE PHARMACOLOGY : 'I, PREC SE PHARMACOlO_Gl]

They are rapid acting blood schizontocides and can be used for
Elimination of liver stages (P vivax and P ova/e)
treatment of both uncomplicated and complicated malaria.
Primaquine adult 30mg daily for 14 days after giving other drugs
l11efloquine is also used for prevention of malaria in non immune
Malaria prophylaxis patients.
Non-immune individuals "
Mefloquine: 2S0mg weekly started 2 1/2 weeks before entering malaria 8 -Aminoquinolines - Premaquine

area and for 4 weeks after leaving They are tissue schizontocide and are used to prevent relapse of ovale
Doxycycline: IOOmg once daily starting 2 days before entering a IUld vivax.
malaria area and for 4 weeks after leaving premaquine is used in radical cure (destroy) the dormant stages in the
liver.
Intermittent treatment of malaria in pregnancy (IPT)
Fansidar(sulfadoxine/pyrimethamine): 3 tablets single dose in the Biguanides
second and third trimester. E!cample:- .:. Proguanil
Pregnant women with HI¥, receive 3 doses of fansidar after the first
Blgua~i~es are slow acting blood schizontocide used for prophylaxis of
trimester with a space of at least one month apart.
malaria In combination with atovaquone.
Key issues to note Sulphonamides
.:. Any patient diagnosed to have malaria should always be given a
Example:- .:. Sulfadoxine.
full course of treatment
$lIlphonamides are slow acting blood schizontocide currently used to
.:. In females of child bearing age, always rule out pregnancy
prevent malaria in pregnant mothers.
before commencement of treatment
.:. Where possible, the first dose should be given under It is usually given in combination with pyrimethamine (Fansidar)
supervision of the health worker Artemisinin derivatives
.:. Give medicine orally, unless the patient has severe malaria,
Ibcamples:- .:. Artemether
vomits repeatedly or is unable to swallow
.:. Artesunate
Classification of antimalarial drugs .:. Dihydroartemisinin
.:. Artemisinin
4 - Aminoquinolines
Examples:- .:. Chloroquine rhey are rapidly acting blood schizontocide used in treatment of
.:. Amodiaquine rmnplicated malaria and uncomplicated malaria when combined with
uther drugs.
These drugs are rapid acting blood schizontocides. Amodiaquine is
Antibiotics:
more effective than chloroquine and is currently used as a first line drug
Doxycycline
in combination with antesunate.
Tetracycline
4 Methanoquinolines Clindamycin
Examples:- .:. Quinine
.:. Mefloquine Ihey are blood schizontocides and are usually given in combination
with quinine in the treatment of resistant malaria.

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V,i
t 2111_11111". I' m.PR~CJSEe1lM6MMI '151 ," ..RECI HARMACOLOGY

Side effects
Q UININE ' ian'al
. I'Ine antlma .:. Headache .:. Tinnitus
.' Ik I'd d a 4-methanolqulno
Quinine IS a Cinchona a a 01 an d'
that is a rapid-acting blood schizontocid~with activity against Plasmo fum
.:. Blurred vision .:. Hypersensitivity reaction
falciparum, P. vivax, P. ovale, and P. malartae. ..
.:. Abdominal pain .:. Nausea
.:. Diarrhoea .:. Hot and flushed skin
Available preparations: Tablets 300mg
Injection 300mg/ml ,
.:. Black water fever .:. Hypoglycaemia

Syrup IOOmg/5ml Drug interactions

Flaci-Quin .:. Cimetidine increases the blood level of quinine
.:. Quinine increases the blood levels of digoxin
Quininmix®, Requin®,
Available brands: .:. The absorption of quinine may be delayed when administered
Agog qUinine@, Quine®
with antacids containing aluminium
Quinin -K. o¢. Plasma levels of warfarin are increased when administered
with quinine
Pharmacokinetics b d f the
uinine is rapidly and almost completely absor e rom ,
~strointestinaltract, widely distributed throughout the ~OdY.,
lit ,IS AftTEMETHER
extensively metabolized in the liver and rapidly excrete main y In AI!IC~ll1ether is a semi-synthetic antermisinin derivative with
Ml'IlIjwnticidal and gametocidal activity against multi-drug resistant
urine.
M'II.ln5 of plasmodium falciparum
,;/i
Indications
.:. Malaria A'/4aUable preparations: Injection 20mg/ml, 40mg/ml, 80mg/
ml, IOOmg/ml
Contraindications
.:. Known hypersensitivity to quinine A¥iIllhlble brands: Artenam®, Artesiane®, Larither®
.:. Complete AV block
.:. Heamoglobinuria "hlilrmacokinetics
.:. Myasthenia gravis "flm,nether is rapidly hydrolysed to the active metabolite
.:. Optic neuritis "I~lydf'()artemisinin.

Dose
tmttc4tions
Oral
Adult: 600mg 8 hourly for 7 days \llli: + Uncomplicated malaria
Children: IOmg/kg 8 hourly for 7 days lilii! \,
~
+ Severe malaria
By slow intravenous infusion
Adult 600mg 8hourly in dextrose 5% • , .ltmtl'l/tlndications
Children I Omg/kg 8 hourly in dextrose 5% and IV run for.4 hour~
Note: Do not give a loading dose to patients who have received qUllllll
or mefloquine during the previous 12-24 hours
t1

I.
.
I;
'I
ii'
II
il
',1\ ,

".
II 111111111
,,'"
'1"111""
+
•
1<. Ilown
,,,.
hypersensitivity to artemether
Ir5t tnmester
f
0 pregnancy

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 PREC PHARMACOLOGY' ,' , PRECISE PHARMACOLOGY
Dose .:. History of convulsion
Oral: .:. Patients with acute depression
1M Injection:
Adult: 300mg as a loading dose on day I Dose
then IOOmg once a day for 4 days For treatment of malaria: 20-25mglkg as a single dose or in 2 divided
Children: 3.2mglkg on day I doses 6-8hours apart
Followed by 1.6mglkg once daily for the next 4 days For prophylaxis
Side effects Adults and Children over 45kg: 250mg (I tablet) once weekly
5·IOI<g: 1/8 of a tablet
.:. Nausea .:. Vomiting
IO-20kg: 1/4 of a tablet
.:. Diarrhoea Dizziness
20.30kg 1/2 of a tablet
.:. Headache Tinnitus
:lO.451<g % of a tablet
Drug interactions Note: Prophylaxis should start at least 2 Y2 weeks before entering
Manl,Jfacturer advises to avoid concurrent use of artmether with the cmdemic area and continue for 4 weeks after last exposure
•
f()Howing drugs;
Side effects
.:. Erythromycin
.:. Nausea Vomiting
.:. Amiodarone
.:. Insomnia Convulsion
.:. Tricyclic antidepressants
.:. Abdominal pain Loss of appetite
.:. Phenothiazines
.:. Visual disturbance .:. AnXiety
MEFLOQUINE .:. Confusion Dizziness or vertigo
.:. Loss of balance Muscle weakness
Available preparations: Tablets 250mg
.:+ Skin rash
Available brands: Mephaquine®, Larium®, Meflotas® t)rug interactions
.:. Mefloquine may antagonise the effect of anti epileptics such
Pharmacokinetics carbamazepine, sodium valproate.
Mefloquine is well absorbed from the gastrointestinal tract, widely +:+ Mefloquine may increase the risk of adverse effects when taken
(listributed throughout the body. It has a long elimination half-life and with other antimalarials
i~ metabolized in the liver. Mefloquine and its metabolites are excreted .:. Mefloquine may increase the risk of bradycardia when given
mainly in the bile and faeces. together with beta blocker, calcium channel blockers and
Indications digitalis
.:. Uncomplicated malaria due to multi-resistant P. falciparum
.:. Malaria prophylaxis ke:ty issues to note
.:. Advise the patient to take mefloquine after a meal
Contraindications +:+ Pregnant mothers should not use mefloquine for prevention
.:. Known hypersensitivity to mefloquine of malaria
.:. Prophylaxis in the first trimester of pregnancy

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 PRECI~ ACOl , PREC PHARMACOLOGY
SULFADOXINE WITH PYRIMETHAMINE Side effects
Pyrimethamine and sulfadoxine act synergistically in the inhibition of .:. Urticaria .:. Nausea
folinic acid synthesis in the parasites. .:. Vomiting .:. Ab dominal pain
.:. Diarrhoea .:. Headache
Available preparations: Tablets 500/ 25mg .:. Vertigo .:. Arthralgia
.:. Serum sickness .:. Tinnitus
Available brands: Fansidar®, Falcistat®, Malarest® Drug interactions
Malaren®, Kamsidar®
.:. Sulfadoxine+pyrimethamine may increase the antifolate effect
Pharmacokinetics of methotrexate
Pyrimethamine with sulfadoxine is well absorbed when taken orall:,
.:. There is an increased antifolate effect when sulfadoxine with
widely distributed and metabolized in the liver and slowly excreted In
pyrimethamine is used with cotrimoxazole
urine.
.:. Sulfadoxine+pyrimethamine may increase the plasma
concetrations of phenytoin
Indications
.:. Treatment of malaria PRIMAQUINE
.:. Prophylaxis of malaria
Available preparations: Tablets 15mg
Contraindications
.:. Known hypersensitivity to any of the ingredients Pharmacokinetics
.:. Severe renal failure ----\
Primaquine is readily absorbed from the gastrointestinal tract, rapidly ,
.:. Infants less than 2months old
1l1E!tabolized in the liver to carboxy primaquine and a small amount is
•:. Blood dyscrasias IlIxcreted unchanged in urine.

Dose Indications
Treatment of uncomplicated malaria .:. Radical cure of P. vivax and P. ovate (eradicates dormant
Adult and Children over 45kg: 3 tablets single dose parasites from the liver)
Children .:. Pneumocystis carinii pneumonia
JO-45kg (I O-14years): 2 tablets single dose Contraindications
20-JOkg (5-1 Oyear) I Y2 tablet single dose .:. Pregnancy
IO-20kg (2-5years) Itablet single dose .:. Lactating mothers
Less than IOkg (up-to 2years) Y2 tablet single dose .:. Children less than Iyear
Prophylaxis .:. Known hypersensitivity to primaquine
Adults and Children over 45kg: I tablet once weekly .:. Active rheumatoid arthritis
JO-45kg I Y2 tablet every 2 weeks
IO-JOkg I tablet every 2 weeks nOle
Less than IOkg 1/2 tablet every 2 weeks M,a111ria: 15mg once daily for 14 days
"n~umocystis carinii pneumonia: 30mg once daily plus c1indamycin
""" ',no450mg 4 times daily for 3 weeks l

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 " " " , ", ': I',: ", PRECISE PHARMACOLOGY I1II111111111

Side effects ~~~."4l1

\ .:. Abdominal pain .:. Epigastric distress h..... ll1ent:
.:. Nausea and vomiting .:. Anorexia
IOOmg twice daily for 7 days following quinine treatment
,*, ftllhylaxis Adults:
. :. Leucocytosis .:. Agranulocytosis I' ,,,1,11 III 1:1ndemic area
IOOmg daily starting 1-2 days before entering

.:. Acute haemolytic anaemia

Drug interactions ~hlt" .'ffeets
.:. Primaquine should not be used with drugs liable to induce :' Nausea and vomiting Diarrhoea
haemolysis or bone marrow depression e.g. methotrexate <I Staining of growing teeth Mouth ulcers
.:. Chloramphenicol should not be co-administered with I;' Headache Photosensitivity
primaquine I~ Vaginal candidiasis Skin rash
Key issues to note ~IN'.,. Interactions
.:. Primaquine should be taken after a meal to avoid stomach ~I' Doxycycline may increase the blood levels of drugs like
upset digoxin and lithium
'1' Antacids and preparations containing iron, calcium and
DOXYCYCLINE ~~lagnesium may reduce the absorption of doxycycline
Available preparations: Capsules IOOmg ,;, I here is a decrease in the therapeutic effects of doxycycline
Tablets IOOmg when it is given with barbiturates, phenytoin and
carbamazepine
Available brands: Remycin®
I ~ ~MOINATION PREPARATIONS
Pharmacokinetics MI HMETHER + LUMEFANTRINE
Doxycycline is readily and almost completely absorbed from the ~'II!lU.1ble preparations: Tablets 20rng/ 120mg, 40mg/240mg
gastrointestinal tract and absorption is not significantly affected by the 80/480mg
presence of food. It is Widely distributed in body tissues and fluids and Suspension I smg/ 90mg /sml
is slowly excreted in the urine.
~~Illl.,ble brands: Coartem®. Lonart@, Artefan®,
Indications Co-artesiane®, Lur(1artem®,Co-Malartem®
.:. Supplement to quinine in the treatment of multi drug resistanl
til-II.... Ions
P. falciparum malaria
.:. Short term prophylaxis of malaria
+ First line treatment in uncomplicated malaria
••lIIt ,.~t1ndications
Contraindications ,t> Hypersensitivity to artemether or lurnefantrine
.:. Pregnancy 'I' Patients with severe malaria
.:. Children "under 12 years -I' Breast feeding
.:. Known hypersensitivity to doxycycline ,1, Family history of sudden death
¢ History of arrhythmias

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 PIlEC IJHAIlMA OGY
" ' PRECISE PHARMACOLOGY
Dose Contraindications
Adults and Children over 12years and body weight 35kg : 4
.:. Known hypersensitivity to either artesunate or mefloquine
Tablets start then 4 tabs after 8hours then 4 tablets twice daily for 2 .:. Prophylaxis against malaria
days (For the tablet of 20mg/ I 20mg) . ~
Take the drug with food or drinks rich in fats such as milk. Dose
Adults: 2tablets (I tab of artesunate 600mg and I tab of mefloquine
Suspension . 7S0mg) once daily for 3 consecutive days
Each sml contain Ismg artemether + 90mg lumefantnne
Children: 10-20kg I sticks pack once a day for 3days
5-71<g 7ml once daily for 3 days
7.5-9.5I<g 10mi once daily for 3 days Side effects
IO-141<g Isml once daily for 3 days .:. Abdominal pain Nausea and vomiting
151<g 20ml once daily for 3 days .:. Insomnia .:. Asthenia
.:. Fatigue Diarrhoea
Side effects .:. Dizziness .:. Anorexia
.:. Abdominal pain .:. Anorexia .:. Headache
.:. Diarrhoea Nausea and vomiting
.:. Skin rash Headache
ARTESUNATE /AMODIAQUINE
.:. Dizziness Pruritus
.:. Fatigue .:. Tinnitus Available preparations: Tablets sOmg/ 200mg

Drug interactions . Available brands: Amonate®, Coarsucam®

Manufacturer advises avoid concurrent use with the following drugs;
.:. Amitriptline Indications
.:. Quinine .:. Uncomplicated malaria
.:. Azithromycin Contraindications
.:. Ciprofloxacin .:. Known hypersensitivity to either artesunate or amodiaquine
.:. Fluconazole .:. History of liver disease
.:. Mefloquine, among others .:. Children below 2 months of age
Dose:
ARTESUNATE /MEFLOQUINE
Available preparations: Tablets 600/ 7s0mg ~'Ilg/kg of artesunate
\
+ IOmg/kg of amodiaquine once daily for 3 days
Stick packs 50/1 25mg Side effects
.:. Abdominal cramps
Available brands: Artequin®
.:. Drowsiness
Indications .:. Skin itching
.:. Uncomplicated malaria due to resistant P. falciparum .:. Diarrhoea
.:. Skin rashes
.:. Severe disturbance of liver function

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-168-
, ~EC~HARMACOLO llUil
DIHYDROARTEMISININI PIPERAQUINE A«'f'EMISININ INAPHTHOQUINE ~.

Available preparations: Tablets 40mg/320mg A'I/.. l1l/\ble preparations:

Tablets I25mg 150mg
Available brands: Duo-c;:otexin®, P-Alaxin
A'I/.. l1l/\ble brands: Arco®
Indications
.:. Uncomplicated malaria ",dlc:l/\tions
t> Uncomplicated malaria due to P. falciparam and P. vivax
Contraindications
.:. Known hypersensitivity to any of the ingredients (",mtraindications
.:. Pregnancy (first trimester) <- Known hypersensitivity to any of the ingredients
Dose .;: .:. Liver impairment
Adults and Children above 40kg -:. Kidney impairment
3 tablets once on day I -:. Pregnancy
3 tablets once on day 2 ()OillC
3 tablets once on day 3 Adults: 8 tablets single dose (equivalent to IOOOmg of artemisnin +'
20 - 39kg i()()mg of naphthoquine)
2 tablets once on day I Children: 7 - IOkg I tablet
2 tablets once on day 2 10- 15kg 2 tablets
2 tablets once on day 3 15 - 25kg 4 tablets
10 - 19k9 25 - 35kg 6 tablets
I tablet once on day I $Ide effects
I tablet once on day 2 .:. Nausea
I tablet once on day 3 .:. Abdominal discomfort
5 - 9kg
1/2 tablet day I ·~.1.2 NITROIMIDAZOLES
1/2 table day 2 l\lltroimidazoles include;
1/2 table day 3 .:. Metronidazole
Side effects .:. Tinidazole
.:. Nausea and vomiting Loss of appetite .:. Secnidazole
.:. Pruritus Diarrhoea .:. Ornidazole
.:. Skin rash Nitroimidazoles are active against anaerobic bacteria and protozoa

Key issues to note METRONIDAZOLE

.:. Advise the patient to complete the course of the drug to avoid Available preparations: Tablets 200mg, 400mg
relapse of malaria IV 500mg/ IOOml
.:. A new course of the drug should not be taken within 4 weeks Dental gel, Topical gel, vaginal gel
after the first treatment Oral suspension 200mg 15ml

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 , '" , , 1';":,' 'I ",'i '" I I';,: 'd ',": I "",' PREC PHARMACOLOGY " I ' PRECgHARMACOLOGY

Available brands: Flagyl®, Metrogyl®, Metrogel®, Metrozole(R), I~" ~ ~";\I'S600-800mg once daily for 3 days
Medizole®, Flazol®, Metlife®, Metrozine®, :~ to yoars Ig once daily for 3 days
hw~,.lve intestinal amoebiasis:
Pharmacokinetics ~~.ull,; BOOmg every 8 hours for Sdays
Metronidazole is readily and almost completely absorbed when ta!<'ill ",I ~llhlldr'.m:
orally. Presence of food may delay but does not reduce extent (,I I " ytn"rs 200mg every 8 hours for 5 days
absorption. It is widely distributed in most body tissues and fluid-, !~ ~ yMrs 200mg every 6 hours for 5 days
including bile, bone , breast milk, liver abscesses, vaginal secretioll',, :, I() yc~ars 400mg every 8 hours for 5 days
etc. It is metabolized in the liver and excreted in urine and small amollllt nhhomoniasis:
in faeces. Adult 2g single dose
,,-.. ulcer and pressure sores:
Indications Adult 400mg every 8 hours for 7 days
.:. Septicaemia .:. Peritonitis .._c; tc~rjal vaginosis :
.:. Acute gingivitis .:. Intra abdominal infectioll Adult 400mg twice daily for 7 days
.:. Rosacea .:. Surgical prophylaxis 'U"ltlcal prophylaxis:
.:. Balantidiasis .:. Amoebiasis Adult IV 400mg 2 hours before surgery up to 3 further doses
.:. Trichomoniasis .:. Giardiasis of 400mg may be given every 8 hours.
.:. Bacterial vaginosis .:. Leg ulcer Ac:ute ulcerative gingivitis:
.:. Tetanus .:. Aspiration pneumonia
:1
I, Adult 200mg every 8 hours for 3 - 7 days
.:. Antibiotic associated colitis Amlbiotic associated colitis disease:
.:. Helicobacter pylori eradication Adult 400mg every 8 hours for 7-1 Odays
.:. Pelvic inflammatory disease ' ..pticaemia, acute peritonitis:
Adult IV SOOmg every 8-12hours
Contraindications
.:. Chronic alcohol dependence tide effects
.:. First trimester of pregnancy .:. Nausea .:. Vomiting
.:. Patients allergic to metronidazole or other nitroimidazole .:. Taste disturbances .:. Anorexia
derivatives
.:. Dizziness .:. Headache
.:. Skin rash .:. Diarrhoea
Dose
.:. Pruritus .:. Constipation
Pelvic inflammatory disease: in combinatio with other drugs 400mg .:. Weakness .:. Ataxia
twice daily for 14 days
.:. Drowsiness .:. Insomnia
Anaerobic infections :800mg stat then 400mg every 8 hours for 7-
.:. Depression .:. Peripheral neuropathy
10 days.
.:. Unpleasant metallic taste
Giardiasis Adult: 2g once daily for 3 days
Children:
1-3years SOOmg once daily for 3 days

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 ", ",,,,,,', ",' : ',' '" " ':, 'I' ,~ISEPHA Y

Drug interactions C::(mtraindications

.:. Alcohol may cause disulfiram like reaction when given .:. First trimester of pregnancy
together with metronidazole .:. Hypersensitivity to nitroimidazole derivatives
.:. Cimetidine may increase levels of metronidazole in the body .:. Alcohol dependence
.:. Metronidazole enhances anticoagulant effect of warfarin·
l)o~c
.:. Plasma concentrations of metronidazole are decreased by
Adult: 500mg twice daily for 5 - 6 days
phenobarbital
t~ .. cterial vaginosis and acute ulcerative gingivitis: 2g single dose
.:. Phenytoin might accelerate the metabolism of metronidazole
Abdominal surgery prophylaxis: 2g single dose 12 hours before
\Iltgery
Key issues to note Ill:lllcobacter pylori eradication: 500 mg twice daily with
.:. Metronidazole may cause GI upset,threrefore advise the
, Iill'ithromycin and omeprazole for 7days
patient to take it with food
IntClstinal amoebiasis: 2g once daily for 2 or 3 days
.:. Advise the patient to avoid alcoholic drinks during treatment
C;:hlldren: I month to 12 months 50-60mg/ kg( max. 2g) one daily for
,because of the possibility of disulfiram- like reaction
Ithtys
.:•.illJlnform the patient that metronidazole may cause unpleasant
lit metallic taste I ~Cftpatic amoebiasis: 2g as a single daily dose given for 3 days or
.:. For intravenous infusion, infuse over20-30 minutes .,,' c:nsionally up to 6 days.
•:. Metronidazole suspenSion is best taken I hour before food
hlr.:homoniasis and Giardiasis:
Adult: 2g single dose
TINIDAZOLE C:hlldren: I month -12 years 50-75mg/kg( max. 2g) single dose
Available preparations: Tablets 500mg
'lld4~ effects
Available brands: Tiniba®, Fasigyn®, Amtiba® .:. Nausea .:. Vomiting
.:. Anorexia Metallic taste
Pharmacokinetics IIi .:. Abdominal pain Diarrhoea
Tinidazole is almost completely absorbed when administered orally, -:. Skin rash Pruritus
widely distributed into body tissues and fluids, crosses the placenta, .:. Urticaria
excreted in urine and to a lesser extent in the faeces. Orug interactions
Indications e:. Cimetidine, ketoconazole, Phenobarbital, rifampicin
.:. Giardiasis decrease the metabolism of tinidazole
.:. Acute ulcerative gingivitis -:. Tinidazole may increase blood levels of lithium and phenytoin
.:. Bacterial vaginosis Kt1ly issues to note
.:. Post operative wound infection e:. Avoid alcohol beverages during tinidazole therapy
.:. Intestinal amoebiasis -:. Advise the patient to take tinidazole with food to reduce
.:. Helicobacter pylori eradication stomach upset
.:. Trichomoniasis O¢. Treat the sexual partner (s) in case of trichomoniasis

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 , PRECISE PHARMACOLOGY , ', PREliSE PHARMACJl1MiJ

SECNIDAZOLE Contraindications
Available preparation: Tablets 500mg, IOOOmg .:. Known hypersensitivity nitroimidazom.
.:. Pregnacy ( first trimester)
Available brands: Flagentyl®, Targera®, Entosec®, Seczol®
Dose:
Indications Giardiasis
.:. Intestinal amoebiasis
Adult, I. 5g daily for I - 2days
.:. Giardiasis
Children, 40mg/ kg daily for I -2days
.:. Trichomoniasis
Trichomoniasis: I.5g single dose
.:. Hepatic amoebiasis
Amoebiasis:
Contraindications Adult, 500mg twice daily for 5-1 Odays
.:. Hypersensitivity to nitroimidazoles Children, 25mg/kg once daily for 5-1 Odays
.:. Pregnancy
.:. Lactation Side effects
Dose .:. Nausea .:. Vomiting
Adults: .:. Taste disturbances .:. Anorexia
Trichomoniasis and Amoebiasis: 2g single dose .:. Dizziness .:. Headache
Hepatic amoebiasis: I.5g daily for 5 days .:. Skin rash .:. Diarrhoea
Children: 30mg/kg daily
PAROMOMYCIN/AMINOSIDINE
Side effects
.:. Metallic taste in the mouth .:. Abdominal pain f)jtromomycin is an amoebicidal and antibacterial aminoglycoside active
.:. Nausea and vomiting .:. Diarrhoea 1t~1"linst v~rious protozoa including Leishmania spp., Entamoeba
.:. Urticaria •:. Dizziness '"stolytrca, and Cryptosporidium spp.
Available preparations: Tablets 250mg
ORNIDAZOLE Syrup I25mg/5ml
Available preparations: Tablets 500mg
Available brands: Gabbroral®, Daboral®, Unibrol®
Available brands: orni®
Pharmacokinetics
Pharmacokinetics Pllromomycin is poorly absorbed from the gastrointestinal tract and
Ornidazole is well absorbed when taken orally, widely distributed in Illost of the dose is excreted unchanged in the faeces.
body tissues, metabolised in the liver and excreted in the urine. II Indications
Indications .:. Intestinal amoebiasis .:. Giardiasis
.:. Giardiasis .:. Balantidiasis .:. Taeniasis
.:. Trichomoniasis .:. Cryptosporidiosis .:. Acute enteritis
.:. Amoebiasis .:. Prophylactic treatment of hepatic coma
.:. Anaerobic bacterial infections .:. Sterilization of the gut before intestinal surg"ery

-175- -176-
 11I'' ' " IIII.lr• • •I]Qmia~B~m~31PHB]AmRMMA~CO!I!LO![GYUI
IIIIIBI.nIIU• •1111• •
Contraindications
.:. Known hypersensitivity to aminosidine (Paromomycin) ~~*ml)ICliIl of anthelmintics
Mf~bendazole .:.
, Dose
Intestinal amoebiasis, giardiasis, balantidiasis:
"
~I Pyrantel .:.
Albendazole
Levamisole
Adult: SOOmg twice a day for S-7days "'" Nlclosamide .:. Praziquantel
Children: 30mg/kg/day in 2 divided doses for S-7days
1III Piperazine .:. Ivermectin
I~I Diethylcarbamazine .:. Thiabendazole
Cryptosporidiosis: ~~U'tNOAZOLE
Adult: SOOmg 4 times a day for 14days tI!I~'I~III,ble preparations: Tablets IOOmg, SOOmg
Prophylactic tre.atment of hepatic coma: Suspension IOOmg/Sml
Adult: Ig twice a day for 6days
Children: 2Smg/kg twice a day for 6days Vermox®. Wormin®, Vermout®, Ben®,
Sterilization of the gut before intestinal surgery: i· Neomex®, Nematrax®. Vermorex®,
Adult: 2g daily 'for 3days ,
I
Children: 2Smg/kg twice a day for 3 days ~h"I'macol<inetics
Gastroenteritis and enterocolitis dueto mixed flora, salmonellosi" 1"lilhll1lldazole is poorly absorbed from the gastrointestinal tract but
and shigellosis:
IIIII1
, ,
"_H!lIIption may be increased by fatty food. It undergoes extensive
Adult: SOOmg twice a day for S-7days II."' PllSS metabolism and is excreted in faeces and as metabolites
Children: ISmg/kg twice daily for S-7days 1,1 1,liIt,) in urine.

1.lIlh Jltlons
Side effects
':. Ascariasis (round worms]
.:. Nausea
.:. Enterobiasis ( pin worms infections)
.:. Diarrhoea
.:. Hook worm infection
.:. Abdominal discomfort
.:. Trichuriasis ( whipworm)

6.1.3 ANTHELMINTICS ~olltraindications

.> Pregnancy
Helminthiasis .:. Hypersensitivity to mebendazole
Helminthiasis refers to worm infestation. .:. Infants and Children less than 2 years
Anthelmintics '-.:...-. i I nl)lllC~
I
Anthelmintics are drugs used to treat worm infestations
f: lie orobiasis
Adult and Children over 2years: IOOmg single dose repeated if
IltllCilssary after 2-3 weeks
A1o<:ariasis, hook worm infections and trichuriasis: IOOmg twice
th,lIy for 3 days or SOOmg single dose. Repeat the course after 3-4
wcmks if necessary.

-177- -178-
 , ',,' " ':' ':i " i: ' I:: ir"~,i, , PREC~PHARMACOLOGY I
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PRECISE PHARMACOLOGY

Side effects ;ililll• .,traindications

.:. Abdominal pain .:. Diarrhoea .... ~~ Pregnancy
.:. Convulsions (in infants) .:. Skin rash ,. Hypersensitivity to albendazole
I .:. Dizziness .:. Insomnia ~ Lactation
.:. Headache ~ Neonates
Drug interactions I~III*.~
.:. Anticonvulsants such as carbamazepine and phenytoin may ~"~:Ill'iasis, Enterobiasis, hook worm infection and trichuriasis
increase metabolism of mabendazole '\dult and Children over 2 years: 400mg single dose, the dose may ..
~I~ll'opeated after 1-4 weeks in Enterobiasis.
Key issues to note
~"'(mgyloidiasis: 400mg once daily for 3 days.
•:. Administer mebendazole tablets with food high in fat to
(\hlldren 1.2years: 200mg single dose (Enterobiasis)
increase absorption
.:. Strict hygiene is essential to prevent re-infection ~ldCl effects
.:. All house hold members should be treated at the same time ill ~> Epigastric pain Nausea and vomiting
case of pil1worm infections ~:. Diarrhoea Itching of the skin
.:. Patient may chew, swallow whole, or mix the tablets with food .:- Headache Dizziness
.:. Urticaria Skin rash
ALBENDAZOLE .:. Dry mouth
Available preparations: Tablets 200mg, 400mg
th'ug interactions
Suspension 200mg/5ml (20ml bottle)
.:. Cimetidine increases albendazole metabolism
Available brands: Zentel®, Alben®, Zestaval®, Albuzol® .:. Serum levels are increased if albendazole is taken with
Zepar®, Zeben®, Womiban® dexamethasone or praziquantel

Pharmacokinetics
f*YRANTEL
Av.\i1able preparations: Tablets 250mg
Absorption of albendazole from the gastrointestinal tract is poor but
Suspension 50mg/ml
may be enhanced by a fatty meal. Albendazole rapidly undergoe"
extensive first-pass metabolism. It is eliminated in bile and only a small Available brands: Combatrin®, Nemocid®
amount appears to be excreted in urine.
'-harmacokinetics
Indications Only a small percentage of a dose of pyrantel is absorbed from the
.:. Ascariasis 1l~1strointestinal tract and excreted as unchanged drug in faeces and less
.:. Enterobiasis Ihan 15% in urine
.:. Hook worm infection
Indications
.:. Trichuriasis .:. Hook worm infections
.:. Ascariasis
.:. Adjul1ct to surgery in hydatid disease .:. Trichinosis
.:. Enterobiasis

-179- -180-
 I!!

:1'1111 1\1:
, ' ',,', ", , "Ii': ' " .,' ': ,: " ' , ' PRECISE PHARMACOLOGY ':';;::"'11 ' ~" , I " ,,'I, 'I ": :'1[I I'I', tJ,',1If, 1,,' ~IllLOGY
PRECISE lJIJ1"'lifIHar..,
I: :111111: , I I , 'I I I H"

Contraindications 11"'
lIill'1ndications
.:. Children less than I year " .:. Taenia saginata (beef tape worm)
.:. Hepatic disease .:. Taenia solium (pork tape worm)
.:. Known hypersensitivity to pyrantel .:. Hymenolepis nana infection (dwarf tape worm)
Contraindications
Dose
.:. Hypersensitivity to the drug
Ascariasis: adults and children: I Omg /kg as a single dose
Dose
Hook worm infection: adult and children: I Omg/kg as a single dose'
.h~ef tape worm: 2g in 2 divided doses with I g taken after breakfast
in severe infections I Omg/kg daily for 4days (
l\IId I g an hour later followed by a purgative 2 hours later.
Enterobiasis: adult and children: IOmg/kg as a single dose with a
()warf tape worm infection:
second dose after 2-4 weeks
Adult and children over 6 years: An initial dose of 2g is given on the
Side effects h"lSt day followed by Ig daily for 6 days
.:. Nausea and vomiting .:. Dizziness Children under 2years: 500mg on the first day then 250mg daily for
.:.
....
.:. Abdominal pain Skin rash ~ days
~:"
( Anorexia .:. Diarrhoea Children 2-6years: Ig on the first day then 500mg daily for 6 days
~ .:. Headache .:. Insomnia Pork tape worm infection
Drug interactions Adult and Children over 6 years: 2g as a single dose after a light
l)f'~!akfast, followed by a purgative 2 hours later
.:. The anthelmintics effects of both pyrantel and piperazine may
be antagonized when the two drugs are used together Children 2-6 years: Ig as a single dose after a light breakfast
Children under 2 years: 500mg as a single dose
Key issues to note
.:. Advise the patient to take the drug with food milk or fruit IIlilde effects
.:. Nausea .:. Abdominal pain
juice
.:. Light headed ness .:. Pruritus
.:. All family members in close contact with the patient should be .:. Loss of appetite .:. Vomiting
treated at the same time .:. Diarrhoea .:. Drowsiness
.:. Strict hygiene is essential to prevent reinfection
, Kc~y issues to note
.:. Shake suspension well before measuring off the dose.
.:. The drug may be taken anytime without regard to meals or time 1,',j"III,'! .:. Advise the patient to chew the tablets thoroughly well before
of the day ,"
1 swallowing with water

NICLOSAMIDE rHIABENDAZOLE
Available preparations: Tablets 500mg Available preparations: Tablets 500mg

Available brands: Mesan® Available brands: Mintezol®

Pharmacokinetics '!I I '~I' Pharmacokinetics

Niclosamide is not significantly absorbed from the gastrointestinal tracl III
III
I': lhiabendazole is readily absorbed from the gastrointestinal tract,
and is excreted mostly unchanged in faeces. ;",;;, , Hletabolized to 5-hydroxythiabendazole and excreted principally in the
w'lne but only 5% in the faeces.

-181- -182-
 ZEd •
Mode of action
Indications f~raziquantel produces contraction and paralysis of worms by affectin
.:. Strongyloidiasis 1'I"lmbrane permeability to calcium. g
.:. Cutaneous larva migrans
.:. Visceralla"'¥l migrans Pharmacokinetics
.:. Dracunculosis ~Il'aziquantel is rapidly absorbed after oral administration but
11IIde.rgoes rapid and extensive first-pass metabolism in the liver to
Contraindications IrllIK:tlve.form and excreted in the urine, mainly as metabolites.
•:. Pregnancy Indications
.:. Known hypersensitivity to thiabendazole
.:. Schistosomiasis (bilhaziasis)
Dose .:. Cysticercosis
Strongyloidiasis: 2Smg/kg twice daily for 2-3 days, for Sdays in .:. Taeniasis
disseminated infections .:. Neurocysticercosis
Cutaneous larva migrans: 2Smg/kg twice daily for 2-Sdays
C::ontraindications
Trichinosis: 2Smg twice daiyl for 2-4 days. .:. Ocular cysticercosis
Dracunculosis: 2S-S0mg /kg twice daily for 3 day
.:. Known hypersensitivity to praziquantel
Side effects Oc)se
.:. Anorexia .:. Nausea and vomiting
.:. Pruritus .:. Headache Ic:histosomiasis: 20mg/kg every 4 hours for 3 doses for I day or
.:. Diarrhoea ~()mg/kg as a single daily dose '
.:. Disturbance of vision .:. 'I'itaniasis: Adult and Children over 4 years' 5 IOmg/k . I
.:. Abdominal pain Fatigue "lolle • - g a smg e
.:. Drowsiness .:. Skin rash
NC!lu~ocys~i~ercosis: Adult and Children over 4 years: SOmg/kg
Drug interactions tll_lIy In 3 divided doses for 14 days with prednisolone given 2-3 days
.:. Thiabendazole may inhibit the metabolism of xanthine lu:,'ore and throughout treatment period to reduce the severity of
derivatives Le. aminophylline, theophylline flclverse effects

Key issues to note !lllde effects

.:. Administer the drug after meals to minimize GI upset and 11 .:. Headache .:. Diarrhoea
distress. .:. Urticaria .:. Loss of appetite
.:. Advise the patient to chew the tablets thoroughly before .:. Pruritus .:. Dizziness
swallowing
I .:. Abdominal discomfort .:. Nausea and vomiting
.:. Advise the patient to improve on personal hygiene including .:. Malaise .:. Fever
hand washing after visiting the toilet. .:. Drowsiness
Orllg interactions
PRAZIQUANTEL .:. Antiepileptics such as carbamazepine and phenytoin may
Available preparation: Tablets ISOmg, 600mg
reduce the bio availability of praziquantel
Available brands: Prazitel®

-183- -184-
 ,'I'
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d PRECISE

Cimetidine increases praziquantel bioavailabil ity Dizziness

Praziquantel may increase plasma concentration of the active .:. Headache
Pregnancy
metabolite of albendazole .:. Abdominal pain
Diarrhoea
Key issues te note . Drug interactions
.:. Advise the patient to swallow tablets unchewed ~Ith some
.:. Levamisole can produce disulfiram like reactions when given
water during meals to prevent vomiting due to bitter .taste together with alcohol
.:. Inform the patient that praziquantel may cause dro:-,slness,
.:. Levamisole increases plasma concentration and toxicity of
therefore he/she should not drive or operate machmery phenytoin
LEVAMISOLE .:. Levamisole may enhance anticoagulant effect of warfarin
Available Preparations: Tablets 40mg, SOmg
Suspension lVERMECTIN
Available preparations: Tablets 3mg, 6mg
Available brands: Ketrax®, Rohisol®
Available brands: Mectizan®,lvermectol®
Pharmacokinetics
. Ie I·s rapl·dly absorbed from the gastrointestinal
Levamlso .. .tract,
fI"armacokinetics
extensively metabolized in the liver and excreted mamly In the urine as llilllrmectin is well absorbed from the gut and is excreted mainly in
metabolites and a small proportion in the faeces. IIlIchanged form in faeces

Indications Indications
.:. Ascariasis .:. Filariasis
.:. Hook worm infections .:. Scabies
.:. Adjunct in malignant disease .:. Pediculosis
.:. Immune booster .:. Strongyloidiasis
.:. Suppressive treatment of onchocerciasis
Contraindications
.:. Breast feeding Cpl1traindications
.:. Hypersensitivity to levamisole .:. Pregnancy
.:. Known hypersensitivity to the drug
Dose .:. Children under ISkg
Ascariasis: ISOmg single dose
l)o'lie
Children: 3mglkg as a single dose '. .
Hookworm infection, mixed ascariasis with hookworm mfectlons: Adult and Children> ISkg
2.Smg/kg as a single dose, repeated after 7 days in cases of seven' Ollchocerciasis: ISOmcg/kg as a single dose repeat every 12months
11111:111 asymptomatic
hookworm infections
'Ulllriasis: 400mcglkg as a single dose
Side effects flllldiculosis , Scabies: 200mcg /kg body weight single dose. May
.:. Nausea and vomiting .:. Fever ""ud to repeat after 2 weeks
.:. Muscle pain .:. Taste disturbance

-185-
-186-
Side effects
• n
.:.
g;J~B~jIQ:'~;J~';'Q'JI,Jijl
Dose
, "'''''' ",' I' "!""; I' , I1
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1,111,11111

Adult: 3.5g in single dose for 2 consecutive days

I,' "":" i ,:,""
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DRECIt'~'AClJLOGY
r- ~'I

.:. Fever Pruritus

.:. Skin rash .:. Tachycardia Children: 75mg/kg daily in single doses for 2 consecutive days
.:. Sore throat .:. Arthralgia Side effects
.:. Myalgia .:. Postural hypotension .:. Nausea .:. Vomiting
.:. Headache .:. Oedema .:. Dizziness Skin rash
.:. Cough
.:. Conjunctivitis .:. Colic pain Diarrhoea
.:. Nausea and vomiting .:. Diarrhoea .:. Abdominal cramps Urticaria
.:+ Mild ocular irritation .:. Somnolence .:. Headache Bronchial spasm
.:. Raised liver enzymes Drug interactions
Key issues to note . . .:. Concomitant use with chlorpromazine may precipitate
.:. Rapid killing of microfilariae may In~uc.e syste.mlc or ocular seizures
inflammatory response in form of Ichlng , skin rash or fever. .:. Piperazine antagonizes the effect of pyrantel pamoate
.:. Instruct the patient to take the drug with water on empty .:. Piperazine may potentiate the extra pyramidal effects of
stomach. chlorpromazine and other phenothiazines
DIETHYLCARBAMAZINE (DEC)
PIPERAZINE Available preparations: Tablets 50mg
Available preparations: Tablets
Suspension Available brands: Hetrazan®

Available brands: Antepar® Pharmacokinetics

Diethylcarbamazine is absorbed rapidly from the GIT, under goes
Pharmacokinetics . Ii :1'1'1 11 nllpid extensive metabolism and excreted in urine.
Piperazine is readily absorbed from the gastrointestinal tract and IS I!' I.

t~xcreted in the urine within 24 hours, partly as metabolites. The rate lrldications
Olt which different individuals excrete piperazine has been reported to .:. Lymphatic filariasis
vary widely. It is distributed into breast milk. .:. Loiasis
.:. Prophylaxis of loiasis
Indications .:. Tissue nematode infections, particularly visceral larvae migrans
.:. Ascariasis
.:. Enterobiasis Contraindications
.:. Threadworm infection .:. Pregnancy
.:. Elderly
Contraindications .:. Infants
.:. Hypersensitivity to piperazine
.:. Debilitated patients
.:. Severe renal impairment
.:. Epilepsy
.:. Pregnancy

-187- -188-

1
1 .'1111111111111111111 11'
 _21 Q;JiB~1IQ:'~';J~'~'Qul,JD .-...-.... , PRECIS PHARMACOLOGY I

Dose CHAPTER SEVEN

Lymphatic filariasis: Adult and children over IOyears: Img/kg
7.1.1 DRUGS USED IN THE TREATMENT OF VIRAL
on the first day and increased gradually over 3days to 6mg/kg daily in
INFECTIONS
divided doses for 21 days. .
Children under IOyears: half the adult dose VIRAL INFECTIONS
Loiasis prophylaxis: Adults: 300mg weekly for as long as exposure
Varicella-zoster virus
occurs
Varicella-zoster is. a herpes virus responsible for both chicken pox and
Side effects herpes zoster (shll1gles). Herpes zoster arises from reactivation of the
.:. Headache .:. Dizziness vir.us which lies dormant in a dorsal root ganglion after the primary
.:. Nausea and vomiting .:. Drowsiness chicken pox infection. It is common among elderly and immuno-
.:. Joint pain .:. Fever lluppressed patients.
•:. Anorexia .:. Malaise Herpes simplex virus
.:. Immunological reactions within a few hours of the first dose
I~ exists i~ two forms i.e.type I herpes simplex virus and type 2 herpes
~lInplex virus.
Key issues to note 'Type I is res~onsible fo: oral ulceration (cold sores) while Type 2
.:. To minimize reactions, treatment is started with a lower dose,
produces gel1ltal ulceration. Recurrent lesions occur from reactivation
Img/kg on the first day, and increased gradually over 3 days to
()f latent virus. in the dorsal root neural ganglia, producing symptoms.
6mg/kg daily in divided doses for 5 days Recurrence. may occur during transient immunosuppression
.:. Treatment can precipitate severe immunological reactions to
iIIccompanyll1g fever, after sun exposure or during and after infections
the dead and dying worms. Therefore, use prednisolone 20mg
.,specially viral. '
daily starting 3 days before.,.treatment and continue for more 3
days after starting treatment Cytomegalovirus (CMV)
.:. Large hydroceles and elephantiasis are generally not reversible
It usually produces mild symptoms in immuno-competent patients
and usually require surgical intervention hilt c~n ~e very severe in immuno-suppressed patients resulting in
.:. Treatment should be closely supervised since hypersensitivity
c:c)mphcat.lons such as retinitis, oesophagitis, gastritis, cholecystitis, and
reactions are common and may be severe pneumol1la. It's treated with IV ganciclovir and oral ganciclovir is used
IC) prevent relapse.
Anti viral drugs available in Uganda include:-
Aciclovir
Ganciclovir
Valaciclovir
ACICLOVIR
Available preparations: Tablets 200mg, 400mg
Infusion 250mg/ IOml
Cream 5%

-189- -190-

••
Available brands:

Mode of action
- • UatB~itQ"~'3~b'Mlllllt\.
Zovirax®, Cyclovax®, Herperax®, Lovir®,
Acivir®
. f· I DNA
11"",'1:'111, ',I ,", : I"
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Herpes simplex prophylaxis: 200-400mg 4 times daily

Children under 2 years: I00-200mg 4 times daily
,j II I

Prevention of recurrence of genital herpes: 400mg twice daily

I
: i' ,
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PRECISE~OLOGY
u.L1i.l11.U.li1

Acyclovir inhibits viral replication by suppressing synthesIs 0 Vlra By IV infusion:

Adult: 5mg/kg every 8hours for 5days, double the dose in
after being activated. Immunocompromised patients
Following phosphorylation by viral and cellular enzymes, . Children:
;lciclovir inhibits viral DNA polymerase and DNA synthesIs. 3months-12years: 250mg/m 2 every 8hours for 5days increased to
SOOmg/m 2 in herpes zoster in immunocomprimised
Pharmacokinetics . .. 0
Aciclovir is poorly absorbed with bioavallablhty of 15-30 y~ when 1-3months: I0-20mg/kg every 8hours for 7days
taken orally. It is widely distributed to body tissues and fluids, mucosae Neonates: 10-20mg/kg 3 times daily for 7days
,md herpetic vasicular fluid and is eliminated unchanged by the Topical application
Apply the cream 5 times daily for 5 days.
kidneys.
Side effects
Indications
.:. Primary genital herpes .:. Skin rashes Nausea
.:. Herpes zoster d .:. Vomiting .:. Abdominal pain
.:. Prophylaxis of herpes simplex in immunocompromise .:. Diarrhoea Fatigue
patients . .:. Urticaria Photosensitivity
•:. Suppression of recurrent herpes slmple~ . .:. Headache Confusion
.:. Acute chicken pox in immunocompromlsed patIents .:. Abdominal pain
.:. Labial herpes simplex (cold sores)
Drug interactions
.:. Herpetic eye infections (eye ointment)
.:. Probenecid increases blood levels of acyclovir
.:. Herpetic stomatitis _
contraindications I(c.,y issues to note
.:. Known hypersensitivity to acyclovir .:. Advise the patient to drink plenty of fluid to minimise renal
.:. Rapid or bolus injection adverse effects
.:. In the treatment of herpes zoster, treatment should be started
Dose . 7d
Herpes zoster/ chicken pox: 800mg 5 times dally for ays as early as possible within 48 hours of onset of rash for
Children: best response
Over 6 years: 800mg 4 times daily .:' The risk of renal injury is increased by dehydration and use of
2-Syears: 400mg 4 times daily . other nephrotoxic drugs
Under 2 years: 200mg 4 times dally
VALACICLOVIR
Treatment of primary genital herpes I

Adult: 400mg 5 times daily for 5-1 Odays occasionally up-to 800mg I
AVllilable preparations: Tablets 250mg, 500mg

times daily AVI,i1able brands: Valtrex®

-192-
-191-
 'P, PRECISE ARMACOLOGY !

Pharmacokinetics GANCICLOVIR
Valaciclovir (a pro-drug) is readily absorbed from the gastrointestinal Available preparations: Intravenous infusion, 500mg
tract following oral administration, and is rapidly converted to aciclovil
capsules 250mg
and valine by first-pass intestinal or hepatic metabolism. Valaciclovir is
eliminated principally as aciclovir in the urine. Available brands: Cymevene®

Indications Pharmacokinetics
.:. Herpes zoster Ganci~lovir is poorly absorbed from the gastrointestinal tract
.:. Genital herpes f()l!o~lng o~al a~ministration, widely distributed to body tissues and
•:. Prophylaxis of herpes simplex infections flUids including Intra-ocular fluid and CSF and excreted unch d.
the urine. ange In
Contraindications
.:. Hypersensitivity to aciclovir or valaciclovir Indications
Dose .:. Local treatment of CMV retinitis
Herpes zoster: Ig 3 times daily for 7days; start within 72 hours (,I .:. Life threatening cytomegalovirus infection in
rash immunocompromised patients
Genital herpes: 500mg twice daily for 5-1 Odays .:. CMVprevention in transplant recipients
Prophylaxis of herpes simplex infection: 500mg once daily for I Contraindications
days. .:. Pregnancy
Side effects .:. Breast feeding
.:. Headache Nausea .:. Hypersensitivity to ganciclovir or aciclovir
.:. Reversible neurological reactions Skin rash .:. Abnormally low haemoglobin, neutrophil and platelet count
.:. GI Disturbances Fatigue l)ose
Drug interactions
.:. Probenecid, cimetidine may increase valaciclovir blood C,MV retinitis induction IV infusion: initially Smg/kg every
121~ours for 14-21 days (treatment)
concentration
.:. Nephrotoxic drugs may increase the nephrotoxicity caused 10. Mluntenance: IV Smg/kg per day for 7 days a week. or 6mg/ kg per
,lilY for 5 days in the week
valaciclovir
()ral: Ig 3tmes daily with food
Key issues to note (:MVpreventi~n i~ AIDS patients; Oral Ig 3 times daily with food
.:. Advise the patient to take valaciclovir after food and with ("MV prevention In transplant recipients: IV Smg/ kg eve 12
plenty of water hours for 7 -14 days ry
.:. Advise the patient to report side effects such as rash,
headache, nausea, vomiting, problems with vision, behavior'II M"inte~ance: IV Smg /kg per day for 7 days
changes etc • oml (maintenance theraphy in patients with CMV retinitis 1000 3
IIIlH~S daily with food.

=-'.'_.
.:. For herpes zoster, start treatment as soon as possible within I mg
48 hours of onset of rash
.:. Taking valaciclovir reduces transmission of genital herpes onl,'
slightly -,,',' ,'" ",,'" - ")
..',,' " 2
-193- ;
I
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-194-

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 111111~cISEI~:MilMit8J)'liGYI

HIV-I is the most common in Uganda and it can easily be transmitted.

.:. Skin rash HIV-2 is more common in West Africa and is not easily transmitted.
.:. Diarrhoea
.:. Abdominal pain Mode of transmission of HIV
.:. Flatulence HIV can be transmitted through:-
.:. Chest pain .:. Having unprotected sex with an infected partner
.:. Headache .:. Use of contaminated instruments e.g needles
.:. Weight loss .:. From mother to child during labour, Delivery and
.:. Insomnia breastfeeding
.:. Anxiety .:. Through blood transfusion of infected blood

Fluids that transmit HIV

Drug interaetiOI1:nce of ganciclovir is reduced by probenecid The following fluids have been implicated in the spread of HIV;
.:. Renal clear .:. Blood
.:. Semen
ote .:. Vaginal fluid
Key issues to n to use condoms while playing sex during
•
••• Ad'Vise menand for atleast 3 months after treatment with .:. Breast milk
treatm el1t
oVl'r Clinical Course of HIV Infection
gancicl child bearing age should be advised to use effective
f HIV infection occurs in 3 phases.
.:. Women °tiVe measures during treatment
contracep ho uld discontinue breast feeding while on treatment Initial phase
.:. Mothers se the drug by 1M or SC injection During this phase, HIV undergores rapid replication, causing blood
.:. Do not glv use offers protection only to the eye under levels of HIV to rise very high. Patients experience a flu-like syndrome
• IntraocLJiar. it does not prevent CMV in the untreated eye or
••• and other signs and symptoms such as fever, lymphadenopathy,
treatment, in st extraocular disease pharyngitis, rash, myalgia, and headache. The immune system mounts a
protect aga counterattack,causingHIVlevelstofalileadingtosymptomstodisappear.
The middle phase
~lftAL DRUGS ~
ANTIRETRO 0 Deficiency Virus (HIV) It is characterized by prolonged clinical latency of averagely 10
Human Imrn
LJ1
\lJ
s and belongs to lentiviridae family. HIV impaires
years. Blood levels of HIV remain relatively low, and most patients
HIV i,S a retrO V'ste rn leading to a reduced number of CD4 T are asymptomatic. However, HIV continues to replicate despite
the Immune S\h
e suppresion of immunity allows' opportunistic
apparent dormancy and CD4 T cells undergo progressive decline.
lymphocytes 'rnalignances to emerge as the disease progresses.
infections and The late phase
During the late phase of HIV infections, the CD4 count
Types of HIV pes of HIV namely:- drops below 200 rendering the patient highly vulnerable
There are tWO t:f to opportunistic infections and certain neoplasms (e.g.
•:. HIV-I Kaposi's sarcoma). The late phase is when AIDS occurs.
•:. HIV-2
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 PRECISE PHARMACOlOCY

Lifecycle of HIV Laboratory diagnosis of HIV Infection

HIV cannot replicate outside a living cell therefore it uses the host HIV inf~tion is diagnosed by testing for antibodies against HIV-I and
cells (0 multiply. The lifecycle of HIV has six stages:- HIV-2 uSing; Enzyme-linked immunosorbent assay (ELISA).
.:. Fusion .:. Reverse transcriptioR
.:. Intergration .:. Translation Other tests carried out include:-
Viral load test
.:. Transcription .:. Viral assembly
Note This helps to determine the degree of viral replication.
CD4 count
Drugs used in the treatment of HIV can target any of the listed stages
of the I.recycle of HIV. It helps to determine the degree of immunosuppression and when to
naft anti-retrovirals.
Fusion
Prevention of HIV
HIV infects cells that carry the CD4 receptor on their surfaces such as
T-helper cells. macrophages, etc. The fusion is aided by viral envelope .:. Proper and consistent use of condoms
.:. Abstaining from sex
glycoproteins that bind (0 the CD4 + celts.
, .:. Being faithful to the sexual partner
Reverse transcription .:. Prevention of mother to child transmission.(Avoid
Following fusion, the viral contents are released into the host cells. Tht: breastfeeding)
viral enzyme reverse transcriptase, carries out the process of translating .:. POst exposure prophylaxis
viral RNA into DNA..
Management of HIV
Intergration .:. Antiretroviral therapy
During this sage. the newly formed viral DNA is intergrated into the .:. Treaonent of opportunistic infections
human DNA by the action of intergrase enzyme. At this point the
human cell is under instruction to make more HIV viral particles. Antiretroviral therapy (ART)
Transcription This is a c~mpr~he~sive care package that involves the diagnosis,
The DNA undergoes replication to form single strands of viral RNA I"b~ratory Investigations, prescription, dispensing and follow up of
patlents on ARVs.
(messenger RNA). At this stage, proviral DNA information is writte.,
in form of messenger RNA. Principles of ART
.:. ART should not be started too Soon i.e (when the CD4 cell
Translation ~ount is within the normal range), or too late (when the
Information carried by messenger RNA is translated into instructions to Immune system has been irreversibly damaged)
manufacture long chains of polypeptides which are then broken dOWl1 .:. Use acceptable and convenient regimens with less side effects
by the help of protease enzyme. .:. The drug combination must be available and affordable
.:. Efficacy of the chosen drug regimens
Viral assembly .:. Triple therapy C3-drug combination) is recommended as a
The viral enzyme protease helps to assemble the viral proteins and vir:l1 standard
RNA to form new HIV particles. The new HIV particles are released
into the blood stream and are able to infect other cells.

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Benefits of ART II!

IIW
Examples:-
.:. Prolongs patient's life ;I .:. Tenofovir(TDF)
.:. Improves quality of life in symptomatic patients
.:. Reduces mother to child transmission of HIV ~ucleoside Reverse Transcriptase Inhibitors (NsRTls)
.:. Decreases frequency of hospitalization rhese d~ugs are converted by cellular enzymes to active phosphorylated
•:. Control viral replication metabolites that incorporate themselves into the DNA of th .
.:. Disappearance of symptoms of AIDs thereby stopping the building process. The DNA produced is inco~Vp'~~~
•:. Less is spent to treat opportunistic infections (01) and provides Md cannot create new virus.
palliative care I1IIIIII
, ;
ExampJes:-
Antiretroviral drugs (ARVs) .:. Zidovudine (AZT)
.:. Didanosine (ddl)
These are drugs used in the treatment of HIV infections. They work by lil .:. Zalcitabine (ddC)
.:. Stavudine (d4T)
inhibiting the enzymes involved in the multiplication of the virus. .:. Lamivudine (3TC) .:. Abacavir (ABC)
Classification of Antiretrovirals Protease Inhibitors
Antiretroviral drugs are classified depending on the site or stage of HIY
These drugs prevent HIV from being successfully assembled and
Iifecycle they affect.
,'eleased fro~ the infected CD4 cell. This normally happens at the last
.:. Non-nucleoside reverse transcriptase inhibitors (NNRTls)
lItage of the vIrus reproduction cycle.
•:. Nucloetide Reverse Transcriptase Inhibitors (NtRTI) Examples:-
.:. Nucleoside reverse transcriptase inhibitors (NRTls) .:. Saquinavir (SQy)
.:. Protease inhibitors (Pis) Ritonavir (RTY)
.:. Indinavir (lDY)
.:. Fusion inhibitors Nelfinavir (NFY)
.:. Lop;navir-ritonavir (lPV/r) .:. Atazanavir (AZY)
.:. Intergrase inhibitors
Integrase Inhibitors
Non-Nucleoside Reverse Transcriptase Inhibitors These drugs interfere with the ability of the HIV DNA to insert itself
Drugs in this class act by binding directly onto the reverse transcriptase Into the host DNA and thereby copy itself.
enzyme, at a site close to the binding site of the normal substrates used Examples:-
in DNA synthesis. Their binding prevents synthesis of DNA .:. Raltegravir
They include:-
.:. Nevirapine (NVP) fusion Inhibitors
.:. Efavirenz (EFZ) These d:ugs bind to viral glycoproteins and, by inhibiting their function
.:. Delavirdine (DLY) block v~raf ~usion with the CD4 receptor of the human cell thu~
preventmg vIral entry. '
Nucleotide Reverse Transcriptase Inhibitor (NtRTI)
Tenofovir is converted intracellularly to the diphosphate. This : I1II EX~;PI~~fuvitride (T-20)
diphosphate halts the DNA synthesis of HIV through competitive .:. Maraviroc
inhibition of reverse transcriptase and incorporation into viral DNA Uses of Antiretrovirals (ARVs)
.:. Treatment of HIV

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·:. Preve~tion of mother to child transmission of HIV CHAPTER EIGHT

.:. Post-Exposure Prophylaxis (PEP)
.:. Pre-exposure prophylaxis (Pre-EP) DRUGS ACTING ON GASTROINTESTINAL SYSTEM
Goals of Anti-Retroviral Therapy .
•:. To reduce the viral load by halting multiplication of the VirUS 8.1.1 DRUGS FOR PEPTIC ULCER DISEASE
.:. To increase the CD4 count .
•:. To reduce the frequency of opportunistic infections 'Peptic Ulcer Disease (PUD)
.:. To prolong life of the patient Ii, Peptic ulcer disease develops when there is an imbalance between
mucosal protective substances such as mucus, bicarbonate and
destructive substances like acid, H. pylori bacteria and pepsin.
Note h I'ty of life of
Antiretroviral drugs do not cure HIV but improve t e qua I
the patient when properly used. Drugs used in the treatment of peptic ulcer disease include:-
.:. Antiacids
Recommended regimens of ART . .:. H receptors antagonist
Most common tegimens contain 2 Nucleoside Reverse Transcr~ptase 2
.:. Proton pump inhibitors
Inhibitors (2NRTls) plus I Non-nucleoside reverse transcnptase
.:. Mucusal protectives
inhibitor (I NNRTI) or a Protease Inhibitor (PI). . .
. . th reader IS advised to use .:. Antibiotics
Due to cotinuous changes, In the regimen, e
the current National Treatment guideline.
Antacids.
These are alkaline compounds that neutralise stomach acids raising the
gastric PH thereby relieving pain. They are often given concurrently
with acid suppressing drugs such as H receptor antagonists and proton
2
pump inhibitors in treatment of peptic ulcer and reflux oesophagitis.
Most antacids contain aluminium hydroxide, magnesium
hydroxide, sodium bicarbonate or calcium carbonate. Other
ingredients added to antacids include simethicone, alginic acid.

Simethicone is added to antacids to relieve flatulence and dyspepsia.

Simethicone may be beneficial in relieving colic pain in infants.
Common brands containing simethicone include; Maalox plus®, Alcid®
and Gestid®.

Alginates are added to antacids as protectants and are useful in the

treatment of reflux oesophagitis. Common brands containing Alginate
Include:- Gavison®.
l.ocal anaethetics such as oxethazine are added to antacids to reduce the

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 , "I:: :>1, :IP" " ,", ' PRECISE PHARMACOLOGY

pain associated with dyspepsia. Common brands containing oxethazine COMMON ANTIACID PREPARATIONS ACICONE-S®
are; mucogel® suspension and mucaine® suspension.
Antacids containing sodium bicarbonate has a fast onset of action but Available preparations. Tablets
their absorption may worsen hypertension and heart failure. Suspension

Indications Composition:
Symptomatic relief of:-
Tablets Magaldrate 720mg
.:. Dyspepsia Simethicone 25mg
.:. Gastro oesophageal reflux disease Suspension Magaldrate 540mg
.:. Peptic ulcer disease Simethicone 40mg
.:. Gastritis
.:. Heartburn Indications
Contraindications " .:. Heart burn in reflux-oesophagitis
.:. Patients with severe abdominal pain of unknown cause .:. Prophylaxis against ulcer complications
.:. Lactation .:. Adjunct to the treatment of peptic ulcer
.:. Patients with cardiovascular problems (antacids with sodium) Dose
Side effects Tablets: I tablet to be chewed 4 times daily after meals or at bed
time
Magnesium containing antacids tend to cause diarrhoea whereas
aluminum containing antacids may cause constipation and delay gastric Suspension: 5-1 Oml 4times daily after meals or at bed time
emptying. A combination of the two may reduce the side effects of AGOCID®
each. Available preparations: suspension
Key issues to note
.:. Antacids should be taken between meals or at ~d time when
Composition: Dried aluminum gel 250mg
symptoms are expected to occur Magnesium hydroxide 250mg
.:. Optimum antacid effect is obtained if taken 1-3 hours after Simethicone 50mg
meals Indications
.:. liquid antacids are generally more effective than tablets and .:. Acid dyspepsia
have rapid onset of action. .:. Heart burn
.:. Antacids are effective for a short period therefore should be .:. Pregnancy heart burn
given on a 6 hourly basis .:. Adjunct to peptic ulcer treatment
.:. Antacids may interact with numerous ther drugs, affecting .:. Reflux oesophagitis
the rate and extent of their absorption. e.g. tetracycline,
ciprofloxacin, Iron, indomethacin and digoxin. A minimum of Dose
at least 2 hours interval should be left between administration 5·1 Oml 4 times daily between meals
of antacids and other drugs

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Indi~:~ti~::rt burn
ALCID®
Available preparations: suspension :lllli,;II'111

"!!"I,!Ji .:. Adjunct in the treatment of peptic ulcers

Composition: Aluminum hydroxide gel 400mg ·it:II!:,
i!!lillll .:. Flatulence
-. Magnesium hydroxide 400mg
Simethicone 50mg
. ,I' !~ ,

.:. Gastritis with belching

.:. Gastric hyperacidity
Indications
.:. Gastritis Dose
i .:. Flatulence 5-IOml 3-4 times daily after meals
'I
:1
.:. Hiatus hernia GAVISCON®
.:. Adjunct to the treatment of peptic ulcer Available preparations: Tablets
.:. Heart burn associated with reflux oesophagitis Suspension
.:. Heart burn in pregnancy Composition: Magnesium trisilicate 25mg
DO!ie .. Aluminum hydroxide ge IOOmg
5-IOml 4 times a day between meals and at bed time Alginic acid 500mg
Sodium bicarbonate 170mg
CENTACID®
Indications
Available preparations: suspension
.:. Heart burn
.:. Acid indigestion
Composition: Aluminum hydroxide gel 250mg
.:. Reflux oesophagitis
Magnesium hydroxide 200mg
.:. Adjunct to treatment of peptic ulcers
Simethicone 40mg
Dose
Indications
Tablets: chew 1-2 tablets 4 times a day after meals and bed time
.:. Acid dyspepsia
liquid /suspension: 5-1 Oml 4 times daily after meals
.:. Reflux oesophagitis
.:. Gastritis
GESTID®
.:. Pregnancy heart burn
Available preparations: Tablets
.:. Hiatus hernia

Dose Composition Magnesium trisilicate 50mg

5-1 Oml 4 times a day between meals and bed time Dried aluminum hydroxide gel 300mg
Magnesium hydroxide 25mg
FILMACID FORTE GEL® Simethicone IOmg
Available preparations: suspension Indications
.:. Gastric pain
Composition: Aluminum hydroxide gel 300mg .:. Heart burn
Magnesium hydroxide 150mg .:. Flatulence
Simethicone 125mg

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Dose Indications
1-2 tablets, chewed or swallowed 4 times daily 1-2 hours after meals .:. Gastritis
.:. Flatulence
MAALOX PLUS® .:. Heart burn associated with reflux oesophagitis
Available preparations: Suspension .:. Heart burn in pregnancy
Tablets .:. Adjunct to the treatment of peptic ulcers
Composition: Dried aluminium hydroxide gel 220mg Dose
Magnesium hydroxide 195mg 5-IOml 3-4 times daily after meals
Activated dimethicone 25mg
INFACOL®
Indications Available preparations: liquid 40mg/ml
.:. Acid indigestion
.:. Heart burn Comp6sition: Activated dimethicone
.:. Flatulence Indications
.:. Adjunct to the treatment of peptic ulcers .:. Colic pains
.:. Reflux oesophagitis .:. Wind pains
Dose .:. Gripes
5-1 Oml 4times daily after meals and at bed time Dose
MUCOGEL® 0.5-1 ml before meals
Available preparations: Suspension
MUCOSAL PROTECTIVE DRUGS
Composition: Aluminium hydroxide gel 8.1 g
Magnesium hydroxide 2g BISMUTH SUBSALICYLATE
Oxethazaine 0.2g Has cytoprotective properties and is bactericidal against H.pylori. It
Indications promotes healing of peptic ulcers by formation of a complex (bismuth/
•:. Gastritis glycoprotein) which coats the base of peptic ulcer.
.:. Reflux oesophagitis It needs an acidic environment to work; hence do not use in
•:. Peptic ulcers combination with antacids.

Dose Available preparations: Tablets 120mg

5-IOml 15min before meals 4times daily and at bed time Suspension

RELCERGEL® Available brands: Pepto-bismol®, Bismol®

Available preparations: Suspension Pharmacokinetics
Composition: Aluminium hydroxide gel 6gm Following oral administration, the drug is only slightly absorbed.
Magnesium hydroxide 80mg Increased gastric pH may increase bismuth absorption. Unabsorbed drug
Simethicone 100mg is excreted in faeces. The absorbed portion of the drug is distributed
Deglycyrrhinized liquorice 400mg throughout body tissues and is slowly excreted in urine and bile.

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Indications PROSTAGLANDIN ANALOGUES

.:. Peptic ulcer
MISOPROSTOL
.:. Nausea
Available preparations: Tablets 200 mcg
.:. Diarrhoea
.:. Abdominal cramps ", Available brands: Cytotec®
.:. Indigestion Mode of action
.:. Prevention of travelers' diarrhoea Misoprostol helps to protect the stomach by suppressing secretion of
Contraindications gastric acid, promoting secretion of bicarbonate and cytoprotective
.:. Hypersensitivity to bismuth salts mucus, and maintaining blood flow.
•:. Moderate to severe renal impairment
.:. Children < 3 years Indications
.:. Peptic ulcer disease
Dose .:. Prophylaxis of NSAID-induced ulcers
Adults: .:. Induction of labour
30ml o~ 2 tabs 4 times daily 30minutes before food .:. Management of pos:Jum haemorrhage
~~!i·
Children: Contraindications :II
9- 12 years: 15ml or I tab 4 times daily .:. Pregnancy or those pi ning to become pregnant
6-9 years: IOml 4 times daily .:. Women in Child-bearing age
3-6 years: Sml 4times daily .:. Breastfeeding
.:. Patients allergic to prostaglandin derivatives
Side effects .:. Inflammatory bowel disease
.:. Black stool
.:. Discolours mucous membranes, tongue and teeth Dose
.:. Constipation By mouth: 800mcg daily in 2-4 divided doses with food for 4-8
.:. Metallic taste weeks
.:. Skin reactions Prophylaxis of NSAID-induced ulcers: 200 mcg 2-4 times daily
.:. Stomatitis taken with NSAID

Drug interactions Side effects

.:. Bismuth subsalicylate decreases absorption of tetracyclines .:. Diarrhoea .:. Nausea
.:. Flatulence .:. Vomiting
.:. It increases toxicity of aspirin due to absorption of salicylate
.:. Abdominal cramps .:. Abnormal vaginal bleeding
Key issues to note .:. Dyspepsia .:. Rashes
.:. Chew or dissolve tablets in mouth before swallowing .:. Dizziness
.:. Shake suspension before using
Drug Interactions
.:. Stop use if symptoms do not improve within 2 days .:. Misoprostol diminishes the bioavailability of aspirin
.:. Magnesium antacids enhance diarrhoea associated with
1111,. misoprostol

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, , I , "", ',,', EPHARMACOLOGY ", ,III' ":i ,iii,: :, 'I ,"i :," " I", ',II'IIi"" ',' I:" ,I,', ,Ii ,: PRECISE PHARMACOLOGY
H 2 RECEPTOR ANTAGONISTS Mi~intenance: 400mg at night :;6
H 2 receptors antagonists reduce gastric acid secretion by blocking
'i
I~
II'•.
"
Reflux Oesophagitis: 400mg 4 times daily for 4 -8 weeks
"
Prophylaxis of stress ulceration: 200-400mg every 4-6 hours
the action of histamine at the H 2 receptor in the parietal cells of the :1
stomach. .. Zollinger-Ellison syndrome: 400mg 4 times daily (maximum dose is
2.4g daily) :111" ,
Examples:- Gastric acid reduction, obstetrics: 400mg at start of labour then
.:. Cimetidine up-to 400mg every 4 hours if required (max 2.4g daily)
•:. Famotidine Dyspepsia. 200mg up to 4 times daily for 4 -8 weeks.
.:. Nizatidine Parenteral route
.:. Ranitidine Slow intravenous injection: 200mg every 4-6 hours over atleast 2
minutes and diluted in 20ml of normal saline."
CIMETIDINE Intravenous infusion: 400mg in IOOml of sodium chloride 0.9%
Available preparations: Tablets 200mg,400mg Infused over 30minutes -I hour, may be repeated every 4-6 hours (max
Injection I OOmg/ml, 2ml 2.*g daily)

Available brands: Tagamet®, Tenomet®, Cemet®, Side effects

Lock-2® .:. Dizziness .:. Headache
Pharmacokinetics .:. Nausea .:. Vomiting
.:. Reversible impotence .:. Loss of libido
Cimetidine is readily absorbed from the GIT when given ~ally. Food
. .:.
"

delays the rate and may slightly decrease the extent of absorpti~n.
'
Mild gynaecomastia .:. Diarrhoea
It is widely distributed,tind partly metabolised in the liver. CimetidtJ,e .:.tiredness .:. d~Finess .'
crosses the placental ba'rrier and is distributed into breast milk. It is
excreted mostly in unchahged form in urine. ' Drug interactions ,
.:. Antacids may decrease the absorption of cimetidine
Indications .:. The effect of ferrous sulphate, indomethacin, ketoconazole,
.:. Peptic ulcers
~conazole and tetracyclines may be decreased by Cimetidine
.:. Stress ulcesr in critically ill patients .( due to decreased absorption
.:. Reflux oesophagitis .:.\Metoclpramide may reduce the bioavailability of cimetidine
.:. Zollinger-Ellison Syndrome due to reduction of gastrointestinal transit time
.:. Dyspepsia .:. Cimetidine decreases the metabolism of Phenytoin,
Contraindications Metronidazole, oral contraceptives, Warfarin and Isoniazid
.:. Hypersensitivity to other H 2 antagonists Key issues to note
Dose .:. Administer cimetidine with food but not with antiacids
Oral route .:. The preferred method of administration of parenteral
Gastric ulcers and duodenal ulcers: 400mg twice daily or 800mg at cimetidine is by continuous infusion but may be given
night for 4-6 weeks intramuscularly

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 " ,,: "".tli ',!> ,:'" :,,,, '" " ,,, , I" " , I' " flREC[l.~LOGY 11111&12. . . . . . . . . ._ PRECrSEIQ:m*IMM!rlir•
•:. Advise the patient to avoid excessive amount of coffee or .:. Anxiety .:. Fatigue
aspirin .:. Anorexia .:. fever
.:. Cimetidine has a weak anti-androgenic effect hence
Drug Interactions
gynaecomastia, impotence and loss of libido may occur ..,
.:. Famotidine reduces absorption of ketoconazole ,
itraconazole, cefpodoxime, cefuroxime due to reduced gastric
FAMOTIDINE
acidity
Available preparations: Tablets 20mg, 40mg
.:. Famotidine increases the absorption of glipizide, tolbutamide
Available brands: Antodine® which may lead to hypoglycaemia

Pharmacokinetics RANITIDINE
Famotidine is readily but incompletely absorbed from the gastrointesti nal Available preparations: Tablets ISOmg, 300mg
tract, partially metabolized in the liver and is excreted unchanged in the Injection 2Smg/ml, 2ml
urine. Famotidine is also found in breast mille
Available brands: Zantac®, Ranidenk®,
Indications "
Ranitin®, Rantac®, Aciloc® , R-Loc®
.:. Reflux oesophagitis
.:. Zollinger-Ellison syndrome Pharmacokinetics
.:. Benign gastric ulcer Ranitidine is readily absorbed from the gastrointestinal tract, widely
•:. Duodenal ulcer distributed, metabolized in File liver and is excreted in urine.
.:. Dyspepsia Indications
Contraindications .:. Peptic ulcer
.:. Hypersensitivity to Famotidine .:. Prophylaxis of NSAID induced duodenal or gastric ulcer
.•:. Gastric malignancy .:. Stress ulcer Prophylaxis
.:. Lactation .:. Gastro oesophageal reflux disease
.:. Children .:. ZOllinger-ErliS syndrome
.:. Dyspesia
Dose
Benign gastric and duodenal ulceration: 40mg at night for 4-8 Contraindications
weeks. Maintenance: 20mg at night (for duodenal ulcer) .:. Patients allergic to ranitidine
Zollinger-Ellison syndrome: 20mg 6 hourly daily for a long period of .:. Children less than 8 years
time
Reflux oesophagitis: 20-40mgtwice daily for 6-12 weeks, maintenance: Dose
iOmg twice daily Peptic ulcer:
Side Effects Adults and Children over 12 years: I SOmg twice daily or 300mg at
.:. Headache Constipation or diarrhoea night for 4 to 8 weeks
.:. Abdominal discomfort Dry mouth Prophylaxis of NSAID induced duodenal or gastric ulcer: ISOmg
.:. Nausea and vomiting Flatulence twice daily

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Gastro oesophageal reflux disease: I SOmg twice daily or 300mg at OMEPRAZOLE

night up to 8 weeks Available preparations: Enteric coated Capsules /tablets 20mg
Moderate to severe cases I SOmg 6hourly daily for up to 12 weeks
Available brands: Gasec®, Omepren®, Omizac®
Zollinger-Ellison syndrome: I SOmg 3 times daily. ",
Ocid®, Belifax®
Stress ulcer Prophylaxis; I SOmg twice daily untill risk factor is
Pharmacokinetics
removed "
Omeprazole is rapidly but variably absorbed after oral administration.
Dyspesia; I SOmg twice daily for 4-8 weeks Absorption is not affected by food. It is almost completely metabolized
IV: SOmg diluted to 20ml with normal saline or dextrose 5% every 6-8 In the liver and 80% of the metabolites are excreted mainly in urine and
hours by slow injection over not less than Smin the rest in faeces.
IV Infusion: 2Smglhour for 2 hours may be repeated every 6-8hours Indications
Side effects .:. Peptic ulcers i,:
.:. Skin rash Malaise .:. Zollinger-Ellison syndrome
.:. HI~Visual disturbance Tachycardia .:. NSAID associated duodenal or gastric ulcer
.:. IWli Gynaecomastia Constipation .:. Gastric acid reduction during anaesthesia
.:. Headache Hypersensitivity reaction .:. Gastro oesophageal reflux disease
.:. Diarrhoea Myalgia .:. Acid related dyspepsia

Drug Interactions Contraindications

.:. Antacids may decrease the absorption of ranitidine .:. allergy to omeprazole or any other component in the capsule
.:. Ranitidine may decrease the absorption of...ketoconazole, .:. Pregnancy
cefpodoxime, cefuroxime .:. Lactation
.:. Ranitidine may increase the hypoglyceamic effects of glipizide
Dose
.:. Ranitidine may interfere with warfarin clearance.
Gastric ulcer or reflux oesophagitis: 20-40mg once daily for 4- 8
PROTON PUMP INHIBITORS weeks ,"
Proton Pump inhibitors(PPls) act by irreversibly binding to and inhibiting
the enzyme H+ / K+ -ATpase (proton pump) of the gastric parietal cells
Duodenal ~cer: 20mg once daily for 4 weeks
NSAID ass iated duodenal or gastric ulcer: 20mg once daily for
> resulting into long lasting but reversible acid suppression.
4 weeks conti ued for further 4 weeks if not fully healed.
Proton pump inhibitors, inhibit gastric acid secretion more than the H 2
Zollinger-Ellison syndrome: Initially 60mg once daily, usual range
receptor antagonist
20-120mg with doses over 80mg given in 2 divided doses.
Examples:-
Acid related dyspepsia: 20mg once daily for 2 to 4 weeks.
•:. Omeprazole
Prophylaxis of acid aspiration: 40mg on the proceeding evening,
.:. Lansoprazole
then 40mg 2-6 hours before surgery.
•:. Pantoprazole
.:. Esomeprazole Side effects
.:. Rabeprazole .:. Headache .:. Nausea
.:. Vomiting .:. Flatulence
\
\

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 , ' , '" ',' PRECISE PHA~MACOI!ffi:U . ,,: ,: i,r'" 'I' 'I, ':' ",:,:' ,: > ' I. ' ",,", PRECISElilllilillilil){llUIifI
.:. Constipation Abdominal pain Contraindications
.:. Skin Rashes Dry mouth .:. Known hypersen:sitivity to benzimidazoles
.:. Diarrhoea Gynaecomastia .:. Pregnancy
.:. Impotence
Dose
Drug Interactions Peptic ulcer disease: triple therapy regimen 40mg of esomeprazole
.:. Omeprazole increases the plasma concentration of diazepam, once daily with amoxyc illin Ig twice daily and c1arithromycin SOOmg
carbamazepine , digoxin, Phenytoin twice daily for 7 days
.:. Omeprazole decreases the plasma conce~tratil!1fl Gastro esophageal reflux disease: 40mg once daily for 4- 8 weeks
Itraconazole, Ketoconazole , cefpodoxime, cefuroxime, depending on the response, maintenance: 20mg daily
iron salts and cyanocobalamin Gastric ulcer associated with NSAID therapy: 20mg once daily for
.:. Omeprazole may increase the absorption and the potential .. -8 weeks
for hypoglycaemia of glipizide , tolbutamide
Side effects
Key issues to note
.:. Taste disturbances Headache
.:.iW\' Administer before food and the capsule should be swallowed
.:. Dizziness .:. Abdominal pain
r whole without chewing
.:. Diarrhoea Skin rash
.:. Capsules should be used within one month of opening the
.:. Nausea Vomiting
package
.:. Dry mouth Flatulence
.:. Possible malignancy must be excluded prior to starting
Drug Interactions
treatment to, avoid delay in diagnosis
.:. Reduction in gastric acidity due to esomeprazole use may
.:. Dosage redu2l!ion may be required in hepatic disease
decrease absorption of Ketoconazole, Itraconazole , Digoxin
ESOMEPRAZOLE and iron
Available preparations: Tablets 20mg, 40mg
Key issues to note
Available brands:

Pharmacokinetics G
Nexium®, S-prazo®, Nexpro®, Esoz®

Esomeprazole is rapidly absorbed following oral ad inistration.

It is extensively metabolized by the liver and excre d in urine and a
.:. Food delays and decreases the absorption of esomeprazole,
therefore take it atleast I hour before meals
.:. The tablet should be swallowed whole; do not chew or crush
LANSOPRAZOLE
small percentage in faeces. Available preparations: Capsule 30mg
Indications
Available brands: Lancid®, Lan-30®, Zolanas-30®'
.:. Gastro oesophageal reflux disease
.:. Zollinger-Ellison syndrome Pharmacokinetics
.:. Peptic ulcer disease Lansoprazole is rapidly absorbed after oral administration, extensively
.:. Prevention Qf relapse of H. pylori associated peptic ulcer metabolized in the liver and metabolites are excreted primarily in
.:. Prevention of gastric and duodenal ulcers associated with faeces via the bile.
NSAID therapy

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"
 , , ", . " ',I' ',I" 'I PREC SE fSHARMACOLOD II III' -_ _1211 1 QI!#e~t PHARMACOLOGY

Indications .:. Lansoprazole may reduce the effect of oral contraceptives,

.:. Peptic ulcers Phenytoin, Carbamazepine, warfarin and Theophylline
.:. Zollinger-Ellison syndrome "
.:. Gastro oesophageal reflux disease Key issues to note
.:. Acid related dyspepsia .:. Swallow capsule whole without crushing or chewing
.:. Prophylaxis of NSAID associated duodenal and benign gastric .:. For patients un able to swallow, open the capsule and pour
ulcer '" the contents on a tea spoon and swallow
.:. Take the drug after meals
Contraindications
.:. Hypersensitivity to Lansoprazole l\ABEPRAZOLE
.:. Breast feeding Available preparations: Tablets 20mg
.:. Pregnancy Injection 20mg
Dose Available brands: Rabeloc®, Rabemac®, Veloz®
Benign gastric ulcer: 30mg daily in the morning for 8 weeks
Pharmacoldnetics
Duodenal ulcer: 30mg daily in the morning for 4 weeks, maintenance:
Rabeprazole is rapidly absorbed from the GIT and is 96% protein
ISmg daily
bound. It is extensively metabolized in the liver and excreted principally
Zollinger-Ellison syndrome: Initially 60mg once daily adjusted
111 the urine. It crosses the placenta and may enter breast milk.
according to response to daily dose of 120mg or more in two divided
Indications
doses
.:. Peptic ulcers
Gastro oesophageal reflux disease: 30mg daily in the morning for
.:. Gastro oesophageal reflux disease
4-8weeks, maintenance: IS-30mg daily.
.:. Helicobacter pylori eradication in combination with antibiotics
Acid related dyspepsia: 30mg daily in the morning for 2-4 weeks.
.:. Zollinger-Ellison syndrome
Side effects
.:. Abdominal pain .:• Diarrhoea or constipation
.:.
Contraindications
.:. Fatigue Nausea .:. Hypersensitivity to rabeprazole
.:.
.:.
Dizziness
Headache
.:.
.:. Fla'Ule(
Skin ra h
.:. Gastric malignancy
.:. Pregnancy
.:. Altered appetite .:. Impote ce .:. Lactation
.:. Malaise .:. Vomiting
Dose
Drug Interactions Benign gastric ulcer: 20mg daily in the morning for 6-12weeks
.:. Lansoprazole may interfere with the absorption of drugs where Gastro oesophageal reflux disease: 20mg once daily for 4-8
gastric pH is an important determinant of bioavailability such as weeks.
ketoconazole, itraconazole, ampicillin, iron salts, digoxin Maintenance: I 0-20mg daily.
•:. Antacids may reduce absorption of lansoprazole when given at Duodenal ulcer: 20mg daily in the morning for 4-8 weeks
the same time Zollinger-Ellison syndrome: Initially 60mg once daily adjusted
according to response up to a max. 60mg twice daily

-219- -220-
Tripple therapy regimen: Rabeprazole 20mg twice daily combined lOose
with c1arithromycin 500 mg twice daily and either amoxicillin Ig twice 'Gastro oesophageal reflux disease: 20-40mg daily in the morning
daily or metronidazole 400mg twice daily for 7days. i'I)1' 4-8 weeks. Maintenance: 20-40mg daily.

Children: Not recommended. !I)uodenal ulcer: 40mg daily in the morning for 2-4weeks.
Side effects l.ollinger-Ellison syndrome: Initially 80mg once daily, adjusted
•:. Headache Diarrhoea ~ccording to response.
.:. Abdominal pain Nausea mlderly: Max dose is 40mg daily
.:. Flatulence Cough Prophylaxis of NSAID associated gastric or duodenal ulcer:
.:. Constipation Insomnia Wmgdaily
•:. Skin rash Dry mouth Benign gastric ulcer: 40mg daily in the morning for 4-8 weeks.
•:. Pharyngitis Rhinitis Children: Not recommended .
.:. Influenza-like syndrome .:. Anorexia Side effects
Drug Interactions .:. Constipation Dizziness
.:.11 Co-administration of rabeprazole with ketoconazole decreases .:. Pruritus Flatulence
ketoconazole plasma level .:. Chest pain Headache
.:. Rabeprazole may increase serum levels and toxicity of .:. Anxiety Skin rash
benzodiazepines when given together .:. Abdominal pain Fatigue
Drug Interactions
PANTOPRAZOLE .:. Pantoprazole may decrease the absorption of ketoconazole
Available preparations: Tablets 20mg , 40mg
and itraconazole
. Available brands: Pantaz®, Pantotab®, Pantecta®
ANTIBIOTICS
Pharmacoldnetics
Pantoprazole is rapidly absorbed from the gastro intestinal tract and
Antibiotics are recommended in the treatment of PUD when H. Pylori
is 98% protein bound. It is extensively metabolized in the liver and
is confirmed. They are given in tripple therapy in combination with
excreted principally in the urine.
proton pump inhibitors.
Indications Common antibiotics used in tripple therapy include amoxicillin,
.:. Peptic ulcers c1arithromycin, metronidazole, tinidazole and tetracycline.
•:. Gastro oesophageal reflux disease
.:. Zollinger-Ellison syndrome
.:. Prevention of NSAID induced ulcer

Contraindications
.:. Hypersensitivity to p~azole
.:. Lactation ;

-221- -222-

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PRECISE PHAR~lJLlJGY
.l:L1i1!l 1
11111111111111• • g;!B~i~PHARMACOLOGYI
Tripple therapy regimen for eradication of H. pylori infection .'IY()SCINE BUTYLBROMIDE
(7 days treatment)
A"j,llable preparations: Tablets IOmg
Syrup Smg/Sml
Injection 20mg/ml

"lI'lailable brands: Bispanol®, Hyomide®, Buscopan®

Esomeprazole Ig twice daily SOOmg twice daily M,:.de of action
20mg twice daily - 2S0mg twice daily 400mg twice daily , 't()$cine butyl bromide exerts a spasmolytic action on the smoth
Lansoprazole Ig twice daily SOOmg twice daily III 'lIuu<:le of the gastrointestinal, biliary and genito-urinary tracts.
30mg twice daily
Ig twice daily - 400mg twice daily Indications
SOOmg twice daily 400mg twice daily .:. Prevention of motion sickness
Omeprazole ' g twice daily SOOmg twice daily
11111!!1 .:. Other forms of nausea and vomiting
I 20mg twice daily SOOmg 3 times - 400mg 3 times .:. Relieve pain of GI spasm (bowel colic)
daily daily .:. Premedicant in anaesthesia
SOOmg twice daily 400mg twice daily .:. Adjunct in the peptic ulcer disease treatment
Pantoprazole Ig twice daily SOOing twice daily
C:ontraindications
40mg twice daily - SOOmg twice daily 400mg twice daily
.:. Reduced bronchial secretion .:. Pyloric stenosis
Rabeprazole Ig twice daily SOOmg twice daily .:. Closed angle glaucoma .:. Hypersensitivity
20mg twice daily - SOOmg twice daily 400mg twice daily .:. Megacolon .:. Porphyria
.:. Prostatic enlargement
I)ose
ANTISPASMODICS
Uy mouth
These drugs reduce spasms associated with peptic ulcer and other Adults: 20mg 4 times daily
GIT disorders. Children: 6-12 years: IOmg 3 times daily
Injection:
Examples: Adult; IM/lV: 20mg 3 -4 times daily
.:. Hyoscine Butylbromide
Side effects
.:.
•:.
Drotaverine
Propantheline
.
.: Dry mouth .:. Flushing of the skin
.:. Tachycardia .:. Increased intraocular pressure
.
:. Fatigue .:. Blurring of vision
.:. Drowsiness .:. Constipation
.:. Acute urinary retention .:. Reduced bronchial secretion

-223- -224-

.~.
• • •!im.I. . . . . . . . . . __ . p i!!a~'fi PHARMACOLOGY I , ' , ,',I: ,"I, '" ",1'1, ",,, ,I, I " i, t:" ;, :' i,', I PRECISE PHARMACOLOGY
Drug Interactions Side effects
.:. Additive sedative effects with alcohol or other CNS .:. Dizziness
depressants .:. Nausea
.:. Concomitant use with dopamine antagonists e.g. ", .:. Headache
metoclopramide, may result in diminution of the effects of both .:. Allergic reactions
drugs on the GIT
Drug interactions
DROTAVERINE .:. Drotaverine may decrease the antiparkinsonian effect of
Available preparations: Tablets 40mg,80mg levodopa, tremor and rigidity may increase
Injection 40mg/2ml
Available brands: Nospa®, Dorein®, Spacovin®
PROPANTHELINE
Available preparations: Tablets ISmg
Mode of action
Available brands: Pro-Banthine®
Drotaverine inhibits phosphodiesterase enzyme IV, leading to elevated
intracellular cAMP levels, which in turn leads to relief of spasm Mode of action
thereby relieving the pain. It also exerts an anti-inflammatory activity It inhibits GI motility and diminshes gastric acid secrection.
similar to the NSAIDs. Indications
.:. Adjunct in the treatment of peptic ulcer disease
Indications
.:. Irritable bowel syndrome
Drotaverine is used as an antispasmodic in the management of pain
.:. Urinary frequency and enuresis (adults)
associated with:
.:. Pancreatitis
.:. Biliary colic
.:. Renal colic Contraindications
.:. Dysmenorrhoea .:. Narrow angle glaucoma
.:. Obstructive disease of the GI tract
Contraindications
.:. Chronic lung disease
.:. Hypersensitivity to Drotaverine
.:. Hypersensitivity to the drug
.:. Severe hepatic impairment
.:. Bladder neck obstruction due to prostatic hypertrophy
.:. Porphyria
Dose
.:. Severe renal impairment
Adult: ISmg 3 times daily atleast I hour before meals and 30mg at
.:. Pregnancy and Lactation
night. Max. 120mg daily
.:. Intestinal obstruction
Elderly:7.Smg 3 times daily
.:. Cardiac insufficiency

Dose Children I month -12 years:

Adult; 40-80mg 8 hourly Antispasmodic ;
Children: >6years; 40mg 8 hourly l -3 mg/kg /day in 3 divided doses
1-6 years; 20mg 8 hourly

-225- -226-
 , ':, ,.'::~'", ""','" PRECISE~

Side effects [)rugs used in the treatment of vomiting include:-

•:. Sensitivity to light .:. Increased intraocular pressure .:. Promethazine .:. Chlorpromazine
•:. Tachycardia .:. Flushing .:. Dimenhydrinate .:. Domperidone
•:. Decreased sweating .:. Arrhythmias .:. Metoclopramide .:. Cyclizine
.:. Orthostatic hypotension •:. Thirst .:. Prochlorperazine .:. Granisetron
•:. Blurred vision .:. Cinnarizine .:. Haloperidol
.:. Dry mouth with difficulty in swallowing .:. Meclozine
.:. Urinary hesitancy and retention Key issues to note
.:. Identify and treat cause if possible
Drug Interactions .:. Ensure adequate hydration
.:. Concomitant administration with tricyclic antidepressants
.:. Antiemetics should be prescribed only when the cause of
results into additive anticholinergic effect vomiting is known
8.1.2 DRUGS FOR NAUSEA AND VOMITING .:. Antiemetics are more effective when given prophylactically
than when given to stop vomiting which has already started
Common terms used
.:. They are unnecessary and sometimes harmful especially
Nausea: is a sensation often leading to the urge to vomit.
when the cause can be treated
Vomiting (emesis): is a forceful expulsion of gastric contents through
the mouth. It occurs due to stimulation of the vomiting centre situated
PROMETHAZINE
in the medulla oblongata of the brain.
Available preparations: Tablets 2Smg
Vomiting centre: is the area in the brain that is involved in
Injection 2Smg/ml ,2ml
stimulating the events that lead to nausea and vomiting.
Syrup Smg/Sml
Chemoreceptor trigger zone: is the area in the brain that is involved
with the sensation of nausea and vomiting.
Available brands: Intamine®, Prozin®, Phenergan®
Prokinetic drug: Drugs that increase the activity of gastrointestinal
smooth muscles of the GIT Pharmacokinetics
Antiemetic drug: It is a drug given to relieve nausea and vomiting. Promethazine is well absorbed after oral or intramuscular administration,
widely distributed, metabolized in the liver and excreted in urine and
Vomiting is not a disease but a symptom of underlying disease or
bile.
disorder of GIT. Common causes of vomiting include:-
.:. Drugs~ opioid analgesics and digoxin Indications
.:. Gastrj,intestin~1 disease , .:. Nausea and vomiting .:. Motion sickness
.:. Motion sickness .:. Urticaria and angioedema .:. Allergic rhinitis
.:. Vestibular disorders like migraine headache .:. Vertigo .:. Pruritus in eczema
.:. Early pregnancy (morning sickness) .:. Postoperative emesis
.:. Psychological Contraindications
.:. Infectious diseases
.:. Known hypersensitivity to promethazine
.:. Porphyria

-227- -228-
 :',,' ; ,':':.' , ,'" I " " " PREC PHARfi\T:liIDliI~

.:. Children under 2 years .:. Advise the patient to avoid prolonged exposure to sun light
.:. Severe CNS depression or coma since promethazine may cause photosensitivity reaction
.:. Vomiting of unknown cause .:. Maintain fluid intake
.:. Lactation .:. Avoid alcohol intake
.:. Concomitant therapy with MAOls
CHLORPROMAZINE
Dose
Available preparations: Tablets 25mg, IOOmg
Nausea and vomiting:
Injection IOOmg/2ml
Adult Oral: 25mg repeated every 4-6 hours, max I OOmg daily
1M: 12.5-25mg every 6 hours as needed.
Available brands: Largactil®
Children: 5-12 years 6.25- 12.5 mg
12-16 years 12.5-25mg l:tharmacokinetics
Motion sickness: Chlorpromazine is readily absorbed from the gastrointestinal tract,
Adult: 25mg at bed time or 2 hours before traveling, repeated if undergoes first pass metabolism and is distributed to the body tissues.
needed upto 4 times daily. It is extensively metabolized in the liver and excreted in the urine.
Children:
Indications
5-10 years: I Omg at bed time and following morning if~ssary
.:. Nausea and vomiting due to radiation therapy and
2-5years: 5mg at night and following morning if necejSary ~
chemotherapy
Side effects .:. Acute and chronic schizophrenia
.:. Drowsiness .:. Anorexia .:. Acute mania, as in bipolar disorder
.:. Dry mouth .:. Constipation .:. Anxiety disorders
.:. Sedation .:. Disorientation .:. Intractable hiccup
.:. Urinary retention .:. Hypotension .:. Severe behavioral disturbances in Children
.:. Skin rashes .:. Dizziness .:. Nausea and vomiting of terminal illness
.:. Headache .:. Fatigue Contraindications
.:. Epigastric pain .:. Hypersensitivity to chlorpromazine
Drug Interactions .:. Comatose states
.:. Alcohol and other CNS depressants may increase CNS .:. Severe CNS depression
depressant effects of Promethazine .:. Bone marrow depression
.:. Promethazine may block the anti-Parkinsonian action of .:. Parkinson's disease
levodopa .:. Liver damage
.:. Additive anticholinergic effects with anticholinergic drugs .:. Cerebral or coronary arteriosclerosis

Key issues to note Dose

.:. Inform the patient that promethazine may cause drowsiness Schizophrenia, Mania, Severe anxiety: Initially 25mg 3 times daily
and impair ability to perform activities requiring mental or 75mg at night adjusted according to response. Maintenance dose
alertness 75-300mg daily

-229- -230-

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I , ' " 1 I ' ,I' 'I I " :"" I I : PRECISE PHARMACOLOGY

Intractable hiccup: 25-50mg 3-4 times daily .:. Nausea and vertigo due to Meniere's disease and other
Severe nausea and vomiting: I0-25mg 4 times daily vestibular disturbances
Children: 0.5-1 mg/kg 6 hourly
Deep intramuscular injection: ., Contraindications
.:. History of hypersensitivity to dimenhydrinate
.Adult: 25-50mg every 4-6 hours until vomiting stops.
.:. Porphyria
Children 1-12years: 0.5-1 mg/kg every 6-8 hours
.:. Neonates
Side effects .:. Breast feeding
.:. Drowsiness Blurred vision
.:. Dry mouth Constipation Dose
.:. Slurred speech Urinary retention Motion sickness: 50-1 OOmg given at least 30 minutes before travel
.:. Poor coordination Somnolence Nausea and vomiting: 50-1 OOmg 2-3 times daily
.:. Hypotension Dizziness Children:
7· I2years: 25-50mg 2-3 times daily
Drug Interactions 1·6years: 12.5-25mg 2-3 times daily
.:. Chlorpromazine may reduce the effect of drugs for
Parkinsonism Side effects
•:. Alcohol and other CNS depressants may increa respiratory .
.: Sedation .:. Dry mouth
depression and hypotensive effect of Chlorprom ine .:. Constipation .:. Urinary retention
•:. Lithium may decrease the absorption of Chlorpromazine and .
.: Drowsiness .:. Dizziness
produce adverse neurologic effects .:. Headache .:. Uncoordination
•:. Concurrent use with antihypertensives may result in additive .
.: Blurred vision .:. Hypotension
hypotensive effects .:. Anorexia
Key issues to note Drug Interactions
.:. Administer chlorpromazine with water, food or milk to .:. Additive CNS sedation and depression may occur when
decrease GI upset dimenhydrinate is used concomitantly with other eNS
.:. Inform the patient that chlorpromazine may cause depressants such as alcohol, barbiturates and tranquilizers
drowsiness and impair ability to perform activities requiring Key issues to note
mental alertness .:. Advise the patient to take the drug atleast 30min before
DIMENHYDRINATE travel
Available preparations: Tablets 50mg .:. Inform the patient that dimenhydrinate may cause
Syrup 12.5mg/4ml, 15mg/5ml drowsiness and impair ability to perform activities requiring
mental alertness
Available brands: Gravinate®, Novomin® .:. Avoid alcohol; serious sedation may occur
Indications
.:. Nausea and vomiting PROCHLORPERAZINE
.:. Motion sickness Available preparations: Tablets Smg
Injection 12.Smg/ml
-231- -232-
 , , I, ' '" PRECISE PHAR Y ILLiS_
Available brands: Stemetil® .:. Tricylic antidepressants may increase the anticholinergic and
Indications sedative effects of prochlorperazine
.:. Nausea and vomiting due to migraine
.:. Relief of vertigo due to Meniere's disease Key issues to note
.:. Labyrinthine disorders .:. Inform the patient to aviod driving or operating machinery
.:. Drug-induced nausea and vomiting since this drug causes drowsiness
.:. Administer the drug with food or water and avoid caffeine
Contraindications .:. Advise the patient to avoid exposure to sun light and artificial
.:. Children less than 2 years .:. CNS depression light sources
.:. Hypersensitivity to the drug .:. Liver damage .:. Use lowest posible dose in children to decrease incidence of
.:. Bone marrow depression .:. Pregnancy extra pyramidal reactions
.:. Breast feeding
METOCLOPRAMIDE
Dose
Available preparations: Tablets IOmg
Nausea and vomiting:
Adults: 5-1 Omg 2-3 times daily Injection 5mg/ml, 2ml ampoule
Vertigo:
Available brands: Plasil®, Reglan®, Camet®
Adults: 5mg 3 times daily
Children: Pharmacokinetics
5-12 years: 2.5-5mg repeated if necessary u;;t01.
3 times daily Metoclopramide is rapidly and almost completely absorbed from the
1-5 years: 1.25-2.5mg repeated if necessary up to times daily gastrointestinal tract following oral administration, undergoes hepatic
1M: Adult: 12.5mg repeated if necessary up to 3 imes daily followed first-pass metabolism and widely distributed in the body. It is excreted
by an oral dose In faeces via the bile.
Children:
Indications
5-12 years: 6.25mg repeated if necessary up to 3 times daily
Disorders of decreased gastrointestinal motility such as:-
2-5years: 2.5mg repeated if necessary up to 3 times daily
.:. Dyspepsia
.:. Gastro-oesophageal reflux disease
Side Effects
.
:. Blurred vision .:. Skin reaction
.:. Diabetic gastroparesis
.
:. Drowsiness .:. Dyskinesia
.:. Stimulation of lactation
.
:. Constipation .:. Dry mouth
Nausea and vomiting due to;
.:. Migraine
.:. Blurred vision .:. Hypotension
.:. Following gastric surgery
.:. Cancer therapy or radiotherapy
Drug Interactions
Contraindications
.:. Alcohol and other CNS depressants may increase CNS
.:. Gastro intestinal obstruction
and respiratory depression and hypotensive effects of
.:. Intestinal perforation
prochlorperazine
.:. 3-4days after gastrointestinal surgery

-233- -234-
 "filliiill '1'llIlIIfifhllIMlAIIIW
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" PRECISE PHARMACOLOGY , ' , I, I I , PRECISE PHARMACOLOGY

.:. I-:Iistory of seizure disorders DOMPERIDONE
.:. Phaechromocytoma Available preparations: Tablets 10mg
Suspension smg/ sml
Dose
Available brands: Motilium®, Motil®
Nausea and vomiting:
Adult and Children; more than 60kg: IOmg 3 times daily Indications
9-18years: Smg 3 times daily ( .:. Nausea and vomiting
5-9years: 2.smg 3 times daily .:. Dyspepsia
3-5years: 2mg 2-3 times daily .:. Gastro oesophageal reflux
1-3years: Img 2-3 times daily .:. Gastroparesis ( diabetic or idiopathic)
Neonate: IOOmcg/kg every 6-8hours .:. Stimulation of lactation
II
Stimulation of lactation Contraindications
i 10mg 3 times daily, reduce dose gradually over 7-10 days before .:. Patients allergic to domperidone
i
I stopping. .:. Prolactinoma
Cancer chemotherapy: Initial dose of up to 2 mg/kg by intravenous .:. Hepatic impairment
infusion over atleast 15 minutes may be given in combination with .:. Mechanical bowel obstruction /perforation
I
the dexamethasone before cancer therapy and repeated every 2 or 3 .:. Pregnancy
hours. II, Dose
II Side effects Nausea and vomiting;
il .:. Hyperprolactinaemia .:. Drowsiness Adults and Children over 35kg: 10 - 20mg 3-4 times daily max .
I .:. Tardive dyskinesia .:. Diarrhoea 80mg daily
.:. Oedema .:. Skin rash
.:. Hypotension .:. Depression
Children up to 34kg: 200 - 400mcg/kg every 8 hours.
Below 151<g: not recommended.
.:. Dizziness .:. Pruritus Gastroparesis;
.:. Headache .:. Restlessness Adult; 10 -20mg, 3-4 times daily for up to 6 months. Take at least
.:. Parkinsonism 30minutes before meals.
Drug Interactions Stimulation of lactation.
•:. Metoclopramide reduces absorption of oral digoxin 10mg 3 times daily, taper dos~ over 7-10 days before stopping.
.:. Metoclopramide increases absorption of aspirin, paracetamol Side Effects
and diazepam .:. Drowsiness Galactorrhoea
Key issues to note .:. Gynaecomastia .:. Amenorrhoea
.:. May cause drowsiness, therefore warn the patient not to drive .:. Constipation Skin rashes
I'

or operate machinery that require mental alertness .:. Reduced libido Diarrhoea
lill,I .:. Advise the patient to take th_e drug 30min before meals and at .:. Hyperprolactinaemia Extrapyramidal reactions
bed time .:. Dry mouth Headache

-235- -236-
 , , PRECIS~LOGY:

Drug Interactions '" Drug interactions

.:. Domperidone reduces absorption of digoxin !,";ii;ii'/ii,' .:. Antidepressants, anti-anxiety drugs and opioid analgesics may
.:. Domperidone may reduce the effects of bromocriptine and "" Ii
'I
Iii
';
increase the sedative effects of cinnarizine
cabergoline ,I Ii

.:. Anticholinergic drugs may reduce the beneficial effects of : :1

I
I!:~ECLOZINE
domperidone I' Available preparation: Tablets 25mg

CINNARIZINE Available brands: Pregnidoxin® (meclozine® /caffeine)

Available preparation: Tablets 25mg Vominore® (meclozine/pyodoxine)
Indications
Available brands: Cinnaron®, Stugeron®
.:. Nausea and vomiting associated with pregnancy
Indications .:. Motion sickness
.:. Vestibular disorders such as; Vertigo, tinnitus .:. Vertigo and other vestibular disorders
.:. Nausea and vomiting in Meniere's disease
Contraindications
.:. Motion sickness
.:. Known hypersensitivity to meclozine
Contraindications .:. Breast feeding
.:. Known hypersensitivity to cinnarizine
Dose
.:. Parkinson's disease
Motion sicl<ness:
.:. Children and neonates
Adult: 25 - 50mg taken about one hour before traveling
Dose Children
Vestibular disorders: 6-12 years: 12.5mg once daily
Adult 25mg 3 times daily 2-6 years: 6.25mg once daily
Children: 5-12years 12.5mg 3 times daily Vertigo and vestibular disorders: Up to I OOmg daily in divided
Motion sicl<ness: doses
Adult 25mg 2 hours before traveling then 12.5mg every 8 hours
Side effects
during journey if necessary
.:. Abdominal pain .:. Dry mouth
Children 5-12years: 12.5mg 2hours before traveling then 6.25mg
.:. Headache .:. Fatigue
every 8 hours during journey
.:. Dizziness .:. Increased appetite
Side effects .:. Drowsiness .:. Pharyngitis
.:.Allergic skin reaction .:. Fatigue Drug interactions
.:. .:.
I '~:''I!
Somnolence Gastro-intestinal disturbance .:. Increased toxicity with alcohol and other CNS depressants
.:.Headache .:. Dry mouth
.:.Weight gain .:. Perspiration GRANISETRON
.:.Drowsiness .:. Constipation Available preparations: Tablets I mg
Injection I mg/ml, 3ml

-237- -238-
 PREcmPHARMACQlQCY PREC HARMAC l!ll!1[1

Kytril® .:. Chest pain .:. Dizziness

Available brands:
.:. Agitation .:. Somnolence
.:. Taste disturbance
Mode of action
Granisetron selectively binds to serotonin receptors in the:. Choice of Antiemetics
chemoreceptor trigger zone, blocking the nausea and vomiting caused The choice of drug depends partly on the cause of nausea and
by the release of serotonin by mucosal cells. vomiting.
Indications Type~vomiting Drugs of choice
Prevention and treatment of Nausea and vomiting associated Vomiting during pregnancy Promethazine. prochlorperazine.
with: metodopramide. pyridoxine
.:. Cancer chemotherapy Postoperative nausea and vomiting Prochlorperazine. metoclopromide.
•:. Radio therapy cvdizine.
•:. Postoperative vomiting Motion sickness Hyoscine. promethazine. cinnarizine.
evdizine
tContraindications
f':. Hypersensitivity to granisetron and related compounds Vomitinq due to vestibular disorders Cinnarizine. orochlorDE!razine
:Drug induced nausea and vomiting Cydizine. prochlorperazine
Dose , 'opioids) 1111 "I,Jl Jji
oillt1>
Cancer chemotherapy Cytotoxic drug induced vomiting Prochlorperazine, metodopramide,
Oral ondansetron. cydizine,
Adults: I ~2mg 60min before chemotherapy start off treatment, then Dexamethasone.
2mg once daily for 7 days each cycle.
-
Children 1month-12years: 20mcg/kg (max. Img) within 1hour before 8.1.3 DRUGS FOR HAEMORRHOIDS AND PilES
start off treatment, then 20mcg/kg twice daily for up to 5days Haemorrhoids (Piles)
during treatment. Haemorrhoids are clusters of venous swellings of the tissues around
By intravenous infusion: the anus caused by straining during bowel movements.
Adult They are associated with constipation, diarrhoea and prolonged
IV 3mg 30min before chemotherapy. straining.
Children I month-12years: prevention 40mc:?lkg (max.3mg) before Haemorrhoids may be divided into two:-
start of cytotoxic therapy, then treatment: 40mcg/kg repeated within .:. Internal haemorrhoids
24 hours if necessary. .:. External haemorrhoids
Most preparations for haemorrhoids contain any of the following:
Postoperative vomiting: .:. Astringents e.g. bismuth subgallate, zinc oxide, resorcinol
Adult, prevention IV Img before induction of anaesthesia.
.:. Local anaesthetics e.g. lignocaine. Cinchocaine
.:. Corticosteroids e.g. hydrocortisone
Side effects .:. Lubricants
.:. Constipation .:. Headache
.:. Vasoconstric.tors
.:. Skin rash .:. Hypersensitivity reaction
.:. Antiseptics

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~~~~~ . Side effects
.:. Creams or ointments are used for external haemorrhoids Hypersensitivity reactions such as;
.:. Suppositories are preferred for internal haemorrhoids .:. Redness
.:. Haemorrhoids developing during pregnancy should be .:. Irritation
managed conservatively as most will resolve after delivery
.:. Local anaesthetics are used to relieve pain associated with
.:. Swelling ' .
~EDIPROCT
haemorrhoids
.:. Corticosteroids are used to reduce inflammation where Available preparations: Cream
infection is not present Suppository
eomposition: Hydrocortisone 500mg
In case of infection
Metronidazole 400mg 8hourly for 5 days is used. Cinchocaine 500mg
jndlcations
Surgery may be required in resistant cases.
I'lnemorrhoids associated with inflammation
Commonly used compound preparations .:. Anal fissures
,\1.:. Anusol ointment/suppository .:. Anal pruritus
.:. Preparation-H ointment .:. Proctitis
ft"
.:. Scheriproct ointment/suppository
C:ontraindications
.:. Sediproct ointment/suppository
.:. Pylocaine ointment. .:. Hypersensitivity to any of the active ingredients
l)ose
ANUSOL
Available preparations: Ointment (:,.eam: Apply the cream into the rectum twice daily; at night and
InOming after bowel movement
Suppository
lIluppository: Insert Isupository twice daily, at night and morning
Composition: Bismuth subgallate 59mg
1Iildc effects
Bismuth oxide 24mg
.:. Local irritation
Zinc oxide 296mg
.:. Skin rash
Indications:
.:. Soothe the pain and irritation of haemorrhoids IIlCHERIPROCT
Available preparations: Suppository
Contraindications Ointment
.:. Serious rectal pathology
Composition: Cinchocaine 0.5%
Dose Prednisolone 0.19%
Suppository: Insert I supository at night and morning
IIldlcations:
Ointment: Apply twice daily, at night and morning
.:. Haemorrhoids

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 " PRECISE PHARMACOLOGY :' i' , , ",', "" I,: ," II' i" ,:, PRECISE PHARMACOLOq
Contraindications SULFASALAZINE
.:. Known hypersensitivity to the active ingredients Available preparation: Tablets 500mg
Dose Available brands: Salazopyrin®
Ointment: Apply twice daily for 5-7days, then once daily for a few I~
Indications
days after symptoms have cleared.
.:. Active ulcerative colitis
Suppository: Insert I suppository daily after a bowel movement for
.:. Severe rheumatoid arthritis
5-7days (in severe cases, initially apply 2-3times daily)
.:. Active Crohn's disease
Side effects
.:. Local irritation Contraindications
.:. Skin rash .:. Children less than 2 years
8.1.4 DRUGS FOR INFLAMMATORY BOWEL DISEASE .:. Pregnancy at term and lactation
Inflammatory bowel disease is a chronic non-specific inflammatory .:. Severe hepatic impairment
i condition of the gastro intestinal tract. .:. Severe renal dysfunction
It is divided into two:- .:. Salicylate and sulphonamide hypersensitivity
'I' '.:. Crohn's disease (affects the gut from mouth to anus) Dose
I
.:. Ulcerative colitis (affects only the large bowel) Acute attack
Both Ulcerative colitis and Crohn's disease frequently run a course Adult: 1-2g 4times daily until remission occurs (3weeks), reduced to
characterized by exacerbations and remissions, tend to be chronic in il maintenance dose of 500mg 4times daily
nature, have similar extra intestinal manifestations and may be associated Children over 2years
with a positive family history of inflammatory bowel disease. Acute attack: I 0-15mg /kg 4-6times daily until remission occurs
Drugs used in the treatment of inflammatory bowel disease either Maintenance: 30mg/kg/day in 4 divided doses.
(ontrol symptoms or modify the disease by inducing and maintaining Rheumatoid arthritis:
long term bowel healing. Adult: 500-1 OOOmg/day for I week increased by 0.5g/ week up to 3g
!:t(lr day
Examples:- !liide effects
.:. Aminosalicylates .:. Anorexia .:. Nausea
.:. Corticosteroids .:. Vomiting .:. Headache
.:. Fever .:. Folate deficiency
AMINOSALICYLATES .:. Skin rash .:. Reversible male infertility
This group of drugs include:- .:. Abdominal discomfort
.:. Sulfasalazine
.:. Mesalazine Drug interactions
Aminosalicylates treat mild to modrate inflammatory and they are .:. Sulfasalazine may increase the.effect of anticonvulsants,
equally effective. The choice is based on the location of the disease an< I methotrexate, oral anticoagulants and oral antidiabetic
side effect profile of the individual drugs. .:. Sulfasalazine may decrease the abssorption of digoxin

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1

, " I , PREC PHARMACftlOGY

Key issues to note .:. Lubricant Laxatives
.:. Administer the drug with food to reduce stomach upset .:. Stimulant Laxatives
.:. Do not administer the drug with antacids .:. Osmotic Laxatives
.:. Sulfasalazine impairs absorption of folic acid, therefore
folic acid supplements may be necessary during treatment mUlK FORMING LAXATIVES
Mc)de of action
CORTICOSTEROIDS !r'lll:IY reli.eve ~onstipation by absorbing water thereby increasing feacal
Corticosteroids are used for treatment of both ulcerative colitis anI I lIill1l5 whIch stImulates peristalsis.
Crohn's disease. They are often able to induce the remission of ulcerativ<' Th4~Y are useful for mild constipation, small hard stools, patients with
colitis but have proved less valubale in maintaining remission. hiwmorrhoids, fissure, and irritable bowel disease and as adjunct in
1111 tlrative colitis.

8.1.5 DRUGS FOR CONSTIPATION (LAXATIVES) Atlifquate fluid intake is important to lubricate the colon and minimize
Constipation is a reduced frequency of defaecation characterise( I ~h~\ risk of intestinal obstruction.
by hardening of the stool, straining on defaecation, or a feeling of .: ",~I'l1ples;
incomplete evacuation. .:. Methylcellulose
.:. Wheat bran
Constipation may be caused by any of the following:-
.:. Ispaghula husk
.:. Lack of fluid or fibre intake
.:. Lack of exercise jlWAGHULA HUSK
.:. Pregnancy "''\I~llIable preparations: Granules 3.5g Isachet
.:. Drugs like Aluminium containing antacids, codeine or iron
A'I'llIl1able brands: Fybogel®
.:. Irritable bowel syndrome
.:. Anorectal conditions like haemorrhoids lmllcations
.:. Psychiatric and neurological disorders .:. Constipation especially in diverticular disease and irritable
bowel syndrome
LAXATIVES .:. Constipation follOWing anorectal surgery, haemorrhoids,
Laxatives are drugs that stimulate defaecation by forming bulk, pregnancy
stimulating peristalsis or providing lubrication. They increase till' .:. Management of diarrhoea
frequency of bowel evacuation or passage of softer or bulk stool. .:. Adjusting faecal consistency in patients with colostomies
Laxatives are used in the treatment of constipation and for bowl·1 I I: C::ollt:raindications
evacuation before investigational procedures, s1Jch as endoscopy, \ .:. Difficulty in swallowing
radiological examination, or before surgery. .:. Intestinal obstruction
Classification of Laxatives -:. Colonic atony
.:. Faecal impaction
Laxatives are classified according to their mode of action as follows> .:- Hypersensitivity to any of the ingredients
.:. Bulk Forming Laxatives
.:. Saline Laxatives

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 PRECI~i*Q:r:!MMIIJLlJGY 1
< j II 11
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E
Children:
Dose
Adult: i sachet or 2 level 5ml spoonful in water given morning and 6-12 years: IOml twice daily adjusted according to response.
I- 5 years: 5ml twice daily adjusted according to response.
evening after meals. . .
Children 6-12years: 1/2 - Ilevel 5ml spoonful in water tWIce dally Children less I year: 2.5ml twice daily adjusted according to
Below 6 years: Give on doctor's advice only response.
Hepatic encephalopathy: 30 -45ml 3 times daily, adjust dose to
Side effects produce 2-3 soft stools per day.
•:. Flatulence and abdominal distension during the first few days of
Side Effects
treatment
.:. Gastrointestinal obstruction or impaction .:. Flatulence
.:. Cramps
.:. Hypersensitivity reaction
.:. Diarrhoea '\;
IOSMOTIC LAXATIVES .:. Nausea
IMode of action
IOsmotic Laxatives are poorly absorbed therefore the unabsorbed solute\
II .:. Abdominal discomfort
.:. Vomiting if excess doses are given
in the intestine draw water from the body into the bowel by osmOSl', i
causing bowel distention which in turn increases peristalsis. . Key issues to note
These drugs are used for acute and rapid evacuation of the bowel wltll
<exception of lactulose.
Examples;
.:. Lactulose
I .:. Administer the drug with juice, milk or water to increase
palatability
.:. Do not take other laxatives while on lactulose therapy

l.UBRICANTS AND FAECAL SOFTENERS

.:. Magnesium salts
Mode of action
LACTULOSE I hey promote stool passage by coating the feacal surface with an oil
Available preparations: Syrup 3.350g/5ml Il)yer that retains fecal fluid and prevents absorption of fecal water by
'he colon.
Available brands: Laxolac®, Duphalac ® Sedalac® I' Kilmples;
Indications .:. Glycerol
.:. Constipation .:. Docusate sodium
.:. Hepatic encephalopathy .:. Liquid paraffin
.:. Mineral oil
Contraindications
.:. Intestinal obstruction 1:~I.YCEROL
.:. Known hypersensitivity to lactulose Av.. ilable preparations: Suppositories 'g
.:. Galactosaemia
bldlcations:
Dose .:. Constipation
Constipation:
Adults- 15ml twice daily.

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'I
BISACODYL
Contraindications Available preparations: Tablets Smg
.:. Patients with known hypersensitivity to glycerin
.:. Glycerin suppositories are contraindicated in patients who are t,'
11Il_ Suppository IOmg

recovering from rectal surgery .. Available brands: Dulcolax®

Dose Pharmacokinetics
By rectum Absorption of bisacodyl after oral administration is minimal, absorbed
Adults: 4g suppository moisteined with water before use, once daily drug is metabolised in the liver and excreted in urine, feaces and
when required breast milk.
Children: Indications
1-12years: 2g suppositories as required .:. Constipation .\1
I month _ I year: Ig suppository once daily when required
.:. Bowel evacuation before investigational procedures or
Side effects surgery
,.:., Rectal discomfort .:. Diarrhoea
.:. Rectal mucosal erosion
.:. Dizziness Contraindications

.:. Mild headache

.:. Nausea .:. Intestinal obstruction

.:. Mild hyperglyceamia

.:. Vomiting .:. Appendicitis
.:. Severe dehydration
Drug Interactions . .. .:. Acute inflammatory bowel disease
.:. Concomitant use with diuretics may result In additive effect<, .:. Hypersensitivity to the drug

Key issues to note Pose

.:. One set of action is 5~30 min Constipation
.:. Do not use longer than I week Adults: 5-1 Omg daily administered at night or I Omg as a suppository or
.:. Prolonged or frequent use may result in dependency ~Ilmma administered in the morning.
Children:
STIMULANT LAXATIVES I O·18years: 5-1 Omg at night increased if necessary to max. 20mg
~.I 0 years: 5mg at night
Mode of action
Stimulant laxatives increase peristalsis by directly stimulating nervI' II Children 2-1 Oyears: 5mg in the morning (rectally)
endings in the colonic mucosa, thereby increasing intestinal motility. ..,, Complete bowel evacuation
They are useful for more severe forms of constipation ~ut tolerance I~
common with regular use and they can produce abdominal cramps.
r Adult: I 0-20mg followed by I Omg as a suppository the next morning
C:hlldren 4-1 Oyears: 5mg at bed time for 2 days before procedure
Mild if necessary by suppository IOmg I hour before procedure.
Examples; *lde effects
.:. Bisacodyl .:. Nausea .:. Vomiting
.:. Senna .:. Diarrhoea .:. Faintness
.:. Castor oil .:. Mild cramps .:. Abdominal discomfort
.:. Suppositories may cause irritation and proctitis

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Drug Interactions
PRECISE P'HARMAClUOllfll r_
Side effects
.:. Antacids, Cimetidine, Famotidine, ranitidine, milk and other .:. Hypokalaemia
drugs that increase gastric PH level may cause premature .:. Atonic non-function colon
dissolution of the enteric coating of bisacodyl resulting into .:. Nausea
abdominal cramping. .:. Vomiting
.:. Diarrhoea
Key issues to note
.:. Abdominal cramps
.:. Patients should swallow tablets whole with a glass of water
.:. Do not administer bisacodyl within I hour of ingesting Key issues to note
antacids milk or dairy products .:. Advise the patient to take the drug with plenty of water
.:. Bisacodyl is habit forming, therefore long term use may .:. Avoid prolonged use of more than I week
result in laxative dependency and loss of normal bowel .:. Chronic use may lead to dependency, vitamin and mineral
function deficiency
.:. One set of action is 6-1 2 hours for tablets, IS-60min for
suppository. Warn the patient that prolonged use of bisacodyl SODIUM CITRATE
J suppositories may cause proctitis. Available preparations: liquid enema
Available brands: Micralax®
SENNA
Available preparations: Tablets 7.Smg Indications
.:. Constipation
Available brands: Senokot® (Sennoside B)
.:. Painful defaecation
Indications .:. Bowel evacuation
.:. Acute constipation
Contraindications
.:. Preparation for bowel examination
.:. Gastro intestinal conditions
Contraindications
.:. Patients with inflammatory bowel disease
.:. Undiagnosed abdominal pain
.:. Appendicitis
Dose
.:. Fluid and electrolyte disturbance
.:. Intestinal obstruction
Adults and Children over 3years: 3ml as a single dose
.:. Faecal impaction Side effects
.:. Excessive use may cause diarrhoea and fluid loss
Dose
Constipation:
8.1.6 ANTI DIARRHOEAL DRUGS
Adults: IS-30mg at night
Diarrhoea is frequent passage of watery stools atleast 3 times or more
Children of 6- 12 years: 7.S-ISmg at night
In a ~ay. It
affec~s all age groups and is more severe and life threatening
In chIldren and Immunocompromised patients.

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.' , " " ~PHARMACOUGY
Diarrhoea may be caused by any of the following:-
ANTISECRETORY DRUGS.
.:. Infections Ihcamples
.:. Inflammation
81smuth subsalicylate
.:. Drugs such as antiacids
'I'$Ismuth subsalicylate appears to produce its antidiarrhoel effect by
.:. Maldigestion
, Inhibiting intestinal secretions. It is recommended in the treatment of
Drugs used in the treatment of diarrhoea include:- Infectious diarrhoea such as travellers diarrhoea. It is available in form
•:. Adsorbents I:" tablets and suspension.
.:. Antimotility drugs
.:. Antisecretory compounds 111testinal microflora
•:. Antimicrobials IExample:Lactobacillus.
.:. Intestinal microflora These drugs are intended to replace colonic microflora which
f'lhstores intestinal function and supresses the growth of Pathogenic
Adsorbent drugs
microorganisms.
Examples - Kaolin
,~ "~ - Pectin
l.OPERAMIDE
- Activated charcoal
Available preparations: Capsules 2mg
ADSORBENT DRUGS Tablets 2mg
Adsorbent drugs act by absorbing the toxins produced by the pathogen',
Available brand: Imodium®, Loperium®, Loperax®
thereby reducing GIT motility. These drugs are used for symptomati(
Kamodium®, Gallop®
relief of diarrhoea
They are not recommended for infectous acute diarrhoea and whell
Pharmacoldnetics
the patient is taking other drugs (prevent absorption of other drugs).
About 40% of loperamide is absorbed from the gastrointestinal tract,
ANTI MOTILITY DRUGS undergoes first-pass metabolism in the liver and is excreted in the
Examples:- I'lleces as unchanged drug and small amount in urine.
.:. Loperamide
Indications
.:. Codeine
.:. Acute diarrhoea
.:. Diphenoxylate
.:. Chronic diarrhoea
.:. Traveller's diarrhoea
Antimotility drugs act by reducing GIT motility thereby allowing enougll
time for fluid absorption from gut contents. '
Contraindications
They are recommended in the treatment of acute and chronic diarrhoe;\
.:. Known hypersensitivity to loperamide
in combination with fluid replacement. .:. Infants below 2 years of age
They are not recommended in Children less than 2 years and infectious .:. Abdominal distension
diarrhoea .:. Acute inflammatory bowel disease
.:. Antibiotic associated colitis
.:. Patients who must avoid constipation

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Dose bldlcations
Acute diarrhoea: .:. Diarrhoea
Adult: 4mg start followed by 2mg every after each loose stool until .:. Pain
when diarrhoea is relieved. Max dose 16mg daily
I I
iI'
.:. Cough suppression (lower dosage)
Children: C:ontraindications
9-12 years: 2mg 4 times daily up to 5 days .:. Hypersensitivity to codeine
4-8 years: I mg 3-4 times daily for up to 3 days only .:. Premature infants
Chronic diarrhoea: .:. Conditions where inhibition of peristalsis should be avoided
Adult; 4-8mg daily in 2 divided doses. such as; abdominal distension
Side Effects .:. Ulcerative colitis
.:. Flatulence .:. Abdominal cramps .:. Acute respiratory depression
.:. Blurred vision .:. Dizziness
.:. Drowsiness .:. Nausea and vomiting I)ose
.:. ,~Headache .:. Abdominal bloating Adults: 30- 60mg 3-4 times daily
.:. Fatigue
,I
Urticaria Children: Not recommended
.:. Constipation .:. Toxic mega colon
.:. Dry mouth .:. Paralytic ileus Side effects Sedation
.:. Hypersensitivity reaction .:. Headache Dry mouth
Drug Interactions .:. Constipation Nausea and vomiting
.:. Concomitant use of loperamide with opioid analgesic may .:. Anorexia Respiratory depression
cause severe constipation .:. Abdominal pain Somnolence
Key issues to note .:. Dizziness Decreased urination
.:. Advise the patient to drink plenty of fluids to prevent .:. Hypotension
dehydration Drug Interactions
.:. Do not exceed maximum daily dosage .:. Alcohol, narcotic analgesics, hypnotic and tricyclic
.:. Loperamide may impair ability to perform activities antidepressants may increase CNS or respiratory depression
requiring mental alertness
Key issues to note
.:. Advise the petient to avoid use of alcohol during treatment .:. Administer codeine with water or food to decrease nausea
.:. Loperamide should not be used alone in patients with
and GI upset
dysentery .:. Avoid long term use because of addictive potential
.:. Codeine may cause drowsiness, therefore do not drive or
CODEINE operate machinery
Available preparations: Tablets 30mg
Pharmacokinetics DIPHENOXYLATE
Codeine is absorbed from the gastrointestinal tract, metabolized in the Available preparations: Tablets
liver to morphine and other metabolites. It is excreted in urine. Combinations: Lomotil®(Diphenoxylate/Atropine) 2.5/0.025mg

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lJi
 " , , 'II' I PRECISE PHARMACOLOGY: Em It ELIEU.mia QiljQ~iJQ:r!liIM!'iju'!ld
Pharmacokinetics
Diz~iness or drowsiness may Ocur , therefore advise the
Diphenoxylate is well absorbed from the gastrointestinal tract, rapidly patient not to drive or operate machinery
and extensively metabolized in the liver to diphenoxylic acid which has
antidiarrhoeal activity. It's excreted mainly as metabolites in the faeces; GASTROINTESTINAL ANTISEPTICS
lesser amounts are excreted in urine. This class inc/udes:-
Indications .:. Paromomycin (aminosidine)
.;. Acute and chronic diarrhoea .:. Nifuroxazide
.:. Control of faecal consistence after colostomy
NIFUROXAZIDE
Contraindications Available preparations: Capsules 200mg
.:. Avoid in patients with jaundice
Suspension 220mg/Sml
.:. Intestinal obstruction Available brands: Diastat®, Antinaf®
.:. Diarrhoea associated with enterotoxin producing bacteria
Dose Pharmacokinetics
Adult: Initially 4 tablets followed by 2 tablets every 6 hours until : lillli/I'Il.:. Nifuroxazide is poorly absorbed from the gastrointestinal tract and
diarrhO'ea is controlled 1'11\
i r: ~'
locally Within the GIT as an intestinal antiseptic for intestinal infecti~~~s
Children:
13-16 years: 2 tablets 3 times daily Indications
10-12 years: I tablet 4 times daily .:. Acute and chronic bacterial diarrhoea
4-9 years: I tablet 3 times daily .:. Gastroenteritis
Below 4years: Not recommended .:. Acute and chronic colitis
.:. Travelers'diarrhoea
Side effects
.:. Anorexia .:. Urticaria Dose
.:. Headache .:. Depression Adult: 200mg 4 times daily
.:. Nausea and vomiting .:. Dizziness Children:
.:. Toxic mega-colon .:. Dry mouth Over Iyear: Sml 4 times daily
.:. Abdominal distension ~rnonths- Iyear: Sml 3 times daily
.:. Pruritus .1~low 2months: Sm/ twice daily
Drug Interactions . Iide effects
.:. It may potentiate the effect of other CNS depressants such
alcohol, barbiturates
;J\ I .:. Well tolerated
ttAROMOMYCIN
Key issue to note Available preparations: Tablets 2S0mg
.:. Atropine is added to diphenoxylate to discourage misuse Syrup ,2Smg/5mf
.:. Prolonged use is not recommended
AVOlilable brands: Gabbroral®

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Indications
• 5--'=~_ PRECISE PIfJJ]MACOLOGY I

.:. Intestinal amoebiasis .:. Giardiasis BISMUTH SUBSALICYLATE

.:. Balantidiasis .:. Taeniasis
Available preparations: Tablets
.:. Cryptosporidiosis .:. Acute enteritis
Suspension
.:. Prophylactic treatment of hepatic coma
.:. Sterilization of the gut before intestinal surgery Available brands: Peptobismol®, Bismol®
Contraindications Indications
.:. Known hypersensitivity to aminosidine .:. Indigestion
.:. Nausea
Dose .:. Control of diarrhoea
Intestinal amoebiasis, giardiasis, balantidiasis: .:. Traveler's diarrhoea
Adult: 500mg twice a day for 5-7days .:. Chronic infantile diarhoea
Children: 30mg/kg/day in 2 divided doses for 5-7days .:. Adjuactive treatment of Helicobacter pylori infection
Cryptosporidiosis:
Contraindications
Adult: 500mg 4 times a day for 14days
.:. Known hypersensitivity to any of the ingredients
Prophylactic treatment of hepatic coma:
.:. Children below 3 years
Adult: Ig twice a day for 6days
Children: 25mg/kg twice a day for 6days Dose
Sterilization of the gut before intestinal surgery: Adult: 2 tablets or 30ml
Adult: 2g daily for 3days Children:
Children: 25mg/kg twice a day for 3 days 9.12years Itablet or 15ml
Gastro enteritis and enterocolitis due to mixed flora, salmonellosis 6·9years 10mi
and shigellosis: 3.6years 5ml
Adult: 500mg twice a day for 5-7days Note: Repeat doses every 30-1 hour as needed up-to 8doses in a day
Children: 15mg/kg twice daily for 5-7days
Side effects
.:. Gray-black stool
Side effects .:. Confusion
.:. Nausea .:. Headache
.:. Diarrhoea .:. Mental depression
.:. Abdominal discomfort .:. Loss of hearing
Key issues to note Drug interactions
.:. Paromomycin may be given with or after food .:. Aspirin may increase the side effects of the bismuth
.:. It may cause malabsorption of sucrose and fats subsalicylate
.:. It may result into overgrowth of nonsusceptible organisms .:. Bismuth may decrease GI absorption and bioavailability of
tetracyclines reducing their efficacy

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Key issues to note . . . oRLI STAT

.:. Advise the patient to chew the tablet or allow It to dissolve m Available preparations: Capsule 120mg
the mouth before swallowing
.:. Advise the patient to stop using the drug if diarrhoea doe..s not Available brands: Xenical®
improve within 2 days or worsen . .
Mode of action
.:. Advise the patient to shake the suspension well before usmg It
Inhibits lipases in the lumen of the stomach and small intestin
preventing absorption of dietary fat.
8.1.7 PROKINETIC DRUGS
Indications
These drugs increase the tone and motility of the Gastrointestinal
.:. Obesity in adults with body mass index> 30 or > 27 with
tract.
other risk factors such as; hypertension , Diabetes.
Example~:
.:. Metoclopramide Contraindications
.:. Domperidone .:. Chronic malabsorption syndrome
·:·I~Cisapride .:. Breast feeding

Prok~et drugs are used in the treatment of gastroesophageal .:. Cholestasis

reflux disease chemotherapy-induced nausea and vomiting, diabetic Dose

gastroparesis. Adults and children above 12 years: 120mg 3 times with each
meal.
Metoclopramide is used for suppressing nausea and vomiting
Side effects
caused by anticancer drug such as cisplatin, dacarbazin~,. to
.:. Flatulence .:. Faecal urgency
suppress postoperative vomiting, emesis caused by radiation U'
.:. Faecal incontinence .:. Abdominal distension
therapy, toxins and opioids. It is also used in the treatment of
.:. Headache .:. Fatigue
diabetic gastroparesis and suppression of gastrosophageal reflux.
.:. Anxiety
8.1.8 DRUGS FOR OBESITY
Drug interactions
Obesity is associated with a wide range of conditions such as;
.:. Orlistat may decrease absorption of fat soluble vitamins
.:. Diabetes mellitus
.:. Hypertension
Key issue to note
.:. Hyperlipidaemia
.:. If a meal does not contain fats, the dose may be omitted
.:. Supplements with fat soluble vitamin, Vitamin D and beta-
Abdominal fat with increased waist circumference 'is associated with
'carotene
increased health risk and may be an indicator for complications of
obesity.
Drugs used include:-
.:. Orlistat

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 ',. ::_rppr p]Ecl~i.Q:m:IMcreo[OGYI , " I I ',': "'''', ii, ,: ' 'I PRECISE PHARMAC

Short acting beta2 agonists such as salbutamol and Terbutaline have a

I GY

rapid onset and short duration of action. They are recommended for
the treatment of acute attack of asthma.
CHAPTER NINE Long acting beta2 agonist such as salmeterol and formoterol have a
", delayed onset and long duration of action. These drugs are usually
- DRUGS ACTING ON THE RESPIRATORY SYSTEM combined with inhaled corticostiroid such as budesonide for the long
term control of chronic asthma
Drugs used in the treatment of respiratory tract disorders include;
.:. Drugs for Asthma
SALBUTAMOL
.:. Drugs for allergic rhinitis
Available preparations: Inhaler IOOmcg
.:. Drugs for cough
.:. Drugs for common cold and flu Nebulized solution Smg/Sml
Syrup 2mg/Sml
Tablets 4mg
9.1.1 DRUGS USED IN THE TREATMENT OF ASTHMA
. r"~
Asthma is a chronic disease of the air way characterised by inflammation Available brands: Ventolin®, Vental®, Kamvent®
and reversible bronchospam. It is associated with symptoms such as
Pharmacokinetics
wheezing, breathlesness, chest tighness and cough.
Salbutamol is readily absorbed from the gastrointestinal tract,
Drugs used in the treatment of Asthma are broadly divided into 2:- metabolised in the liver, rapidly excreted in the urine as metabolites
.:. Bronchodilators and as unchanged drug and a small amount is excreted in the faeces
.:. Anti inflammatory drugs.
indications
.:. Prophylaxis and treatment of asthma
Classification of anti asthmatic drugs
.:. Chronic obstructive pulmonary disease
Class Examples .:. Arrest premature labour
Bronchodilators Beta2 agonists
Xanthine derivatives Contraindications
Anticholiner~ic .:. Hypersensitivity to Salbutamol
Anti-inflammatory drugs Corticosteroids .:. Eclampsia and severe preclampsia
Mast cell stabilizers
Leukotriene receptor antagonists Dose
Oral
Adults: 4mg 3-4 times daily, max. single dose 8mg
BETA2 AGONISTS Children:
Beta2 agonists promote bronchodilation by stimulating beta2 receptors 7- 12 years: 2mg 3-4 times
in bronchial smooth muscles. They are further divided into 2 namely 2 - 6 years: 1-2 mg 3-4 times daily
shorting acting and long acting beta2 agonists. Imonth- 2 years: IOOmcg /kg 3-4 times daily

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 ,, , " ' , ' ,,' ': , ,"" 1,\: ' ,,' PRECISE PHARMACOLOGY

Aerosol inhalation Contraindications

Adult: 100-200 mcg (1-2 puffs, for persistent symptoms up to 4 times .:. Known hypersensitivity to any of the ingredients
daily)
Dose
Children: 100mcg (I puff) increased to 200mcg (2 puffs) if nece~sary,
By inhalation of powder: 1-2puffs twice daily, increased if necessary
~ for persistent symptoms up to 4 times daily.
::0 max. 4puffs twice daily, reduced to I puff once daily if control is
Nebulized solution
maintained
Children: > 2 years 2.5 - smg, repeat 3 - 4 times daily as necessary
Children 12-17years: 1-2 puffs twice daily, reduced to I puff once
< 2 years 0.1 mg/kg up to 2.smg repeat 3-4 times daily.
daily if control is maintained
Prophylaxis in exercise induced bronchospasm:
Under 12years: not recommended
Adult: 200-400mcg (2puffs) .
COPD: 2puffs twice daily
Children: I00-200mcg up to 4times daily
'Side effects
Side effects .:. Hoarseness .:. Candidiasis of mouth and throat
.:. Tachycardia .:. Palpitations .:. Tremor .:. Palpitations
,~r

·:·illtArrhythmias .:. Insomnia .:. Headache .:. Muscle cramps

.:. Ii(, Nervousness .:. Muscle cramps .:. Sleep disturbance .:. Hypersensitivity
.:. Angioedema .:. Headache .:. Skin reaction
.:. Fine tremor especially of hands
Key issues to note
.:. Hypersensitivity reactions
.:. Patients should not be initiated on symbicort during an
Drug interactions exacerbation or if they have significantly worsening asthma
.:. Diuretics or digoxin risk of cardiac arrhythmias is increased .:. Once asthma symptoms are controlled, consider reducing
.:. Corticosteroids, risk of hypokalaemia and hyperglycaemia are the dose gradually
increased
XANTHINES
Key issues to note l(anthiilesinc:lude:-
.:. Salbutamol may delay labour in pregnant mothers near term
.:. Aminophylline
FORMOTEROL .:. Theophylline odcrN' "'-e f
Available preparation: Dry powder for inhalation ~(JI'i0tPt,..('!...rfyi,· ,k
(combination preparation) They act by relaxing bronchial smooth muscle by inhibiting p...... \i 1'( ''',: C<J~"
phosphodiesterase, the enzyme which breaks down cyclic AMP. 4
Available brands: Symbicort® (Budesonide 160mcg, Aminophylline is usually preferred to theophylline when greater
formoteroI4.smcg) solubiUty in water is required, particularly in intravenous formulations
Indications AMINOPHYLLINE
.:. Prophylaxis of asthma Available preparations: Tablets 100mg
.:. Chronic asthma Injection 2s0mg/ I Oml
.:. Chronic obstructive pulmonary disease

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 , ,," " ,,', ' ",' PRECISE PHARMACOLOGY

Indications .:. Smoking may decrease aminophylline blood concentration

.:. Acute severe asthma .:. Caffeine may intensify the adverse effects of aminophylline on
.:. Reversible airway obstruction the CNS and heart
.:. Relieve apnoea in neonates Key issues to note
.:. Nocturnal asthma .:. Rapid IV injection should be avoided as it may result into
hypotension, seizures and arrhythmias (less than 20-25mg/
Contraindications min) is required .
•:. Porphyria
.:. Patients taking oral aminophylline should not receive
.:. Known hypersensitivity to aminophylline
intravenous aminophylline unless plasma concentration is
Dose available to guide dosage
Chronic asthma .:. Patients should avoid caffeine-containing beverages and other
. Oral: 100-200mg 3-4times daily, after food sources of caffeine
Acute severe asthma not treated with Theophylline before
CORTICOSTEROIDS
Adult: IV loading dose 5 - 6mg/kg slowly over 20 - 30 min diluted in
Corticosteroids may be given parenterally, orally or as inhalers
normal saline or dextrose 5%.
Inhaled corticosteroids include:-
Maintainance: IV Infusion 0.5mg/kg/hour.
.:. Beclomethasone
Children: IV loading dose 4-6mg/kg slowly over 20-30mins suitably
.:. Budesonide
diluted and 1.5 -2.5 mg per kg in those using oral theophylline.
.:. Fluticasone
Maintenance: By IV infusion
6months - 9yrs: I mg/kg/hour These drugs are the most effective in the treatment of chronic asthma.
10 - 16 years: 0.8mg/kg/hour. Corticosteroids reduce bronchial mucosal inflammation and bronchial
hyper-reactivity.
Side effects They are recommended for the prophylaxis of asthma in patients who
.:. Restlessness
have not responded to beta2 agonist or if symptoms disturb sleep more
.:. Anxiety Tremor
than once a week.
.:. Palpitations Headache
Corticosteroid inhalers must be used regularly for effective control of
.:. Insomnia Dizziness
symptoms.
.:. Convulsions Arrhythmias
Alleviation of symptoms usually occurs after 7days of initiating
.:. Urticaria Epigastric pain
treatment.
•:. Gastrointestinal irritation
.:. Hypotension especially if given by rapid injection
BECLOMETASONE
Drug interactions Available preparations: Metered Inhaler 50 mcg
.:. Beta blockers may decrease the effects of aminophylline
.:. Cimetidine, ciprofloxacin, erythromycin, norfloxacin may Available brands: Becotide®, Beclate®
increase aminophylline blood concentratio~ and risk of
Indications
aminophylline toxicity
.:. Prop~ylaxis of asthma
.:. Phenytoin, rifampicin, carbamazepine may increase
aminophylline metabolism

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Side effects
' 8 PRECiSE PHARMACOLOGY I
Contraindications
.:. Status asthmatics .:. Hoarseness
.:. Hypersensitivity to beclometasone .:. Candidiasis of mouth and throat
.:. Acute infections uncontrolled by antimicrobial chemotherapy .:. Mild irritation in the throat
.:. Coughing
Dose
Adult: 200mcg twice daily or 100mcg 3-4 times daily .:. Infection in the oropharynx
Children: 50-100 mcg 2-4 times daily or I OOmcg twice daily .:. Contact dermatitis
.:. Urticaria
Side effects
.:.. Oropharyngeal candidiasis SYSTEMIC CORTICOSTEROIDS
.:. Hoarseness These drugs are given either orally or by injection
.:. Paradoxical bronchospasm Examples:-
.:. Adrenal suppression .:. Prednisolone /prednisone .:. Hydrocortisone
.:. Impaired bone metabolism .:. Betamethasone .:. Dexamethasone
.:. Glaucoma and cataract .:. Triamcinolone .:. Methylprednisolone

BUDESONIDE ~mllllllllllllllllll
Available preparations: Turbuhaler (Dry power for inhalation) Class Examples
100mg/dose, 200mg/dose, 400mg/dose
Short acting Hydrocortisone
Available brands: Pulmicort ®
Intermediate- Prednisolone 4
Indications
acting Prednisone 4
.:. Prophylaxis of asthma
.:. Childhood croup
Methylprednisolone 5
Triamcinolone 5
Contraindications Long-acting Dexamethasone 30
.:. Hypersensitivity to Budesonide Betamethasone 25
.:. Active pulmonary tuberculosis
Dose
Adult and children over 12 years: 200mcg twice daily adjusted as PREDNISOLONE
necessary. May be reduced to 200mcg daily in well controlled asthma. Available preparations: Tablets 5mg
Mild to moderate asthma: 200-400mcg as a single dose each
Available brands: Kampred®
evening ;>lI'

Children over 6 years: 100- 400 mcg twice daily Indications

Mild to moderate asthma: 200-400mcg as a single dose each .:. Bronchial Asthma
evening .:. Cerebral oedema
.:. Allergic reactions

-269- -270-
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.:. Acute leukaemia .:. Advise the patient not to decrease dose or discontinue
.:. Rheumatic disease without doctor's approval
.:. Inflammatory bowel disease
.:. Suppression of inflammatory reactions DEXAMETHASONE
.:. Acute or chronic adrenal insufficiency Available preparations: Tablets O.5mg
Injection 4mg/ml
Contraindications
.:. Systemic infection (unless life threatening) Available brands: Dexona®
-I
Ii .:. Avoid live virus vaccines
II
Pharmacoldnetics
II
.:. Hypersensitivity to prednisolone
II Dexamethasone is readily absorbed from the gastrointestinal tract,
1'1
Dose ,r' crosses the placenta with minimal inactivation and excreted in urine
I' Initially: 10-20mg daily (up to 60mg in severe diseases) preferably
taken in the morning after breakfast, and often be reduced within a
within 24 hours.
ml Indications
few days but may need to be continued for several weeks or months.
Maintenance 2.5 -15mg daily but higher doses may be needed
.:. Cerebral oedema
Children
.:. Rheumatic diseases
I - 6 years: 5mg daily up to 15mg in severe cases
.:. Anaphylaxis
7-12 years: 5-IOmg. daily up to 30mg in severe cases
.:. Septic shock !~
.:. Nausea and vomiting due to anti cancer drugs
Side effects .:. Bacterial meningitis (in combination with antibiotics).
.:. Dyspepsia Peptic ulcer .:. Acute exacerbation of chronic allergic disorders Ir
•:. Osteoporosis Increased appetite
Contraindications
.:. Glaucoma .:. Acne
.:. Hypersensitivity to dexamethasone
•:. Skin atrophy
•:. Weight gain
.:. Adrenal suppression
Striae
.:. Systemic infections
.:. Menstrual irregularities
.:. Avoid live virus vaccines
Drug interactions Dose
.:. Prednisolone may decrease the effect of diuretics, insulin, oral II Oral
antidiabetics and potassium supplements Adult: 0.5 - 2mg daily but higher doses may be required depending on
.:. Prednisolone may increase the risk of digoxin toxicity caused the severity of the condition.
by hypokalaemia Children: 10-1 OOmcg /kg daily in 1-2divided doses
.:. Prednisolone may decrease the patient's anti-body's response Injection: 1M or slow IV or infusion
to vaccines Adult: 0.5-24mg daily
Children: 200-400mcg /kg daily in 1-2divided doses
Key issues to note
Cerebral oedema associated with malignancy:
.:. Take the drug after meals, with food or milk to decrease Gi
IV injection (as dexamethasone phosphate): initially IOmg then
upset
4mg by 1M every 6 hours for 2-4days gradually reduced and stopped
.:. Advise the patient to avoid alcohol, limit caffeine
over 5-7days.

-271- -272-
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1I1. . . . 1.
Children: IV O.2Smg/kg/day in divided doses for up to 2 days then Contraindications
gradually taper down over the next 5 days. .:. Hypersensitivity to betamethasone
Side effects .:. Systemic fungal or acute infection
.:. Hypertension Increased appetite
Dose
.:. Hyperglyceamia Muscle atrophy
Tablets: O.S-Smg daily, reduced to lowest effective dose when
.:. Oedema Cataracts
possible
.:. Glaucoma Peptic ulcer
By 1M injection or slow IV: 4-20mg repeated up to 4 times in 24
.:. Weight gain Hypokalaemia
hours
.:. Growth suppression in children
Depot (diprofos): 1-2ml deep 1M, frequency of administration will
Drug interactions depend on the severity of the patient's condition
.:. Increased risk of hypokalaemia when used concurrently with
Side effects
amphotericin B or loop diuretics .:. Muscle wasting .:. Osteoporosis
.:. Concurrent use with aspirin may lead to increased gastro .:. Increased appetite .:. Delayed wound healing
,llintestinal tract side effects .:. Striae .:. Acne
.:. Menstrual irregularities .:. Hypopigmentation
Key issues to note
.:. Headache .:. Diabetes mellitus
.:. Administer the drug with food or milk to minimmise GI
.:. Gastrointestinal disturbance and bleeding
side effects
.:. Growth retardation in Children (prolonged use)
.:. Advise the patient to avoid alcohol and limit caffeine intake
.:. Advise the patient to avoid exposure to measles or chicken Drug interactions
pox .:. Betamethasone may alter insulin requirements and effects of
.:. Inform the patient not to decrease dose or stop treatment antidiabetic drugs and oral anticoagulants
without doctor's recommendation .:. Anticonvulsants may reduce the effects of Betamethasone
.:. Increased hyperglycaemia and hypokalaemia may occur when
BETAMETHASONE
Betamethasone is given together with thiazide diuretics
Available preparations: Injection
Tablets O.Smg HYDROCORTISONE
Available preparations: Injection IOOmg
Available brands: Diprofos injection®
Available brands: Cardilan®, Primacort®, Stricort®
Indications Indications
.:. Rheumatoid arthritis .:. Osteoarthritis .:. Hypersensitivity reactions including anaphylaxis
.:. Lumbago .:. Sciatica .:. Inflammatory bowel disease
.:. Contact dermatitis .:. Cystic acne .:. Asthmatic attack
.:. Ulcerative colitis .:. Ganglion cyst .:. Haemorrhoids
.:. Bronchial asthma .:. Allergic bronchitis .:. Rheumatic diseases
.:. Allergic rhinitis .:. Drug reactions .:. Adrenocortical insufficiency
.:. Atopic dermatitis .:. Keloids

-273- -274-

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.:. Angioedema
, '" , " , , ''', PREC PHARMACOLOGY
w_
Indications
PREClsEI~HARMACO[OGY I

1'1

Contraindications
-. .:. Rheumatoid arthritis
I!I
.:. Systemic infections .:. Steven's Johnson syndrome
"I
.:. Avoid live virus vaccines in those receiving immuno suppressive .:. Bronchial asthma
'II
doses .:. Allergic rhinitis
II
,I .:. Hypersensitivity to hydrocortisone .:. Drug hypersensitivity reaction
II
.:. Ulcerative colitis
Dose .:. Crohn's disease
Anaphylaxis; acute severe asthma and shock: .:. Keloids
1M Islow IV injection or infusion .:. Osteoarthritis
Adult: I 00-500mg 3-4 times daily .:. Cerebral oedema associated with malignancy
Children: By slow IV injection:
6-12years: I OOmg 3-4 times daily Contraindications
I-Syears: 50mg 3-4 times daily .:. Hypersensitivity to methylprednisolone
Up to Iyear: 25mg 3-4 times daily .:. Systemic infection
.:. Intra thecal route
Side effects Dose
.:. Dyspepsia Peptic ulceration By deep 1M (Depo-medrol): 40-120mg every 2-3 weeks if
.:. Adrenal suppression Menstrual irregularities IH:lCessary.
•:. Weight gain Increased appetite Intra-articular injection into soft tissue: 4-80mg according to the
.:. Glaucoma .:. Acne ~Ize of the affected joint
.:. Nausea Malaise Graft rejection: Up to Ig daily by IV infusion for 3 days

Drug interactions Side effects

.:. Anti convulsants, Rifampicin reduce the effectiveness of .:. Dyspepsia
hydrocortisone .:. Peptic ulceration
.:. Hydrocortisone reduces the action of antidiabetic drugs .:. Abdominal distention
.:. Hydrocortisone reduces the effect of antihypertensive drugs .:. Hypertension
.:. Hydrocortisone may decrease the patient's antibody response .:. Sodium and water retention
.:. Menstrual irregularities
to vaccines, increase vaccine side effects and potentiate virus ! i
replication when given with live virus vaccine .:. Depression
.:. Growth suppression in infancy and childhood

METHYLPREDNISOLONE Drug interactions

Available preparations: Injection 40mg, 500mg .:. Rifampicin, carbamazepine, phenobarbitone and phenytoin
:,
i enhance the metabolism of corticosteroids and therapeutic
Available brands: Solu-medrol®, effects may be reduced
Depo-medrol®

-275- -276-

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.:. Estrogens and oral contraceptives enhance the effects of .:. Estrogens and oral contraceptives enhance the effects of
methylprednisolone triamcinolone
.:. Concurrent use with NSAIDs increases the risk of GI .:. Triamcinolone may increase the elimination of salicylates
.:. Concurrent use with NSAIDs increases the risk of GI
ulceration
ulceration
Key issues to note Key issues to note
.:. Do not give live virus vaccines to patients on prolonged .:. Do not give live virus vaccines to patients on prolonged
systemic therapy systemic therapy
.:. Avoid abrupt withdrawal of therapy following high- .:. Avoid abrupt withdrawal of therapy following high-dose or
dose or long term therapy long term therapy

TRIAMCINOLONE LEUKOTRIENE RECEPTOR ANTAGONISTS

Available preparations: Injection 40mg This class includes:
.:. Zafirlukast
Available brands: Triamdenk®
l .:. Montelukast
Indications These drugs act by suppressing the effects of leukotrienes,
.:. Suppression of inflammatory and allergic disorders compounds that promote bronchoconstriction as well as eosinophil
.:. Rheumatic diseases infiltration, mucus production and air way oedema
.:. Keloids
ZAFIRLUKAST
.:. Alopecia areata
Available preparations: Tablets 20mg
Contraindications
Available brands: Accolate®
.:. Hypersensitivity to any of the ingredients
.:. Systemic infections Pharmacokinetics
.:. Administration by IV, intrathecal or intraocular injection Zafirlukast is rapidly absorbed after oral administration, extensively
metabolised in the liver and excreted in feaces.
Dose
By deep 1M injection: 40mg into gluteal muscle for depot effects Indications
repeated according to patient response. .:. Prophylaxis of asthma
.:. Exercise-induced asthma
Side effects
.:. Anaphylactic reactions " Contraindications
.:. Increased susceptibility and severity of infection .:. Hypersensitivity to zafirlukast
.:. Sodium and fluid retention ' .:. Breast feeding
.:. Impaired wound healing .:. Hepatic impairment
.:. Euphoria Dose
.:. Menstrual irregularities and amenorrhoea Adult: 20mg twice daily atleast I hour before or 2 hours after meals
Drug interactions Children under 12 years: Not recommended
.:. Barbiturates and carbamazepine reduce serum
concentrations of triamcinolone

-277- -278-

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Dose
Side effects Adult and Children over 15 years: IOmg daily in the evening
Nausea
.:. Headache Children:
.:. Diarrhoea Fever
6 years -14 years: Smg daily in the evening
Malaise
.:. Insomnia 6 months -5 years: 4mg daily in the evening
Vomiting
.:. Dyspepsia Side effects
.:. Abdominal pain
.:. Dizziness .:. Headache .:. Abdominal pain
Drug interactions .. .:. Cough Thirst
.:. Blood levels are increased by aspIrin . .:. Dry mouth Diarrhoea
.:. Blood levels are decreased by erythromycin and .:. Dyspepsia Nausea and vomiting
theophylline . with .:. Oedema Palpitation
.:. Zafirlukast increases effects and risk of bleeding .:. Dizziness Fatigue
.:. Dental pain
warfarin
.:. Hyperkinesia in young Children
Key issues to note f I
.:. Give the drug atleast I hour before or 2 hours a ter a mea. Drug interactions
.:. Advise the patient to take the drug as prescribed even dUring .:. Rifampicin, Phenobarbital may decrease the duration of
symptom free periods action of montelukast.
.:. Do not used the drug to treat acute episodes of asthma .:. Prednisone may decrease the biovailability of montelukast
.:. Advise the patient not to decrease the dose or stop unless Key issues to note
instructed by the doctor .:. Administer the drug in the everning without regard to meals
.:. Nursing women should not take zafirlukast . al .:. Advise the patient to take the drug regularly even during
.:. Inform the patient to report symptom~ such as abdomln symptom free periods
pain, nausea, fatigue, itching or anorexia .:. Do not use the drug to treat acute episodes of asthma
MONTELUKAST
Available preparations: Tablets Smg 9.1.2 DRUGS FOR ALLERGIC RHINITIS
Rhinitis is an inflammation of the nasal mucous membrane and is
Pharmacokinetics . b r d characterised by periods of nasal discharge, sneezing, and nasal
Montelukast is rapidly absorbed from GI tract extensively meta 0 Ise
l:ongestion.
in the liver and excreted in feaces. Rhinitis may be allergic or non- allergic in origin
Indications Allergic rhinitis
.:. Prophylaxis of Asthma Allergic rhinitis is defined as a nasal mucous membrane inflammation
.:. Allergic rhinitis <:aused by a hypersensitivity response to foreign allergens mediated by
.:. Prevention of exercise induced bronchospasm
IgE antibodies.
Contraindications Drugs used in the treatment of allergic rhinitis include;
.:. Acute asthma attack .:. Antihistamines
.:. Hepatic impairment .:. Decongestants
.:. Hypersensitivity to Montelukast
-280-
-279-

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.:. Corticosteroids lmllcations

.:. Mast cell stabilisers .:. Conjunctivitis .:. Acute urticaria
.:. Allergic rhinitis .:. Insect stings
ANTIHISTAMINES .:. Pruritus of allergic origin .:. Severe angioedema
Antihistamines are the mainstay in the treatment of seasonal <lll<t
(::ontraindications
perennial allergic rhinitis. They relieve symptoms such as rhinorrho(·.l,
.:. Hypersensitivity to chlorpheniramine
oedema, nasal itching, sneezing and occular symptoms such ."
.:. Acute attack of asthma .:. Third trimester of pregnancy
conjuctivitis.
.:. Breast feeding .:. Narrow-angle glaucoma
They are more effective when taken before the start of symptoms
l:)ose
Classiffication of antihistamines lay mouth,
Antihistamines are classified as follows: Adult and Children over 12 years: 4mg every 4 - 6 hours
.:. Sedating antihistamines Children:
.:. Non sedating antistamines 6 ·-12 years: 2mg every 3-4 times daily
(!II
1.5years: I mg 3 times daily
SEDATING ANTIHISTAMINES 6 months -12months: I mg twice daily
They are also called first generation antihistamines. Sedatin!-:
Side effects
antihistamines cross the blood brain barrier and are associated witll .:. Drowsiness .:. Dizziness
marked sedation and depression. .:. Epigastric pain .:. Headache
Examples:- .:. Palpitations .:. CNS depression
.:. Chlorpheniramine ..
.:. Urinary retention .:. Dry mouth
•:. Hydroxyzine
.:. Blurred vision .:. Sweating & tremor
•:. Promethazine,
.:. Cyproheptadine Drug interactions
.:. Chlorpheniramine potentiates sedative effects of barbiturates,
CHLORPHENIRAMINE hypnotics, opioid analgesics
Available preparations: Tablets 4mg .:. Increased sedative effects with alcohol
Syrup 2mg / Sml
I<ey issues to note
.:. Advise the patient to take the drug after food to minimise GI
Available brands: Piriton®, Piton®
distress
.:. Inform the patient that chlorpheniramine may cause
Pharmacokinetics
drowsiness and impair ability to to perform activities requiring
Chlorpheniramine is well absorbed following oral administration,
mental alertness
distibuted to body tissues, including the placenta. It is metabolized in
.:. Advise the patient to avoid direct exposure to sunlight since
the liver and excreted in urine.
it may cause severe sunburn
.:. Avoid alcohol while taking this drug

-281- -282-
 QitCISE PHARMACOLOGY] PRECISE PHARl'illOOLfJGY
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.:. Skin rash Dry mouth

HYDROXYZINE
Available preparations: Tablets 25mg, 50mg .:. Urinary retention Constipation
Syrup IOmg / Sml .:. Nausea Bitter taste
Drug interactions
Available brands: Atarax® . .:. Alcohol and other CNS depressants may increase CNS
IfJharmacokinetics depressant effects when given concurrently with hydroxyzine
Hydroxyzine is well absorbed when taken orally ,metabolised in the .:. Additive anticholinergic effect with other drugs possessing
liver and excreted primarily in urine. anticholinergic properties such as haloperidol, phenothiazines
i!
Key issues to note
Indications
.:. Hydroxyzine may be administered with or without meals
.:. Pruritus
.:. It may cause drowsiness and impair ability to perform
.:. Anxiety
activities that require mental allertness
.:. Urticaria
.:. Advise the patient to avoid alcohol intake during treatment
.:. Nausea and vomiting
.:. Pre-operative sedation
.:. Adjunct to opioid analgesia in the management of cancer PROMETHAZINE
Available preparation: Tablets 25mg
Contraindications Syrup IOmg / 5ml
.:. Pregnancy Injection 25mglml
.:. Hypersensitivity to hydroxyzine
.:. Breast feeding Available brands: Phenergan®, Intamine®, Prozine®
.:. Neonates
Pharmacokinetics
IDose promethazine is well absorbed from the GIT, Widely distributed in the
IPruritus: body, enters the brain and crosses the placenta. It is metabolized in
j~dult: 25mg at night increased if necessary to 25mg 3 - 4 times daily. the liver and slowly excreted in urine and feaces.
Children:
!Over 6 years: Initially 15 -.25mg at night, increased if necessary Indications
to 50 - IOOmg daily in 3-4 divided doses. .:. Nausea and Vomiting
6months-6 years: Initially 5 - 15mg at night, increased if necessary .:. Motion sickness
to 50mg daily in 3A divided doses. .:. Rhinitis
.:. Urticaria
Below 6 months: Not recommended.
.:. Insomnia
Anxiety:
.:. Emergency treatment of anaphylactic reaction
.Adult: 25-1 OOmg 4 times daily
Pre-operative sedation: 50-1 OOmg 3-4times daily
Contraindications
Side effects .:. Known hypersensitivity to promethazine
.:. Sedation Dizziness .:. Severe CNS depression
.:. Drowsiness .:. Weakness .:. Comatose patients

-283- -284-

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.:. Acute asthmatic attacks CYPROHEPTADINE
.:. Neonates (pre-mature infants) Available preparations: Tablets 4mg
.:. Children less than 2years Syrup 2mg / 5ml
Dose Available brands: Periactin®, Uniactin®,
By mouth Oraxin®, Toractin®
Adult: 25mg at night increased to 25mg twice daily if necessary
Children Pharmacokinetis
6- 10 years: 5-1 Omg twice daily or 10 - 25mg at night ~yproheptad~ne i.s rapi~ly absorbed from the GIT, distributed to body
2 - 5 years: 5mg twice daily or 5 - 15 mg at night tissues and flUids, including the placenta and breast milk. It is metabolized
< 2 years: Not recommended In the liver and excreted in urine.
Motion sickness: 25mg at bed time or night before traveling Indications
By deep intramuscular injection .:. Urticaria
Adult: 25 - 50mg, max 100mg .:. Allergic rhinitis
Children: 5 - 10years: 6.25 - 12.5 mg .:. Angioedema
Side effects .:. Allergic conjunctivitis
.:. Sedation .:. Confusion .:. Pruritus
.
:. Restlessness .: . Tremor .:. Migraine (vascular cluster headache)
.:. Depression .:. Convulsion .:. Stimulates appetite in under weight patients
.:. Drowsiness .:. Dizziness
Contraindications
.:. Hypotension .:. Anorexia
.:. Constipation .:. Dry mouth .:. Patients with known hypersensitivity to cyproheptadine
.
:. Urinary retention .: . Headache .:. Patients experiencing asthmatic attack
.:. Blurred vision .:. Neonates
.:. Thickening of bronchial secretion .:. Third trimester of pregnancy
.:. Narrow angle glaucoma
Drug interactions
.:. Concurrent use with MAO inhibitors may result in increased Dose
sedation and anticholinergic side effects Allergy:
.:. Additive CNS depression with alcohol and other CNS Adult: 4mg 3 - 4 times daily max. 32mg daily
depressants Children
7- 14 yrs: 4mg 2 - 3 times daily max 16mg daily.
Key issues to note
2 - 6 yrs: 2mg 2 - 3 times daily max. 12mg daily
.:. Promethazine may be given with food, milk or water to
Under 2 years: Not recommended
decrease GI distress
Migraine: 4mg with a further 4mg after 30 min if necessary,
.:. May cause drowsiness and impair ability to perform work
II I' maintenance 4mg every 4 - 6 hours
which need mental allertness or physical coordination
.:. Coffee or tea may help reduce drowsiness Side effects
.:. Patients should avoid alcohol during therapy .:. Sedation Drowsiness
.:. Dizziness Muscle weakness
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 , , '
," , I" I PREC PHARMACIJLIiIGY ", " " PRECISE PHARMAcm:IiM'JI
.:. Headache .:. Hypotension Indications
.:. Epigastric distress .:. Fatigue Ii
Ii: Symptomatic relief of allergy such as
.:. Appetite stimulation .:. Tremo )I'
.:. Allergic rhinitis
.:. Ataxia .:. Dry mouth
.,
'II ii'
.:. Allergic conjunctivitis
.:. Constipation .:. Urinary retention 1
.:. Atopic dermatitis
.:. Weight gain .:. Blurred vision
IIIIII1II
.:. Chronic Urticaria
.:. Dry throat
Contraindications
.:. Hypersensitivity to cetirizine
Drug interactions
.:. .Breast feeding
.:. Alcohol and other CNS depressants may increase CNS
.:. Pregnancy
depressant effects
.:. Acute attacks of asthma
.:. Cyproheptadine may decrease the effects of fluoxetine

Key issues to note Dose

.:. Cyproheptadine may be given without regard to meals Adult and Children over 6 years: IOmg daily or Smg twice daily
.:. Avoid alcohol while taking the drug Children
2 - 5 years: Smg once daily or 2.Smg twice daily
NON-SEDATING ANTIHISTAMINE 6 months-Iyear: 2.Smg once daily
Non sedating anthistamines are less sedating than the first generation.
Examples Side effects
.:. Cetirizine ...
.:. Somnolence .:. Insomnia
.:. Loratadine .....
.:. Headache .:. Dizziness
.:. Desloratadine
.:. Dry mouth .:. Abdominal pain
.:. Levocetrizine
.:. Nausea and vomiting .:. Diarrhoea
.:. Ebastine.
.:. Bronchospasm .:. Pharyngitis
.:. Malaise
CETIRIZINE
Available preparations: Tablets I Omg Drug interactions
Syrup Smg ISml .:. Alcohol and other CNS depressants may increase CNS
depression
Available brands: Zyrtec®, Finallergy®, Zyncet®
Allercet®, Alerid® Key issues to note
.:. The drug can be given without regard to food
Pharmacokinetics .:. Cetirizine may cause drowsiness and impair ability
Cetirizine is rapidly and almost completely absorbed from the GIT, II
:1
to perform activities requiring mental alertness
undergoes slow first pass metabolism and is excreted in urine primarily Ii .:. Cetirizine may cause dry mouth therefore advise the
I
as un changed drug. patient to drink alot or to use sugarless gum
.:. Avoid alcohol while taking cetirizine

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It
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LORATADINE .:. Advise the patient to drink plenty of water since it

Available preparations: Tablets IOmg may cause dry mouth
Syrup Smg I Sml .:. Advise the patient to avoid exposure t sunlight since it
may cause severe sun burn
Available brands: Claritin®, Loridin® DESLORATADINE
Mosedin®, Ezede® Available preparation: Tablets smg
Pharmacokinetics Syrup 2.smg Isml
Loratadine is rapidly absorbed from GIT, distributed to the liver, lungs Available brands: Aerius®
GI tract, is metabolised in the liver to active metabolite and excreted
in urine and feaces. Pharmacokenetics
Oesloratadine is rapidly and almost completely absorbed from the GI
Indications tract, distributed in the liver, lungs and breast milk, metabolised in the
Symptomatic relief of allergy such as liver to active metabolites and excreted via urine and feaces.
.:. Allergic rhinitis
Indications
.:.", Chronic urticaria
.:. Symptomatic relief of allergy
,lJij • •
Contraindlcatlons .:. Allergic rhinitis
.:. Hypersensitivity to Loratadine .:. Urticaria
.:. Breast feeding
Contraindications
.:. Pregnancy
.:. Hypersensitivity to Loratadine
Dose .:. Pregnancy
Adult and Children over 6 years: I Omg once daily .:. Breast feeding
Children: 2-6 years: Smg once daily .:. Neonates
Dose
Side effects
Adult and Children over 12years: Smg once daily
.:. Dry mouth .:. Dizziness
.:. Headache .:. Nausea
Children:
1-6 years: 1.2smg once daily
.:. Fatigue .:. Somnolence
6-12 years: 2.smg once daily
.:. GI upset .:. Photosensitivity
.:. Skin rash .:. Weight gain Side effects
.:. Headache .:. Fatigue
Drug interactions .:. Somnolence .:. Dizziness
.:. Clarithromycin, erythromycin, fluconazole, ketoconazole, .:. Nausea .:. Dyspepsia
cimetidine, and fluoxetine may increase the blood levels and .:. Myalgia
effect of loratatine
Drug interactions
Key issues to note .:. C1arithromycin, erythromycin, fluconazole, ketoconazole,
.:. Loratadine may be taken on an empty stomach or cimetidine, and fluoxetine may increase the blood levels and
before meals effect of desloratatine

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 'EP UiliWSE P,HARMACOLOGf] ,,' 1" :,,',' ,,,' ,: I.': "~II: ,;: I, 1,1 ",,:' PRECISE PHAR

.:. It may cause drowsiness and impair ability to perform

Key issues to note . . activities that may require mental alertness
.:. Advise the patient to drink plenty of water Since It may cause
EBASTINE
dry mouth
.:. Desoloratadine may be administered without regard to m~als Available preparations: Tablet IOmg
.:. Advise the patient to avoid alcohol during treatment Available brands: Ebast®
Indications
LEVOCETIRIZINE
Symptomatic relief of;
Available preparations: Tablet Smg
Syrup 2.Smg / Sml .:. Allergic rhinitis
.:. Urticaria
Available brands: Xyzal®, Levosine®
Contraindications
Pharmacokenatics
Levocetirizine is well absorbed from the GI tract distributed to the .:. Hypersensitivity to ebastine
body tissues, under goes limited hepatic metabolism and excreted un .:. Neonates
.:. Urinary / GIT obstruction
changed in urine and feaces.
Dose
Indications Adult: IOmg once daily
.:. Allergic rhinitis
Children > 6yrs: Smg once daily
.:. Urticaria
Side effects
Contraindications .:. Headache
.:. Hypersensitivity to the levocetirizine .:. Dry mouth
.:. Drowsiness .:. Pharyngitis
.:. Breast feeding .:. Nausea .:. Abdominal pain
.:. Severe renal impairment .:. Insomnia .:. Epistaxis
.:. Dyspepsia
Dose Drug interactions
Adults and Children over 6 years: 5mg once daily .:. Concomitant use of ketoconazole, itraconazole,
Children: 2-5 years 2.5mg once daily c1arithromycin or erythromycin increases the plasma level of
Side effects ebastine and cause QTc interval prolongation
.:. Somnolence
.:. Fatigue Key issues to note
.:. Rhinitis
.:. Dry mouth .:. Avoid alcohol while taking the drug
.:. Migraine .:. Take the drug with plenty of fluids
Drug interactions
.:. Alcohol may increase CNS depression LORATADINE AND PSEUDOEPHEDRINE
Available preparations: Repetabs tablets (Ioratadine Smg
Key issues to note pseudoephedrine I20mg)
.:. Levocetirizine may be administered without regard to meals
in the evening
-292-
-291-
 ': ,:'," ,:'

Available brands:
, " ,,', ,,: ' I I" "'; ': ,',';,'" ': 'I;: ,'''', ,'i'

Clarinase®, Mosedin plus®

PRECISE PHARMACOLIGY
•
Available brands: Cirrus®
Indications
Indications
Relief of symptoms associated with allergic rhinitis and common cold
Relief of symptoms associated with allergic rhinitis such as;
such as:-
.:. Nasal congestion .:. Sneezing
.:. Nasal congestion
.:. Rhinorrhea .:. Nasal itching
.:. Sneezing
.:. Ocular itching
.:. Rhinorrhea
.:. Pruritus Contraindications
.:. Lacrimation .:. Patients with known hypersensitivity to any of the ingredients
.:. Severe hypertension
Contraindications .:. Patients with urinary retention
.:. Known hypersensitivity to any of the ingredients .:. Patients with increased intraocular pressure
.:. Narrow angle glaucoma
.:. Urinary retention Dose
•:. Severe hypertension Adult and Children over 12years: I capsule twice daily for a max.
.:. Severe coronary artery disease of 3weeks
.:. Hyperthyroidism Side effects
.:. Dry mouth Headache
Dose .:. Insomnia Somnolence
Adult and Children over 12years: I capsule/tablet twice daily .:. Tachycardia Nervousness
.:. Dizziness .:. Vertigo
Side effects .:. Nausea
.:. Insomnia .:. Dry mouth Drug interactions
.:. Nervousness .:. Dizziness .:. Antacids increase the rate of pseudoephedrine absorption
.:. Fatigue .:. Nausea .:. Kaoline decreases the absorption of pseudoephedrine
.:. Abdominal distress .:. Anorexia
.:. Tachycardia .:. Decreased libido BETAMETHASONE AND DEXCHLORPHENIRAMINE
.:. Tremor .:. Postural hypotension ~vailable preparations: Tablets Betamethasone O.2Smg and
I
I'
,
.:. Increased sweating Dexchlorpheniramine 2mg.
Drug interactions ,
.:. Antacids increase the rate of pseudoephedrine absorption Available brands: Celestamine®

CETIRIZINE AND PSEUDOEPHEDRINE Indications

Available preparations: Capsules (cetirizine Smg + .:. Severe allergic rhinitis
pseudoephedrine 120mg) .:. Bronchial asthma
.:. Atopic dermatitis
.:. Contact dermatitis

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 , ':' ' , , I , PRECISE PHARMACOLOGY p#B~nPHARMACOLOGY I
.:. Drug reactions 'Topical decongestants relieve congestion within a very short time
IIIII .:. Serum sickness nnd are also associated with fewer side effects compared to oral
.:.Allergic conjunctivitis decongestants.Topical decongestants are applied directly to swollen
•:. Keratitis nasal mucosa via drops or sprays.
Prolonged use of topical drugs more than 7 days can result in rebound
Contraindications congestion. Oral decongestants take time to relieve congestion but the
•:. Known hypersensitivity to any of the ingredients effects last longer than topical decongestants.
.:. Patients with systemic fungal infections
~xamples of Decongestants
.:. Premature infants
~
...o pical decon~estants Oral decon~estants
Ephedrine Ephedrine
Dose ....
Adult and Children over 12years: 1-2tablets 4 times daily after Xylometazoline Pseudoephedrine
meals max. 8tablets per day Phenyleph ri ne
I.Children 6.12years: 1;'2 tablet 3 times a day max. 4 tablets per day
EPHEDRINE
Side effects Available preparations: Nasal drops 0.5%, 1%
.:. Sedation Dizziness
Available brands: Isoryn® , Ivyfrin®
.:. Disturbed coordination Epigastric distress
.:. Dry mouth Sodium retention Indications
.:. Fluid retention Hypertension Relief of nasal congestion associated with;
.:. Muscle weakness Peptic ulcer .:. Allergic rhinitis
.:. Skin atrophy Impaired wound healing .:. Common cold
.:. Menstrual irregularities .:. Sinusitis
.:. Thickening of bronchial secretions
Contraindications
Drug interactions
.:. Infants less than 6months
.:. Concurrent use of Phenobarbital, phenytoin, rifampicin may
enhance the metabolism of corticosteroids reducing their Dose
therapeutic effects 1-2 drops into each nostril up to 4 times daily for a max. of 7 days

DECONGESTANTS
Side effects
These are drugs that reduce swelling of the mucus membrane and I;
.:. Local irritation .:. Nausea
suppress the production of mucus helping to clear blocked nasal passage I'i .:. Headache .:. Anxiety
and sinuses. .:. Restlessness .:. Insomnia
They are divided into two:- .:. Tremor .:. Dry mouth
.:. Topical decongestants
.:. Burning sensation .:. Stinging
.:. Oral decongestants
.:. Rebound congestion with prolonged use

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 ", ," " " , ", ,'" ...,;r.CISE PHARMACOLOGY
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Key issues to note Key issues to note

.:. It may cause wakefulness or nervousness therefore take oral .:. Use of the drug should be restricted to a few days only
preparations atleast 4 hours before bed time .:. For therapy of longer duration, systemic decongestants are
.:. Do not use nasal drops for more than 7 days to avoid rebourH I preferred to topical agents
congestion
.:. Do not use the drug in infants less than 6 months, as rebound
OXYMETAZOLINE
congestion may cause difficulty in breathing
Available preparations: Nasal drops

XYLOMETAZOLINE Available Brands: Sinarest®

Available preparations: Nasal drops Indications
Available brands: Otrivin®, Xylomepha® Relief of nasal congestion associated with
.:. Acute and chronic rhinitis
Indications .:. Common cold
Symptomatic relief of nasal congestion associated with;
.:. Sinusitis
.:. Allergic rhinitis .:. Other allergies
.:. Common cold
.:. Sinusitis
Contraindications
.:. To facilitate intranasal examination
.:. Known allergy to oxymetazoline
Contraindications
.:. Glaucoma Dose
.:. Hypertension Nasal drop 0.05% apply 1-2 drops into each nostril 3 times a day for
.:. Diabetes mellitus S days
.:. Hyperthyroidism Side effects
.:. Difficulty in urination secondary to prostate enlargement .:. Hypertension Dizziness
.:. Palpitations Insomnia
Dose .:. Nervousness Anxiety
2-3drops of 0.1 % into each nostril 2-3times daily, when required. .:. Nausea and vomiting Headache
Max. duration 7days
Children over 3 months: 1-2 drops of 0.05% (paediatric nasal drops) Key issues to note
into each nostril 1-2 times daily .:. Use the drug for not more than 5 days since it may result in
severe rebound congestion on prolonged use.
Side effects
.:. Local stinging .:. Burning INTRANASAL CORTICOSTEROIDS
.:. Sneezing .:. Headache Intranasal corticosteroids are highly effective, safe and well tolerated
.:. Nausea .:. Palpitations In the treatment of allergic rhinitis. They relieve symptoms such as
•:. Insomnia .:. Dryness of mouth and throat itching, sneezing, rhinorrhoea and nasal congestion .
.:. Rebound congestion on prolonged use Corticosteroids are first-line treatment for the prophylaxis of

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Example Indications
.:. Beclomethasone .:. Allergic rhinitis
.:. Mometasone furoate .:. Nasal polyps
.:. Fluticasone
Contraindications
.:. Budesonide
.:. Hypersensitivity to any of the ingredients
.:. Presence of untreated localized infection involving the nasal
BECLOMETHASONE
mucosa
Available preparations: Nasal spray(SOmcg/metered spray)
Dose
Available brands: Beconase®, Beclate® Allergic rhinitis
Adult and Children over 12years: I OOmcg (2sprays) into each nostril
Indications
once daily, increased if necessary to a max of 200mcg into each nostril
.:. Allergic rhinitis
once daily
.:. Vasomotor rhinitis
When control of symptoms is achieved reduce to SOmcg into each
Contraindications nostril once daily.
'+:. Hypersensitivity to any of the components Children 6-1 I years: SOmcg (I spray) into each nostril once daily
Dose Nasal polyps:
Adult and Children over 6years: I OOmcg (2sprays) into each nostril Adult over 18years: IOOmcg into each nostril once daily, increased if
twice daily. Max. 400mcg daily. Dose may be reduced to I spray twice necessary after S-6weeks to I OOmcg into each nostril twice daily
daily when symptoms are controlled.
Side effects
Side effects .:. Headache .:. Epistaxis
.:. Unpleasant taste Unpleasant smell .:. Pharyngitis .:. Nasal burning
.:. Epistaxis Glaucoma .:. Nasal irritation .:. Nasal ulceration
.:. Skin rash Urticaria
.:. Oedema of the lips Key issues to note
.:. Dryness and irritation of the nose and throat .:. Shake well before use
.:. Clear nasal passage by blowing nostrils before use
Key issues to note
FLUTICASONE
.:. Shake the container of the nasal spray well before use
.:. Gently blow the nostrils to clear nasal passage
Available preparations: Nasal spray
before administration Available brands: Flixonase®
.:. Advise the patient not to spray in the eye
Indications
.:. Allergic rhinitis
MOMETASONE FUROATE .:. Nasal polyps
Available Preparations: Nasal spray (SOmcg/metered spray)
Contraindications
Available brands: Nasonex® .:. Hypersensitivity to any of the ingredients

-299- -300-
 , " ": ': '" 'i:,::"" ,PRECISE PHARMACOLOGY PRECISE IQ:rMMlJBrllrlijl

Dose .:. Angioedema

Rhinitis: IOOmcg (2sprays) into each nostril once daily preferably in the. .:. Dryness of the nose and throat
morning increased to twice daily (max) if required. Reduce to SOmq: .:. Ulceration of mucous membrane
into each nostril once symptoms are controlled
Nasal polyps: 200mcg into each nostril once or twice daily. Considt!l MAST CELL STABILISERS
alternative treatment if no improvement after 4-6weeks These drugs prevent the release of inflammatory mediators (e.g.
hl5tamine) from sensitized mast cells in response to exposure to an
Side effects
Hllergen by stabilizing mast cells membranes, thus preventing the physical
.:. Local irritation
~ymptoms of allergies. Mast cell stabilizers are used for prophylaxis
.:. Nasal bleeding
! c>f allergic rhinitis especially in Children. These drugs include; sodium
.:. Headache i 'II" f.l'Omoglycate
ii:
.:. Dryness of the nose and throat
BUDESONIDE SODIUM CROMOGLYCATE
Available preparations: Nasal spray 64mcg/metered spray Available preparations: Nasal Spray
Available brands: Rhinocort aqua ® Nasal drops 2%, 4%
Available brands: Nasotal®
Indications
.:. Allergic rhinitis Indications
.:. Vasomotor rhinitis .:. Prophylaxis of allergic rhinitis
.:. Nasal polyps
Contraindications:
Contraindications .:. Known hypersensitivity to the drug
.:. Hypersensitivity to any of the ingredients
Dose
Dose Adult and Children: Ispray into each nostril 4-6times a day
Rhinitis
Side effects
Adult and Children over 12years: 128mcg (2 sprays) into earl I
Sodium cromoglycate is well tolerated but rare side effects include;
nostril once daily in the morning or 64mcg into each nostril twice daily.
.:. Irritation of nasal mucosa
Reduce to 64mcg (I spray) into each nostril once daily once symptom',
.:. Sneezing
are controlled.
.:. Headache'
Nasal polyps:
.:. Nose bleeding
Adult and Children over 12years: 64mcg (I spray) into each nostl II
twice daily up to 3 months
9.1.3 DRUGS USED IN THE TREATMENT OF COUGH
Side effects Cough is a useful natural response to irritation of the lungs and airway
.:. Sneezing ;Iimed that removing foreign substance or excessive secretions. Cough
.:. Nasal stinging may occur as a symptom of an underlying disorder such as asthma,
.:. Skin rash pneumonia, sinusitis or gastro oesophageal reflux disease.

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 III 17 7 PRECID PHARMA'COW'

It may be classified as follows:

Mucolytic expectorants
Mucolytics reduce the viscosity of bronchial secretions by breaking
.:. Non-productive cough down the structure of tenacious sputum there by facilitating its removal
.:. Productive cough by coughing. Mucolytics are often used in chronic bronchitis and chronic
IlSthma where sputum production is high.
Productive cough Examples:-
Productive cough is characterized by the presence of sputum and .:. Bromhexine
may be associated with conditions such as chronic bronchitis, asthm:I, .:. Carbocisteine
.:. Ambroxol
pneumonia.
It's commonly treated with cough expectorants or mucolytics
Common compound preparations containing mucolytics include;
.:. Rhinathiol syrup®
Non productive cough
This type of cough is associated with no mucus production and i:<o .:. Brozedex®
regarded as a useless cough. It is commonly associated with commOl1 .:. Ascoril®
.:. Bisolvin®
cold. it
Non productive cough is treated with cough suppressants or .:. Ambrodil®
antitussives. Demulcents
Demulcent cough preparations coat the mucosa of the pharynx and
Cough expectorants
Cough expectorant is s drug that facilitates the expulsion of mucus J)rovide short lived relief of the irritation that provokes the cough
and other materials from the lungs. reflex
Cough expectorants contain one or more of the following:- 'They contain soothing substances such as:-
.:. Guaifenesin .:. Ammonium chloride .:. Glycerol
.:. Ipecacuanha .:. Squil .:. Honey
.:. Volatile oils .:. Guaicol .:. Liquorice
'I .:. Iodides .:. Sodium citrate .:. Sucrose syrup
.:. Creosote Compound preparations containing demulcents include:-
.:. Simple linctus
Preparations which contain cough expectorants include;
.:. Menthodex lozenges
.:. Cadistin syrup®
.:. Zecuf lozenges
.:. Cadiphen syrup®
.:. Histalin syrup® Cough suppressants
.:. Hydrylin syrup® Cough suppressants act centrally to reduce the sensitivity of the cough
.:. Delased chesty® centre. They should be avoided in chronic obstructive airway diseases
.:. Actified expectorant® as they may also depress respiration. Most cough suppressants are
.:. Menthodex syrup® opiate derivatives and may cause con~tipation and abuse. They should
.:. Zecuf herbal syrup® be avoided in Children below one year. -- ~'''''''_

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 PRECISE PHARMACilLOGY a 7 PRECISE Al!;!iUJli!aI]LOGY I
Cough suppressants include:-
.:. Codeine
.:. Pholcodine CHAPTER TEN
.:. Dextromethorphan
DRUGS USED IN THE TREATMENT OF CARDIOVASCULAR
Pholcodine and dextromethorphan are considered to have DISORDERS
fewer adverse effects than codeine
These drugs are used in the treatment of conditions such as:-
Compound preparations containing cough suppressants include:- .:. Hypertension
.:. Benyllin with codeine® .:. Angina pectoris
.:. Benyllin DM® .:. Heart failure
.:. Rhinathiol dry cough® .:. Hyperlipidaemia
.:. Piritex with codeine® .:. Arrhythmias
.:. Hydryllin DM®
.:. Piritex Junior® 10.1.1 DRUGS USED IN THE TREATMENT OF
.:. Actified syrup® HYPERTENSION
.:. Delased dry cough® HYPERTENSION
.:. Zedex® Hypertension is the persistent elevation of blood pressure higher than
normal (140/90mmHg).

Common terms used in hypertension

Blood pressure: This is the pressure of blood against the walls of the
main arteries
Diastolic blood pressure: This is the pressure exerted in the vessel
when the ventricles are relaxing and refilling.
Systolic pressure: This is the pressure exerted in the vessels when
the ventricles are contracting.

Orthostatic hypotension (postural hypotension): This is the

decrease in blood pressure that occurs when a person stands erect.

Peripheral vascular resistance: This is the pressure that blood must

overcome as it flows in the vessel.
Isolated sytolic hypertension. It is defined as systolic blood pressure
greater than or equal to 140mmHg with diastolic blood pressure less
than 90mmHg. It is common in elderly patients.

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 , PRE PHARMACOLOGY 7
Malignant hypertension. It is a rapidly progressing, potentially fad 'rreatment is directed at elimination of the cause
form of hypertension with diastolic pressure exceeding 120mmHg.
Management of hypertension
Non-pharmacological measures
Hypertensive emergency. It is characterised by severe elevatioll
.:. Encourage regular exercise e.g. walking, jogging
in blood pressure > 180/ 120mmHg complicated by target organ
.:. Advise the patient to lose weight (If over weight)
dysfunction. These situations require immediate reduction of Blood
.:. Advise the patient to limit alcohol intake
Pressure to limit target organ damage.
.:. Advise the patient to restrict salt intake
.:. Advise the patient to stop smoking
Hypertensive urgency. It is a situation with severe elevation of blood
.:. Encourage diet high in fruits and vegetables
pressure without target organ dysfunction.
.:. Advise the patient to relax and manage stress
.:. Diet should be low in saturated fats and cholesterol
Stages of hypertension
Note; non-pharmacological measures may be employed alone in
I)re-hypertension or in combination with drugs in mild to severe
< I 30 < 80 Norma: hypertension.
130-139 81-89 High normal (pre-hypertension) Drugs used in the treatment of hypertension may be classified as
140-15';1 90-99 Mild hypertension (stage I) follows:-
160-179 100-109 Moderate hy ertenslon (stage 2) .:. Beta blockers .:. Calcium channel blockers
18C-20S I 10-l19 Severe hypertensior (sta e 3) .:. ACE inhibitors .:. Angiotensin II antagonist
> 209 > I 19 Very severe hypertension (stage 4 .:. Alpha II blockers .:. Direct Vasodilators
Classification of hypertension .:. Diuretics
Hypertension may be classified as:- .:. Centrally acting antihypertensives
.:. Essential (Primary) hypertension
.:. Secondary hypertension ..
Choice of antihypertensives in different conditions
Essential hypertension
C.. oncomitant disease Drugs recommended
Diabetes mellitus Calcium channel blockers, ACE inhibitors
Essential hypertension is the most common type of hypertension
C.ongestive heart failure Diuretics, ACE inhibitors
contributing to over 90% of the cases of hypertension encountered in
Angina pectoris Beta blockers, calcium channel blockers, ACE
medical practice. The cause of essential hypertension is not known. ,
.. inhibitors and diuretics as alternative
Secondary hypertension Asthma, chronic Calcium channel blockers, diuretics and ACE
Secondary hypertension is an elevation of blood pressure due to 311 P..ulmonary disease inhibitors
identifiable cause such as; H.iyperlipidaemia ACE inhibitors; calcium channel blockers
.:. Renal disease previous myocardial Beta blockers, calcium channel blockers, ACE
.:. Drugs like oral contraceptives nfarction inhibitors and diuretics
.:. Pre-eclampsia chronic renal disease Diuretics, calcium channel blockers, beta blockers
.:. Renovascular disease and ACE inhibitors

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 , , ,PRECISE PHARMACOLOGY qp]le
BETA BLOCKERS Contraindications
These drugs are recommended in the treatment of hypertensioll .:. Hypersensitivity to Atenolol
angina pectoris and in post myocardial infarction. .:. Sinus bradycardia
Beta blockers are classified as follows: .:. Second and third degree Heart block
Non Selective beta blockers .:. Symptomatic heart failure
.:. Propranolol
.:. Sotalol Dose
S~lective beta. I blockers
Hypertension: 25 - 100mg once daily (I OOmg is only slightly better
.:. Atenolol than 50mg)
.:. Bisoprolol Angina: IOOmg once daily or 50mg twice daily
.:. Metoprolol Arrhythmias: 50 - IOOmg daily
Alpha and beta blockers Migraine prophylaxis: 50-1 OOmg daily
.:. Carvedilol
.:. Labetalol Side Effects
Mode of action
.:. Fatigue .:. Hypotension
Beta blockers competitively block response to beta receptors resulting
.:. Impotence .:. Muscle ache
in a decrease in heart rate and heart contractility thereby lowering
.:. Dizziness .:. WheeZing.
blood pressure.
.:. Insomnia
ATENOLOL Drug interactions
,Available preparations: Tablets 25mg, 50mg, 100mg .:. Cimetidine may increase atenolol blood concentration
.:. Diuretics and other antihypertensives may increase hypotensive
Available brands: Tenormin®, Totamol®, Velorin® effect of atenolol
Atelor®, Betagard®, Cardinol®, Tensimin®. .:. Atenolol may mask the symptoms of hypoglycaemia and prolong
hypoglycaemic effect of insulin and oral hypoglycaemics
Combinations: Tenoret® (Atenolol/Chlorthalidone) 50/12.5mg
.:. NSAIDs may decrease antihypertensive effects of Atenolol
Tenoretic® (Atenolol/Chlorthalidone) 100/25mg .:. Alcohol enhances hypotensive effect of atenolol
Pharmacokinetics .:. Concurrent use with digoxin increases the risk of AV block and
About half of the dose is absorbed following oral administration, crosses bradycardia
the placenta and is distributed into breast milk. Atenolol undergoes .:. Oral contraceptives antagonize the hypotensive effect of
little or no hepatic metabolism and is excreted unchanged in the urine. atenoloi
.:. Concurrent use with verapam!1 results in severe hypotension
Indications and heart failure
.:. Hypertension
.:. Angina pectoris Key issues to note
.:. Cardiac arrhythmias .:. Atenolol should be used with caution in patients
.:. Prophylaxis in migraine with diabetes since it may mask symptoms of hypoglycaemia
.:. Acute myocardial infarction

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II'II
H 00 PlillS ~i I g:';';J~"~tBI]"Jt\l
Q:!#Ufl PHARMACOLOGY I
.:. Atenolol may be administered with or without food
.:. Abrupt withdrawal of the drug should be avoided Le. it Mlgrain~ pro~hylaxis and essential tremors: Initially 40mg 2-3
i .~mes dally;. Maintenance: 80 - 160mg daily. I
should be discontinued over 1-2 weeks through gradual
reduction of the dose ~ ,rophylaxls ~fter ~yocardial infarction: 40mg 4 times daily for 2-3
dl"ys.80mg twIce dally beginning 5-21 days after infarction.
PROPRANOLOL Al1)(Iety 40~g once daily. Increase to 40mg 3 times daily if neccessary.
Available preparations: Tablets 40mg, 80mg Arrthyt(lmlas and Thyrotoxicosis I0-40mg 3-4 times daily
ftllde Effects
Available brands: Inderal® .:. Fatigue
.:. Nausea Sleep disturbance
Pharmacokinetics .:. Vomiting
.:. Diarrhoea
Propranolol is almost completely absorbed from the gastrointestin;11 Constipation
.:. Headache
tract, but first-pass metabolism results in low bio-availability. Cold extremities
.:. Bradycardia
It crosses the blood-brain barrier and the placenta, and is distribute! I Hypotension
.:. Heart failure
into breast milk. It is metabolised in the liver and excreted in urine and Bronchospasms
.:. Sexual dysfunction
faeces.
Indications Drug interactions
.:. Hypertension .:. Propranolol may enhance the blood lowering effect of other
.:. Angina petoris antihypertensives
.:. Migraine prophylaxis .:. Cimetidine, .hydralazine may increase the effect of propranolol
.:. Thyrotoxicosis .:. Indomethacin may reduce the anti-hypertensive effect of
.:. Arrhythmias propranolol
.:. Essential tremor .:. Oral contraceptives antagonize the hypotensive effect of
.:. Anxiety with symptoms like palpitation, tremor propranolol
.:. Prophylaxis after myocardial infarction .:. Concurrent use with digoxin increases the risk of AV block a d
bradycardia • n
Contraindications
.:. Hypersensitivity to propranolol .:. Rifampicin increases the metabolism of propranolol leading to
reduced plasma concetration
.:. Uncontrolled heart failure
.:. Marked bradycardia Key issues to note
.:. Hypotension
.:. Advis~ the patient to avoid alcohol
.:. Asthma
.:. ~roprano.'o' should ~e used with caution in patients with
Dose dlab.etes since .it may mask the symptoms of hypogylcaemia
Hypertension: Initially 80mg twice daily, increased at weekly intervals .:. ~dvlse the p~tlent not to discontinue the drug abruptly since
as required; Maintenance: 160 - 320mg daily in 2 divided doses. It ma~ ~esult In rebound hypertension or angina
Angina pectoris: Initially 40mg 2 times daily. Maintenance: 120- .:. Admlnlste,r propranolol with food
240mg daily in 2 divided doses.

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 ,l I' 11'1 I III I 11'11 I I
,", ' ", '" : PRECISE PHARMACOLOGY I'" ,':: ' ,',,,,, I " I , ':', I "RECISE PHARMA

CARVEDILOL .:. Malaise .:. Dry mouth

Available preparations: Tablets 3. I 25mg, 6.2Smg, 12.5mg, 2Smg .:. Dizziness .:. Diarrhoea·
i:
1,; Drug interactions
Available brands: Dilatrend®, Carvil®, Cardoz®, CadalolCil'
.:. Cimetidine may increase carvedi/ol blood concentration
Vacodil® • II .:. Rifampicin may decrease carvedilol blood concentration
.:. Carvedilol may increase hypotensive effect of diuretics
Pharmacokinetics .:. Carvedilol may mask the symptoms of hypoglycaemia
Carvedilol is well absorbed from the gastrointestinal tract but undergoe:, caused by oral antidiabetic drugs
considerable first-pass metabolism in the liver. The metabolites are Key issues to note
excreted in bile. .:. Inform the patient that Carvedilol may cause fatigue, dizziness,
Indicati~ns I~w blood pressure (especially when standing). Patient should
.:. Hypertension rise slowly from sitting or lying position
.:. Angina pectoris .:. Advise the patient not to drink alcohol
~:. Stable mild to severe heart failure as an adjunct to convention;ll
.:. Advise the patient not to discontinue the drug abruptly since it
I"
W1 treatment (ACE inhibitor, diuretics) may lead to rebound hypertension
rt; .:. Advise the patient to take the drug with food and to avoid
Contraindications driving during initiation of therapy
.:. Severe chronic heart failure
.:. Hypersensitivity to carvedilol BISOPROLOL
.:. Hepatic impairment Available preparations; Tablets Smg, IOmg
:1
.:. Asthma
.:. Marked bradycardia Available brands: Corbis®

IIill .:. Metabolic acidosis

Pharmacokinetics
.:. Lactation
1
:'1'1 B!sopr?lol..is well .absorbed following oral administration, with high
i,',,,I' Dose bloavarlabrllty. It is metabolized in the liver to inactive metabolites and
,IIII',I, Hypertension: Initially 12.Smg once daily, increased after 2 days to Is excreted in urine.
usual dose of 2Smg once daily
'II
,Ii Heart failure: Initially 3.12Smg twice daily with food for 2 weeks Indications
II~
increased to 6.2Smg twice daily then to 12.Smg twice daily, then 2Smg .:. Hypertension
I'
i twice daily in patients with severe heart failure , .:. Angina pectoris
Angina pectoris: Initially 12.5mg twice daily increased after 2 days to .:. Adjunct In stal;>le moderate to severe heart failure
2Smg twice daily.
Contraindication~
Side effects .:. Cardiogenic shock
.:. Postural hypotension .:. Bradycardia .:. Second or third degree AV block
'I, .:. Fatigue .....:. Sinus bradycardia
.:. Headache
I

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 , PRECISE PHARMACOLOGY Iii, a 5ltlE • i_I
Dose Examples:-
Hypertension and angina: initially Smg, increased to IOmg jf .:. Nifedipine
necessary .:. Amlodipine
Adjunct in heart failure: initially I.2Smg once daily in the morning. .:. Felodipine
for I week, then increase to 2.Smg once daily for I week, then 3.75mg
once daily for I week, then Smg once daily for 4 weeks, then 7.5mg Non dihydropyridines
once daily for 4 weeks, then IOmg once daily " These drugs act on vascular smooth muscle and the heart. Since they
Side effects suppress AV conduction, they are useful in cardiac arryhythmias
Examples:- .
•:. Headache Hypotension
.:. Verapamil
.:. Dizziness Fatigue
.:. Diltiazem
.:. Bradycardia Insomnia
.:. Muscle cramps Diarrhoea Mode of Action
Calciu m channel blockers decrease the influx of calcium into smooth
Drug interactions musc les thereby red' I
. h . uClng vascu ar tone which results in reduction of
.:. Cimetidine increases the plasma levels of bisoprolol pen~; era! resIstance and blood pressure.
If
.:. Concurrent use with digoxin potentiates bradycardia and
NIFEDIPINE
results in additive prolongation of AV conduction time
.:. NSAIDs reduce antihypertensive effects of bisoprolol
:!lllw Available preparations: Tablets lOmg, 20mg retard,
.:. Rifampicin increases metabolism of bisoprolol and reduces its 30mg long acting
,Available brands:
effects Adalat®, Nifelat®, Nifedipine-denk®,
Depin®, Zenusin®, Nicardia®, Calcigard®
Key issues to note Pharmacokinetics
.:. Do not discontinue the drug abruptly after along Nifedipine is rapidl d I
'. Y an a most completely absorbed from the
term therapy since it may cause exacerbation of angina or gastroln~estlnal tract, but bio-availabilityis reduced by first ass
myocardial infarction mhetab.olism.. It is.extensively metabolised in the liver and excret~ in
.:. Advise the patient to avoid driving or operate machinery if t e unne as Inactive metabolites.
I'
I, dizziness or weakness occur' Indications
,'Ii, .:. Some patients may experience side effect such as dizziness,
.:. Hypertension
'I Iightheadedness, sexual impotence and depression
1: 11 .:. Prophylaxis of angina pectoris
1

CALCIUM CHANNEL BLOCKERS

II11'1 Contraindications
These drugs are used in the treatment of hypertension and angina
, I'
II
I
I I
i
pectoris and are safe for patient with asthma, hyperlipidaemia, diabetes
.:. Hypersens!tivity to nifedipine
I
.:. Unstable or acute attccks of angina
and renal dysfunction. They are subdivided into 2 groups namely:
.:. Porphyria
Dihydropyridines
.:. Cardiogenic shock
Drugs in this group produce significant blockage of calcium channels In
blood vessels and minimal in the heart.

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 " , ' , :' I'!: I,' '" I' : , ' PRECISE PHARMACOLOGY

Dose AMLODIPINE
The dose and frequency of administration varies depending on the Available preparations: Tablets Smg, 10mg,
preparations used. \!: :!ll!1' (
i Ilill'
I Capsules Smg, 2.Smg
Short acting nifedipine is given 3 times a day, nifedipine retard is givel'
twice daily and long acting nifedipine is given once daily. • 1IIIIIIIIIi!I' Available brands: Norvasc®, Amtas®, Asomex®, Amlong®,
Hypertension: Adults: 10-20mg twice daily, increased to 20-40mg 1
,,1
1 , Lowvasc®, Lofral®, Amlodac®, Amedin®
twice daily (Nifedipine retard) : Pharmacoldnetics
11
Nifedipine long acting: 30 - 90mg once daily Arnlodipine is well absorbed following oral administration. It is
Angina pectoris: Nifedipine retard; I 0-40mg twice daily or nifedipine II extensively metabolised in the liver and excreted in urine.
long acting: 30-90mg once daily. ! Indications
.:. Hypertension
Side effects t-r'
.:. .:. .:. Prophylaxis of angina pectoris
Oedema of ankle Headache
.:. Flushing .:. Dizziness Contraindications
.:. Tachycardia .:. Palpitations .:., Unstable angina
.:. Impotence ..:. Tremors .:. Known hypersensitivity to amlodipine
.:. Muscle cramps .:. Dry mouth .:. Breastfeeding
.:. Constipation .:. Nausea Dose
Drug interactions Hypertension or angina: Initially Smg once daily, increased after 10-
•:. Beta blockers may have additive hypotensive effect when given 14 days to a max of I Omg once daily if necessary.
together with nifedipine
.:. Nifedipine may increase digoxin blood concentration Side Effects
.:. Nifedipine increases the plasma concentration of digoxin I I: .:.
Headache .:. Dizziness
.:. Rifampicin increases the metabolism of nifedipine leading to .:.
Oedema .:.
II Iii .:. Fatigue
reduced plasma concentrations Flushes .:. Hypotension
.:.
Malaise .:. Bradycardia
Key issues to note
.:. Administer nifedipine with food and swallow sustained :j , h.+:. Palpitations .:. O~
I
.:.
Taste disturbances .:. Abdominal pain
release tablets without chewing
.:. Advise the patient to avoid alcohol Drug interactions
.:. Advise the patient to rise slowly from prolonged sitting or .:. Cimetidine increases serum levels of amlodipine
lying position .:. Rifampicin may decrease serum concentrations of amlodipine
.:. Advise the patient not to stop using the drug suddenly .:. Erythromycin may reduce clearance of amlodipine
.:. Inform the patient that excessive hypotension may occur .:. Barbiturates reduce plasma concetrations of amlodipine
especially at the begining of treatment
Key'issues to note
.:. Amlodipine may be administered without regard to food but
take with caution with grape fruit juice

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 , ' ," I, PRECISE' II I I LOGY I F777' 7 "77 77
7

•
PRECISE PHARMACOLOGY I
.:. Inform the patient not to discontinue the drug abruptly Drug interactions
.:. Erythromycin,may increase the plasma concentration of
.:. Inform the patient to report to the clinician in case of
felodipine I
irregular heart beat, shortness of breath, swelling of the feet
.:. Propranolol plasma concentration may be increased by
and hands, pronounced dizziness and hypotension.
felodipine resulting into enhanced hypotension
.:. Felodipine may increase the blood levels of digoxin resulting
FELODIPINE into increased risk of toxicity
,Available preparations: Tablets Smg, 10mg
Key issues to note
.Available brands: Plendil® .:. Administer felodipine as a whole tablet and advise the patient
II'.1 not to chew. or crush the tablet
Pharmacokinetics
:111
11
Felodipine is almost completely absorbed when given orally but .:. Advise the patient to avoid grape fruit juice since it increases
II 1 undergoes extensive first-pass metabolism.' It is extensively metabolised the effect of felodipine
[,11 '11
in the gut and the liver and is excreted almost entirely as metabolites in .:. Advise the patient to avoid excessive salt intake
III
urine and faeces. .:. Advise the patient to avoid alcohol while taking the drug as it
I
II' may cause an excessive drop in the blood pressure
I
Indications
.:. Hypertension DILTIAZEM
.:. Angina pectoris Available preparations: Tablets 180mg

Contraindications Pharmacokinetics
.:. Pregnancy Diltiazem is well absorbed when taken orally, undergoes first pass
.:. Unstable angina metabolism and is distributed to body tissues. The drug enters breast
.:. Uncontrolled heart failure milk and is metabolized in the liver and excreted in urine.
•:. Known hypersensitivity to felodipine Indications
.:. Within one month of myocardial infarction .:. Hypertension
Dose .:. Stable and unstable angina pectoris
Hypertension: Initially Smg once daily in the morning .:. Coronary artery spasm I\\[
Maintenance 5 - I Omg once daily
Contraindications
Angina pectoris: Initially Smg daily in the morning, increased if
.:. Known hypersensitivity to diltiazem
necessary, to I Omg once daily
.:. Impaired hepatic or renal function
Side effects .:. Sick sinus syndrome
.:. Flushing Dizziness
Palpitations .:. Heart block (second or third)
.:. Headache
Peripheral oedema .:. Lactation
.:. Impotence
.:. Urinary Frequency Fatigue .:. Cardiogenic shock
.:. Constipation Nausea
Dose
Angina: 60mg 3 times daffy, increased to 360mg daily if necessary
elderly; initially 60mg twice daily, increased to 360mg daily

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 : " ' PRECISE PHARMACOLOGY IIIE.2& Ii I LIE [
Extended release preparations: 120-180mg once daily for angina. of blood vessels which lowers the blood pressure.
180-240mg for hypertension II"
CAPTOPRIL
Side effects Available preparation: Tablets 2Smg
.:. Dizziness .:. Headache
.:. Light-headedness .:. Rash Available brands: Epistron®, Angiopril®
.:. Peripheral oedema .:. Nausea Pharmacokinetics
.:. Flushing .:. Arrhythmias Captopril is absorbed throughout the GIT and presence of food may
Drug interactions reduce ~bsor.ption. It is distributed to body tissues except the CNS,
.:. Concurrent use with beta blockers and digoxin may increase metabolrzed In the liver and excreted in urine and small amounts in
feaces.
risk of bradycardia and heart block
.:. Cimetidine may increase diltiazem serum concentration Indications
.:. Cardiac effects of anaesthetics may be potentiated by diltiazem .:. Mild to moderate hypertension
.:. Diltiazem may decrease the metabolism and increase serum .:. Congestive heart failure
concentrations of cyclosporine, carbamazepine, digoxin, .:. Diabetic nephropathy
midazolam, lovastatin .:. Prophylaxis after infarction
.:. Rifampicin may decrease diltiazem serum concentrations
Contraindications
Key issues to note .:. Hypersensitivity to captofil and other ACE inhibitors
.:. The tablets should be swallowed whole, do not cut, crush or .:. Pregnancy (
chew .:. Heredi~ary or idiopathic angioedema
.:. The patient should report irregular heart beat, shortness .:. Bilateral or single renal artery stenosis
of breath, swelling of the hands or feet, pronounced dizziness,
Dose
constipation
.:. Patient should not discontinue the medication abruptly H~pert~nsion: Initially 12.Smg twice daily. Maintenance dose: 2Smg
tWice darly, max SOmg twice daily in severe hypertension.
ANGIOTENSIN CONVERTING ENZYME INHIBITORS He.art fa;lure (adjunct): Initially 6.2S-12.Smg under close supervision.
(ACEls) M~lnte~ance dose: 2Smg 2-3 times daily, max ISOmg daily.
These drugs are useful in the treatment of hypertension and heart Diabetic nephropathy: 7S-1 OOmg daily in divided doses
failure. Side effects
Examples:- .:. Hypotension
Tachycardia
.:. Captopril Lisinopril .:. Chest pain
Dyspepsia
.:. Enalapril Quinapril .:. Palpitation
Hyperkalaemia
.:. Ramipril .:. Fatigue
Taste disturbances
.:. Non productive cough
Mode of Action Malaise
Drug interactions
ACE inhibitors act by inhibiting the conversion of Angiotensin I to
.:. Alcohol, diuretics may increase the effect of captopril
Angiotensin II (a powerful vasoconstrictor). This results into relaxation
.:. NSAIDs may decrease the effect of captopril

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Hilillllllllillil 1II1111111111111.,mll"l
 "':
, " ~CII:
£&1 12 ]L ilt a_au
.:. Potassium sparing diuretics, potassium supplements may cause II Dose "
i
hyperkalaemia Hypertension: Initially I Omg once daily
Key issues to note Usual maintenance dose; 20mg once daily
.:. Advise the patient to rise slowly to sitting or standing position Heart failure (adjunct): Initially 2.Smg once daily under close medical
to minimise orthostatic hypotension supervision increased in steps not greater than IOmg at interval of 2
.:. Inform the patient that dizziness,fainting, light headedness may weeks
III
occur during the first few days of trearment I Diabetic nephropathy: Initially 2.Smg once daily. Maintenance dose
•:. Advise the patient to take the drug on an empty stomach IOmg daily increased to 20mg if needed.
about one hour before food Side effects
.:. Captopril should not be administered together with antacids .:. DiZZiness
because they hinder its absorption Sleep disturbances
.:. Headache
.:. Vertigo
.:. The dose administered and frequency of administration should .:. Fatigue
be reduced in renal impairment Impotence
.:. Cough
I~ Mood changes
L1SINOPRIL .:. Skin rash
Dry mouth
Available preparations: Tablets Smg, IOmg, 20mg .:. Nausea
Palpitations
.:. Vomitin?
Available brands: Zestril®, Linopril®, Sinopril® , Listril®, Postural hypotension
.:. Chest 'fin
Adecanil®, Dapril®, Auroliza®, Colace®
Drug interactions
Combinations: Zestoretic® (Iisinopril/hydrochlorthiazide)
.:. Aspirin or any other NSAID may inhibit the
20/12.Smg
antihypertensive effect of Lisinopril
Pharmacokinetics
.:. Postassium sparing diuretics may increase the risk for
Lisinopril is slowly and incompletely absorbed from the gastro intestinal
hyperkalaemia when given together with lisinopril
tract followi~f oral ~dmin,istratio~, crosses, the placenta, may enter
.:. Allopurinol may increase hpersensitivity reaction to ACE
breast milk~ metabolized In the liver and IS excreted unchanged In inhibitors
urine.
.:. Lisinopril enhances insulin sensitiviy
Indications .:. Concurrent use with alpha blockers(prazocin, doxazocin) may
.:. Hypertension exaggerate first dose hypontensive response ~I

.:. Heart failure '1',

Key issues to note
.:. Prophylaxis following myocardial infarction,
.:. Diabetic nephropathy , .:. Advis: ~h~ patient to rise slowly to sitting or standing position 1/, rr
to minimise orthostatic hypotension
Contraindications
.:. Inform the patient that dizziness,fainting, light headedness may
.:. Breast feeding III :W
. Occur during the first few days of treatment
.:. Known hypersensitivity to Iisinopril l,f'I II"
ij'" I

.:. Lisinopril may cause changes in the taste, persistant dry cough
.:. Pregnancy (second and third trimester) ; III
.:. Bilateral renal artery stenosis
therefore advise the patient to report to the doctor in case the lilli,
above side effects occur
I(
II,
-323-
-324-
Ij'l,
, II
,
, ,I I
, ',:
 7 PRECISE lij:r~i;MACOLOGYI III 222
ENALAPRIL Key issues to "ote
Available preparations: Tablets Smg, IOmg .:. Avoid a~cohol while taking enalapril
Available brands: Envas®, Ena denk®, Enapril®, Euril® .:. Enaloapnl may be given before or after meals
.:. Advise the patient to avoid sUdden po 't o h
Pharmacokenetics " . " Sl Ion c anges to
minimise orthostatic hypotension
Enalapril is readily absorbd from the GI tract; metabolised in the liver to
active metabolites and excreted in urine.. QUINAPRIL
Indications Available ~reparations: Tablets 5mg, IOmg, 20mg
.:. Hypertension
Available brands: Accupro®
.:. Heart failure
Pharmacokinetics
Contraindications
QUinapril is absorbed rapidly but food d I . b
•:. Hypersensitivity to enalapril
0 •

I'netabolized in the liver t~ active form de ~ys Its a s~rptloon. It IS

.:. History of angioedema related to previous treatment with an r(~aces. ",. an IS excreted In unne and
I.. ACE Inhibitor
.:.If Pregnancy Indications ."
.:. Bilateral renal artery stenosis .:. Hypertension
Dose .:. He,rt failure
Hypertension: Initially Smg once daily. Maintenance dose 20mg onCl'
Contraindications
daily. Max. 40mg once daily.
Heart failure: Initially 2.Smg daily, increased over 2-4weeks to tl1I' .:. Kn~wn hypersensitivity to qUinapril
maintenance dose of 20mg daily in 1-2 divided doses. Max. 40mg daily .:. Patients with history of angioedema with ACE inhibi
.:. Pregnancy tors
Side effects
.:. Fatigue Orthostatic effect [)ose
.:. Hypotension Headache Hypertension: Initially IOmg once daily incre d t .
.:. Dizziness Cough d()se of 20-40mg once daily ase 0 a maintenance
.:. Skin rash Nausea and vom.iting
1:lderlyl renal impairment: initially 2.5mg dail d
.:. Diarrhoea
0

Anorexia ill maintenance dose of 20-40mg daily y, Increase gradually to

.:. Depression Blurred vision
.:. Dry mouth Peptic ulcer Congestive heart failure: Initially 2 5mg once d "I I'
Ilose I 0-20mg once or twice daily . al y, usua maintenance
.:. Impotence Muscle cramps
~Ide effects
Drug interactions
.:. Headache
.:. Diuretics potentiate hypotensive effect of enalapril .:. Dizziness
.:. Rhinitis
.:. Enalapril may increase lithium levels in the blood when .:. Cough
.:. Fatigue
given concurrently with lithium .:. Dyspepsia
.:. Nausea and vomiting
.:. Use with potassium-sparing diuretics may result in an additiv(' .:. Abdominal pain
.:. Diarrhoea
·:·Chest pain
hyperkalemic effect .:. Myalgia
.:. Insomnia
.:. NSAIDs may decrease hypotensive effect .:. Hypotension
.:. Nervousness
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~Illllll'!!
 •
Drug interactions . .
Dose
: 'i,I' :', ,', , :: " , " ,,',', '<11"""""'" PRECISE PHARMAC8LlIlGY

Hypertension: Initially 1.2Smg once daily, increased at intervals of 1-

.:. QUinaprii increases the lithium seru~ levels and
s of lithium toxicity when given concurrently ~weeks to usual dose of 2.S-Smg max. IOmg once daily.
sympt 0 m . h Heart failure: Initially 1.2Smg once daily, increased if necessary after
.:. QUinaprii reduces the absorption of tetracycline w en
I ·2weeks to a max. I Omg daily in I -2 divided doses.
given together . .'
Myocardial infarction (started in hospital 3-10 days after
.:. DiureticS potentiate hypotensive effect of qUinapnl
Infarction): Initially 2.Smg twice daily, increased after 2 days to Smg
!Key issues to note . . .. . twice daily. Maintenance dose 2.S-Smg twice daily
.:. Advise the patient to rise slowly from sitting position to f·rophylaxis of cardiovascular events: Initially 2.Smg once daily,
minimise orthostatic hypotension Increased after I week to Smg once daily, then increased after a further
.:. Inform the patient that dizziness, fainting, light headedness :lweeks to I Omg once daily.
't'
may occur during the first few days of treatm~nt
.:. Quinapril may cause changes in the taste, perslstant dry . Side effects
cough therefore advise the patient to report to the doctor III III .:. Headache .:. Dizziness
~ case the above side effects occur +:+ Fatigue .:. Cough
.:. Impotence .:. Postural hypotension
RAMIPRIL
Available preparations: Tablets 2.Smg, Smg, IOmg
.:. Vomiting .:. Vertigo
.:. Chest pain .:. Loss of appetite
Available brands: Variace®, Corpril~, Hopecard®, Ramclor(lI) .:. Dry mouth .:. Confusion
Ramitas®, Topnl® .:. Depression .:. Decrease<;Uieido
Pharmacokinetics
.:. Muscle cramps
. '1' bsorbed rapidly but food reduces the rate but not extelll I)rug interactions
Ramlpn IS a d ' . t bit .
. It '\S metabolized to both active an inactive me a 0 II' .
o f absorption. .:. Potassium sparing diuretics or potassium supplements ,;s;.'I).~
and is excreted in urine. can increase the risk of hyperkalaemia c;,\;;,~ ~
.:. NSAIDs may reduce the effect of ramipril and~'\"t) {
Indications
cause deterioration of renal function
.:. Hypertension
.:. Patients on diuretics may occasionally experience
.:. Heart failure
.:. Prophylaxis after myocardial infarction excessive reduction of blood pressure after initiation
.:. Prophylaxis of cardiovascular events or stroke of ramipril therapy
.:. Ramipril enhances the hypoglycemic effect of insulin
Contraindications
.:. Hypersensitivity to ramipril . Koy issues to note
.:. Patients with a history of angioedema related to prevIous .:. Advise the patient to rise slowly to sitting or standing position
treatment with ACE inhibitors to minimise orthostatic hypotension
.:. Pregnancy .:. Inform the patient that dizziness, fainting, light headedness
.:.,l;Volume depletion may occur during the first few days of trearment

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II
I
 I • I J I I I I• 1 Id PR PHARMACOILOGY ., . ,>, ': d .',' , ", : , ' , ", PRECI~ HARMAC)JliIifI
.:. Ramipril may cause changes in the taste, persistent dry Side Effects
cough therefore advise the patient to report to the doctor in .:. Dizziness .:. Diarrhoea
case the above side effects occur .:. Taste disturbance .:. Urticaria
.:. Myalgia .:. Vertigo
ANGIOTENSIN II RECEPTOR ANTAGONISTS .:. Fatigue Migraine
These drugs include:- Drug interactions
.:. Losartan
.:. Fluconazole may decrease conversion of Losartan to active
.:. Valsartan
metabolites resulting in loss of anti-hypertensive effects
.:. Telmisartan
.:. NSAIDs may reduce the hypotensive effect of Losartan
They are normally used as an alternative in patients who cannot toleranet'
.:. Potassium sparing diuretics may increase the risk of
side effects such as dry cough associated with ACE inhibitors.
hyperkalaemia when given together with Losartan
Mode of Action _' .:. Cimetidine may increase the effect of Losartan
They produce a fall in blood pressure by direct antagonism of the .:. Alcohol may potentiate hypotensive effect of losartan
vasoconstrictor angiotensin II at the AT , receptor site.
l'l
Key issues to note
LOSARTAN
.:. Avoid tasks that require alertness, until response to drug is
Available preparations: Tablets 50mg, 100mg
established (possible dizziness effect)
Available brands: Losacar®,Tozaar®, Losartec®, Losartas®, .:. Advise the patient not to take any OTC preparations or
nasal decongestants without recommendation of a clinician
Combinations: Presartan-H50®(losartan/Hydrochlorthiazide) .:. Advise the pati~not to stop taking the medication unless
Tozaar-H® told by the clinician
.:. The drug may be taken with or without meals
Pharmacokinetics
Losartan is readily absorbed from the gastrointestinal tract following
VALSARTAN
oral administration, undergoes first-pass metabolism forming active I Available preparations: Tablets 40mg, 80mg, 160mg
and inactive metabolites. Losartan is excreted in the urine and faeces. II
Available brands: Valzaar®, Diovan®
Indications
.:. Hypertension
Combinations: Co-diovan®(valsartan/hydrochlorthiazide)
.:. diabetic nephropathy
160/12.5,160/25,80/12.5
Contraindications
Pharmacoldnetics
.:. Known hypersensitivity to losartan
Valsartan is rapidly absorbed following oral administration. It is
.:. Pregnancy (2 nd and 3rd trimester)
not significantly metabolised and is excreted in faeces and urine as
.:. Lactation
unchanged drug.
Dose
Usually 50mg once daily, increased after several weeks to I OOmg once
daily if necessary

-329- -330-
 · . , PRECISE PHARMACOLOGY ,: : '; ,. , ,,' PRECIWHARMACOLllGY
Indications .:. The drug should not be taken with alcohol
I .:. Hypertension .:. Advise the patient to rise slowly from sitting position to
.:. Post-myocardial infarction minimise orthostatic hypotension
Contraindications CA",DESARTAN
.:. Breast feeding Available preparations: Tablets 2mg, 4mg, 8mg
.:. Hypersensitivity to valsartan
Available brands: Amias®, Cantar®
.:. Severe hepatic impairment
.:. Pregnancy (second and third trimester) Indications
.:. Biliary obstruction .:. Essential hypertension
.:. Cirrhosis .:. Heart failure
IDose Contraindications
Hypertension: 80mg once daily, increased after 4 weeks to 160m~~ .:. Cholestasis
daily if necessary Max. 320mg. .:. Breast feeding
IElderly over 75 years: Initially 40mg once daily .:. Hypersensitivity to candesartan
IMyocardial infarction, Initially 20mg twice daily, increased over
.:. Pregnancy (2nd and 3rd trimester)
several weeks to 160mg twice daily if tolerated. .:. History of angioedema
Side effects .:. Severe hepatic impairment
.:. Fatigue .:. Nausea and vomiting Dose
.:. Insomnia Headache
Hypertension: Initially 8mg~..(1mg in hepatic impairment) once daily
.:. Heartburn .:. Hyperkalaemia
increased if necessary at intervals of 4weeks max.32mg once daily.
.:. Dizziness •:. Hypotension
Usual maintenance dose 8mg once daily.
.:. Myalgia •:. Orthostatic hypotension
Heart failure: Initially 4mg once daily, increased at intervals of at least
Drug interactions 2 weeks to a target dose of 32mg once daily.
•:. Diuretics produce additive hypotensive effect when given
together with Valsartan Side Effects
.. .:. Concomitant use of potassium-sparing diuretics, potassium .:. Headache .:. Vertigo
suppliments may lead to hyperkalemia .:. Blood disorders Nausea and vomiting
.:. Combination with' NSAIDs may reduce the hypotensive .:. Back pain Hyperkalaemia
effect of valsartan and increased risk of worsening renal .:. Vomiting Rash
function .:. Arthralgia Myalgia
!Key issues to note .:. Somnolence Dyspepsia
.:. Valsartan may cause injury and even death to the unborn baby .:. Depression Muscle cramps
if taken during the second or third trimester .:. Pruritus Dizziness
.:. Advise the patient not to stop taking the medication unless .:. Fatigue Diarrhoea
recommended by the doctor I,

.:. Advise the patient to take enough fluids to maintain hydration

.• '""
-331-
f II -332-

~,.,.
-
'
;
,'"
-- "
.
~
 Q3iM~iIQ:m;J~,'rtBIJIIIf\1 ~ECISE PHARMAClJLltGY
aUUS22JZI , ' I I

.:. Telmisartan enhances the hypotensive effect of other

Drug Interactions .... .
.:. Candesartan may increase the risk of lithium tOXICity antihypertensives
.:. Potassium sparing diuretics, potassium supplements may .:. Potassium sparing diuretics, potassium supplements may
increase the risk of hyperkalaemia increase the risk of hyperkalaemia
.:. NSAIDs may reduce antihypertensive response of .:. Systemic corticosteroids may reduce the hypotensive effect of
telmisartan
Candesartan
Key issues to note
TELMISARTAN
Available preparations: Tablets 40mg, 80mg .:. Advise the patient to maintain proper fluid intake
.:. Advise the patient to avoid tasks that require alertness until
Available brands: Telvas® response to the drug is established
Combinations: Telvas_H®(telmisartan/hydrochlorthiaz.ide) DIRECT ACTING VASODILATORS
"'I' i
These drugs are rarely used as first line drugs and are reserved for
Indications
,'esistant cases of hypertension and for treatment of hypertensive
~ .:. Hypertension
i,mergencies. These drugs also cause sodium and water retention
Cci1ntraindications therefore are useful when combined with diuretics to counteract
.:. Pregnancy the sodium retention. They are also combined with Beta blockers to
.:. Bi1Iiary obstruction prevent the reflex tackcardia.
•:. Known hypersensitivity to telmisartan
.:. Severe hepatic impairment Examples;
.:. Hydralazine
.:. Lactation
.:. Minoxidil ,~
~~ . f
Hypertension: Initially 40mg once daily increased If necessary a ter at Mode of Action
least 4 weeks, max. 80mg once daily Hydralazine reduces blood pressure by acting directly on the arterial
smooth muscle to cause vasodilatation and reduction in total peripheral ii',
Side effects vascular resistance.
Chest pain
.:. Myalgia
Diarrhoea HYDRALAZINE
.:. Vertigo
.:. Anxiety Available Preparations: Injection 20mg/ml
.:. Diz.ziness
.:. Arthralgia Tablets 25mg
.:. Sinusitis
.:. Blood disorders Flatulence
Available brands: Apresoline®
.:. Back pains Heart burn
.:. Upper respiratory tract infections Pharmacokinetics
Orally administered hydralazine is rapidly and completely absorbed
.:. Eczema
from the gastrointestinal tract but undergoes considerable first-
Drug interactions . pass metabolism in the gastrointestinal mucosa and liver. It is widely
.:. Telmisartan increases digoxin plasma concentration . distributed, metabolised in the liver by acetylation and excreted in
.:. Telmisartan slightly decreases warfarin plasma concentration urine as metabolites.

-333- -334-
 , " : '."," I ,I'" "', '":',, ': ' ,,', "'" PRECISE PHARMACOllffiUl
I~dications .:. Beta blockers and thiazides are often used with hyralazine
.:. Hypertensive crisis to prevent tachycardia and fluid retention
.:. Moderate to severe hypertension .:. Advise the patient to avoid driving until the effect of the drug
.:. Moderate to severe chronic congestive heart fail.ure (in is established
combination with long acting nitrates)
CENTRALLY ACTING ANTIHYPERTENSIVE DRUGS
.:. Hypertension secondary to pre-eclampsia/eclampsia
CO~traindications They are effective antihypertensives but are no longer considered drugs
•:. Known hypersensitivity to hydralazine of choice as they are less tolerated than other antihypertensives.
.:. Severe tachycardia Methylodpa is a drug of choice in treatment of hypertension in
pregnancy.
•:. Heart failure with high cardiac output
Examples:-
.:. Myocardial insufficiency due to mechanical obstruction
.:. Methyldopa
.:. Idiopathic systemic lupus erythematous
.:. Clonidine
.:. Porphyria
Dos~" Mode of Action
~Ypertension: By mouth 25mg twice daily, increased to usual max These drugs reduce blood pressure by acting in the CNS to reduce
activity of the sympathetic nervous system.
50rng twice daily.
~eart failure: 25mg 3-4 times daily, increased every 2 days if necessary. METHYLDQPA
~aintenance dose 50 - 75mg 4 times daily. Available preparations: Tablets 250mg
By intravenous infusion, hypertension with renal complications
Available brands: Aldomet®, Medopress®
a~d hypertensive crisis: initially 200- 300microgram/minute,
Il)aintenance 50 - 150 microgram/minute. Pharmacokinetics
S· Methyldopa is variably absorbed from the gqstrointestinal tract when
Ide Effects
.:. Headache taken orally, crosses the blood-brain barrier, extensively metabolised in
Dizziness
the liver and excreted in urine.
.:. Severe tachycardia Flushing
.:. Hypotension Palpitation Indications
.:. Angina .:. Joint swelling .:. Hypertension especially in pregnancy
.:. Oedema Anorexia Contraindications
.:. Heart failure Gastrointestinal disturbances .:. Hypersensitivity to methyldopa
DI'..g
I. •Interactions
• .:. Active liver disease
.:. Diuretics, other antihypertensives may increase hypotensive .:. Depression
effects of hydralazine .:. Phaeochromocytom'a
.:. Indomethacin may decrease hypotensive effects of hydralazine .:. Porphyria
Dose
K~y issues to note
Adult: Initially 250mg 2-3times daily, increased gradually, at an interval
.:. Prolonged treatment of more than 6 months may induce
of atleast 2 days until desired response is obtained, ~1ax. 3g daily
lupus like syndrome

-335- -336-
 \1

~HARMACOlOGY I : PRECISE OlgGY

Elderly: Initially 12Smg twice daily, increased gradually, max. 2g daily. Mode of action
:11 ' These drugs competitively inhibit post-synaptic alpha receptors, which
111
Side effects , 1,1 results in vasodilation of veins and arterioles. This leads to a decrease
.:. Sedation Dizziness II:
i!
"iillli: in total peripheral resistance and blood pressure.
',I Iii i
•:. Dry mouth Constipation They also block alpha receptors in non vascular smooth muscle e.g.
.:. Stomatitis Oedema the bladder neck,where alpha-blockade reduces resistance to urinary
11,'1

.:. Myalgia Postural hypotension flow.

.:. Impaired mental acuity Decreased libido
••• Impotence Bradycardia PRAZOSIN "----
\ .;. Hemolytic anaemia Available preparations: Tablets I mg, 2mg, Smg
Drug interactions
.:. Enhanced hypotensive effect when methyldopa is given with Available brands: Hypovase®, Minipress®
ACE inhibitors, alcohol, atenolol or propranolol
.:. Methyldopa may impair tolbutamide metabolism, enhancing Pharmacokinetics
its hypoglycaemic effects I Prazosin is well absorbed after oral administration, extensively

~i~::~~~;~~~~~::~~~u~C~ro
.:. Hypotensive effect of methyldopa is antagonized by NSAIDs
.:. Hypotensive effect of methyldopa is antagonized by
oestrogen
.:. Oral iron therapy reduces bioavailability of methyldopa in urine

Key issues to note

.:. Methyldopa may be administered with out regard to food .:. Benign prostatic hyperplasia
.:. Advise the patient to avoid alcohol during treatment .:. Raynaud's syndrome
.:. Warn the patient that Methyldopa may cause drowziness and
impair activities requring mental alertness . . Contraindications
.:. Advise the patient to rise slowly from prolonged sitting or .:. Hypersensitivity to quinazolines
lying position .:. Congestive heart failure due to mechanical obstruction
.:. Inform the patient that transient sedation or depression may
occur Dose
.:. Advise the patient not to stop the drug abruptly Ii
,,
Hypertension: O.Smg twice daily increased to I mg 2-3 times daily
after 3-7days.
ALPHA ADRENOCEPTOR BLOCKING DRUGS
Maintenance dose 20mg daily in 2-3 divided doses.
These drugs may be used in combination with other drugs in the
Heart failure: O.Smg 2-4 times daily increased to 4mg daily in divided
treatment of resistant hypertension.
doses.
In addition to lowering blood pressure, they also improve urinary flow
Maintenance dose 4-20mg daily in divided doses
rates in benign prostatic hypertrophy.
Benign prostate hyperplasia: initially O.Smg twice daily for 3-7
III Examples:-
days
.:. Prazosin .:. Doxazosin
Maintenance dose 2mg twice daily.
•:. Terazosin

-337- -338-

1'1
j'
;
..1,
,
 , " ' PRECI~jjPHARMACOLOGY '" " ,,' I ' " PRECISE PImJlli1if:OOJLOGY
Raynaud's syndrome: Initially O.5mg twice daily increased if Indications
necessary after 3-7days to the usual maintenance dose 1-2mg twice .:. Hypertension
daily .:. Benign prostatic hyperplasia

... Contraindications
Side Effects
.:.
Headache .:. Dry mouth
II!IIIIIIIIIII .:. Hypersensitivity to other quinazolines
.:.
Drowsiness .:. Oedema
.:. Lactation
.:.
Postural hypotension .:. Urinary Incontinence Dose
.:.
Dizziness .:. Priapism Hypertension: I mg daily, increased after 1-2weeks to 2mg once
.:.
Urinary frequency .:. Weakness daily, and thereafter to 4mg once daily, max. dose 16mg daily
.:.
Palpitations .:. Nausea Benign prostate hyperplasia: Initial dose I mg once daily preferably
.:.
Somnolence at bed time. ...
Maintenance dose- 2 - 4mg daily, max 8mg daily
Drug Interactions
.:. Oestrogen, NSAIDs may decrease the effect of prazosin Side effects
.:. Concomitant use with propranolol or other beta blockers may .:. Postural hypotension .:. Oedema
cause severe hypotension .:. Dizziness .:. Asthenia
.:. Rash .:. Nausea
Key issues to note .:. Vertigo .:. Headache
.:. Advise the patient to avoid alcohol .:. Fatigue .:. Rhinitis
.:. Inform the patient that prazosin may cause dizziness or
drowziness and impair ability to perform activities requiring Drug Interactions
alertness .:. Oestrogen, NSAIDs may decrease the effect of doxazosin
Ii .:. Advise the patient to rise slowly from sitting or lying position .:. Sildenafil, tadalafil may potentiate hypotensive effects of
II':1 .:. Advise the patient to take the first dose of prazosin at bed time I doxazosin
I:
',I to avoid dizziness
Key issues to note
I
,
ililli .:. Advise the patient to avoid tasks that require alertness until
DOXAZOSIN
response to the drug has been established
Available preparations: Tablets 2mg, 4mg
!III .:. Inform the patient that Doxazosin may cause fainting especially
with the first dose
Available brands: Cardura®
.:. Advise the patient to take the first dose of prazosin at bed time
to lessen the likelyhood of first dose effect
Pharmacokinetics
Doxazosin is readily absorbed from the GIT after oral administration, 10.1.2 ANGINA PECTORIS
extensively metabolized in the liver and excreted in bile and faeces Angina pectoris is a painful sensation in the chest, especially on the left
and a small amount in urine. ~Ide, which radiates to the left shoulder and arm. It occurs when there
is an imbalance between oxygen supply and oxygen demand.

-339- -340-

....UII11• •IEliJiliDIJI!!l"····'
 F

1_ PREC ~1IQ:Mili'i!itiIJLOGn
Drugs used in the treatment of angina pectoris, either decrease Indications
oxygen demand or increase cardiac oxygen supply. .:. Prevention and treatment of angina
.:. Left ventricular failure
Examples
.:. Nitrates (:ontraindications
.:. Hypotension .:. Hypovolaemia
.:. Beta blockers
.
:. Head trauma
» .:. Angle-closure glaucoma
.:. Calcium channel blockers
.
:. Marked anaemia .:. Cerebral haemorrhage
Other drugs include:-
.
:. Aortic stenosis .:. Hypersensitivity to nitrates
.:. Aspirin Dose ~
.:. Lipid lowering drugs Heart failure: Orally 40mg 4 times daily
NITRATES Sustained release preparations: 40mg once or twice daily
Nitrates are the most common drugs used in the treatment of angill.1 Prophylaxis of Angina: 10 - 20mg 6-8hourly daily
They may be used to terminate an acute angina attack, prevent effoll i~ Side Effects
or stress induced attack or for long term prophylaxis, usually III , I' .:. Postural hypotension .:. Tachycardia
combination with beta blockers or calcium channel blockers. .:. Flushing .:. Headache
Examples .
:. Restlessness .:. Dizziness
.:. Isosorbide Dinitrate •• Palpitation .:. Nausea
•:. Isosorbide Mononitrate •, Vomiting
.:. Nitroglycerin .'
Drug Interactions
Sublingual/buccal tablets and sprays are used for rapid relief of angill.1 .:. Alcohol and antihypertensives may increase the risk of
pain. Sustained release tablets are used for prophylaxis of angin., orthostatic hypotension when given together with isosorbide
pectoris dinitrate
Mode of Action ISOSORBIDE MONONITRATE
These drugs act by dilating the veins which restrict the amount of bloo( I It is an active metabolite of Isosorbide dinitrate.
returning to the heart (pre-load), thereby reducing cardiac work. AI
higher doses, they also dilate arterioles which cause the peripheral Available preparations: Tablets 20mg
resistance to fall (after-load), reducing the work of the heart. Available brands:; ~'Solotrate®
ISOSORBIDE DINITRATE Indications
It is a long acting nitrate but with a slower onset of action than .:. Prophylaxis of angina
nitroglycerine. .:. Congestive heart failure
Available preparations: Tablets 20mg/40mg Contraindications
Available brands: Isoket® .:. Hypothyroidism .:. Hypersensitivity to nitrates
.:. Hypotension .:. Cerebral hemorrhage

-341- -342-

_~I~1111111111111 11l1I1111II1111111!!l>li.~IIII"1!
 , '" \,' '\ PRECISE PHARMACOLOGY
43*B~1jg:M:JMM'!lnq
& II .:. Marked anaemia
& .:. Head trauma .:. Constrictive pericarditis
Severe anaemia .:. Hypovolaemia
Angle-closure glaucoma Dose
Acute angina: sublingual O.Smg repeated every 3minutes until the
~;~~ 2-3 times daily or 40mg twice daily pain is relieved.
Spray: 1-3 emissions, sprayed onto to the oral mucosa preferrably
Side Effects Flushing the tongue
.:. Hypotension .:. Tachycardia Side Effects
•:. Headache Palpitation .:. Throbbing headache .:• Flushing
.:. Dizziness •:. Abdominal pain .:. Nausea and vomiting ~ .:• Weakness
.:. Nausea and vomiting Confusion .:. Heartburn Dizziness
.:. Restlessness .:. Postural hypotension Tachycardia
.:. Vertigo
Drug Interactions "
Drug Interactions orbide mononitrate may be
0
.:. Orthostatic hypotensi~ may be produced when glyceryl
••• The hypotensive effect of ISOS 'th hypotensive effect trinitrate is concurrently given with calcium channel blockers
• enhanced by alcohol and other drugs WI /
"ETA BLOCKERS
Key issues to no
te
, f h ossible side effects suc
has headadw '_.Ita blockers used in the treatment of angina include:-
the patient 0 t e p h .:. Propranolol
.:. Inform , dO ntinuation of t erapy 0

which may not require ISCO h d before administratlo .:. Atenolol ,

I
.:. Chewable tab ~ts s 0
h uld not be crus e
k changes in position slowly to
.:. Advise the patient to ma e
"
.:. Metoprolol 'oA
nlM:ll blockers may be used with Nitrates or with dihydropyridine
prevent fainting 0 bode mononitrate
0 I/lkilim channel blockers.
•:. Avoid alcohol while taking Isosor I
HIlde of action
DI\:TE (NITROGLYCERINE) ~4.1,\ blockers decrease the heart rate, myocardial contractility and
GLYCERYL TRINIT JV"'. \~llli:ld pressure, thereby decreasing myocardial oxygen demand.
I It is a short acting nitrate
'I
,I Tablets 500mcg
'\
Available preparations: tAICIUM CHANNEL BLOCKERS
Spray
.: "It 111m channel blockers used in angina pectoris include:-
,, ~ Nifedipine
, \1 '¢t Amlodipine
Indications h i ' and treatment of angina
.:. Prop y axiS \ .c. Felodipine
.:. Heart failure
~"Ht" e)f action
:~ .11,hl~ angina, calcium channel blockers relax smooth mLlscies of
Contraindications , iPlJlJllul'ill blood vessels leading to a decrease in after load which
.:. Hypersensitivity t~ ~Itrates
•:. Hypotensive conditions ~'"'Il"'"i myocardial oxygen demand.
.:. Hypovolaemia -344-
-343-
 I I " I • .1 ; " , • PRE EPHARMA& •

10.1.3 DRUGS FOR HEART FAILURE Available brands:

Heart failure is a clinical syndrome caused by the inability of the heart Lasix®, Agomide®, Frusina®
to pump sufficient blood to meet the metabolic demands of the body Pharmacokinetics
Inadequate perfusion of the tissues leads to a variety of symptoms such Frusemide is well absorbed from GIT.· ".
and excreted in the urine andf ' partIally metabolized In the liver
as:- breathlessness, fatigue and oedema. " • . aeces.
In d Icatlons
Drugs used in the treatment of heart failure include:- .:. Oedema
•••• Hypertension
.:. Diuretics
.:. Cardiac glycosides Contraindications
.:. ACE inhibitors .:. Renal failure with anuria
.:. Beta blockers .:. Dehydration ~
.:. Kn own hypersensitivity to frusemide
:1
,
10.1.8 DIURETICS volaemia
I Diuretics are the first line drugs in the treatment of heart failure. .:. Severe pokalaemia
They are recommended in all patient with clinical evidence of fluid .:. Severe h ponatraemia
retention. .:. Pr
ecomatose state~)SSociates with liver cirrhosis
Classification of Diuretics Dose
Diuretics are classified as follows:- Adult
.:. Loop Diuretics. Oedema: oral, initially 40m . h "
.:. Thiazide diuretics. dlll/y, 80mg or more daily," g ,.n t e mornmg, maintenance 20-40mg
.:. Potassium-sparing diuretics.
C . n reSistant oedema
h.ldren: I -3mg/kg daily, max. 40mg daily
•:. Carbonic anhydrase inhibitors. Hypertension: 20-40mg twice daily.
LOOP DIURETICS _low IV/1M: initially 20-50' .
I\()t less than every 2 hou mtmcreased If necessary in steps of 20mg,
Loop diuretics are potent diuretics used in the treatment of moder;1lr'
1:>111)', max. 1.5g daily rs. oses greater than 50mg, by IV infusion
to severe heart failure. They may be used alone or in combination Will \
thiazides especially metolazone to achieve a profound diuresis. Children: O.5-1.5mglkg daily, max. 20mg daily
Examples •'Ide Effects
.:. Frusemide
.:. Bumetamide
I .:. Gout Hyperglycaemia
.:. Rash
.:. Tinnitus
Mode of Action .:. Nausea
Deafness
Loop diuretics inhibit reabsorption of sodium chloride from Ilttl
.:. Hypotension
Dehydration
ascending limb of the loop of Henle' .:. Hypokalaemia
.:. Abdominal cramps
.:. Hyponatraemia .:. D'larrhoea or constipation
FRUSEMIDE .:. Hypomagnesaemia
Available preparations: Tablets 40mg <. Increased urinary frequency
Injection 20mg/ml

-345-
-346-

/
 !l!!!!iI""UiiiiM&,i .

Drug Interactions - g • PRECI~E P1:rMMMI!!l1ij"

.:. Amphotericin B may increase the risk of nephrotoxicity caused

by frusemide.
II
-
Pharmacokinetics
,
Bendrofluazide is completely absorbed fro '.
~mall percentage is metabolised in h ' m the ?astrolntestlnal tract, a
t e liver a~s excreted unchanged
.:. Frusemide may decrease the effect of anticoagulants. ...
In the urine.
.:. Frusemide may increase the risk of lithium toxicity
.:. Gentamycin may increase risk of ototoxicity when given Indications
concurrently with frusemide .:. Oedema

~1 1:~1
.:. Cephalosporins en,pance the nephrotoxicity caused by .:. Hypertension ~
frusemide
.:. Frusemide may increase the risk of digitalis toxicity Con~raindications--- )
•••
Hypersensitivity to Bendrofluazide
Key issues to note .:.
Refractory hypokalaemia
.:. Frusemide may be administered with food or milk to .:.
Hyponatraemia
),mpi, decrease distress .:.
Sy t
mp omatic Hyperuricaemia
.:. Frusemide may cause photosensitivity reaction e.g. exposure .:. Hypercalcaemia
It to sunlight may cause severe sunburn .:. Addison'9isease

THIAZIDE AND RELATED DIURETICS Dose

Thiazide diuretics are used in the treatment of mild heart failure and Oedema: Initially 5 - 10m d 'r '
are the diuretics of choice in treatment of hypertension. They are ' maintenance 5-1 Omg I 3 f g al y kin the morning or alternate days'
II. H - Imes wee Iy ,
relatively weak to be used alone in heart failure. ypertension: 2.Smg daily in the mor .
Examples necessary. nlng higher dbses rarely
.:. Bendrofluazide
.:. Hydrochlorothiazide Side Effects
.:. Chlorthalidone .:. Gout
.:. Nausea
,. .:. Metolazone .:. Fatigue
.:. Dizziness
.:. Impotence
Mode of Action ~ i
.:. Hypokalaemia
.:. Postural hypotension
••• H
They act by inhibiting sodium and chloride re-absorption at proxim;,t-i • ypomagnesaemia
.:. Hyperglycaemia .:.
sites of the distal convoluted tubule. Excretibn of potassium alHI Hyperuricaemia
.:. Hyponatraemia
. magnesium is also enhanced while calcium excretion is diminished.
Drug Interactions
BENDROFLUAZIDE .:. The effects of digoxin m b '
Available preparations: Tablets Smg .:. NSAID ay e Increased by bendrofluazide
_:. B d sfl ma~ reduce the diuretic effect of bendrofluazide
Available brands: Aprinox®, Benduric® en ro uazlde may in I" h'
crease It rum levels in the blood

-347-
-348-
 gMB~;tg:'MMM'II'ID
, , 1.1 I

am 2££ .:. Impotence Muscle cramps

CHLORTHALIDONE (Chlortalidone) .:. Dizziness Hyperglycaemia
Available preparations: Tablets 50mg .:. Weakness Aplastic anaemia
.:. Fatigue Restlessness
Available brands:
Hygroton® .:.
.:.
Impotence
Dry mouth At, .':. Diarrhoea
Headache
+ ~o letio y
nd dehydration
Pharmacokinetics
Chlortalidone is erratically absorbed from the gastrointestinal tract and
bioavailability varies according to the preparation used. It crosses the Drug Interadlons
placental barrier, distributed into breast milk and excreted unchanged .:. NSAIDS antagonise hypotensive acti '
.:. Ther~ is increased risk of h 0
~~I~~~=I~:n:hen
on. of chlorthali?One / '
in the urine.
are given concurrently with cortlcoster6ids
Indications
.:. Hypertension Key issues to note
Jm .:. Mild to moderate chronic heart failure .:. Advise the patient to take the dru .
't~~ .:. Oedema due to nephrotic syndrome prevent sleep disturbances g early m the morning to
;t .:. Ii Ascites due to cirrhosis in stable patient .:. Chlorthalidone m ca .. .
advise the patien ~o uS~dsensltlvlty to sunlight therefore
.:. Diabetes inspidus .:. It may ca e tt aviol , prolonged exposure to sunlight
Contraindications
.:. Hypersensitivity to chlorthalido ne or sulphonamides
a ac <s therefo ad'
report ba if sudd .. . g h
", vise t e patient to
en JOint pam 0 .urs
.:. Symptomatic hyperuricaemia
METOLAZONE
.:. Severe renal impairment
Available preparations: Tablets 2.Smg, Smg
.:. Refractory hypokalaemia
.:. Hyponatremia Available brands: Metoz®
.:. Addison's disease
.:. Pregnancy Pharmacokinetics
tract, crosses the placenta a~de i: y~bs~rbedf~omthegastrointestinal
Metolazoneisslowlyandincom I t I
Dose
Hypertension: 25mg once daily in the morning, increased to 50m~ .~)(creted in urine in unch anged form.dlstrrbuted mto breast milk . It is
daily, if necessary
Cardiac failure and Oedema: 25-S0mg daily in the morning,
~; Indications
increased if necessary to 100 - 200mg daily in the morning, (reduce to .:. Hypertension
lowest effective dose for maintenance). .:. Oedema
Diabetes inspidus: Initially IOOmg daily reduced to maintenance
dose of SOmg daily Contraindications
.:. HypersensitiVity to sulphonamides " ,
.:. Symptomatic hype' , or thiazide diuretics
Side Effects .:. Orthostatic hypotension rurrcaemla
.:. Anorexia .:. Hepatic encephalopathy
.:. Nausea
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 .:. Refractory hypokalaemia
PRECISE PHARMA Y
• .:.
&
Met 0 Iazone may cause gout k
Qi!iB~iIQ:t:lilMMII'IJifI
.:. Addison's disease
.a~tac s~ adVise the patient to
0

notify the clinician if sudd

.:. Hepatic coma en JOint pain occurs
.:. Electrolyte defeciency states
Dose POTASSIUM_ SPARING DIURETICS
Hypertension: Initially Smg daily in the morning either alon~ or with These drugs are relatively wea~ourectic
as single drugs for heart ~ 0' 'h s and are not effective for use
other antihypertensives. Maintenance Smg on alternative days. al ur. ey are used b'
ot her diuretics to prevent los f
0

. In com Ination with

Oedema: 5 - I Omg once daily in the morning increased if necessary to diuretics. ~s 0 potassium caused by thiazide or loop
20mg or more in severe cases max. 80mg daily.
Example;;
Refractory cases: Metolazone can be combined with frusemide or
.:. Spironolactone
other loop diuretics.
Mode of Action
Side Effects
They inhibit sodium re-absor tion in h
.:. Anorexia Orthostatic hypotension
0

aldosterone. As a s . P t . e distal tubule by antagonizing

•:. Nausea Pancreatitis , Interfere With sod' / .
cmd reduce urinary pot 0 Jum potassium exchange
0

•:. Gout Muscle cramps asSIU excretion.

.:. Fatigue Light headedness SPIRONOLACTONE
.:. Dizziness Hepatic encephalopathy
Available preparations:
.:. Hyperglycaemia Fluid and electrolyte imbalance Tablets 2Smg, SOmg
.:. Aplastic anaemia Available brands:
Aldactone~
.:. Volume depletion and dehydration f·harmacokinetics
Spironolactone is well absorb d
Drug Interactions Inetabolised in the liver d e f~om t e gastrointestinal tract,
0

.:. Metolazone may reduce renal excretion of lithium increasing an excreted In un and faeces
Indications .
its toxicity
.:. Metolazone potentiates hypotensive effects of moo. I -:- Liver cirrhosis aSSOciated d
-:. Refracto' '. oe ema and ascites
other antihypertensives. This may be used for therapeullc .:. . ry o~dema In congestive heart failure
advantage ASCites assOciated with malignancy
.:. Colestyramine and colestipol may bind metolazone, -:. Nephrotic syndrome
preventing its absorption .:. Hypertension
.:. NSAIDs may reduce the antihypertensives effects "I .:. Primary hyperaldosteronism
metolazone (;ontraindications
,-, P
Key issues to note - regnancy
-:. Hyperkalaemia Breast feeding
.:. Metolazone increases urination therefore take early in the <l.ly .:. Hyponatraemia
to prevent sleep disturbances 0:. Addison's disease •
~ ~ Severe renal impairment
.:. Metolazone may cause sensitivity to sunlight, advise patierll" It, I .. Hypersensitivity to spironolactone
avoid prolonged exposure to sunlight

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 PRE
I 1&
Dose
Congestive heart failure: 100mg daily, increased to 400mg daily, in
\.1 ~:::::t~f:~::t7cs
"'1 .
1II I'1
induce diuresis by elevating the osmolarity of the
glomerular fll~rate, thereby hindering the tubular re-absorption of
severe cases. Maintenance dose 25-200mg/day i.::... water. Excretion of sodium and chloride is increased.
Oedema: initially I OOmg daily, maintenance is 25-200mg daily •
Hypertension: 25-1 OOmg once daily MA~NITOL _
Nephrotic syndrome: 100-200mg/day Available preparatio~ Intravenous infusion 20%
Pharmacokinetics
Side effects
Fever F~lIowing intravenous infusion, mannitol is excreted rapidly by the
.:. Ataxia
.:. Weakness kIdneys before any significant metabolism can take place in the liver.
.:. Nausea and vomiting
Headache
.:. Confusion Indications
Impotence
.:. Diarrhoea .:. Cerebral oedema
Skinrash
.:. Dehydration .:. acute aucom
Drowsiness
.:. ~ Deepening of the voice .:. Acute renal failur due to ~assive haemorrhage, trauma,
Renal impairment
.:. 'll\l! Menstrual irregularities shock and major surgery
Gynaecomasticia
.:. ~~ Hyperkalaemia .:. To promote urinary excretion of toxic substances e.g. lithium
.:. Hyponatraemia and salicylates
Drug Interactions Contraindications (
.:. Serum concentration of digoxin may be increased when given .:. Pulmonary oedema .
together with spironolactone .:. Intracranial bleeding 9
.:. • NSAIDS may decrease the antihypertensive effects of .:. Congestive heart fail~re
spironolactone .:. Hypersensitivity to mannitol
.:. Potassium supplements, ACE Inhibitors, angiotensin II .:. Severe dehydration
antagonists may increase the risk of hyperkalaemia caused by .:. Renal fai~est dose produces diuresis)
spironolactone
.:. Spironolactone may decrease the anticoagulants effect of Dose ,
Cereb~al oedema: by IV infusion I g/kg as a 20% solution
heparin
[)luresls: By IV infusion 50-200g. over 24 hours preceded by a test
Key issues to note dose of 200mg/kg by slow intravenous injection
.:. Spironolactone may be administered with food
.:. It may cause drowziness and impair ability to perform Side effects
activities requiring metal alertness .:. Oedema Headache
.:. Thromophlebitis Fever
OSMOTIC DIURETICS .:. Chills Thirst
These drugs include:- .:. Hypotension .:. Electrolyte imbalance
.:. Mannitol

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-353-
/
 Nicotinic acid Nicotinic acid Lowers LDL - cholesterol.
.:. Circulatory overload .:. Nausea and vomiting derivatives Increases HDL - cholesterol.
.:. Increased urinary frequency and urine volume Fibrates. Gemfibrozil Lowers VLDL Triglycerides
Increases HDL and LDL c h0 Iesterol
Drug interactions Others 0 . - 3 marine Lowers VLDL triglycerides
.:. Mannitol may increase the risk of digoxin toxicity associated
triJ:!lycerides.
with mannitol induced hypokalaemia
STATINS
10.1.4 DRUGS FOR HYPERLlP1DAEMIA Statins includes drugs such as:-
Hyperlipidaemia refers to the presence in the blood of an abnormally •••
• S'Imvastatin
high concentration of cholesterol and/or triglycerides in the form of
.:. Atorvastatin
lipoproteins. .:. FIl,AIClStaXin
It may be divided into two:- .:. Pravastatin
.:. Primary hyperlipidaemia Mode of Action
.:. Secondary hyperlipidaemia Statins competitively inhibit 3- h dro
(HMG-CoA) reductase enzy Yh xy-3methylglutaryl co-enzyme A
Wt hyperlipidemia is where the raised plasma lipid concentration
e~5me
Primary . me, t e rate limiting .
$yntheSls especially in the liver. In cholesterol
is the result of a genetic defect.
Secondary hyperlipidaemia may be due to metabolic problems such SIMVASTATIN "
as diabetes mellitus, chronic renal failure, excessive alcohol intake.
Available preparations: Tablets IOmg, 20mg
hypothyroidism etc. l
The main risk is atherosclerosis in which fatty deposits called atherom. Available brands: ~ocor®, Athenil®, Zosta®
build up in the arteries, restricting and disrupting the flow of blood. The '11 Slmvax® ' S'Imvas ®
R,
S'Imstat@
'
restriction of blood flow may lead to formation of blood dot resultirw
I' larmacokinetics
into a stroke or heart attack.
Drugs used in the treatment of hyperlipidaemia indude:-
.:.
.:.
.:.
.:.
Statins
Bile acid binding resins
Fibrates
Nicotinic acid and its derivatives
)' $Irnvastatin is absorbed from t he gastrointe f I
tlu<tensive first-pass metabolism in the .
I'll metabolites and a small

.:.
.
Indications
percentage In urine.

Prima'! hyperchol~sterolemia
j
s Ina tract, undergoes
~Iver. and excreted in the faeces

.:. Others (omega 3) .:. Combined hyperlipidaemia

Common Drugs for hyperlipidemia and their effect on different lipid" .:. Prevention
mellitus of cardiovas cu Iar events In
. patients with diabetes
Drug effect on lipids
Drug group Example
.:. Ho mozygous familial hypercholesterolemia
Bile acid binding Cholestyramine
Lowers LDL - cholesterol
(
Colestipol .1I11t:raindications
resins Lowers LDL - cholesterol and
Simvastatin <- Hypersensitivity to Simvastaf
Statins
Atorvastatin -:- Active liver disease In
Triglycerides.

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-355-
 )
Qa!e~1'Q:t:1jl~,d"w,
Indications '------
.:. Pregnancy :;: ~ombin.ed or mixed hyperlipidaemia

d
~ebventlon
la etes of cardiovascular events in patients with type 2
.:. Breast feeding
Dose
Initially IOmg at night adjust according to response at intervals of 4 .:. p.
nmary hypercholesteroleml'a
.:. Homozygousandhetero
weeks to 40mglday. ... Contraindications zygousf ' , hypercholesterolemia
amillal
Side effects Dizziness
.:. Headache .:. Hypersensitivity to atorvastat'
Abdominal pain .:. Active liver disease In
.:. Nausea flatulence .:. Pregnancy
.:. Constipation Diarrhoea .:. Lactation
.:. Myalgia Peripheral neuropathy
.:. Skin rash Pancreatitis Dose
.:. jaundice Adults: initially IOmg daily ad' d
of 4 weeks to 40mg/day max J~~te according to response at intervals
Drug Interactions Children: . mg per day.
.:. Simvastatin slightly enhances anticoagulant effect of warfarin
t:. Concomitant use with digoxin may cause a slight elevation 01 I IO-17years: IOmg once daily
serum digoxin concentration l1\\ Prevention
Sid" of c ardO,ovascular events: IOmg once daily
Key.:.issues to note
Advise female patients of child bearing age to use two effectivl' \ e ellects
forms of contraception to avoid becoming pregnant unless sill' ! 0:. Insomnia Dizziness
\ .:. Weight gain Chest pain
is abstaining I .:. Back pain Malaise
.:. Advise the patient to report symptoms of myalgia, mus< h'
.~. Nausea Headache
m('.ll~
tenderness or weakness .:. Skin rash Muscle pain or weakness
.:. Advise the patient to take the drug with out regard to
0:0 Impotence Tinnitus
preferably in the evening for increased effect
.:. Anorexia Peripheral neuropathy
.:. Dosage adjustments should be made
', -:- Angina
every 4weeks. If the cholesterol level falls below the tar~:<l' , I
,~.,'ug Interactions
" -:. Atorvastatln . may increase th '
range, dosage may be reduced _:. Digoxin, itraconazole e anticoagulant effect of warfarin.
' oral contraceptiv
at orvastatin blood concent t' es may increase
ATORVASTATIN , fl ra Ion result' .
In ammation pain and k Ing Into severe muscle
Available preparations: Tablets IOmg, 20mg .;. A ' ' wea ness
Available brands: lipitor®, Atorva®, Atostin®, lipiget®, ntaClds, colestipol and propranolol decreases atorvastatin
activity

Pharmacokinetics <- C1arithromycin

of atorvastatin and eryth romycln
' elevate plasma concentrations
Atorvastatin is rapidly absorbed from the gastrointestinal t I ,1' I I

undergoes first-pass metabolism, metabolised in the liver and ex( \." .... '
as metabolites in bile.
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-357-
Key issues to note

the evening
PRECISE PHARMACOLOGY]

•:. Take atorvastatin with out regard to meals but preferably in

Contraindications
.:. Severe renal impairment
.:. Patients hypersensitive to gemfibrozil
j .

.:. Advise the patient to report symptoms of myalgia, muscle .:. Alcoholism
tenderness, weakness or gastric upset .:. Gall stones
.:. Female patients of child bearing age should be advised to use .:. Hepatic impairment
effective contraception .:. Breastfeeding
FIBRATES
Fibrates are suitable for treatment of moderate hypercholesterolaemia
,~
I
.:. Pregnancy

especially when there are low levels of HDL-cholesterol or increased Adult dose
triglycerides. Adults: 600mg twice daily given 30minutes before breakfast and
Examples Supper.
•:. Gemfibrozil !" Children: Not recommended .
.:. j., Fenofibrate
Side effects
Mod~ of action .:. Dyspepsia Dizziness
They inhibit peripheral lipolysis and decrease hepatic excretion 01 .:. Abdominal pain Diarrhoea
free fatty acids, this reduces hepatic triglyceride production, inhibit" .:. Constipation Nausea
synthesis of VLDL carrier apolipoprotein, decreases VLDL productiol' .:. Vomiting Rash
and increases HDL concentration. .:. Vertigo .:. Taste disturbance
.:. Reduced libido Dry mouth
GEMFIBROZIL .:. Headache
Available preparations: Capsules 300mg Myalgia
.:. Fatigue
Tablets 600mg
!)rug Interactions
Available brands: Lopid®
.:. Gemfibrozil may improve glucose tolerance and have an
Pharmacokinetics additive effect with insul(n or sulphonylureas
Gemfibrozil is readily absorbed from the gastrointestinal tract; prot(·" I .:. Gemfibrozil enhance anticoa¥ulant effect of coumarins
binding is about 96% excreted mainly in urine and a small amount III
I(...,y issues to note
faeces.
.:. Gemfibrozil may cause dizziness or blurred vision, warn the
Indications patient not to drive or operate machinery which may require
.:. Severe hypertriglyceridaemia with risk of Pancreatitis (adjull( I mental alertness
to diet) .:. Advise the patient to report side effects when they become
.:. Mixed hyperlipidaemia and dyslipidaemia associated with severe
diabetes
tt,NOFIBRATE
.:. Hypercholesterolaemia ~
AVIlllable preparations: Capsules 200mg
.:. Primary prevention of cardiovascular disease in rhen with
III
hyperlipidaemia .. AVrlllable brands: Lipicard®

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 ", , ' , PRECISE PHARMACOLOGY

•
Pharmaco~inetics
77
d when taken with food, distributed
BILE ACID BINDING RESINS
These drugs include:-
.:. Colestyramine
Fenofibrate IS well absorbe . etabolized in the liver and
widely, crosses the placenta. It IS m .:. Colestipol
excreted in urine. ,", Mode of Action
Indications These drugs bind bile acids in the intestinal lumen, preventing their
.:. Hyperlipidaemias re-absorption and increasing bile acid excretion in the faeces. This
increased excretion of bile acids results in an increased oxidation of
Contraindications cholesterol to bile acids and the lowering of serum chole~erol.
.:. Gall bladder disease
.:. Severe hepatic and renal impairment COLESTYRAMINE
Available preparations: Powder 4gm/sachet
.:. Pregnancy
,1
\
.:. Breast feeding Available brands: Questran®
il:\
.:. Hypersensitivity to fenofibrate
I!,I'I Indications
lii~I, Dose ' I .:. Primary hyperlipidaemia
I Initially 200mg daily taken during a main mea .:. Pruritus associated with partial billiary tract obstruction
.:. Hypercholesterolemia
Side effects
.:. Abdominal pain .:. Skin rash Contraindications
..:. Urticaria .:. Complete Billiary obstruction
.:. Nausea .:. Pruritus .:. Patients hypersensitive to cholestyramine
.:. Vomiting :.
... Vertigo .:. Active peptic ulcer disease
.:. Diarrhoea .:. Fatigue
.:. Flatulence t)o~e
.:. Headache Adults: Initially 4g twice a day increasing to maintenance dose over
~,4 weeks to the usual range of 12-24g daily in 2-3 divided doses max
lrl~ daily.
Dr~.g i~~~~:;:~senhances oral anticoagulant effect and may l'tmrltus: initially 4g 1-2times a day., Mix with water or juice
increase risk of bleeding " d
, . d muscle toxicity if fenoflbrate IS use _let.· effects
.:. There IS mcrease . 'b'
'th HMG~CoA reductase mhl Itors .:. Constipation Nausea
concurrentIy WI .:. Vomiting Rash
-:. Headache Dizziness
Key issues tO ndotfe ct'lon the dose of fenofibrate may need to be -:. Abdominal pain Flatulence
.:. In renaI ys un ,
t.t "K Interactions
.:. ~:~~~~~ate should always be taken with f~~o enhance its ,to Colestyramine may reduce absorption ofother oral medications
absorption \ such as paracetamol, thiazide diuretics, warfarin, tetracycline,
digoxin and folic acid

-362-
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 2 'II PRECISE PHARMACOLOGY] " PRECISE PHARMACOLOGY
.:. Long term use of colestyramine may interfere with absorption Drug Interactions
of fat soluble vitamins .:. Colestipol may delay or reduce the absorption of oral drugs
such as digoxin, propranolol and tetracycline
Key issues to note
.:. Advise the patient to take other medication one hour before Key issues to note
or 4 hours after cholestyramine .:. Advise the patient to take granules with alot of water
.:. Advise the patient to maintain adquate oral fluid intake to .:. Advise the patient to take other drugs atleast I hour before
avoid constipation especially with high doses or 4 hours after colestipol I~
.:. Advise the patient to take colestyramine at meal time
1Iil'

COLESTIPOL
Available preparations: Granules Sglsachet
Available brands: Colestid®
l.
Pharmacokinetics
Colestipol is not absorbed from the gastrointestinal tract but binds bill'
acids in the intestines and is eliminated in faeces.
Indications
.:. Hyperlipidaemia
.:. Hypercholesterolemia
.:. Diarrhoea associated with excess bile acids

Contraindications
.:. Hypersensitivity to colestipol
.:. Complete billiary obstruction
.:. Hypovitaminosis

~~~~y Sg 1-2 times daily, increasing gradually at intervals of 1-2 monti", I' :11.1.1 1
up to 30g daily in a single dose or 2 divided doses as necessary
(Mix the granules with milk, juice etc)

Side effects
.:. Abdominal discomfort 0 .:. Constipation
.:. Nausea \ .:. Faecal impaction
.:. Flatulence .:. Hemorrhoids
.:. Vomiting .:. Skin rashes
.:. Irritation of the tongue

-363- -364-
 , , ' , ISf PHARMACOLOGY IIKn:n"F 1 7

J &1
Contraindications
.:. Haemophilia .:.
Thrombocytopenia
CHAPTER ELEVEN .:. Severe hypertension .:.
Severe liver disease
.:. Recent eye surgery .:. Tuberculosis
BLOOD AND BLOOD FORMING ORGANS ", .:. Peptic ulcers
11.1.1 ANTICOAGULANTS .:. Known hypersensitivity to heparin
These are drugs which. prevent the clotting of blood. Anticoagulants .:. Acute bacterial endocarditis
help to maintain normal blood flow in people who are at risk of clot Dose
formation. They can either prevent the formation of blood clots or Deep venous thrombosis, pulmonary embolism and unstable
stabilize an existing clot so that it does not break. angina~
Anticoagulants are divided into two: - Adults: By IV injection, loading dose of 5000 units (10,000 units in
.:. Parenteral anticoagulants severe pulmonary embolism), followed by continuous infusion of 18
•:. .Oral anticoagulants units/kg/hour or by Sc injection of 15,000 units every 12hours.
" Children and small adults: loading dose 50 units/kg then IS - 25
PARENTERAL ANTICOAGULANTS units/kg/hour by intravenous infusion Or subcutaneous injection of 250
These drugs are normally used when immediate action is required. units/kg every 12hours.
Examples:-
Side effects
.:. Heparin
.:. Hemorrhage .:. Anaphylaxis
.:. Enoxaparin (low molecular weight heparin)
.:. Hyperkalaemia
Headache
HEPARIN .:. Chills
Nausea and vomiting
.Available preparations: Injection 5000 IU/ml .:. Epistaxis
Urticaria
.:. Thrombocytopenia
Available brands: Cal-heparin®, Heparen®
[)rug Intera~~ions
Pharmacokinetics .:. Heparin increases the risk of haemorrhage when given
After intravenous or subcutaneous injection, onset of action I', together with oral anticoagulants like warfarin
immediate, within 1-2 hours. Heparin is extensively bound to piasli 101 I<.llly issues to note
proteins and is excr~ in the urine mainly as metabolites. .:. Advise the patient to report any signs of bleeding from the
Indications gums, under the skin, urine or stool
.:. Deep vein thrombosis .:. Advise the patient to limit alcohol intake during treatment
.:. Pulmonary embolism I .:. Do not administer 1M due to pain, irritation,and hematoma
formation
.:. Prophylaxis in general and gynaecological surgery
.:. Prophylaxis in orthopaedic Surgery .:. When given together with oral anticoagulants, heparin
.:. Myocardial infarction should be withdrawn once effective oral anticoagulation is
established
.:. Unstable angina

-365- be -366-
, ",:, , ' " , ,,' PRECISE liLIIlGY " ,': " ': I, '1"1' , ' , ' : ,"', ":,,' PREC ARMACO
' I I I I I

Thromboembolic disease in pregnancy: By subcutaneous injection

ENOXAPARIN
Injection 20mg, 40mg, 60mg, early pregnancY,body weight:
Available preparations:
Over 90kg: IOOmg twice daily
80mg 70 - 90kg: 80mg twice daily
IOOmg
Clexane®, Lomoh®, Parine® 50 - 70kg: 60mg twice daily
Available brands:
Less than SOkg: 40mg twice daily.
Pharmacokinetics
Enoxaparin is rapidly absorbed after subcutaneous injection, metab~lised Side effects
.:. Thrombocytopenia
in the liver and excreted in urine, as unchanged drug and metabolites.
.:. Mild bleeding
.:.if Irritation and pain at injection site
Indications
.:. Prophylaxis of thromboembolic disorders associated with .:. Hypersensitivity and erythematic reactions
orthopaedic or general surgery
, Drug interactions
.:. Unstable angina
.:. Aspirin may increase the risk of bleeding when given
.:. Deep vein thrombosis
concurrently with Enoxaparin
.:. Myocardial infarction
.:. Oral anticoagulants may give additive anticoagulant effect
.:. Pulmonary embolism
when given together with Enoxaparin
Contraindications
.:. Hypersensitivity to enoxaparin Key issues to note
.:. Peptic ulcer .:. Advise the patient to report any unusual bleeding or bruising
.:. Severe or uncontrolled hypertension to the clinician.
•:. Acute bacterial endocarditis
.~ Major bleeding disorders ORAL ANTICOAGULANTS
.:. Haemorrhagic stroke Oral anticoagulants are effective in primary and secondary prevention
.:. Drug induced thrombocytopenia (If venousthrombo-embolism.
Exampl~s:-
Dose
Prophylaxis of deep vein thrombosis (surgical patients): 20m}~ .:. Warfarin
2hours before surgery then 20mg every 24hours for 7 - 10 days WARFARIN
Orthopaedic surgery: 40mg 12hours before surgery then 40mg every Available preparations: Tablets 3mg, Smg
24hours for 7-IOdays. '
Prophylaxis of deep vein thrombosis in medical patients: 40m}~ Available brands: Marevan®
every 24hours for at least 6 days and max. 14days. . Pharmacol<inetics
Treatment of deep vein thrombosis or pulmonary embolism: I i Warfarin is readily absorbed from the gastrointestinal tract, crosses the
I.Smg/kg every 24hoLJrs for at least Sdays. 'I placenta but does not occur in significant quantities in breast milk. It is
Unstable angina~bcutaneous injection Img/kg every 12houl', , clxtensively metabolised in the liver, excreted in urin= and bile.
usually for 2-8days (minimum two days).
; "il:
ilil! -368-
-367-

Hit mL.
 ~;ae~1$ PHARMACOLOGY PRECISE PHARMACOLOGY
nutt I :' I I . I I

.:. Warfarin may be administered on an empty or full stomach

Indications .
.:. Prophylaxis of embolism in rheumatic heart disease and atrial .:. Adequate anticoagulation is not observed until about 3-4 days
after initial administration of warfarin, heparin should be used
fibrillation
.:. Prophylaxis after insertion of prosthetic heart valve concurrently if immediate effect is required
.:. Prophylaxis and treatment of venous thrombosis and pulmonary 11.1.2 ANTI PLATELET DRUGS
embolism Antiplatelet drugs inhibit thrombus formation by decreasing platelet
.:. Myocardial infarction aggregation. They are used to prevent further thromboembolic events
In patients who have suffered myocardial infarction, ischaemic stroke
Contraindications
or transient ischaemic attacks, or unstable angina.
•:. Hypersensitivity to the drug
.:. Peptic ulcer
Exa'1Ples
.:. Aspirin (low dose)
.:. Severe hypertension
.:. Clopidogrel
.:.
.:.
Bacterial endocarditis
Pregnancy
.:. Dipyridamole ~
.:. Alcoholism ASPIRIN
.:. Bleeding disorders Available preparations: Tablets 75mg, IOOmg

Dose Available brands: Ecorin®, Aspirem®, Ascard®,

Initially 5mg daily for 2 - 5days then adjust according to response to Bayer aspirin cardio®
usual maintenance dose of 3- 9mg daily.
Indications
Side effects .:. Acute myocardial infarction
.:. Haemorrhage Hypersensitivity
Diarrhoea .:. Unstable angina
.:. Rash I

.:. Jaundice Headache .:. Primary and secondary prevention of stroke

.:. Hepatic dysfunction Nausea
Pancreatitis
Contraindications
.:. Vomiting .:. ~hildren and adolescents under 16years
.:. Skin rash Urticaria
Abdominal cramps .:. Hypersensitivity to aspirin or NSAIDs
.:. Nausea and vomiting
.:. Aspirin sensitive asthma
Drug Interactions .' '. .:. Active peptic ulcer
.:. Drugs that decrease warfarin anticoagulant effec.t Include.- .:. Breastfeeding
alcohol, carbamazepine, phenytoin, cholestyramlne, .:. Haemophilia
rifampicin, oral contraceptives and vitamin ~. Dose
.:. Concomitant use with amiodarone, metronidazole, 15mg daily. 150-300mg daily may be required in acute conditions (MI,
cimetidine and streptokinase may increase the anticoagulalll Ilfllte ischaemic stroke, un~table angina)
effect of warfarin
~Ide Effect
IKey issues to note . .:. Bronchospasms
.:. Warn the patient that bleeding may Qccur especially at the
.i.'.,
'\ .:.()Nausea and vomiting
begining of treatment and with high Closes

-369- -370-

I'
\
 ~ARMACOLOGY 1111 PRECI~ •I : : u: I I

.:. Increased bleeding time ~> Breastfeeding

.:. Urticaria ~~ Severe hepatic disease
.:. Ringing in the ears
~~.~C!l
.:. Dizziness
~'~Iute coronary syndrome: initially 300mg then 75mg once daily
.:. Heartburn
rW111l aspirin)
.:. Gastro intestinal bleeding
Allute myocardial infarction: initially 300mg then 75mg daily (with
Drug interactions '" lIIWl~ll'in)
.:. Aspirin increases the risk of bleeding when given together ",'cwention of atherosclerotic events in peripheral artery
with oral anticoagulants, heparin ~j"t.lw\se, after myocardial infarction or ischaemic stroke: 75mg
.:. Aspirin decreases the diuretic effect of spironolacatone and 11111<:.. daily
frusemide
.:. Aspirin decreases the antihypertensive effect of captopril and .ldCl effects
beta blockers .:+ Dyspepsia .:. Headache
,~

Key issues to note <. Abdominal pain .:. Fatigue

.:. The drug should be administered with food <. Diarrhoea .:. Dizziness
.:. Avoid alcohol while taking aspirin. <. Bleeding disorders .:. Skin disorder
.:. Avoid use of OTCs preparations for pain without .c. Vomiting .:. Constipation
recommendation of a clinician <. Gastric and duodenal ulcer .:. Flatulence

CLOPIDOGREL O~'ug Interactions

Available preparations: Tablets 75mg <. Clopidogrel increases the effect of aspirin on platelets
Available brands: Plavix®, Clopi®, Deplatt® <. There is an increased intensity of bleeding when c1opidogrel is
given with warfarin
Pharmacokinetics
Clopidogrel is rapidly absorbed, extensively metabolized in the liver 1C41Iy issues to note
and is excreted in urine and faeces. -:. Clopidogrel may be administered without regard to food
Indications .:. C1opidogrel may cause dizziness and impair ability to perform
.:. Acute coronary syndrome activities requiring mental alertness
.:. Thromboembolic disorders including Ml, peripheral arterial .:. Clopidogrel may increase bleeding time, therefore inform the
disease and stroke dentist that you are on this drug
.:. Symptomatic atherosclerosis OIPYRIDAMOLE
.:. Acute myocardial infarction J\vililable preparations: Tablets 25mg, IOOmg, 200mg-R

Contraindications J\vOlilable brands: Persantin®

.:. Hypersensitivity to c1opidogrel Indications
.:. Active bleeding .:. Adjunct to warfarin therapy in prevention of post operative
thrombolytic complications of cardiac valve replacement

-371- -372-

'!11------------- ~~----~~
••..i:i:I:lillIlIlUU
 I ' , 'PRECISE PHARMACOLOGY
I
STREPTOKINASE
M,/ocardial infarction .
~ p
ondary prevention of ischaemlc stro ke Available preparations: Injection 1,500,000IU
.:. Sec
Available brands: stpase®
'l1dications
Contral ersensltlvlty
, , ' to d"d
Ipyn amo Ie Indications
.:. Hyp
.:. Acute myocardial infarction
Dose Orllg daily in 3-4 divided doses before food .:. Deep :vein thrombosis
300 - 60 .:. Pulmonary embolism

I.;
S'd Effects
,hrobbin~ headache
IJ,/potenslo n
.:. Skin rash
Facial flushing
.:. Acute arterial thromboembolism
Contraindications
.:. II Dizziness .:. Active internal bleeding
.:. M,/t1lgia .:. Recent trauma to the head
.:. Vomiting
.:. N ",u
""
sea
.:. Severe uncontrollable hypertension
IJ,/persensitivity reaction Diarrhoea
.:. II .:. Uncontrollable clotting disorders
.:. Intracranial surgery
Il1teractions . ' , .
Drug re is an increased risk of bleeding when dlpyndamole IS .:. Recent cerebral vascular accident
••• ,he
•
" h b I'
iven with anticoagulants, aspirin, t rom, 0 ytlCS an
d hepann
. .:. Severe allergic reactions ,~
.:. Recent abortion or delivery ( •
.:. JiPyridamole. may increase the hypotensive effect of
antihypertensives Dose "
Myocardial infarction: IV infusion I ,500,000units over 30-60
• lJe s to note
Key ISS dvise the patient to take drug on an empty stomach I hour minutes.
••• A Deep vein thrombosis, pulmonary embolism, acute arterial
• before or 2 hours after food ...' "
vise the patient to notify the cliniCian If she or he IS uSing thr~boembolism, arterial thrombosis: By IV infusion 250,000
.:. Ad units infused over 30minutes, then 100,000 units/hour for upto 12-72
other drugs that affect bleeding
hours according to the patient's condition.
1t-1ROMBOLYTICS . Side effects
I 1.1.3 Iytics are drugs used to break up or dissolve blood clots .:. Fever Nausea
bo
Throm already formed. Thrombolytic enzymes are used to lyse the .:. Headache Nephritis
, hat obstruct coronary or pu.Imonary art enes,
that have . .:. Skin rash and itching Hypotension
~rom~t / .:. Vomiting Malaise
ExampleS , .:. Convulsions
• Streptokinase
••• Ilrokinase .:. Superficial bleeding at punctu~ site
.:. lJ
Drug interactions
de of ,Action . .
Mo by converting plasminogen to plasmin which catalyses the .:. Heparin, oral anticoagulants, aspirin, dipyridamole may
They act n of fibrin and therefore is able to dissolve blood clot, increase the risk of bleeding when given together with
breakdoW Streptoki nase

-373- -374-
 ," , ", , " , " 'PREC PHARMACOL8GY
PRECISE PHARMACOLOGY
Epistaxis: Ig 3times daily for 7 days
11.1.4 ANTIFIBRINOLYTIC DRUGS
These drugs inhibit the dissolution of blood clots. Side effects
.:. Nausea .:. Vomiting
Examples'
.:. Diarrhoea .:. ',Hypotension
.:. Tranexamic acid
.:. Thrombosis .:. Disturbances in colour vision
TRANEXAMIC ACID
Available preparations: Tablets/Capsules 500mg 11.1.5 DRUGS USED IN THE TREATMENT OF ANAEMIA

Available brands: Tranlok®, Hemsamic® Anaemia is defined as a decrease in haemoglobin concentration below
Combinations: Tranfib-MF®(tranexamic acid/mefenamic that necessary for tissue oxygenation.
acid) 500/250 It may be caused by increased RBC loss, decreased production of
RBCs or increased destruction of RBCs.
Mode of action .
Tranexamic acid acts primarily by blocking the binding of plasminogen FERROUS SULPHATE
and plasmin to fibrin. Available preparations: Tablets 200mg
Pharmacokinetics Available brands: Cyano iron®, ferol®
Tranexamic acid is rapidly and completely absorbed from the ~IT, .

Indi~~ti7~11 deficiency anaemi~

crosses the placenta, distributes into breast milk. It is metabolized In II:,

the liver and excreted in urine.

Contraindications
Indications
.:. Menorrhagia . .:. Haemolytic anaemias
•:. Prevention of bleeding in prostatectomy and dental extractIon .:. Peptic ulcer disease
in patients with haemophilia .:. Patients receiving blood transfusion

-
.:. Haemosiderosis
.:. Epistaxis
.:. Thrombolytic overdose .:. Haemochromatosis
.:. Prophylaxis of herEtditary angioedema ~mll~···
Dose
Contraindications Iron deficiency anaemia 200mg2 - 3 times daily.
•:. Hypersensitivity to tranexamic acid Prophylaxis of anaemia 200mg daily.
•:. Severe renal impairment
.:. Thromboembolic disease Side effects
Dose .:. Constipation .:. Dark stool
Oral .:. Diarrhoea .:. Gastro-intestinal irritation
Menorrhagia (inhibited when menstruation has started): Ig 3 .:. Anorexia .:. Nausea
times daily for 3-4days .' .:. Epigastric pain
Hereditary angioedema: I-I .5g 2-3 times dally

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 " • I PRECISE PHARMACOLOGY
00_11
z Side effects
.:. Nausea .:. Headache
Drug interactions . .dine decrease the absorption of ferrous .:. Insomnia .:.
.:. Antacids and C1metl Irritability
sulphate . . rease the serum levels of ferrous
.:. Skin rash .:. Fever
.:. Chloramphenicol may mc .. .:. Diarrhoea .:. Bronchospasm
sulphate anti-infective effect of qUinolo nes Drug Interactions
.:. Ferrous sulphate decreases .:. Folic acid may decrease serum phenytoin concentrations
when given concurrently. . I .:. Antifolate drugs such as trimethoprim may interfere with folic
.:. The drug may be given WIth mea s acid metabolism and may cause deficiency in patients with low
folic acid stores
FOLIC ACID ., Tablets Smg .:. Chloramphenicol may antagonize the hematologic response
Available p r e p a r a t I o n s , . R
to folic acid
d' Foladd®, Asflic®, Folon®
Available bran s. VITAMIN 8 12 ,
Pharmacokinetics df his available in 2 forms namely:-
Folic add is rapidly absorb~ /0; the
to all body tissues, meta 0 I'ze
gastrointestinal tract, distribute( I
in the liver to the active form and .:. Hydroxocobalamin
.:. Cyanocobalamin
excreted in urine. Av.~arations: Injection t 000 microgram/ml
(Cyanocobalamin)
Indications . . e aloblastic anaemia . 1000 microgram/ml (Hydroxocobalamin)
.:. folate-defIcIent mg. h olytic states or renal dialySIS
h laxis in chronic aem Indications
.:. Prop y , tube defect in pregnancy
.:. Prevention of n~ura .:. Prevention and treatment of vitamin B'2 deficiency states
.:. Nutrition supphment .:.: Treatment of cyanide poisoning
.::..ntraindications
.:. Hypersensitivity to vitamin 8 12 ,
contraindicatdions dent malignant disease
.:. Folate epen . IlwHl
•:. Aplastic anaemia . . ""mlcious anaemia: 1M injection I000 microgram 3times a week for
.:. Hypersensitivity to folic aCId 111\\\:"Wl\ltlks, then 1000 microgram every 3 months(hydroxycobalamin).
: f~'1110-1 000 microgram on alternate days, for 1-2 weeks, then 250
Dose . . . Smg once daily for 4 months, up to ")\11. ~'1h Ic>gram weekly, until blood count is normal. maintenance dose 1000
loblastlc anaemIa.
Mega . labsorption states.. I '
daily may be given m ma d f t' 400 microgram daily b(' (,I' I 'lIlt Ingram monthly(cyanocobalamin)
. f neural tube e ec , '" "Iflhylaxis of macrocytic anaemias associated with
PreventIon 0 . frst '2 weeks of pregnancy.
ception and dunng the I I t be defect: Smg daily fro II \ III ".Muln B 12 deficiency: 1M 1000 microgram every 2-3 months
con f.. rency of neura u
Prevention 0 recur . til 12th week of pregnancy. II" ,It IIKocobalamin),
least 4 weeks before conception un
childrelr. 2 d '\y
folic acid deficiency: I ~ mg al
-378-
-377-
Tif ,"" ,."",

iF 1/11 lill PRECISE PHARMACOLOOfI

" : :::, , ": " PRECISE PHARMACOLOGY
Side effects ~)(.lle
.:. .:.
Ii
.:.
Itching
.:.
Fever
~i~rICt capsule/suscap/tablet once daily.
•
iii
;: I
.:.
Chills
Hot flashes .:.
Anaphylaxis
Nausea
.. ~Ide effects
.:. Dizziness .:. Hypokalaemia .:. Sensation of fullness
! I:
i
.:. Headache .:. Nausea and vomiting
i "
.:. Diarrhoea
Drug interactions .:. Constipation
.:. Aminoglycoside antibiotics, excessive alcohol and phenytoill
may decrease the absorption of vitamin B I2 from the GIT
.:. Chloramphenicol may antagonize the haemato-
poietic response to vitamin B I2
Key issues to note
.:. Vitamin BI2 should not be given before diagnosis is confirmed
except in emergencies
.:. Serum potassium levels should be monitored
.:. Do not use oral vitamin B I2 in malabsorption
.:. Patient should not discontinue treatment without consultin~:
the clinician
.:. Avoid alcohol while taking the drug

COMBINATION PREPARATIONS

FERROUS SALTS WITH FOLIC ACID

i.
Available preparations: Capsules
Suscaps
Tablets

Available brands: Akiferrin-F® , Fefol®, Fef®, Fefan®

Indications
.:. Prevention of iron and folic acid deficiencies in pregnancy, after
delivery and lactation
Contraindications
.:. Known hypersensitivity to any of the ingredients I~
11

.~,
",11

-379- II
-380-

1111'I,""!IIIIIIIIi"
 PRECISE PHARMACOLOGY
SULFONYLUREAS
Sulfonylureas are structurally related to sulfonamides. They are divided
,I
Into generations as follows;
C~~Pl'ER TWELVE
First generation
ENDOCRINE A~D METABOLIC DRUGS .:. Tolbutamide
12. 1.1 DRUGS USED I~ DIABETES MELLITUS .:. Chlorpopamide

Diabetes mellitus is a chronit diSorder characte~ized by hyperglycaemia, •Second generation

altered metabolism of carbohYdrates, proteins and fats, due to insulin : .:. Glibenclamide ..
deficiency or resistance. •:. Glimepiride
.:. Gliclazide
~..
'.'
.
Classification of Diabetes Mellitus
.:. Glipizide
Diabetes mellitus is classified into two:-
.:. Type I diabetes mellitus Mode of action
k .:. Type 2 diabetes mellitus Sulfonylureas act by stimulating insulin secretion from the beta cells of
, the pancreas thus inreasing insulin levels. Increased insulin secretion
IllType I diabetes mellitus
I'csults in lowering of blood glucose levels. These drugs are only effective
This type of diabetes is d~e to autoimmune destruction of the beLl
In the presence of functioning beta cells.
cells. It is more common i~ yOUng children than adults. Patients wltll
type I diabetes require eXOgenous insulin for survival. TOLBUTAMIDE
Type 2 diabetes mellitus . .
Available preparations: Tablets 500mg !
Type 2 diabetes usually prllSents in obese adults and family history 1\ .~harmacokinetics
very strong. It is caused bYinsl.llin dificiency and insulin resistance. 'rolbutamide is readily absorbed after oral administration, metabolised
III the liver and excreted in the urine and faeces chiefly as metabolites.
Drugs used in the treatme~t of diabetis mellitus include:-
.:. Oral antidiabetic drugS Indications
.:. Insulin .:. Type 2 diabetes mellitus
Oral antidiabetic drugs C:ontraindications
Oral antidiabetic drugs an~ uS~d in the treatment of type 2 diabetes .:. Severe hepatic and renal impairment
mellitus which has not respOl)ded to life syle modification. .:. Presence of ketoacidosis
.:. Breast feeding
Classification of oral antidiabetics .:. Pregnancy
Oral antidiabetics are c1as~ifiecl as follows:- .:. Porphyria
.:. Sulfonylureas .:. Insulin dependent diabetes mellitus
.:. Biguanides
Dose
.:. Thiazolinediones
Adult 500 -1500mg daily in 2 divided doses. Max. 2g daily.
•:. Alpha-glucosidase in~i bitors

-382-
-381-
 I II I \, j I \ \\1 r'l\ ,I \ \ I', \ '\ ) I '\\
PRECIS COLOGY
r WES " [,,, .. ' .. ",', " "I , i: I' l

Indications
Side effects .:. Type 2 diabetes mellitus
.:. Diarrhoea
.:. Nausea and vomiting
.:. Skin rash , Contraindications
.:. Constipation
.:. Tinnitus
.:. Dyspepsia .:. Presence of ketoacidosis
.:. Taste alteration
.:. Hypoglycaemia .:. Type I diabetes mellitus
.:. Headache .:. Severe renal and hepati~im . ment
.:. Pregnancy and breastfee ng
Drug Interactions
.:. Betablockers may mask hypoglycaemic symptoms caused by .:. Previous hypersensitivi to the drug

tolbutamide Pose
.:. Hypoglycaemic effect caused by tolbutamide may be reduced Itl,ltlally Smg in the morning, dose adjusted according to response max.
by corticosteroids ISmg/day. '
.:. Disulfiram-like reaction may occur when tolbutamide is takell
Side effects
concurently with alcohol
.:. Headache Dizziness
.:. Hypoglycaemic effect of tolbutamide may be increased by
.:. Weakness Nausea
sulfonamide antibiotics,ranitidine and cimetidine
.:. Epigastric fullness .:. Weight ~;;?!n
Key issues to note .:. Hypoglycaemia .:. Heart burn
.:. Tolbutamide should be given with or imediately after food
.:. Elderly, debilitated patients and those with impaired renal 01 Drug interactions
hepatic function usually require a lower initial dose .:. Beta blockers may mask warning symptoms of hypoglycaemia
.:. Because of its complete metabolism, and short duration of caused by glibenclamide
action, it is recommended in the elderly .:. Hypogly~aemic. eff~ct of glibenclamide is reduced by
.:. The drug should not be taken at bed time because of the drugs which are Insuhn antagonist such as bendrofluazide oral
potential for nocturnal hypoglycemia contraceptives,and glucocorticoids '
.:. Avoid alcohol while taking tolbutamide .:. Metformin has a synergistic hypoglycaemic action with
glibenclamide
.:. ~Icohol in~reases hypoglycaemic effect caused by
GLiBENCLAMIDE
ghbenclamlde and may also cause disulfiram - like reaction
Available preparations: Tablets Smg
.:. An enhanced hypoglycaemic response to glibenclamide
Available brands: Daonil®, Glibol®, Glibetics®, Euglucoll(l~) may occur when given together with drugs such as aspirin
Betanase®, Diaben®, Glamide®
cimetidine, fluconazole, and ketoconazole '
Combinations: Duotrol® (Glibenclamide/metformin) 5/',011 ~.Y issues to note .'
.:. Glibenclamide should be given with or 30 min. before a meal
Pharmacokinetics .:. Warn the patient of the possibility of hypoglycaemia and advise
Glibenclamide is reliably and almost completely absorbed when ~',IVltl' ,
on how to manage it
orally, metabolized in the liver to weakly active metabolites and excn'lull "
.:. Encourage the patient to maintain life style modifications
in urine and faeces

-383- -384-
 , , ',:, 'PREC11JPHARMACOlOGY
" ,
.:. Beta blockers may increase the hypoglycaemic effect of
Glibenclamide tablets should be stored in a cool dry place Clml: !
l
glimepiride and mask signs of hypoglycaemia
protected from ligh
.:. Corticosteroids, lithium, thiazide diuretics may decrease the
Avoid alcohol while taking the drug
effects of glimepiride
GLiMEPIRIDE .:. Glimepiride may increase the effects of oral anti agulants
Available preparations: Tablets I mg, 2mg, 3mg, 4mg .:. Antacids enhance rate of absorption of glimep' Ide
.:. ACE Inhibitors increase the risk of hypoglyce ia caused by
Available brands: Amaryl®, Euglim®, Diapride® glimepiride
Glyree®
Key issues to note
Pharmacokinetics .:. Avoid alcohol while taking this drug
Glimepiride is well absorbed, crosses the placenta and enters into brca"l

~
.:. Advise the patient not to discontinue the drug without
mille It is metabolized in the liver and excreted in urine and feaces.
,. consulting the health care provider

I,j Indications
.:. Type 2 Diabetes mellitus
.:. The drug may be taken with breakfast or the first main meal of
the day \
f
"i ,1: 'Contraindications GLiPIZIDE
,~

I .:. Ketoacidosis Available preparations: Tablet Smg

.:. Severe hepatic impairement
Available brands: Glynase®
.:. Pregnancy
Pharmacokinetics
'f" .:. Severe infection
,I ,:
.:. Major surgery Glipizide is rapidly and completely absorbed from the GI tract, extensively
.:. Type I diabetes mellitus InE!tabolized in the liver to inactive metabolites and excreted in urine
Imd a small amount in faeces.
,I Dose
Initially I mg once daily, adjusted according to response in I mg steps .11 'ndications
',\1. i'll,
1-2 week intervals, usual max. 4mg daily. .:. Type 2 diabetes mellitus
,il Contraindications
Side effects
\1~ .:.Weight gain .:. Hypoglycaemia .:. Diabetes ketoacidosis
, ~, .:.
, Headache
.:. Rash .:. Type I diabetes mellitus
III .:.Nausea
.:. Vomiting .:. Severe renal and hepatic impairement
.:.Drowsiness .:. Anorexia .:. Pregnancy and breastfeeding
I .:.Diarrhoea .:. Anorexia .:. Impaired adrenal and thyroid function
.:.Blurred vision .:. Tremor .:. Hypersensitivity to the drug
.:.Heart burn Dose
:'1 Initially 2.S-Smg daily, shortly before breakfast or lunch. Gradually
Drug interactions . .
111\ .:. Cimetidine, ranitidine, fluconazole, ciprofloxacJn may JncreJSC' IIlcreased if necessary, max. 20mg/day. (Doses> ISmg should be
,I' the hypoglycaemic effect of glimepiride "mn" diVided)
II :1
lili
-386-
II, -385-

f "I,
'I
 ISE PHARMAC[iJJi'JifI
I
.:. Type I diabetes mellitus
Side effects
"l .:. ..:. Constipation
.:. Pregnancy and breastfeeding
i Weight gain
II
.:.
III
, I,

:"1\1
: II
.:.
. :.
Heart burn
Vomiting .:.
.:.
Nausea
Headache
Altered taste se~sation
Dose
Initially 40-80mg daily, gradually increased if necessary, to 320mg daily
.:. Somnolence Doses above 160mg should be given in 2 divided doses
I 1'1
11
.:. D rowzi ness .:. Fatigue
Side effects
,'1
, I
, I .:. Nervousness .:. Hypoglycaemia
.:. Weight gain Diarrhoea
lil [ I .:. Nausea Rash
I
Drug interactions .
.:. Beta blockers may increase the hypoglycaemlc effect of .:. Vomiting .:. Dyspepsia
glipizide and mask signs of hypoglycaemia .:. Constipation
.:. Glipizide induced hypoglycaemia may be worsened by alcoh<.1 .:. Hypoglycaemia
intake . .:. Headache
•:. Thiazide diuretics may antoganize the hypoglycaemic action of Drug interactions
glipizide .:. Beta blockers may increase the hypoglycaemic effect of
~ Key issues to note gliclazide and mask signs of hypoglycaemia
.:. Avoid alcohol while taking glipizide .:. Alcohol increases hypoglycaemic effect caused by gliclazide
.:. The drug should not be discontinued without consulting the .:. Systemic miconazole increases hypoglycaemic effect caused by
health care provider gliclazide
.:. The drug may be taken with breakfast or the first main me,ll III .:. Gliclazide may increase the anticoagulant effect of warfarin
of the day Key issues to note
.:. The drug may be taken with breakfast or the first main meal of
GLiCLAZIDE the day
Available preparations: Tablets 80mg .:. Avoid alcohol while taking the drug

Available brands: Glycinorm® BIGUANIDES

iii'
l3iguanides are the drugs of choice in the treatment of type 2 diabetes
Pharmacoldnetics mellitus in over weight patient. They do not increase insulin secretion,
Gliclazide is readily absorbed from the GIl; extensively metabolized III
therefore do not usually cause hypoglycaemia or weight gain.
the liver to inactive metabolites and excreted in urine Metformin is the only available biguanide. It may be combined with a
ulIlphonylurea to provide better glycaemic control.
Indications
.:. Type 2 diabetes mellitus Mode of action
Bigllanides act by decreasing production of glucose by the liver and
Contraindications
•:. Hypersensitivity to gliclazide also promote the uptake of glucose by tissues.

~III .:. Diabetes ketoacidosis

.:. Severe renal and hepatic impairement
I,ll
'",J

-388-
-387-

:dil'IIlIlIlI_1I1111111111111111111111
 "'II

, '" ',' PRECISE PHARMACOLOGY

, '

.:. Nifedipine may enhance the absorption of metformin

METFORMIN
Tablets SOOmg, 8S0mg, 1000ITlg .:. Metformin may interfere with vitamin B12 absorption
Available preparations:
.:. Cimetidine increases peak metformin blood concentrations
Available brands: Glyformin®, Glucophage®, Glucomet®. Key issues to note
Metformin-Denk®, Glycomet®, Bigomet®, .:. Advise the patient not to change or discontinue the drug
Combinations: Avandamet® (rosiglitazone/metformin) 2/500 without consulting the prescriber
Pionorm-m® (pioglitazone/metformin) 30/500 .:. avoid alcohol during treatment
i I: .:. Advise the patient to take the drug with meals
Piosafe mf® (pioglitazone/metformin) 15/500
.:. Extended release tablets should be taken whole without
Pharmacokinetics
Metformin is slowly and incompletely absorbed when taken orally 1IIIl'i ." chewing or crushing
"
IIi'
11:1
Food delays or decreases the extent of absorption. It is excreted mainly ALPHA GLUCOSIDASE INHIBITORS
as unchanged drug in urine. Iii These drugs include:-
.:. Acarbose
Indications
.:. Type 2 diabetes mellitus i I Mode of action:
.:. Polycystic ovary syndrome They inhibit alpha-glucosidase enzymes in the small intestines, resulting
Into delayed digestion and absorption of starch and sucrose. This
Contraindications
•:. Renal dysfunction reduces the rise in blood glucose that occurs after meals.
.:. Pregnancy
.:. Hepatic dysfunction .:. Breast feeding ACARBOSE
.:. Acute metabolic acidosis Available preparations: Tablet 50mg, IOOmg
.:. Pancreatitis
Available brands: Glucobay®
Dose
Initially SOOmg with breakfast for I week, then 500mg with breakl.i·.t Pharmacokinetics
and evening meal for atleast I week, then SOOmg with breakfast, IUIl( II Acarbose's oral absorption is poor and unchanged drug remains in
and evening meal, max. 2g daily in divided doses. the gastrointestinal tract to exert effect. It is metabolized by intestinal
enzymes and microbial flora. Metabolites are excreted in urine and
Side effects
•:. Vomiting unabsorbed drug is excreted in faeces .
.:. Nausea
.:. Anorexia Diarrhoea Indications
.:. Rash Metallic taste .:. Type 2 diabetes mellitus
.:. Lactic acidosis .:. Abdominal pain
Contraindications
.:. Malabsorption of vitamin B12
.:. Inflammatory bowel disease
Drug interactions .:. Intestinal obstruction
.:. There is increased risk of hypoglycaemia when Metformin is .:. Hepatic and renal impairment
given with, Digoxin or Furosemide .:. Previous abdominal surgery .. / '
.:. Alcohol increases the risk of lactic acidosis associated with
metformin

-389- -390-

""il!'!""'IIIIIII_IIIIIIIIII~lm~II_IIIIIIIIIIIIIII:.: '!llIlIImlllllllllllllllli
 " , 1" PRECISE PHARMAC I GY I • II I I I

.:. Pregnancy Examples

.:. Breastfeeding .:. Pioglitazone
.:. Hernia .:. Rosiglitazone
Dose
':'1'11 Mode of action
illlll:II 'They
Initially SOmg daily, gradually increased to SOmg 3 times daily, In;reased I increase the sensitivity of peripheral tissues to insulin and may
after 6-8weeks to I OOmg 3 times daily if necessary. IIlso lower glucose production by the liver.

Side effects PIOGLITAZONE

.:. Flatulence Available preparations: Tablets ISmg, 30mg
.:. Diarrhoea
.:. Abdominal pain Available brands: Diavista®, Pioz®, Pionorm®, Glizone®,
.:. Abdominal distention Piosafe®
Pharmacokinetics
Drug interactions J)loglitazone is rapidly absorbed, undergoes extensive hepatic
•:. Acarbose may inhibit the absorption of digoxin metabolism and is excreted in urine and faeces .
.:. Beta blockers may increase the risk of hypoglycaemia Indications
.:. Intestinal adsorbents such as charcoal reduce the effect of .:. Type 2 diabetes mellitus
acarbose
.:. Colestyramine enhances the side effects of acarbose Contraindications
.:. Hepatic impairment
.:. History of heart failure
Key issues to note
.:. Combination with insulin
.:. Advise the patient to take the drug with the first bite of the
.:. Pregnancy
main meal .:. Breast feeding
.:. Inform the patient that hypoglycaemia may occur when .:. Type I diabetes mellitus
acarbose is used in combination with sulfonylnureas or insulin .:. Hypersensitivity to pioglitazone
.:. GI effects may be decreased by reducing starch content in the .:. Diabetic ketoacidosis
diet
Dose
Itlitially 15 -30mg once daily, increased to 4Smg once daily according
THIAZOLIDINEDIONES
Ie) response
They are also known as "glitazones"
. Thiazolidinediones have no effect on insulin secretion and are known Side effects
as insulin sensitizers. .:. Headache .:. Gastrointestinal disturbance
They are recommended for monotherapy for type 2 diabetes .:. Weight gain .:. Oedema
especially in over weight patients or in combination with metformin .:. Anaemia .:. Dizziness
or sulfonylureas. .:. Haematuria .:. Impotence
.:. Myalgia .:. Visual disturbance
.:. Pharyngitis

-391- -392-
 , ':' " : ' ':'1" PRECISE PHARMACOLOGY

Drug interactions :11111' Drug interactions

.:. Ketoconazole inhibits the metabolism of pioglitazone .:. There is increased effect when rosiglitazone is given wit
.:. Pioglitazone may alter the effect of oral contraceptives
.:. Gemfibrozil increases the plasma concentration of
III11111 gemfibrozil, fluconazole, pioglitazone or sulphonamides
.:. There is decreased effect when rosiglitazone is given with
pioglitazone
; ii III! carbamazepine, phenytoin. phenobarbital and Rifampicin
.:. Rifampicin decreases the plasma concentration of .:. Glucosamine may reduce the effectiveness of rosiglitazone
pioglitazone Key issues to note
Key issues to note .:. The drug may be taken without regard to meals
.:. Advise the patient to avoid alcohol during therapy .:. Advise the patient to avoid alcohol during treatment

ROSIGLITAZONE INSULIN
Available preparations: Tablets 4mg,8mg Insulin is a hormone produced by the beta cells of the pancreatic islets of
Reglit® langerhans. It plays an important role in the regulation of carbohydrate,
Available brands:
I. protein and fat metabolism.
Pharmacokinetics Insulin lowers blood glucose by inhibiting glycogenolysis and
Rosiglitazone is well absorbed when taken orally. extensively gluconeogenesis in the liver, stimulates glucose uptake by muscles and
metabolized in the liver and excreted in urine and faeces. >adipose tissues.
Insulin is used in the treatment of type I diabetes mellitus and is also
Indications used in type 2 diabetes mellitus in the following cases:-
.:. Type 2 diabetes mellitus .:. Severe infection
Contraindications .:. Major surgery
.:. Hepatic impairment .:. Ketoacidosis
.:. History of heart failure .:. During pregnancy
.:. When hyperglycaemiadoes notrespond to non pharmacological
.:. Combination with insulin
measures and oral antidiabetics
.:. Pregnancy
Sources of Insulin
.:. Breast feeding
.:. Known hypersensitivity to rosiglitazone 11111111: Insulin for therapeutic use is extracted from the pancrease of any of the
,
I'ollowing:-
Dose .:. Cattle
Initially 4mg daily, may be increased to 8mg daily in 1-2 divided dose', .:. Pig
.:. Human
Side effects 'fypes of insulin preparations
.:.Gastro-intestinal disturbance .:. Headache
rhere are 3 main types of insulin preparations which differ in time of
.:.Anaemia
.:. Oedema 11 Illlset and duration of action. They include:-
.:.Altered blood lipids .:. Diarrhoea
.:. Hypoglycaemia
.:. Fatigue
I .:. Short acting insulin e.g insulin soluble

.:. Increased appetite .:. Sinusitis It is the only insulin that can be given by IV bolus, IV infusion
.:.Back pain
.:. Weight gain or 1M

-393- -394-

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.:. Intermediate acting insulin e.g insulin zinc suspension(Lente) Drug interactions
Have slower on set of action but with prolonged duration of .:. Alcohol may increase the effects of insulin
action. They are formulated to dissolve more gradually when .:. Beta blockers may mask signs and symptoms of
administered hypoglycaemia
.:. Long acting insulin e.g glargine(lantus) Has duration of action .:. Corticosteroids antagonize effects of insulin and result in
of 24 hours increased glucose levels
!Insulin administration .:. ACE Inhibitors may increase the hypoglycaemic effect of
insulin
Iinsulin is usually given subcutaneously in the buttock, abdomen,
anterior thigh and dorsal arm. Absorption is usually most rapid frolll Key issues to note
the abdomen, followed by the arm then the buttock and thigh. .:. Advise the patient to watch out for symptoms of
The rate of absorption is increased by massage, hot bath or exercise, hypoglycaemia such as fatigue, confussion, headache, hunger,
The type of insulin used depends on the type of diabetes, patients age rapid breathing
and blood glucose levels. .:. Advise the patient to always carry a quick source of sugar to
~~

SOLUBLE INSULIN rectify hypoglycaemia when it OCcurs

Available preparations: Injection 100 IU/ml .:. Injection sites should be rotated to avoid lipodystrophy
ISOPHANE INSULIN
Available brands: Actrapid®
,Intermediate acting)
Indications I nsulin suspension modified by addition of protamine and/or zinc in
•:. Type I diabetes mellitus H:>rder to prolong the duration of action.
.:. Diabetic ketoacidosis Available preparations: Suspension for injection. 100 iu/ml
;I
.:. During pregnancy, surgery, trauma, infections and fever
Contraindications Available brands: Insulatard Hm®, Biosulin N®
.:. Hypersensitivity to insulin hl'ldications
.:. Hypoglycaemia .:. Diabetes mellitus
Dose
~ i ontraindications
Insulin dosage is individualized and determined in accordance willi 1'' 1 .:. Hypoglycaemia
needs of the patients, usual range 0.3-1 unit/kg/day :
.:. Hypersensitivity to insulin
.:. Intravenous administration,
Side effects
.:. Hypoglycaemia .:. Local reaction',
'~ose
.:. Skin rash .:. Urticaria
•:. Oedema .:. Abdominal blo,11 H'• ,. subcutaneous use: Adults and Children according to individual
I
~ i ~Iu irement.
.:. Fat hypertrophy at injection site .:. Blurred visioll

-395- -396-

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Available brands: Neo-mercazole®, anti-thyrox®

Side effects
.:. Hypoglycaemia Indications
.:. Allergic reactions .:. Hyperthyroidism including grave's disease
.:. Fat hypertrophy at injection site .:. Preparation for thyroidectomy in hyperthyroidism
Drug interactions .:. Adjunct to radio-iodine therapy ;!i

.:. Corticosteroids and diuretics may antagonise the effect of Contraindications

insulin .:. Hypersensitivity to carbimazole
.:. Beta blockers may mask signs of low blood sugar'
Dose
Key issues to note Hyperthyroidism: Initial dose IS-40mg daily, up to 60mg daily in
.:. Insulin need is increased during stress, infection, physical ~Invere cases, in divided doses for 4-8 weeks. Maintenance S-ISmg
activity or trauma <t<tily
.:. The injection sites should be rotated to prevent Children: Initially 2S0mcg/kg 3 times daily adjusted according to
·lipohypertrophy IChsponse.
•:. Educate the patient on self administration of insulin injection",
including timing of doses and monitoring blood glucose :\l:ide effects
.:. Inform the patient about the potential causes of ·:·Nausea Jaundice
hypoglycaemia e.g reduced food intake,diarrhoea,excessive .:. Headache Arthralgia
intake of alcohol and vomiting .:. Rashes .:. Vomiting
.:. Renal or hepatic impairment may reduce insulin requiremel' l .:. Pruritus Hair loss
.:. Mild leucopaenia
12.1.2 DRUGS FOR THYROID DISORDERS
.:. Bone marrow depression
HYPERTHYROIDISM (THYROTOXICOSIS) .:. Mild gastro-intestinal disturbance
Hyperthyroidism is over activity of the thyroid gland with consequelll HYPOTHYROIDISM
excessive secretion of thyroid hormones.
1 HypothyrOidism is a clinical syndrome resulting from deficiency of
.'1:.1'(11::1'

It is characterised by anxiety, tremors, weight loss, excessive

1 thyroid hormones.
sweating, increased appetite, moist palms, heat intolerance, ,

, II IS characterised with weight gain, puff face, fatigue, lethargy,

heat failure, diarrhoea, protruding eyes, menstrual disturbance,
iilii, ' Wcna I<ness, C onstipation, Cold intolerance, Hoarse voice,
palpitations.
dry course skin, heavy menstrual period, physical and mental
Drug used for hyperthyroidism include:-
~Iowness .
.:. Carbimazole
•:. Propylthiouracil In Children, parents may notice poor development and poor school
.:. Iodine solution aqueous ItCH'formance (permanent mental and physical retardation)

CARBIMAZOLE
I Available preparations: Tablets Smg

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-398-

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LEVOTHYROXINE (THYROXINE)
Available preparations: Tablets 100 mcg
CHAPTER THIRTEEN
Indications
DERMATOLOGICAL DRUGS
.:. Hypothyroidism .
•:. Diffuse non-toxic goitre
13.1.1 DRUGS FOR ECZEMA
Contraindications ~:(::r.ema (dermatitis) refers to a variety of skin conditions characterized
.:. Thyrotoxicosis by superficial skin inflammation and itching. Eczema may be acute
.:. Hypersensitivity to thyroxine with redness of the skin, papules, vesicles and blisters or chronic with
.htckening, scaling, pigmented and increased markings (lichenification).
Dose
Hypothyroidism 'types of Eczema
.:. Atopic dermatitis
Adult: Initially 50-100 mcg daily, preferably before breakfast.
.:. Contact dermatitis
Adjusted in steps of 25-50mcg every 3-4 weeks until normal
.:. Seborrhoeic dermatitis
metabolism is maintained usual maintenance dose 100-200mcg daily.
Cardiac disease, severe hypothyroidism and patients over 50
II l:>rugs used in the treatment of atopic dermatitis include:-
years: Initially 25mcg daily or 50mcg on alternate days adjusted in .:. Emollients
steps 25mcg every 4 weeks. .:. Topical corticosteroids
.:. Oral antihistamines
Side effects
.:. Antibiotics
.:. Angina pain Restlessness
.:. Keratolytics
.:. Diarrhoea .:. Vomiting
.:. Palpitation Skin rash ":mollients
.:. Tachycardia Sweating 1ll1ollients are hydrophobic agents that seal the surface of the skin
.:. Headache Fever ."d reduce water loss. Apply them twice daily preferably after bathing
.:. Flushing Tremor when the water content of the skin is at its greatest.
.:. Muscular weakness Heat intolerance
'l:)Cilmples
.:. Skeletal muscle cramps Hair loss in Children
.:. E45 cream,
.:. Excessive loss of weight
.:. Aqueous cream
Drug Interactions .:. Sudocream.
•:. Levothyroxine may increase the effect of oral anti coagulants
.:. Colestyramine may reduce the absorption of levothyroxine Antihistamines
.:. Amiodarone may affect thyroid activity and levothyroxine I hey relieve the itching associated with atopic dermatitis. Sedating
dosage may need adjustment ilfltlhistamines are preferred to non-sedating antihistamines.
•:. Anti epileptic drugs may reduce the effect of levothyroxine
iI
t'umples
I .:. Hydroxyzine
.:. Chlopheniramine

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Promethazine
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-

Contraindications
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.:. Cetirizine. .:. Acne vulgaris
Antibiotics .:. Broken skin
.:. Rosacea
Systemic antibiotics such as macrolides (erythromycin, azithromycill),
penicillins (Cloxacillin, Flucloxacillin, ampiclox) are recommended ill .:. Untreated bacterial, fungal or viral skin infections
the treatment of secondary bacterial infection associated with atopi< Dose
dermatitis. Apply film layer twice daily until improvement occurs, then less
Topical antibiotics are rarely used because of their potential to caw;(' rl'l:lquently, once a day or intermittently
hypersenstivity.
Side effects
.:. Atrophic changes

ill~
Topical Corticosteroids
They are used where emollients do not provide adequate relief. TI1l' .:. Worsening of untreated infections
patient's age, severity of the disease and site of involvement determilll' .:. Burning sensation or irritation of the skin
.:. Pimples
the type and strength of the topical corticosteroid to be used.
.:. Thinning of the skin
Examples
.:. Discoloration
.:. I" Hydrocortisone .:. Betamethasone
.:. Skin rash
.:. C1obetasol .:. Beclomethasone
.:. Fluocinolone .:. Mometasone furoate
I~ETAMETHASONE
.:. Triamcinolone acetonide .:. Diflucortolone
Available preparations: Cream 0.1 %, 0.5%
HYDROCORTISONE Ointment 0.1 %, 0.5%
Available preparations: Cream 1% Available brands: Betnovate®, Mediven®, Diproderm®,
Ointment 1% Diprosone®, Betaderm®, Elyvate®,
Available brands: Lucin®, Zona®, Dawacort®, Elycort®, Betasol®, Beprosone®
Metracort®, Hydrokant® Combination with antibiotics
In combination with antifungals .:. Diprogenta® (Betamethasone+gentamicin)
.:. Betaderm-N®
Candacort® (c1otrimazole + hydrocortisone)
.:. Betnovate-N®
Daktacort® (Miconazole + hydrocortisone)
Zaricort® (Miconazole + hydrocortisone) Combination with salicylic acid 3%
Decocort® (Miconazole + hydrocortisone) .:. Diprosalic
Unisten-HC® (c1otrimazole + hydrocortisone) .:. Beprosalic
.:. Mediven-S
Indications
Indications
.:. Atopic dermatitis
.:. Contact dermatitis .:. Atopic dermatitis
.:. Contact dermatitis
.:. Seborrhoeic dermatitis .:. Psoriasis

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.:. Intractable pruritus

.:. Insect bite reaction
Contraindications
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.:.
PRECISE PHAR

Prickly heat --
illllillii, Contraindications
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,i!I!II:
.:. Hypersensitivity to fluocinolone
.:. Untreated skin infections
i!11111I
.:. Untreated skin infection Broken skin , :!III!! .:. Rosacea
.:. Rosacea Peri-oral dermatitis ·i ' .:. Acne
.:. Peri anal and genital pruritus .:. Acne Dose
.:. Herpes simplex and chickenpox infection
Apply a thin layer to the affected area 1-2 times daily for not more than
Dose il weeks
Adults and Children over 2 years: Apply a thin layer 1-2 times daily Side effects
until improvement occurs, maintenance apply once a day or less ofterl .:. Skin irritation
Side effects .:. Acne
.:. Exacerbation of local infection .:. Decrease in skin pigmentation
.:. Skin irritation .:. Thinning of the skin
.:. Skin thinning .:. Wrinkled scars on the skin (striae)
.:. Striae .:. Dilated small vessels in the skin (Telangiectasia)
.:. Hypopigmentation . . CLOBETASOL
.:. Suppression of the hypothalamic pituitary adrenal aXIs with Available preparations: Creams 0.05%
prolonged use 'j,,',,',
Ointment 0.05%
.:. Acne at the site of application I'
Available brands: Dermovate®, Delor®, Cloderm®, Glyvate®
FLUOCINOLONE Tasol®
Available preparations: Cream Combinations
Ointment '~onaderm-GM® (c1obetasol + miconazole + gentamicin)
Gel MCG® (c1obetasol+miconazole+gentamicin)
Available brands: Synalar® Indications
.:. Eczema
Combination with antibiotics .:. Psoriasis
Synalar-N® (Fluocinolone + Neomycin) .:. Lichen planus
Avalon-NF® (Fluocinolone + Neomycin)
Indications Contraindications
.:. Eczema .:. Hypersensitivity to c1obetasol
.:. Psoriasis .:. Rosacea
.:. Intractable pruritus .:. Acne vulgaris
.:. Contact dermatitis .:. Peri-anal and genital pruritus
.:. Prickly heat .:. Neonates and infants
.:. Viral infections such as herpes simplex and chicken pox
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Dose ~'~~IIC!l
Apply a thin layer 1-2 times daily for up to 4 weeks Apply a thin layer to affected area once daily
Side effects
~ldll effects
.:. Striae .:. Hypopigmentation
I> Skin atrophy
.:. Thinning of the skin .:. Redness of the skin
.:. .:. Urticaria
.> Burning and itching of the skin
.:.
Pruritus
Skin atrophy .:. Acne form eruptions
<. Skin Irritation
.c. Striae
Key issues to note .c+ Hypopigmentation
.:. Longterm therapy should be avoided where possible, .> Allergic contact dermatitis
especially in infants and children as adrenal suppression call I> Secondary infection
occur
.:. If required for use in children, treatment should be review, -.1 1~4~Y Issues to note
weekly .c. If irritation or sensitization occurs, treatment should be
.:. If used on the face, treatment should be limited, if possible, II' withdrawn
5 days .:. Local and systemic toxicity is common especially when used on
If
.:. If applied to the eyelids, avoid contact of the preparation Willi a large area of damaged skin
the eyes
IHIClOMETASONE DIPROPIONATE
MOMETASONE FUROATE A\I'llllable preparations: Cream 0.025%,
Available preparations: Cream 0.1% Ointment 0.025%
Ointment 0.1 %
C;:(tmbinations
Lotion 0.1%
"t:1domin® (Beclomethasone+ miconazole + neomycin)
Available brands: Elocom® (' Mldid-B® (Beclomethasone+c1otrimazole)
I: Illben- G® (Beclomethasone + c1otrimazole + gentamicin)
Indications
.:. Eczema Itldlcations
.:. Psoriasis .:. Eczema
.:. Seborrheic dermatitis (lotion) .:. Psoriasis
C::ontraindications
Contraindications
.:- Untreated skin infection
.:. Hypersensivity to mometasone
.:. Broken skin
.:. Untreated bacterial, fungal and viral infections
":- Rosacea
.:. Wide spread plague psoriasis
.:. Acne
.:. Acne vulgaris
-:. Herpes simplex and chicken pox infection
.:. Perianal and genital pruritus

-405- -406-

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W!II

13.1.2 DRUGS FOR PSORIASIS

Dose
Apply a thin layer 2 times a day 1111111111'IIPsoriasis is a chronic, non infectious inflammatory skin disease
'1. lIi!;"characterized by enhanced epidermal proliferation leading to redness
of the skin, scaling and thickening of the skin.
Side effects '111i!'
.:. Skin irritation I,!'I Drugs used in the treatment of Psoriasis include;
.:. Skin thinning 'Topical drugs
.:. Striae .:. Moisturilisers Keratolytics
.:. Hypopigmentation . . .:. Vitamin D analogues Coal tar preparations
.:. Suppression of the hypothalamic pituitary adrenal axiS with
.:. Topical corticosteroids Retinoids
prolonged use
.:. Dithranol
.:. Acne at the site of application
Systemic drugs
DIFLUCORTOLONE VALERATE .:. Methotrexate
Available preparations: Creams O. 1% .:. Retinoids
Ointment O. 1%
I!mollients
Available brands: Nerisone® limollients are frequently used to help soften and soothe the skin
~hereby reducing scaling, cracking and dryness.. They are useful in
Indications I::cmditions characterized by dryness, scaling and cracking of the skin
•:. Eczema ijl/ch as psoriasis and eczema.
.:. Psoriasis
ICc~ratolytics
Contraindications I<.c~ratolytics such as saliclylic acid ointment 2%, 5%, 10% and 20% are
.:. Hypersensitivity to diflucortolon~va~erate. Ulu~d to break down keratin and soften skin which improves penetration
.:. Untreated bacterial, fungal and viral mfectlons I'll other drugs such as coal tar or corticosteroids.
•:. Wide spread plague psoriasis
Vitamin D analogues
Dose Ihls class of drugs includes calcipotriol. They are used in mild to moderate
Apply a thin layer 1-2 times daily for up to 4 weeks I:.hronic plaque Psoriasis. They regulate epidermal proliferations and
,hfferentiation and also have immunosuppressant properties. Patient
Side effects
.-r<:eptance is good since they do not smell or stain clothes and do not
.:. Skin atrophy
•:. Burning and itching of the skin II.-ye the risk of skin atrophy seen with topical steroids.
.:. Irritation
.:. Striae C.)al tar preparations
.:. Hypopigmentation ~. 01\1 tar preparations include crude coal tar ointment. It is preferred
.:. Secondary infection lwlimited or scalp psoriasis and has an advantage of inducing remission
~II psoriasis longer than other topical drugs. It's more effective than
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-407- -408-

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, ,' PREC HARMACOLOG
- - -
Anthracen Derivatives Dose
Dithranol Adult: Initially 25-30mg with food once a day for 2-4 weeks .
Dithranol decreases cell division and is very effective in healing plagl W Maintenance, basing on clinical response and tolerance: 25-50mg once
psoriasis. It may be used in increasing strength from 0.1 % upto 2%.but daily for further 6-8 weeks.
not on the face or genitalia. Children: Initially 0.5-1 mg/kg daily, max daily dose 35mg (though it is
Dithranol has a disadvantage of being irritant to normal skin and also not often recommended).
stains skin, hair and linen
Side effects
Topical corticosteroids .:. Vertigo
Topical corticosteroids have quicker onset of action than coal tar allil .:. Nail fragility .:. Sticky skin
dithranol. They may be useful when treating face and genitalia alld .:. Taste disturbance .:. Blurred vision
have an advantage of being clean and non irritant. Withdrawal of high .:. Impaired night vision .:. Somnolence
potency corticosteroids can produce a rebound phenomenon. .:. Dryness of the mucous membrane
Methotrexate Drug interactions
Methotrexate has cytostatic and immunosuppressant effect and it 1'1
.:. Acitretin decreases contraceptive effect of progestin only
very effective in the treatment of resistant and Widespread psoriasis. contraceptives
Retinoids (Vitamin A derivatives) .:. Acitretin inreases potential for hepatotoxicity caused by
Acitretin is used orally in the treatment of severe psoriasis resistant (., methotrexate
other forms of therapy. Most patients develop major side effects SUI II
Key issues to note
as dry mucuos membrane, itching and peeling of the skin.
.:. Women of child bearing age should use contraception during
ACITRETIN treatment acitretin
Available preparations: Capsules 10mg .:. Advise the patient not to use other vitamin A preparations
concurrently with Acitretin
Available brands: Neotigason®
SALICYLIC ACID
Indications Available preparations: Ointment 2%, 5%, 10%, 20%
.:. Severe extensive psoriasis resistant to other drugs Indications
.:. Keratinisation disorders S~,licylic acid is applied topically in the treatment of hyperkeratonic and
.:. Severe congenital ichthyosis i11111: ,c:nling skin conditions such as:
.:. Dandruff
Contraindications .:. Seborrhoeic dermatitis
.:. Hepatic and renal impairment .:. Psoriasis
.:. Pregnancy .:. Acne
.:. Breast feeding .:. Cutaneous warts
.:0 Corns and calluses

-409- -410-

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 PRECISE PHARMACOLOGY _liU.8 PRECI[fPHARMAcOLmij1l

Contraindications Available brands: Dovonex®

.:. Hypersensitivity to salicylic acid Indications
.:. Broken or infected skin .:. Plaque psoriasis
.:. Scalp psoriasis
Dose
Ointment: Apply 1-2 times daily Contraindications
Side effects .:. Hypersensitivity to calcipotriol
.:. Mild irritation .:. Disorder of calcium metabolism
.:. Skin ulceration Dose
.:. Excessive dryness Apply once or twice daily to the affected area. Less frequent applications
.:. Sensitivity '11ay be adequate after initial period.
COAL TAR Stop treatment after satisfactory improvement and re-start if disease
Available preparations: Ointment I'e-occurs.
h' Cream
':j\j" Shampoo Side effects
f Polytar®shampoo, Alphosyl® Cream
.:. Skin irritation
,Available brands: .:. Redness of the skin and scaling
Indications .:. Allergic contact dermatitis
.:. Eczema .:. Changes in pigmentation
.:. Psoriasis .:. Skin atrophy
.:. Dandruff .:. Photosensitivity
.:. Seborrhoeic dermatitis .:. Pruritus

Contraindications DITHRANOL
.:. Do not use on sore, acute in the presence of infection Available preparations: Ointment 0.1 %, 0.5%, 2%, 3%
.:. Hypersensitivity to coal tar Indications
Dose .:. Sub acute and chronic psoriasis
: I Apply 1-3 times daily, starting with the lower strength preparation Contraindications
,

Side effects .:. Acute and pustular psoriasis

II
.:. Irritation .:. Hypersensitivity to dithranol
.:. Acne like eruption of the skin Dose
.:. Stains skin, hair and clothes PIIooriasis: Apply to the affected part starting with a lower concentration
III •:. Photosensitivity (01-1 %) for at least 2-3 weeks or until the skin is entirely clear.
CALCIPOTRIOL Intermittent course may be needed to maintain response. Use with
Available preparations: Cream 0.005% foal tar may help to reduce the irritation without affecting efficacy.
I Ointment 0.005%

-411- -412-
 7
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BENZOYL PEROXIDE
Side effects
Benzoyl peroxide may be used with topical or oral antibacterial drugs.
•:. Local burning sensation
.:. Irritation Available preparations: Creams 5%, 10%
.:. Staining of skin, hair and clothing Gel 5%
.:. Allergic reaction
,Available brands: Panoxyl gel®, Oxy®, Benzox®
ICHTHAMMOL Indications
Available preparations: Ointment
.:. Acne vulgaris
Indications Contraindications
.:. Chronic Iichenified eczema
.:. Hypersensitivity to benzoyl peroxide
Contraindications
Dose
.:. Hypersensitivity to ichtham
Apply to clean skin twice daily starting with a lower strength of 5%
Dose j~'''' then gradually increase to 10%. Improvement ocucrs after 4 weeks.
Apply .1-3 times daily
Side effects
Side effects .:. Skin dryness or peeling
.:. Skin irritation .:. Skin rash
.:. Hypersensitivity reaction .:. Mild bleaching
.:. Mild stinging
13.1.3 DRUGS FOR ACNE . ' '. .:. Local dermatitis
Acne is a com mon condition caused by excessive production of the Skill • .:. Redness of the skin
natural oil (sebum) leading to blockage of hair follicles. It commonly .:. Allergic contact dermatitis
affects adolescents but may occur at any age.
Key issues to note
Acne primarily affects the face, neck, back and pustules.
.:. Wash affected area with mild soap and warm water prior to
Drugs used in the treatment of Acne include; application as this enhances beneficial effects
Topical preparations .:. Full benefit may not be seen until after 4-6 weeks
.:. Peroxides .:. If irritation occurs, apply less frequently or use a lower
.:. Retinoids strength preparation. If it persists or becomes severe stop
.:. Antibacterials treatment
.:. Avoid contact with the eyes, mouth and other mucuos
Systemic preparations
membranes
.:. Oral antibacterials
.:. Preparation may bleach clothes
.:. Retinoids
nETINOIDS
PEROXIDES .
Topical preparations in this group inc~ude Benzoyl Peroxide. They 'opical retinoids available in Uganda include; tretinoin and adapalene
have both antibacterial and keratolytic effects. illl(j systemic retinoids include; isotretinoin. They are effective in the
II tliltment of acne in which comedones, papules and pustules are

-413- -414-
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dominant. Oral retinoids such as isotretinoin are recommended in

severe acne.
, , , , , '" , , , PRECISE PHA

.:. Vitamin A supplements increase the risk of adverse effects

from isotretinoin
.:. Tetracycline may increase the risk of high pressure in skull
leading to headache, nausea and vomiting
ISOTRETINOIN
Tablets I Omg, 20mg Key issues to note
Available preparations:
.:. The drug is not recommended for the treatment of pre-
Available brands: Roaccutane®
pubertal acne and those less than 12 years of age
.:. Women of child bearing age should use contraceptives during
Indications
.:. Severe acne treatment
.:. Acute exacerbation of acne usually occurs in the initial phase
Contraindications of t~eatment, but subsides with continued therapy
.:. Hyperlipidaemia .:. AVOId exposure to intense sunlight
.:. Renal impairment
.:. Patients should be advised to use skin moisturizing ointments
.:. Hepatic impairment
or creams and lip bulm to minimize dryness of the skin and
.:. ,:~i Breast-feeding
lips
.:. Pregnancy
.:. Hypervitaminosis A ADAPALENE
.:. Known hypersensitivity to the drug Adapalene is derivative of retinoid with comedolytic, keratolytic and
;: i\I\tlnflammatory activity.
Dose
Initially 0.5mg/kg daily with food, dosage may be increased to I mg/I'l', Available preparations: Gel 0.1 %
after 4 weeks according to response and tolerance. Treatment pen( III
Available brands: Deriva®
ranges from 4-6months
tudlcations
Note -:- Acne vulgaris (mild to moderate acne)
Prescription is limited to dermatologists
C.)ntraindications
Side effects .:. Dryness of the lips -:. Hypersensitivity to adapalene
.:. Dryness of the skin
.:. Headache .:- Breast feeding
.:. Muscles / joint pain
.:. Mild acne flare .:. Pregnancy
.:. Abdominal pain
.:. Nausea and vomiting
.:. Flaking of the skin
.:. Dry sore mouth
')••,a
.:. Dry eyes "!,ply once a day at bed time for at least 8-12 weeks.
•:. Cheilitis
.:. Visual disturbances
.:. Epistaxis 'h'"
....
effects
Dryness Pruritus
Drug interactions , <- Burning sensation Scaling
.:. Skin drying preparations like cosmetic and anti acne prepar; III( 111' ·'00 Skin irritation Sun burn and acne flares
increase dryness and irritation caused by isotretinoin Stinging

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-415-
 PRECISE PHARMACOLOGY
Q3IQ~1IQ:'~';J~/h'B']I,ltf1
I, I I \ \ I II' I I' I ,:,

F 41F
.:. Advise the patient to avoid using topical preparations with
Key issues to note . high alcoholic content during treatment period
••• Avoid excessive exposure to sunlight .:. Advise the patient not to apply rretinoin to a broken skin or
.;. Advise the patient not to apply to the lip~ or mucous mucous membrane such as eyes, mouth
membrane, sunburned skin or broken skm . . .:. Patients should be advised to apply the medication to dry
.:. Inform the patient that adapalene may aggravate acne early rn skin atleast 30 minutes after washing to minimize erythema
course of therapy . d fter and irritation.
•:. Inform the patient that clinical response may be notice a .:. Inform the patient that a flare of acne may appear suddently
8 - 12weeks after starting treatment followed by clinical clearing of acne
within 8 -12 weeks
TRETINOIN
Cream 0.05% ANTIBACTERIALS
Available preparations:
Gel 0.25% Antibacterials commonly used in the treatment of acne include oral
antibiotics such as doxycycline, erythromycin and co-trimoxazole and
Optimal®, Retino-A®
Available brands: topical antibacterials such as c1indamycin and erythromycin.
,~
Indications
.:. Acne vulgaris CLiNDAMYCIN
Clindamycin inhibits P. oenes and provides comedolytic and
Contraindications
antinflammatory activity
.:. Pregnancy . .
.:. Known hypersensitivity to tretlnorn
Available preparations: Solution 1%

~~::kin should be cleansed to avoid excessive oiliness ~nd d~ied

Gel 1.2%
15·
30 minutes before applying tretinoin thinly, once or tWIce dally for .1 Available brands: Dalacin T®, T3mycin®
minimum of 12 weeks C-mycin®, Acnegon®
Indications
Side effects
.:. Burning and stinging .:. Acne vulgaris
.:. Dry or peeling skin . Contraindications
.:. Increased sensitivity to sun light .:. Known hypersensitivity to c1indamycin
.:. Redness of the skin Dose
Apply a thin film layer twice a day for at least 3 months
Drug interactions ..' . I
.:. Sulphur, benzoyl peroxide, salicylic a:ld and. re~orcrno may
Side effects
potentiate adverse reactions seen wIth tretrnorn .:. Contact dermatitis
.:. Burning or stinging
Key issues to note r
ht
.:. Inform the patient that excessive exposure t~ su~ Ig may .:. Skin irritation
cause severe sunburn, skin rash, redness or Itchrng .:. Skin dryness

-418-
-417-
 7 PREClm PHARMAcm!IIij"
F Ri1iY£ilij:t;Jil&btH,'I,I[I
Key issues to note MUPIROCIN
.:. Advise the patient to shake well the solution/gel before use
Available preparations:
.:. Inform the patient not to use topical c1indamycin solution or I ii!liI! Ointment 2%
: 1ll1,'
gel to the eye or administer orally Available brands:
Bactroban®, Supirocin®, Monsin®, Murin®
.:. Benzoyl peroxide should not be used concurrently with Indications
c1indamycin solution .:. Pyoderma
Impetigo
.:. Open wounds
ACNE ROSACEA .:. Furuncle Infected eczema
.:. Burns Carbuncle
Rosacea is a chronic inflammatory condition mainly affecting the face.
Cellulitis
It affects an older age group than acne and its characterized by markc< I .:. Venous ulcers
tendency of the skin to flush and formation of papules and pastules.
Contraindications
Drugs used in the treament of acne rosacae include:- .:. Hypersensitivity to mupirocin
Mild to moderate cases Dose
Tetracycline: 500mg twice daily for 6- f 2 weeks
Apply 3 times daily for up to I Odays
Doxycycline I OOmg once daily for 6-12 weeks
Metronidazole topical gel: Apply to affected area once daily ( I %) 01
Side effects
twice daily for 0.75%
Localised skin reactions such as'
Severe cases: Isotretinoin
.:.Burning sensation '
.:. Stinging
.:. Drying of the skin
13.1.4 TOPICAL ANTI-INFECTIYES .:. Redness of the skin
.:. Pruritus
.:. Pain and swelling
Bacterial infections of the skin may result from invasion of skin structull'~
by endogenous skin flora or by exogenous pathogenic organisms Key issues to note
Examples:- .:. Advise th patient not to apply the drug in the d
.:. Impetigo Folliculitis .:. Child e °th ° eyes an mouth
r n ~I Impetigo should be kept home until approriate
.:. Cellulitis Erysipelas treatment IS started
.:. Furuculosis Burns .:. Do ~?t mix with other preparations as this may lead to loss of
.:. Diabetic foot Skin ulcers stability and reduction in antibacterial activity
Antibacterial topical preparations are normally used for mild cases bill
METRONIDAZOLE
should be used for a short period of time to avoid development c,'
A 'lIable preparations: Gel 1%
resistance and contact allergy.
Common topical antibacterials include:- A llable brands:
Metrogy/®
.:. Mupirocin Metronidazole Indications
.:. Silver sulfadiazine Fusidic acid
.:. Bacitracin Gentamycin .:. Wounds and ulcers
.:. Tetracycline Neomycin .:. Decubitus ulcers
.:. Clindamycin Chlorhexidine .:. Acne rosacea

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 PRECISE PHARMACOLOGY
PREC~~ARMACOlOGY
Dose Side effects
Acne rosacea: Apply a thin layer onto affected area twice daily. .:. Itching
Wounds and ulcers: Apply to affected part 1-2 times daily whell .:. Skin irritation
dressing is changed .:. Skin rash
Side effects .:. Skin discolouration due to deposition of silver
Local reactions induding:- l(ey issues to note
.:. Redness .:. Avoid use during last month of pregnancy if possible because of
.:. Dryness possible risk of jaundice and haemolytic anaemia in neonates
.:. Skin irritation

I~
.:. Inform the patient that silver sulfadiazine is for external use
Key issues to note only and may dicolour the skin
.:. Inform the patient that acne rosacea usually improves within J ••ACITRACIN
weeks but treatment should continue for atleast 8 -12 week-. Available preparations: Cream
.:. Topical metronidazole used to reduce unpleasant odour of Powder
fungating wounds should be used for prolonged period to
Combinations:
avoid return after treatment is stopped.
Ucatrine® (Bacitracin,neomycin,cysteine, gylcine, threonine)
SILVER SULFADIAZINE flllrnacin® (Neomycin and bacitracin)
Available preparations: Cream 1% Illdications
.:. Wounds
Available brands: Burn Cure®, Asgud®, Silver kant!1l1
.:. Impetigo
Combinations: Silverex® (silver sulfadiazine+chlorhexidine) .:. Varicose ulcers
.:. Pressure sores
Indications .:< Burns
Prevention and treatment of infections in:- .:. Trophic ulcers
.:. Second and third degree burns
.:. Legs ulcers C:ontraindications
.:. Cuts and wounds .:. Allergy to one of the components
.:. Pressure sores l)olle
AI,ply the cream 3 times daily for a max of 4weeks
Contraindications 'Ide effects
.:. Serious allergic reactions to sulphonamides or chlorhexiclll II .> Skin irritation
.:. Neonates less than 4 weeks old c> Skin rashes
Dose "tty Issues to note
Apply to the affected area once daily until healing is progres<'lwly I
0:- Treatment should not be continued for more than 7 days
satisfactory. without medical supervision

-421- -422-
rznT H. Indications
PR

.:. The affected area should be cleaned before applying the drug .:. Burns .:. Diabetic foot
.:. After treatment course, administration should not be repeated .:. Bed sores .:. Surgical wounds
for atleast 3 months .:. Circumcision wounds .:. Leg ulcer
.:. Prolonged use may result in overgrowth of non-susceptible
.:. Cracked heels and cracked nipples
organisms including fungi .. Contraindications
.:. Hypersensitivity to any of the ingredients
GENTAMYCIN
Dose
Available preparations: Cream 0.1% Apply twice a day for atleast 2-4 weeks

Available brands: Farcocin® Side effects

Mtlbo is well tolerated but allergic reaction may occur occasionally
Combination preparations
Diprogenta® (betamethasone + gentamycin) rETRACYCLINE
MCG®(dobetasol, miconazole + gentamycin) Available preparations: Ointment 3%
Ecodax. G® (econazole, gentamycin and Beclomethasone)
Candiderm® (c1otrimazole, Bedomethasone and gentamycin) Available brands: Intacycline ®
Tornys® (c1otrimazole + gentamycin) Indications
.:. Infected cuts and wounds
Indications .:. Supefical folliculitis
.:. Impetigo .:. Infected insect bites and stings
.:. Infected eczema
.:. Sycosis barbae (;ontraindications
.:. Pyoderma
.:. Furunculosis -:. Patients allergic to tetracyclines
.:. Infected insect bites and stinv.-
.:. Infected superficial burns
.:.Infected Seborrhoeic dermatill\ UOle
.:. Infected cuts
~pply to the affected area 3 times a day
Contraindications
.:. History of hypersensitivity to gentamycin '''''NGAL INFECTIONS
lINEA
Dose
Apply to the affected area 3-4 times daily
I I i\l l:
I
,~~'II\'I.1 is a superficial fungal infection of the skin hair or nails
"l'IlIIlllIfltophytes ,cause y
db

Side effects
•:. Skin irritation and itching
.:. Redness of the skin \
\1\
.
l\\\\\\h I~ las~ed according to the areas affected i.e.
"
,I~I"
•
t

.;.
mea pedis/athletes foot (affects the feet)
T~nea cruris (affects the groin)
B-SITOSTEROL
Available preparations:

Available brands:
Ointment 0.25%

Mebo®
i
',\
,
':\\ \\\1,
,: L
Illllli!11
jlll!llli
~
+
+
tfo
T~nea cor~~ris/ringworm (affects the trunk)
Tmea capitiS (affects scalp and hair)
Tmea unguium (affects the nails)
Tinea manuum (affects the hand)

-424-
-423-
 QiUB~1jPHARMACOlOGY I , ' " , ' ,,"" "" PRECISE PHARMACOLOGY
2 a
d in the treatment of superficial fungal infections include; ':1\1\\"1 Dose
D rugs use ••• Isoconazole ! \1", Apply a thin layer 2-3 times daily for 4-8 weeks
.:. Clotrimazol e .;. Ketoconazol e Candida balanitis and vaginal candidiasis: Apply 2-3 times a day
.:. Miconazol e .:. Tioconazol e :\il:, for 3 weeks.
•:. Terbinafine .:. Econazole Tinea versicolor: apply 2-3 times a day for 3 weeks.
Ter:naf~:o:az:~~e effective in the treatment of skin fungal infection
Side effects
than azoles but it is expensi~e. f I results when treating fungal \\11\' Clotrimazole is well tolerated when applied topically but mild burning
Topical antifungals do not gl:e success u I,:: sensation and itching may occur.
~~;~~~:;;~:~:I:~i~n~n~s~a~~spond poorly to topical antifungals Key issue to note
.:. Use combination of c1otrimazole with a steroid until
inflammation subsides then continue with c1otrimazole alone
CLOTRIMAZOLE
Available preparations: Cream 1%
powder, KETOCONAZOLE
lotion Available preparations: Cream 2%
Canesten®, Candimar®, Mycoril®. Shampoo 2%
Available brands: Unisten®, Clonem®, Clotri-Denk~ll Available brands: Nizoral®, Dezor®, Pristinex®, Ketomac®
Combinations: . ) Combinations: Keto plus® (Ketoconazole+pyrithione)
.:. Candacort® (c1otrimazole + hydrocortisone
••• Candid -B® (c1otrimzole+beclomethasone) . ) h,dications
.;. Candiderm®(clotrimazole + beclomethasone + gentamycm .:. Athlete's foot
.:. Ring worm
.:. Tinea cruris
Indications .:. Tinea versicolor -:- Skin candidiasis
.:. Skin candidiasis
.:. Ring worm .:. Tinea versicolor
.:. Athlete's foot
.:. Tinea cruris .:. Seborrhoeic dermatitis/dandruff (shampoo)
.:. Otitis externa (fungal)
.:. Vaginal candidiasis
.:. Candida balanitis C::ontraindications
.:. Tinea barbae .:. Hypersensitivity to ketoconazole
In combination with steroids .:. Avoid using the shampoo if the skin of the scalp is broken
.:. Seborrheic dermatitis 1)I)~c
.:. Candidal nappy rash ~f)ply 1-2 times daily for 4 weeks
~llIcoconazole Shampoo
Contraindications f h . redients f)~"druff/seborrheicdermatitis: apply to wet hair twice weekly for
.:. Hypersensitivity to clotrimazole or any 0 t e mg iii, • ~ weeks
i
'n""" versicolor: apply once daily for 5 days
I
I,

-426-
-425-
Side
7

PRECISE IgWmMIIIIlLoGY I

effects is well tolerate d b ut ml'Id itching , burning and irritation

Ketoconazole .:.
-.
Contraindications
Children under 2 years
may occur. .:. Hypersensitivity to miconazole
BIFONAZOLE Dose
Available preparations: Solution 1%
Apply to the affected part of the skin 1-2 times daily for 2-5 weeks
Gel 1%
Cream 10/0 Side effects

Available brands: Neltolon®, Mycospar®, Mycogem® Miconazole is well tolerated though local skin irritation and sensitivity
I'caction may Occur
Indications
.:. Athlete's foot Candida balanitis Key issues to note 'Il

.:. Skin candidiasis .:. Tinea versicolor .:. Inform the patient that miconazole cream is for external use
.:. Tinea cruris Body ringworm only
J..
.:. Advise the patient to avoid contact with eyes
Contraindications
.:. Hypersensitivity to bifonazole nOCONAZOLE
Dose Available preparations: Cream 1%
Apply once a day for 2-4 weeks Available brands: Tiocon®
Side effects . es Indications
Mild skin redness and irritation may occur In rare cas .:. Athlete's foot .:.
Tinea cruris
.:. Fungal nail infections .:.
MICONAZOLE Ringworm
Available preparations: Cream 2%, Contraindications
Powder .:. Hypersensitivity to tioconazole
.:. Pregnancy
Available brands: Daktarin®, Zarin®, Micozol®, Dacinazole Oii
Decozol®, Dermidex®, Miconaz® ':)ose
"pply to the affected area twice a day for 4 weeks
In combination with corticosteroids .
'Iutlgal nail infections: apply to the nail and surrounding skin twice a
.:. Zaricort (miconazole + hydrocortls~ne)
tflly (or up to 6 months (may be extended to 12 months)
.:. Daktacort (miconazole + hydrocortisone)
~Idc~ effects
Indications
.:. Impetigo IlfH:onazole is well tolerated however, but local oedema, nail
.:. Ringworm I I

•:. Tinea versicolor .1I'loloration, dry skin, periungual inflammation, nail pain, rash and
.:. Athlete's foot .."foliation may OCcur.
.:. Skin candidiasis .:. Tinea cruris
.:. Seborrhoeic dermatitis (in combination with steroids)

-427-
-428-
 PRECISE
~;Jig~1IQ:'~';J~"~'B,II'Iijl
•
, ' , ",', I ,

a Side effects
ECONAZOLE .:. Skin irritation Redness
Available preparations: Cream .:. Mild burning sensation Itching in rare cases
.:. Allergic reactions
Combinations: Ecocort® (econazole+triamcinolone)
Ecodax® (econazole + gentamicin + beciomethas'One)
Key issues to note
Indications .:. Advise the patient to avoid contact with eyes, nose and mouth
.:. Skin candidiasis
.:. Athlete's foot .:. Inform the patient that terbinafine cream is for external use
.:. Vaginal candidiasis
.:. Ring worm only
.:. Tinea cruris
.:. Tinea versicolor .:. Ad.vise th~ patient to use terbinafine cream for the prescribed
perrod of time even if the signs and symptoms disappear
Contraindications
.:. Known hypersensitivity to econazole
BUTENAFINE
Dose Available preparations: Cream 1%
Apply to the affected area 2-3 times daily for 2-4 weeks
Available brands: Fintop®
Side effects
Econazole is well tolerated but rarely contact dermatitis may occur Indications
.:. Athlete's foot
TERBINAFINE .:. Tinea versicolor
Available preparations: Cream 1%
.:. Tinea cruris
Lamisil®, Fungisafe® .:. Ring worm
Available brands:
Indications C::ontraindications
Athlete's foot .:. Application to eye area should be avoided
.:. Skin candidiasis
Tinea cruris -:. Hypersensitivity to butenafine
.:. Tinea versicolor
.:. Ring worm
C:)ose
Contraindications Athletes foot: Apply twice daily for 7 days or once daily for 14 days
.:. Hypersensitivity to terbinafine PUllb'Worm and Tinea cruris: Apply once daily for 14 days
.:. Children under 12 years of age tinea versicolor: Apply once daily for 14 days. .

Dose 'Iclt· effects

Skin candidiasis; Apply 2 times daily for 2weeks .:. Burning /stinging
Tinea versicolor: Apply 1-2 times daily for 2 weeks .:. Redness of the skin J
Athletes foot: Apply once daily for I week .:. Itching at the site of application
Ring worm: Apply 1-2 times daily for 2 weeks .:. Contact dermatitis

-430-
-429-
 &1 Ql1le~i*Q;'.'iJbt;tBI]IIJ61
SELENIUM SULPHIDE Available brands:
Available preparations: Lotion 2.5% Whitfields®, Tinoderm®
Shampoo Indications
Mild infections particu/arly:-
Available brands: Selsun® .:. Ring worm
Indications .:. Athlete's foot
.:. Dandruff
.:. Seborrhoeic dermatitis .:. Fungal infection of the scalp in combination with Griseofulvin
.:. Tinea versicolor Contraindications
.:. Adjunct to the systemic treatment of tinea capitis .:. Patients hypersensitive to any of the ingredients
Contraindications .:. Do not apply to exudative lesions, mucus membrane
.:. Allergy to any of the ingredients Dose
.:. Concomitant use with metallic hair dyes
Apply twice daily until the infected skin is shed (4weeks)
Dose Side effects
Dandruff and seborrhoeic dermatitis: Massage 1-2 tea SPOOllfll1 Mild inflammatory reactions
into yvet scalp, allow it to remain for 2-3 minutes and rinse afterwald~,
apply twice in a week for 4 weeks. SULPHUR
Tinea versicolor: Apply to affected area with a small amount of Wale' I , Available preparations: Ointment J0%
leave it for 2-3 minutes and rinse the body thoroughly. Apply onu' .1 Combinations:
day for 7 days. Seproderm® (salicylic acid/sulphur)
Indications
Side effects ..:.. Dandruff
.:. Local irritation .:. Seborrhoeic dermatitis
.:. Hair discoloration .:. Ring worm
.:. Weakness .:. Scabies
Key issues to note .:. Acne
:'
.:. Inform the patient to wash her hands thoroughly and to , Ii <:mltraindications
remove all jewelry before using the lotion ..:. Known hypersensitivity to sulphur
.:. Advise the patient to avoid contact with the eyes and
C)ol'e
inftammed skin area
.:. Inform the patient that selenium sulphide shampoo is fOI III 111111 Apply twice a day
externa use only 'ldfl effects
~klll Irritation and dermatitis
BENZOIC ACID WITH SALICYLIC ACID
Available preparations: Ointment (benzoic acid 6% VinAL INFECTIONS
+ salicylic acid 3%) ;~ il !!il::llll1rnon viral infections treated with topical antivirals include:-
'Ii! ,.o. Herpes zoster

-431-
-432-
 , , , ' I I , 'PRECISE PHARMAC

.:. Chicken pox Side effects

.:. Herpes simplex .:. Dry or flaking skin
.:. Warts .:. Stinging or burning
Herpes zoster .:. Itching
Herpes zoster is an acute inflammatory viral infection caused by .:. Redness of the skin
reactivations of latent varicella zoster virus 01N) Key issues to note
It is more common in immuno-suppressed patients like HIV+ patiellt~
.:. Advise the patient to avoid contact with the eyes and inside
and elderly above 50 years the mouth
It is characterized by; painful vesicular eruptions, fever and malaise
.:. Treatment should be started as early as possible at the first
Chicken pox sign of the lesion
Chicken pox is a communicable disease caused by Varicella '3.1.5 DRUGS FOR WARTS
Zoster virus 01N).lt is more common in Children where it is not usually
Warts are caused by human papilloma virus and the lesions are found in
severe but it can also affect adults especially immunocompromj·,llcl
different parts of the body such as hands, feet and anogenital areas.
where it is very severe.
It is characterized by; intense itching, skin rash on the face, chest ~1I111
~arts are classified according to the location and morphology;
, lanter warts; are found on the soles of the feet and are sometimes
back, headache, fever and malaise. f.1l1ed verrucas.
Anogenital warts; (condylomata acuminata) involve the vulva, vagina,
Herpes simplex
It is a viral infection caused by herpes simplex virus type I which cau',1'_ lit 11'1111111 C:tIlrvix, penis, rectum and urethra.
cold sores around the mouth, or type 2 which causes genital herpc. 'rrtlatment
Anogenital warts
ACYCLOVIR .:. Podophyllin solution
Available preparations: Cream 5% Cutaneous warts
.:. Salicylic acid
Available brands: Zovirax®, Cyclovax®, Heperax®, .:. Podophyllin solution
Cyclovir® .:. Silver nitrate
Indications "OOOPHYLLUM
I .:. Herpes zoster
AViliiable preparations: Solution 25%
•:. Herpes labialis ...'"
1'1
hU/lcations
~
.:. Genital herpes
II
.:. Condylomata acuminata
Contraindications
I .:. Planter warts (in combination with other keratolytics)
.:. Allergy to acyclovir
.':ol1traindications
Dose .:. Pregnancy
Apply every 4hours (5 times a day) for 5-10 days. .:. Breast feeding
-:. Children

-433-
-434-
 , , ' " " 1\, , , PRE I

•
Dose
Condylomata acuminata: Apply carefully to warts avoiding contact
Side effects
.:. Burns on surrounding skin
.:. Stains skin and c10things
with normal tissue, rinse off after 4 hours. .:. Skin irritation
The procedure is carried out once a week for atleast 4-6 weeks
Planter warts: apply solution once a day, wash off with water and 13.1.6 DRUGS FOR SCABIES
soap after 6hours. ~ca~~~ is an intense ~r~ritus parasitic infection of the skin caused
.y coptes sca~lel. The predominant symptom is pruritus which
Side effects IS caused by an allergiC reaction to the parasite
.:. Abdominal pain
.:. Nausea and vomiting Drug; used in the management of scabies include: -
Confusion
.:. Skin irritation ••• Benzyl benzoate
.:. Peripheral neuropathy .:. Sulphur
.:. Staining of the skin and cIothings .:. Permethrin
.:. Lindane (gammabenzene haxachloride)
Key issues to note .:. Ivermectin
.:. Pregnant women should be warned of the risk of fetal toxoc'lllY
Pediculosis
',I!! and teratogenicity of podophyllum
IIPodiculosis
I" is an infestation of hair of the scalp ' body an d pu b'IC region
, by
()~: t 'bs tra,nsm Itted by close personal contact or indirectly by sharing
SILVER NITRATE om s, cothes, hats, and brushes.
Silver nitrate pencil 40%, 95%
Available preparations: II Is caused by:-
Caustic pencil®, Avoca®
Available brands: .:. Pediculus humanus var capitis (head louse)
Composition +:+ Ped~culus hum~nus var corporis (body louse)
Caustic 40%: Silver nitrate 40% /Potassium nitrate 60% .:. Pediculus phthlrus pubis (pubic louse)
Caustic 95%: Silver nitrate 95% / Potassium 5%
K·c.'lY issues to note
Indications .:. Clothing~ and bed sheets of person with body lice should be
.:. Warts washed In hot water or dry cleaned and ironed
.:. Umbilical granulomas .:. Second~ry in.fe~tion should be treated using topical or
.:. Over granulation tissue systemIc antImIcrobials
hl:NZYL BENZOATE
Contraindications AVio\lIable preparations: Lotion 25%
.:. Known hypersensitivity to any of the ingredients

~!
.~
A~"i1able brands: Opele®, Scabees®, SP lotion®
Dose
Common warts: Apply moist caustic pencil tip for 1-2 minutes, n'pel'" t"dlcations
after 24 hours up to a maximum of 3 applications. .:. Scabies
Umbilical granulomas: Apply moistened caustic pencil tip fot I I .:. Pediculosis
minutes while protecting surrounding skin with vaseline.

---436-
-435-
 " PRECISE PHARMACOL G
Q;Jij'SE~:'~';j6"'Q,JI'Ia
•
Contraindications
SF

.:. Hypersensitivity to benzyl benzoate

GAMMABENZENE HEXACHLORIDE
Available preparations: Lotion 1%
Available brands: Scabisin®
.:. Inflamed or weeping skin
Indications
Dose .:. Scabies
Scabies: Apply over the whole body, repeat without bathing on
the following day, and then wash off after further 24 hours. The 3,,1 Contraindications
application may sometimes be necessary after 5days. .:. pregnancy
Pediculosis: Apply to the affected area and wash off 24 hours later. .:. Infants
further application may be needed after 7- 14 days.
Dose
Apply after bathing once a day for 4-5 days
Side effects
.:. Local irritation particularly in children
.:. Burning sensation especially on the genitalia 13.1.7 ANTIPRURITIC DRUGS
'lruritus may be caused by systemic diseases such as obstructive
.:.~Itching and dermatitis
,j
li\undice or skin diseases such as scabies, insect bites and stings, eczema
PERMETHRIN t,t.c. Management involves identifying the cause of itcthing and treating
Available preparations: Lotion 5% II though some times it may need symptomatic treatment to relieve
\I\\tlcnt's anxiety.
Available brands: Ascabs®
hlpkal preparations commonly used for pruritus include Calamine and
Indications I II:ltamiton.
•:. Scabies
C::ALAMINE
Contraindications II IS used in the treatment of pruritus because of it's soothing,
.:. Known hypersensitivity to permethrin iIIlluflflammatory and antipruritic action.
•:. Infants under 2 monhs
~'Iio1l1able Preparations: Lotion 15%

Dose A"Ii\lIable brands: Caladin®

Scabies: Apply the lotion over the whole body and wash off after B II \
hours. t\:.lmbinations: Caloderm® (calamine/zinc oxide)

Side effects hllh<:"tions

Itching of the body (pruritw.)
.:. Local irritation
Burning and stinging
II I. ~lIIl1l1s due to;
.:. Redness of the skin '\ II
I,
....Y Scabies
Oedema • Insect bites and stings
.:. Skin rash
.:. Tingling ... Chicken pox

-438-
-437-
Dose
N_r 2._ n PRECI~il~:!MMMI!.nijl ,
f

',I
I
,'"
I JI

I I,
IJ
"
I
PRECI H

Sunlight is categorized according to wavelength as follows:-

Ultra violet (200-400nm) light
Apply to the affected part 3 times daily
Visible (400-750nm) light
Key issues to note Near infrared (> 750nm) light
.:. Advise the patient to avoid contact with the eye, and mucous
membranes of the nose, mouth and genital area Ultra violet radiation (UV) is responsible for most of the acute and
.:. Treatment should be discontinued in case of allergic skin chronic biological effect of sun light
reactions It is divided as follows depending on the wavelength.
•:. Considered safe in pregnancy and lactation
UVA (wave length 320-400nm) produces skin tanning with little
CROTAMITON ~lrythema. It is also responsible for many photo sensitivity reactions and
Available preparations: cream 10% photo dermatosis
Available brands: Eurax®
UVB (wave length 290-320nm) it is 1000 times stronger than UYA in
Indications pro~ucing e~hema.and also produces sunburn. It contributes to photo
.:. Pruritus (including pruritus due to scabies) agemg and skm tannmg.
Contraindications
.:. Acute exudative dermatoses Sun burn: this is damage to the skin caused by excessive exposure to
.:. Hypersensitivity to any of the ingredients the sun's rays especially UYB. Sun burn may vary from reddening of the
!\kln to the development of large painful fluid filled blisters
Dose rai~ skinned ~eople have the least tolerance and tend to burn easily
Apply to the affected area 2-3 times daily until pruritus has subsided
while dark skmned (black or brown) can withstand the exposure to the
Children below 3 years apply once daily. 1l1ln for longer periods.
ill
Key issues to note
-lo .:. Advise the patient not to apply near the eyes at bottom skin Sun ~creens and sun blockers are chemicals usually in form of creams
t~:. The preparation should not be applied to broken skin or Oils that protect the skin from the damaging effects of ultra violet
I.ldiations from the sun. II:
13.1.8 DRUGS FOR ALOPECIA
Sun screens absorb some of the UYB radiations ensuring that less of it
Alopecia is the absence of hair from areas where it normally grow'.
I l!aches the skin.
Drugs used in the treatment of alopecia include:-
.:. Finasteride Classification of sun screens
.:. Minoxidil
Physical barriers
13.1.9 Preparations for Prevention of Sun Burn
I hese contain chemicals such as zinc oxide, titanium dioxide, calamine
Exposure of skin to sunlight is beneficial in moderation since ultra violc-I
which deflect both UYB and UYA rays
light is vital for the synthesis of vitamin D. Excessive exposure of tl".
skin to sunlight is dangerous particularly in light skinned persons wilt I
tan poorly. Acute sunburn is the first sign for photo damage and in till'
long-term, photo damage manifests as premature ageing of the skill

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 Q;J3Bl'1 I g,,;,.J{,r4BI)IIId :,' I' n, :: :';: " ' ..... " • ,,' : .. ,': ";' :, , ' i" ,; PRECISE PHARMACOLOGY
• 77P
Chemical barriers ,
These contain chemicals which reduce the amount of UV light reachlll}',
the skin, CHAPTER FOURTEEN
Examples:- DRUGS FOR THE EYE
.:. Oxybenzone Drugs used in the treatment of eye infections and disorders include:-
.:. Mexenone .:. Antibacterials .:. Antivirals
.:. Corticosteroids .:. Local anaesthetics
Sun protection factors (SPF) , .:. Drugs for glaucoma .:. Anti allergic drugs
l
This refers to the degree of protection given by a sun screen agallls .:. Mydriatics and cycloplegics .:. Drugs for dry eyes
sun burn. It is a measure of the amount of UVB radiation a ~unscre(,11 .:. Non steroidal anti-inflammatory drugs
absorbs. The higher the number, the greater the protection. SUII
protection factor ranges from 2-50. Antibacterial eye preparations
Antibacterial eye preparations are used for local bacterial infections
$uch as conjunctivitis, trachoma or blepharitis.

Conjunctivitis
Conjunctivitis is a superficial inflammation of the conjuctiva resulting
from a variety of causes such as bacteria, viruses or allergies.
Acute bacterial conjunctivitis; is commonly caused by staphylococci
'."i ! or streptococci in adults, haemophilus influenzae and Moraxella
mtarrhalis in Children. Other causes include; Gonococci and
Chlamydia, trachomatis.
Neonatal conjunctivitis (ophthalmia neonatorum)
Neonatal conjunctivitis is any conjunctivitis with discharge occurring
I
within the first 28 days of life (new born). It is usually due to
Neisseria gonorrhoea or chlamydia trachomatis :r II
'I'

II is managed by: Iii \1

' \'

.:. Cleansing the neonate's eyes immediately after birth

.:. Use of antibiotics topically e.g. tetracycline I % eye ointment,
erythromycin 0.5% eye ointment
.:. Use of systemic antibiotics e.g. ceftriaxone 50mg/kg by 1M
single dose or spectinomycin 25mg/kg 1M single dose
.:. Prophylaxis involves treating the infected mother during
pregnancy

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 7: II ~r PRECISE 1~:rJ;JMlJBH!HD

Trachoma
14.1.1 ANTIBACTERIALS
Trachoma is an inflammation of the conjunctivae and the cornea dUl'
to chlamydia trachomatis infection. The reservoir is chronic ey('
TETRACYCLINE
infection and transmission may be via fingers and flies.
Available preparations:
Trachoma may be treated using tetracycline eye ointment, erythromycill Eye ointment 1%
eye ointment or oral Azithromycin Available brands:
Intacycline®, Ocumycin®
Blepharitis Indications
Blepharitis is inflammation of the eye lids due to infection. It usu(lily .:. Trachoma
presents as a chronic condition and may require prolonged treatmclIl, .:. Prophylaxis of neonatal conjunctivitis
typically involving local hygiene to remove encrustations and topiul .:. Bacterial blephartitis
application of a broad-spectrum antibacterial ointment. e.g. tetracyclirH1, .:. Bacterial conjunctivitis
chloramphenicol .:. Keratitis

Contraindications
Keratitis
.:. HypersensitiVity to tetracycline
Keratitis is the inflammation of the cornea caused by infections SLl< " .:. Photodermatosis
as bacteria, fungi, viruses, or protozoa usually following trauma In
the surface of the eye. Common pathogens associated with bactl'l!.11 Dose
keratitis include; staphylococci, streptococci, Pseudomonas Sf'!' Conjuctivitis:
and Enterobacteriaceae. Children over 8 years and d I A
"hlchom • A I 3 . ~ u ts: pply 3-4 times daily for I week.
a. pp y times dally for J month
Bacterial keratitis is potentially sight-threatening and requires prOII!J" '~rophylaxis of neonatal conjunctivitis' A' J
aggressive treatment with broad-spectrum antibacterials such .l'
bt:lt'll at birth after cI . h . ' pp Yto the eye of the new
eanslng t e eyes With sterile gauze.
gentamycin, tobramycin or ciprofloxacin. Systemic treatment n",y ~'de effects
occasionally be required ,••1rely seen but include'
.:. Rash '
Bacterial corneal ulcer .:. Stinging
Bacterial corneal ulcer is associated with severe eye pain, red eye'> ,11111 .:. Burning sensation
swollen eyelids. It is normally due to the gram positive, gram neg,lu", .:. Photodermatosis
cocci and gram negative bacilli.
Treatment involves use of antibiotic eye drops such as ciproflox.I' Ill, .~ JlVTHROMYCIN
gentamycin or tobramycin.
"'vi,lIable preparations: Eye Ointment 0.5%

Stye AVAilable brands: Oftafmolosa cusi®

Stye is an abscess in the gland of the eyelashes characterized by Itilt , llllllcations
discharge and swollen tender eye lid. It is treated using tetracyclilll' fiy' ' .:. Prophylaxis of neonatal conjunctivitis
ointment. -:. Superficial bacterial infection of the eyes

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J
 , 'ARMACIiILOGY
• • • • • • • • • • • • • • •.-==:1P~ROOl!E!ISEIQ:MiW:IB,].r1OCI
Contraindications CHLORAMPHENICOL
.:. Known hypersensitivity to erythromycin Available preparations: Eye drops 0.5%
Dose Eye ointment 1%
Superficial bacterial infections: Apply 1-2 times daily Available brands: Ivyphenical®, Ocumycin®, Optachlor®,
_ Prophylaxis of neonatal conjunctivitis: Apply once daily Paracetin®
Side effects Combination with corticosteroids
.:. Allergic reactions Methachlor® (Chloramphenicol + dexamethasone)
GENTAMYCIN Prednicol® (Prednisolone + chloramphenicol)
Available preparations: Eye drops 0.3% Indications
Eye lear drops .:. Bacterial conjunctivitis
Available brands: Garamycin®, Colircusi®, Ivygentacin® .:. Prophylaxis after surgery
.:. Prophylaxis after superficial trauma
Combination with corticosteroids .:. Bacterial blepharitis
Genta dexa® (gentamycin + dexamethasone) .:. Allergic conjunctivitis
Garasone® (gentamycin + betamethasone)
Contraindications
Indications .:. Hypersensitivity to chloramphenicol
.:. Corneal ulcer
.:. Corneal bacterial abscess Dose
.:. Conjunctivitis Instill I drop every 2 hours for 2 days, then reduce frequency to 4times
•:. Keratitis it day and continue for 48 hours after healing.
.:. Blepharitis Ointment may be used at night as an adjunct to eye drops or as a single
•:. Kerato conjunctivitis II! 'IJtent 3 times daily.
.:. Pre operative sterilization of the conjunctivae Side effects
.:. Burning or stinging Irritation
Contraindications .:. Pain
Watery eyes
.:. Known hypersensitivity to any of the ingredients .:. Photosensitivity Unpleasant taste
.:. Angioedema Local reaction
Dose
1-2drops instilled into the affected eye every 4hours, in severe casc'" CIPROFLOXACIN
instill 2 drops every hour. Available preparations: Eye drops 0.3%
Side effects Available brands: Ciloxan®, Ceprolen®, Ciprobid®, Xcipro®
.:. Allergic reaction (eye irritation)
.:. Pain Indications
.:. Stinging .:. Corneal ulcer
.:. Burning sensation .:. Severe bacterial conjunctivitis
.:. Keratitis

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 Contraindications
,, PRECISE PH

.:. Hypersensitivity to ciprofloxacin or other quinolones

Dose
LaG

Side effects
.:.
.:.
-
Hypersensitivity reactions
Mild stinging
Corneal Ulcer .:. Local irritation
Instill 2drops into the affected eye every ISminutes for the first 6hours, .:. Inflammation
then every 30 minutes for the remaining hours of the first day, thell
14.1.3 DRUGS USED IN ALLERGIC CONJUNCTIVITIS
apply every hour for the second day and then 2drops every hour frolll
Allergic conjunctivitis is a type I hypersensitivity reactioll' associated
the 3rd to 14th day.
with symptoms such as; tearing, itching, burning, reddening of the eyes,
Bacterial conjunctivitis
and frequently rhinitis will co-exist.
Apply I drop 2hourly for 2days then I drop 4 hourly for Sdays.
Drugs used in the treatment of allergic conjuctivitis include:-
.:. Corticosteroids
Side effects
.:. Mast-cell stabilizers
.:.1 Local burning of the eyes .:. Lacrimation
} .:. Foreign body sensation .:. Corneal staining CORTICOSTEROIDS
":t<
.:. .:. BETAMETHASONE
Itching of the eyes Bad taste
.:.
ij(,
Lid oedema .:. Photo phobia Available preparations: Eye drops O. 1%
.:. Visual disturbances .:. Nausea
Available brands: Probeta®, Betnesol®, Vista-methasone®

14.1.2 ANTIVIRAL DRUGS

These drugs are used in the treatment of viral infections such as HerplI\
~ombinations: Betadrop-N ®(Betamethasone + neomycin)
(.mrasone® (Betamethasone + gentamicin)
simplex infections which cause dendritic cornea ulcers.
Probeta-N® (Betamethasone + neomycin)
'I
,
They include:-
"

.:. Acyclovir Indications

.:. Allergic conjunctivitis
ACYCLOVIR
.:. Other local inflammations of the eye
Available preparations: Eye ointment 3%
Contraindications
Available brands: Cusiviral ®, Zovirax ® .:. Glaucoma
Indications .:. Presence of bacterial, viral, fungal infections
.:. Herpes simplex keratitis .:. Hypersensitivity to betamethasone

Contraindications Dose
.:. Known hypersensitivity to acyclovir Itt~l:11I1-2 drops into the eye every I or 2 hours until signs of improvement
illlCl seen.
Dose IIdc effects
Apply 5 times daily at 4hourly intervals. Treatment should continlil' f"l .:. Raise in intra-ocular pressure
, 1

at least 14 days or 3 days after healing is complete. .:. Thinning of the cornea
'ii"
"';',,1
, I' .:. Cataract on prolonged use

~ 1'~'
j I
j
'i'l
~
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7

HYDROCORTISONE
IF 22 = PRECISE JrHARMACOLOD
Dose
PREQ~iIA:6',JI~ntRl'1IIHfl

Available preparations: Eye suspension I %

Apply every 1-2 hours until controlled then reduce to I drop 2-4 times
daily.
Available brands: Ivysone®
Side effects
Indications
.:. Allergic conjunctivitis .:. Glaucoma
.:. Local treatment of inflammation including post operative .:. Optic nerve damage
inflammation .:. Delayed wound healing
Contraindications
.:. Known hypersensitivity to hydrocortisone DEXAMETHASONE
.:. Undiagnosed red eye Available preparations: Eye drops O. 1%
Dose
2-3drops to be instilled into the affected eye every 4 hours, reduced to Available brands: Maxidex®, Dexacip®
3-4 times a day when inflammation subsides II
1'1
Combinations: Maxtrol® (dexamethasone + neomyin +polymyxin)
Side effects
Dexona® (dexamethasone +neomyin)
.:. Burning sensation
Tobradex® (dexamethasone + tobramycin)
.:. Discomfort Indications
.:. Itching .:. Allergic conjunctivitis
.:. Foreign body sensation .:. Anterior uveitis
.:. Increased tear production
.:. Non specific superficial keratitis
.:. Sensitivity to light
.:. Corneal injury from chemical, radiation or penetration by
Foreign bodies
PREDNISOLONE
.:. Post operative to reduce inflammatory reactions '1
1Ii
Available preparations: Eye drops 1%
Contraindications
Available brands: Enconopred®
.:. Herpes simplex and other viral diseases of the cornea and
conjunctivae
Indications .:. Ocular tuberculosis
.:. Allergic conjunctivitis
.:. Known hypersensitivity to dexamethasone
.:. Iritis
.:. Patients with soft contact lenses
.:. Corneal injury from chemical or penetration of foreign bodl'"
()C)~e
Contraindications
Apply 1-2 drops instilled into the affected eye 4-6 times daily.
.:. Viral diseases of the cornea and the conjunctivae
I 'I I' 'I:lver.e inflammation: I drop every hour, then reduce frequency
•:. Known hypersensitivity to any of the ingredients 'I~ ,;Who. wh.,n Inflammation is controlled.

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 • ., ." ',. , '" • I "i. :" PRECISE PHARMACOLOGY
Q#B~1# PHARMACOLOGIj
II: '

ill U SSP In j
Contraindications
.:- Known hypersensitivity to the preparation
Side effects ,',',
.:. Intra ocular pressure :II',
Dose
.:. Cataract Apply the eye drops 4 times daily
.:. Thinning of the ~orne~ b xacerbated by steroid; , Side effects
.:. Viral and fungal infection may e e
-:. Burning and stinging
.:. Mild stinging or burning
14.1.4 NON-STEROIDAL ANTI-INFLAMMATORY EYE
MAST-CELL STABILIZERS PREPARATIONS
.:. Lodoxamide These include:
.:. Cromoglycate .:. Pranoprofen
-:- Diclofenac
LODOXAMIDE Eye drops 0.1 %
Available preparations:
PRANOPROFEN
Alomide®
Available brands: Available preparations: Eye drops 0.1 %
Available brands: Oftalar®
Indications . ., .
.:. SeasonaI al lergic conlunctlVltls
... Indications
•:. Vernal keratoconjunctivitis -:- Ocular inflammation associated with cataract surgery
Contraindications .d Contraindications
.:. Known hypersensitivity to lodoxaml e -:- Known allergy to the drug

Dose . 4 years: I drop 4 times daily Dose

Adults and chIldren over '2 drops in the affected eyes every 6 hours
Side effects . Stinging sensation Side effects
_:_ Mild burning sensation Lacrimation .:. Redness of the eye
.:. Itching Dizziness .:. Itching
.:. Flushing .:. Irritation
.:. Blurred vision .:. Tearing

SODIUM CROMOGLYCATE 0 14.1.5 DRUGS FOR GLAUCOMA

Available prparations: Eye drops 4 Yc \\\\\\\\ C:II~\lIcoma is a condition in which loss of vision occurs because of an
Available brands: Cusicrom® IIl1\lormally high pressure in the eye. Intra-ocular pressure rises when
Ihlm~ is an imbalance between production and drainage of aqueous
ill,
Indications . .. .'" 1I~lmour in the eye.
111«'
.:. Allergic conjunctivitis ., .
•:. Seasonal kerato conjunctivitis
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 ······,·"....".."'..""nftlu""'''mllmnlllnnm'''''m''un''''''nmnn''''n''''''nm"""lIfnnllllll.lII£._"a_,hIllllUnIllllUfilllllhrilllll""'"

,, " " " PRECISE PHARMACOLOGY

I I I II_W'LE£&I,.
Glaucoma is divided into two:- Indications
.:. Primary open angle glaucoma (chronic simple glaucoma) .:. Glaucoma
.:. Angle closure glaucoma (closed angle glaucoma) .:. Ocular hypertension
Chronic Open Angle Glaucoma Contraindications
It refers to optic nerve damage often associated with elevated intr;t .:. Uncontrolled heart failure
ocular pressure. It is a chronic slowly progressive condition in which
.:. Known hypersensitivity to tim%l
both eyes are usually affected and the condition is asymptomatic unt II .:. Asthma
advanced stage when severe damage has occurred. .:. Obstructive airway disease
This type of glaucoma is due to the blockage in drainage through tllll
Dose
trabecular meshwork.
Instill one drop of 0.25% in the af:Cect d .
Angle Closure Glaucoma •' e eye tWIce d'J 'f h
I" not satisfactory, instill I drop of 0.5% sol . .al y, I t e response
Angle closure glaucoma is a medical emergency and a patient presci II " Iwice daily. utlon In the affected eye
with painful red eyes, sweating, nausea and vomiting as a result "I
rapid raise in intra ocular pressure. It results from blockage of aque< JI J~ Side Effects
humour flow into the anterior chamber. .:. Fatigue
.:. Stinging Burning
Drugs used in the treatment of glaucoma either reduce lOP hy .:. Diplopia Pain
decreasing production of aqueous humour or by increasing its outill lW .:. Hypersensitivity Hypotension
Common drugs used include;- Bronchospasms
.:. Coldness of the extremities
.:. Beta blockers .'.
• D ecreased corneal sensitivity
I
I,
.:. Carbonic anhydrase inhibitors KClY issues to note
.:. Miotic drugs
.:. The potential of timolol to mask the s
hypoglycaemia in diabetic patients Sh~l11u/dPtboms an~ signs of
.:. Prostaglandin analogues
III ~t e conSidered
BETA BLOCKERS 'IU: AXOLOL
.:. Timolol AVIIUable preparations:
Eye drops 0.5%
.:. Betaxolol
"'vllilable brands:
Betoptic®
, IrlCflcations
Mode of action
.:. Glaucoma
They inhibit beta receptors in the ciliary epithelium there by red[/{ 1/1/1
aqueous humour. They have no effect on accommodation or pupil ' ' _1 .:. Ocular hypertension
::ontraindications
which makes them the treatment of I st choice for glaucoma.
.:. Asthma
,I
I
1)1
.:. Reversible COPD
TIMOLOL
.:. Pregnancy
','

,Ii,
,,1,,:1.\

"
Available preparations: Eye drops 0.25% 0.5%
.:. Patients with sinus bradycardia great h
II Available brands: Cusimolol®, Accumol® block er t an a first degree
I',
,
-:. Known hypersensitivity to betaxolol
',

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 PRECISE PHARMACOLOGY

•
, ' ':', I ,

201 5
Dose
Dose Glaucoma: 250mg 1-4 times daily
Idrop instilled twice daily \\\\\\1\ Epilepsy: 250mg - Ig daily in divided doses
'\ ,I:
Side effects , ql,' Children: 8-30mg/kg daily max 750mg daily
.:. Discomfort of short duration Peri-operative reduction of intra ocular pressure: Initially 250-
.:. Decreased corneal sensitivity 500mg maintenance 250mg every 4hours as required to a max of Ig
.:. Itching daily
.:. Redness of the skin
.:. Keratitis Side effects
.:. Photophobia .:. Nausea .:. Polyuria
.:. Vomiting .:. Fatigue
CARBONIC ANHYDRASE INHIBITORS .:. Diarrhoea .:. Dizziness
Acetazolamide .:. Headache .:. Thirst
.:. Reduced libido .:. Depression
Mode of action .:. Taste disturbance .:.
'ii'
Loss of appetite
Inhibits carbonic anhydrase II (found in the eye) which reduces aque(J1I~
humour formation MIOTIC DRUGS (muscarinic agonists)
F1ilcocarpine
ACETAZOLAMIDE Pilocarpine is used in angle-closure glaucoma to contract the pupillary
Available preparations: Tablets 250mg muscle to produce miosis and open up the drainage channels in the
~nterior chamber of the eye.

Available brands: Diamox®

,IILOCARPINE
Indications Available preparations: Eye drops 2%, 4%
.:. Open angle glaucoma Available brands: Isoptocarpine®
.:. Secondary glaucoma
.:. Epilepsy Imlications
.:. Diuresis ( ,I .:. Chronic open angle glaucoma
.:. Preoperative reduction of intra ocular pressure acute all~. II
.:. Ocular hypertension
closure glaucoma) .:. Emergency treatment of acute angle closure glaucoma
.:. To antagonize effect of mydriasis and cyloplegia following
Contraindications surgery
.:. Hypokalaemia
.:. Hyponatraemia •;mltraindications
.:. Severe hepatic impairment .:. Acute uveitis
.:. Renal impairment -:. Acute iritis
.:. Sulphonamide hypersensitivity .:. Some form of secondary glaucoma
.:. Metabolic acidosis

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 ----·.·.·--········ .. ••••• .... • .... ,'.' .... UlllIIJI!J"

, , ' , PRECI~ PHARMACOL

.:. Acute inflammatory disease of anterior segment ATROPINE

.:. Known hypersensitivity to pilocarpine
Available preparations: Eye drops 1%
Dose
I drop instilled 4 times daily
Available brands: Isopto Atropine®, Opta-atropine®
Indications
Side effects
.:. Refraction procedures in young children
.:. Frontal headache
.:. Anterior uveitis
.:. Ocular irritation
.:. Blurred vision Contraindications
.:. Lacrimation .:. Narrow angle glaucoma
.:. Myopia Dose
.:. Superficial keratitis Uveitis:
Adult: I drop 3 times daily
PROSTAGLANDIN ANALOGUES Children: I drop 3 times daily
Latanoprost Refraction:
These drugs increase uveoscleral/outflow of aqueous humolll ::1111
Adult: 1-2 drops I hour before examination
Latanoprost is a synthetic analogue of dinoprost that is used topic III)'
C:hlldren: I drop twice daily for 1-2 days before examination
to reduce intra-ocular pressure in patients with open angle glauco'II.•
and ocular hypertension. One drop of a 0.005% ophthalmic solutioll I~
1II1de effects
instilled once daily in the evening. .:. Transiet stinging
.:. Dry mouth
MYDRIATICS AND CYCLOPLEGICS .:. Blurred vision
Mydriasis .:. Photo phobia
This is the widening of the pupil which occurs normally in the dim h~:llt .:. Tachycardia
Cycloplegia .:. Headache
This is the paralysis of the ciliary muscles of the eye. -:. Local irritation
.:. Raised intra ocular pressure on prolonged use
Drugs that dilate the pupil (mydriatics) and paralyse accommOd;ltICIII
(Cycloplegics) are used topically in the examination of the eye .11,,1
other ophthalmic procedures).

Antimuscarinics
Antimuscarinic drugs are divided into two depending on the POt('II' ~
and duration of action .
•:. Short acting antimuscarinics with weak mydriatic eHe'( ,.
include tropicamide 0.5%
.:. Long acting antimuscarinics e.g. atropine, cyclopentol.ltc'

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 • PRI~eISE PHARMACOLOGY I
----
AMITRIPTYLINE
Available prepartions:
Available brands:
Tablets 25mg
QiJfJlSEIiI:h';lj\'~taIJllld

Laroxyl®, Tridep®
CHAPTER FIFTEEN
Pharmacokinetics
DRUGS USED IN THE MANAGEMENT OF CENTRAL Amitriptyl!ne is ~bsorbed rapidly from the GIT, distributed wider into
NERVOUS SYSTEM DISORDERS ~~e b~~y, Includb,ng. CNS and breast milk, metabolized in the live~to
e ac Ive meta ollte and excreted in urine.
15.1.1 DRUGS USED IN THE TREATMENT OF DEPRESSION Indications
Depression is a mental state characterised by diverse pyschological .:. Depresslon
. wereh sedation is required
symptoms such as low mood, loss of interest and enjoyment .:. Nocturnal enuresis in children
of activities and reduced energy. Depression is associated with .:. Peripheral neuropathy
symptoms such as; ""~". .:. Post herpetic neuralgia
.:. f.
IJI
Fatigue .:. Migraine prophylaxis
.:. Anxiety .:. Tension headache
.:. Sleep disturbance .:. Adjuvant in pain management
.:. Reduction in libido
.:. Decreased productivity Contraindications
.:. Changes in appetite or weight .:. Known hypersensitivity to the drug
.:. Loss of concentr~tiQn .:. Recent myocardial infarction
.:. Loss of interest (depressed mood) .:. Severe liver disease
.:. Thought of death and suicide .:. Manic phase
.:. Co ma or severe respiratory depression
~

Drugs used in the treatment of depression include:- .:. Prostatic hypertrophy

.:. Tricyclic antid,~pressants .:. Glaucoma
.:. Selective Serotonin reuptake inhibitors (SSRls) Dose
.:. Monamine oxidase inhibitors (MAOls) Depression
.:. Other antidepressant drugs (Atypical antidepressants)
Adul~: initially 75mg daily in divided doses or as a single dose at bed
ItIne Increased, gradually according to response to 150mg
Tricyclic antidepressants Nocturnal enuresis
These drugs inhibit the reuptake of norepinephrine and serotonin at Children:
the presynaptic neuron prolonging neuronal activity.
' .. 10 years: I0-20mg at night
examples
.:. Amitriptyline I /··16 years: 25-50mg at night: Max period of treatment is 3 months
.:. Imipramine
.:. Clomipramine ,I· '1111
"eripheral neuropathy: Initially I0-25mg daily at night increased if
"~cessaryto 75mg daily.

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-460-
WI
I'

~
,1 1 , 1 I I 'I I I II 1
1"'11'1 '1'11
, PRECISE PHARMACOLOGY, ~ISE PHAR
I I I I Ill t !1)

, '" '" , i " " ,, , ''

'I,IMIPRAMINE
Migraine prophylaxis: Initially I Omg at night increased according to
,.,Available preparations: Tablets 25mg
resPOnse to maintenance dose of 50-75 mg at night.
Adjuvant pain management: I 0-25mg at night up to a max of Available brands: Antidep®
150l11g
,Pharmacokinetics
Side effects ~~iP~a~in.e is a~sorbed rapidly from the GIT, distributed widely into
",• Drymouth Nausea he o. y, Including CNS and breast milk, metabolized in the liver to
.:. Sedation .:. Tremors t e active metabolite and excreted in urine.
•:. Constipation Sweating
Indications
.:. postural hypotension Skin rashes
.:. Depression
':. Difficulty with micturition Headache
Urticaria .:. Noctural enuresis in children
.:. Blurred vision
.:. Panic disorders
.:. Cardiac arrhyt hmias Hypomania
.:. Weight gain .:. Vascular headache prophylaxis
':' Unpleasant taste .:. Cluster headache
Increased appetite
':' Somnolence .:. Management of chronic pain
.:. Ph otosensitivity
.:. Anorexia nervosa
':' Interference with sexual function
Contraindications
Drug Interactions .:. Known hypersensitivity to impramine
'~I Cimetidine, valproic acid, may increase amitriptyline blood .:. Recent myocardial infarction
concentration and risk of toxicity .:. Severe liver disease
':. Alcohol, anticonvulsants, phenothiazines and sedative .:. Manic phase
hypnotics may increase CNS.depression caused by .:. Epilepsy
amitriptyline .:. Prostatic hypertrophy
.:. Carbamazepine reduces the serum concentration of
Dose
amitriptyline
.:. Concurrent use of amitriptyline with phenylephrine, ephecl"I1~' Ii ~er;~~s~~~ Initially 75mg daily in di~ided doses gradually increased
r .. g, up to 150mg may be given as a single dose at bed time
may increase blood pressure
f.lderty: Initially 10mg daily gradually increased to 30-50mg daily .
•:. Amitriptyline may decrease the hypotensive effect of
N octurnal enuresis
methyldopa Children:
Key issues to note Over II years: 50-75 mg at bedtime' Max p . d f
rt'Ionths . erlo 0 treatment 3
':. Inform the patient that full therapeutic effect may delay up I (I ~ i
weeks 11·1 I years: 25-50mg
.:. Avoid alcoholic beverages while taking this drug 7years: 25 mg
't. Warn the patient not to stop taking the drug suddenly ,•ItniC
. d"Isord ers: 25-75 mg daily increased by 25-50 2
·t. The drug causes drowsiness and may impair activities thaI dilys to 150mg daily. mg every -3
need mental alertness

-461- -462-
 I PRECISE Igm1ilMC[[I![IOCI IIII
Side effects Indications
.:. Fatigue .:. Sweating .:. Major depression
.:. Dry mouth .:. Constipation .:. Obsessive compulsive disorders
.:. Orthostatic hypotension .:. Blurred vision .:. Panic disorders
.:. Impaired concentration .:. Somnolence .:. Cataplexy and associated narcolepsy
.:. Increased appetite .:. Photosensitivity .:. Premature ejaculation
.:. Urinary retention
Contraindications
.:. Hypersensitivity to the drug
Drug Interactions
.:. Recent myocardial infarction
.:. Imipramine may decrease the hypertensive effect of centrally
·IIIII!I .:. Mania
acting antihypertensive
.:. Arrhythmias
.:. Alcohol and other CNS depressants may increase the
.:. Severe liver disease
hypotensive effects and CNS depression caused by
j" Imipramine
.:. Concomitant treatment with monoamine oxidase inhibitors
.:. Narrow angle glaucoma
.:.': Cimetidine may increase Imipramine blood concentration all< I
risk of toxicity Dose
.:. Phenytoin may decrease Imipramine blood concentration Depression: Initially I Omg daily increased gradually according to
.:. Phenothiazines may increase the anticholinergic and sedatiw n~sponse to 30-ISOmg daily in divided doses or as a single dose at bed
effects of Imipramine Iii time max.2S0mg daily.
.:. Concurrent use of imipramine with phenylephrine, ephedrinl'
Obsessive compulsive disorder: 2Smg daily increased over 2weeks
may increase blood pressure
1;0 IOO-ISOmg daily max. 2S0mg daily.
Key issues to note ".mic disorders: 12.S-ISOmg daily max 200mg
.:. The full effect of the drug may not become apparent until 4 (,
Side effects
weeks after initiation of therapy
.:. Dry mouth
.:. Dry mouth caused by the drug may be relieved with chewlll~: Fatigue
.:. Disturbances in micturition Headache
gum
.:. Drowsiness Tremors
.:. The drug should not be discontinued abruptly, instead it
.:. Dizziness
should be tapered gradually Constipation
.:. Sexual dysfunction Somnolence
.:. Weight gain especially women Impotence
CLOMIPRAMINE
.:. Orthostatic hypotension Blurred vision
Available preparations: Tablets 2Smg
.:. Difficulty in passing urine Increased appetite
Available brands: Anafranil® .:. Ejaculation failure
Pharmacokinetics Drug Interactions
Clomipramine is well absorbed from the GIT, undergoes extensiV<' .:. Alcohol and other CNS depressants may increase CNS and
first pass metabolism, metabolized in the liver, excreted in urine allil respiratory depression and hypotensive effects of
faeces. clomipramine

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 , , ", "
PRECISE PHARMACOlOG ',:, ,:', "':',, I"'", ,,'" ",l,,, ':.', PRECISE PHARMACOLOGY
, "

.:. Cimetidine may increase clomipramine blood concentration Indications

.:. Major depression
and risk of toxicity
.:. Phenothiazines may increase the anticholinergic and .:. Obsessive compulsive disorder
sedative effects of clomipramine .:. Bulimia nervosa
.:. Premenstru~1 dysphoric disorders
.:. Panic disorders
Key issues to note .
.:. Minimize the risk of overdose by dispensing the drug In sm;lll .:. Post traumatic stress disorder
.:. Hot flushes
quantities
.:. Do not withdraw the drug abruptly Contraindications
'II
.:. GIT side effects may be minimized by taking the drug after a ".:. Hypersensitivity to fluoxetine
m~ . I' .:. Severe renal failure
•:. Avoid concurrent use of the drug with OTC cold preparatloll', ,. .:. Unstable epilepsy
.:. The drug causes drowsiness and may impair activities that .:. Manic phase
j",'~ need mental alertness
@i
l)ose
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRls) I)epression: 20mg once daily increased after 3-4 weeks if necessary.
Their efficacy is similar to that of tricyclic antidepressant~ but ~aV<' I(,"~ III lind at appropriate intervals thereafter, max. 60mg once daily
side effects because of low affinity for muscarinic, histaminergic and f!lderly: 20-40mg once daily, max. 60 mg
adrenergic receptors. ••ulimia Nervosa: 60mg once daily, max 80mg once daily
Examples ()bsessive compulsive disorder: Initially 20mg once daily increased
.:. Fluoxetine .:ttter 2weeks if necessary. max. dose 60mg
.:. Paroxetine I!'Iderly: 20-40mg once daily max. 60mg
•:. Sertraline '-"nic disorders: IOmg once daily do not exceed 20mg daily.
.:. Citalopram '-remenstrual dysphoric disorder: 20mg once daily
!lUcie effects
Mode of action
The antidepressant action of SSRls is by inhibiting the reuptake of t 11r; .:. Headache .:. Anxiety
.:. Insomnia Tremor
neuro transmitter, serotonin
.:. Somnolence Sedation
FLUOXETINE -:. Constipation Fatigue
Available preparations: Capsules 20mg -:. Abdominal pain Mania
Prozac®, Nuzac®, Trizac®, Fludac'!'" .:. Dry mouth Sweating
Available brands:
Flocept ® .:0 Dizziness Pharyngitis
Pharmacokinetics . .:- Nervousness Euphoria
Fluoxetine is well absorbed after oral administration, metabolizec 1111 -:. Sleep disturbance Dyspnoea
the liver to the active metabolites and excreted in urine. <. Drowsiness
Drug Interactions

il
III -466-
I', -465-
 PRECISE PHARMACOLOGY

• 771'
7
, , " I I
7

Dose
.:. Alcohol and other CNS depressants may increase CNS
Major depression, social anxiety disorder, post traumatic
depression . stress disorder, generalized anxiety disorder: Usually 20mg each
.:. Fluoxetine may increase phenytoin blood concentration and
morning, usual range 20-S0mg daily max. SOmg daily, elderly 40mg
risk of toxicity daily
.:. Fluoxetine may increase the effect of warfarin therefore, the
Panic disorder: initially IOmg each morning increased gradually in
dose may need adjustments steps of IOmg to a usual dose of 40mg daily max. 60mg daily, elderly
.:. Fluoxetine may increase the blood levels and toxicity of lithiUJlI
40mg daily
.:. Fluoxetine inhibits metabolism of carbamazepine and
Obsessive compulsive disorder: 20mg each morning increased in
haloperidol steps of IOmg gradually to the usual dose of 40mg once daily, max.
Key issues to note 60mgdaily '1:
.:. Full antidepressant effect may be delayed until 4 weeks of
treatment Side effects
.:. Give a lower dose in patients with hepatic and renal .:. Acute glaucoma .:. Insomnia
• ,~. .
'~l\if Impalrmen
t .:. Somnolence .:. Constipation
. therapy
•:~,~'~v. Avoid taking alcohol durmg .:. Sweating .:. Nervousness
.:. Tremor .:. Nervousness
PAROXETINE
Tablets 20mg
.:. Nausea .:. Diarrhoea
Available preparations: .:. Blurred vision .:. Yawning
Available brands: Xet®, Seroxat® .:. Dry mouth .:. Drowsiness
.:. Sexual dysfunction .:. Peripheral oedema
Pharmacokinetics
Paroxetine is well absorbed from the GIT, undergoes first pass
.:. Decreased appetite .:. Hepatic disorders
metablism, distributed to body tissues, metabolized in the liver and
.:. Postural hypotension
excreted in urine and faeces as metabolites. Drug Interactions
.:. Paroxetine may increase the effect of anticoagulants
Indications .:. Paroxetine may increase the toxicity of tricyclic antidepressants
.:. Major depression .:. Sedative drugs are likely to increase the sedative effects of !'II
.:. Obsessive-compulsive disorders
.:. Post traumatic stress disorder in women Paroxetine
.:. Panic disorders
.:. Phenobarbitone, phenytoin decrease the plasma
.:. Social anxiety disorder concentrations of paroxetine
.:. Generalized anxiety disorders .:. Cimetidine increases the plasma concentrations of paroxetine
.:. Social phobia K.,y issues to note
Contraindications .:. Improvement in symptoms may take 2-4 weeks to be realized
.:. Patients with known hypersensitivity paroxetine Iii 'l\
.:. Avoid taking alcohol during therapy
.:. Breast feeding III .:. The drug may be administered without regards to meals,
,,"
.:. Manic phase !I though food may reduce GIT side effects

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SERTRALINE
Available preparations:
Available preparations:
, ' PRECISE PHARMACOLOGY

Tablets SOmg, 100mg

Inosert®, Lustral®, Serenata®
IIII

'-
.:. Somnolence
.:. Dizziness
.:. Nervousness
.:. Postural hypotension
Insomnia
Tremors
Confusion
Pharmacokinetics Pancreatitis
.:. Aggressive behaviour
It is well absorbed after oral administration, food enhances the Hepatitis
.:. Liver failure
.:. Amnesia
rate and extent of absorption. It undergoes extensive first pass .:. Menstrual irregularities
metabolism, metabolized in the liver and excreted in urine and faeC(~" Thrombocytopenia
as metabolites. Drug Interactions
.:. Se,:r~line
may increase the blood concentration and risk of
Indications of digoxin and warfarin
tOXICIty
.:. Depression
.:. MAOls in~ibito:~ may cause neuroleptic malignant syndrome,
.:. Obsessive compulsive disorders
. hypertensIve crrslS when given together with sertraline
.:. Social phobia Kl!lY Issues to note
.:. Panic disorder
.:. Therapeutic effect may take several weeks to be realized
.:. Post traumatic stress disorder in women
.:. The .drug may be administered Without regard to food but
.:. Premenstrual syndrome avoid grape fruit jUice
Contraindications .:. Avoid taking alcohol during therapy
.:. Known hypersensitivity to sertraline .:. Inc~e .patient experiences somnolence, the drug may be
.:. Children under 18 years admInistered at bed time

Dose (:ITAlOPRAM
Depressive illness: SOmg once daily gradually increased if necess;1I y Available preparations: Tablets 20mg, 40mg
to a max. 200mg once daily, usual maintenance dose SOmg daily. AWliiab/e brands: Ce/epra®, Celica®, Feliz®
Obsessive compulsive disorder
Adults and adolescents over 12 years: Initially SOmg once daily '-fUlrmacokinetics
increased if necessary to usual dose range of SO-200mg daily. 1111\ readily absorbed from the GIT, metabolized by the liver, excreted
III UI'fl1e and faeces.
Children 6-12 years: Initially 2Smg once daily increased if necess.1I y
to SOmg once daily after one week. htdlcations
Panic disorder, social phobia: Initially 2Smg once daily, increase( III Ii! .> Major depression
necessary after a week to 50 mg once daily, maintenance dose SOftlY. iIIIl l <. Panic disorder Ii,
once daily Ii of alcohol abuse
Premenstrual syndrome: SOmg once daily starting 14 days befof (, 'iiiIi: .;..... Treatment
Diabetic neuropathy
the anticipated start of menstruation until the first full day of men'.,·,
~ :ontraindications
Side effects .... Hypersensitivity to the citalopram
.:. Headache .:. Fatigue t¢I Children below 18 years
.:. Nausea .:. Dry mouth

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 \ h l' P i1M'
2 2&2 11'.11 . '
~dminist~ation, distributed widely in the body including the CNS and
Dose e:~~esttemdll.k, m:tabodlizfed slowly by the liver to the active metabolite
Depression: 20mg once daily in the morning or evening increased if
In unne an aeces.
necessary to a max of 60mg daily (elderly 40mg).
Panic disorder: Initially IOmg daily increased to 20mg after 7days, Indications
usual dose 20-30mg daily, Max. 60mg daily (elderly 40mg dailyf .:. Depression
Contraindications
Side effects
.:. Nausea .:. Headache .:. known h.~persensitivity to tricyclic antidepressants or
.:. Dry mouth .:. Diarrhoea maprotlhne
.:. Somnolence .:. Diaphoresis .:. Ac ut e recovery phase of myocardial infarction
.:. Insomnia .:. Tremors .:. Use within 14days of therapy with MAOls
.
:. Increased sweating .:. Abnormal ejaculation .:. Severe hepatic impairment
\:I,
.:. Constipation .:. Fatigue .:. Acute poisoning with alcohol
.:. Decreased libido .:. Skin rashes
.:. Increased appetite .:. Impotence
Dose

.:. Palpitation .:. Yawning

Mild to moderate depression: 25mg 1-3 times daily or 25-75m
once a day depe~ding
on the severity and patient's response g
.:. Nervous .:. Coughing
. :. Dizziness .:. Taste disturbance Sever;l~eOPresslon: 25mg 3 times daily or 75 mg once daily up to a
rnax 0 mg as a Single dose or in divided doses.
.:. postural hypotension .:. Abnormal dreams
Side effects
Drug interactions .:. Fatigue .:. Drowsiness
.:. Citalopram may increase the anticoagulant effect of warfarin .:. Sleep disturbance .:. Constipation
.:. Citalopram increases metoprolol serum concentration .:. Agitation .:. Dry mouth
.:. Anxiety .:. Weight gain
Key issues to note .:. Increased appetite .:. Dizziness
.:. If patient enters into manic phase, treatment may be gradually .:. Postural hypotension .:. Sedation
discontinued .:. N~usea and vomiting .:. Diarrhoea
.:. Therapeutic response may take 5-6 weeks .:. Unnary retention .:. Urticaria
.:. The drug may be administered without regard to food .:. Headache .:. Sweating
.:. The drug may cause drowsiness and impair activities requ'lrlll~
O,.ug Interactions
mental alertness .:. Concur.rent use of maprotiline with phenylephrine,
OTHER ANTIDEPRESSANTS ephednne may increase blood pressure
MAPROTILINE A.dditive depressant effect may occur when maprotiline is
Available preparations: Tablets 25mg, 50mg glve~ together with other CNS depressants
Barb'tu~~tes and heavy smoking induce the metabolism of
Available brands: Ludiomil® ~aprotiline resulting in a decrease in the therapeutic effect

Pharmacokinetics et~ blockers may inhibit the metabolism of maprotiline

It is absorbed slowly but completely from the GIT after oral whICh may result into increased toxicity

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II
 , " PRECISE PHARMACr!lEGY

Key issues to note

.:. The therapeutic response may take atleast 4 weeks to be Dr~:s u~e~ in the treatment of mania include'-
• Lithium carbonate .
apparent
.:. Sodium valproate
.:. The drug should not be discontinued abruptly
.:. Carbamazepine
.:. Avoid alcohol during therapy
.:. Lamotrigine
.:. To minimize the risk of seizures, the total daily dose should be
less than 200mg
LITHIUM CARBONATE
Available preparations:
15.1.2 DRUGS USED IN THE TREATMENT OF MANIC Tablets 300mg
DISORDERS Available brands:
Camcolit®
Mania is ~ state of mind characterized by excessive cheerfulness and Pharmacokinetics
increased activity.
It is completely absorbed from the G
Signs and symptoms distributed widely into the bod' I~ after oral administration,
.:. I~ Hyperactivity .:. Excessive enthusiaslll metabolized and is excreted Y'hlncludl~g br~ast milk. It is not
•:. ~~ Decreased need for sleep .:. Flight of ideas unc anged m unne.
·:·If Inflated self esteem .:. Talkativeness Indications
.:. Extreme self confidence .:. Delusions .:. P h yi axis of mania
rop
Acute mania usually begins abruptly and symptoms increase .:. 1ireat ment of acute mania
.:. M . h
over several days. Manic episodes may be precipitated by; use of

I'
anrc p ase of the bipolar disorder
.:. Recurrent depression
antidepressants, lack of enough sleep, stressors, CNS stimulants and
.:. A .
bright light. ggress/ve or self-mutilating behaviour
II
Contraindications
Bipolar disorder (manic depression) is a mixed affective disorder III
which the patient experiences alternating episodes of hypomania 01
mania and depression.
.Management of Manic disorders
Mild symptoms of mania;
, .:. Pregnancy
.:. Severe renal impairment
.:. Cardiac disease
.:. Lactation
.:. Untreated Hypothyroidism
II Lithium alone or in combination with benzodiazepine .:. Disturbance of electrolyte balance
Severe symptoms of mania; -:. Hypersensitivity to the drug
Lithium plus antipsychotic drugs I)ose
:11; "cfllit and Children over 12 years:
Note Acute mania: 300mg 3-4 times' .
In acute attack of mania, lithium carbonate may be given concUlTc'"l1y "mphylaxis: Initially 300-400m d:~ mamtenance dose 2Ag/day
with antipsychotic in order to bring the symptoms under control '.1111' , 'Ide effects g y
lithium carbonate has a slow onset of action which takes up to 2w fl uh,: .:- Nausea
before therapeutic benefit is fully achieved c> Diarrhoea Polyuria
.:. Vertigo
'li oe· MUscle weakness
Tremors
-473- Ii i(
-474-

II,
,j(
 .:. Loss of concentration
PRE I

Weight gain
• • • •12112•••1.111_
• • • • • • • QiI#e~iIQ:MM6teU'Hi\'1
Classification of Epilepsy
.:. Hypothyroidism Oedema
.:. Impaired renal function Mild drowsiness Epileptic seizures (fits) present in several different forms depending on
•:. Hypermagnesaemia Sexual dysfunction the site of the discharge and whether the discharge remains localized
or spreads.
.:. Disturbances of thyroid function
.:. Exacerbation of psoriasis Partial Seizures
Drug Interactions . These are epileptic seizures in which the neuronal discharge remains
.:. Concurrent use of lithium with thiazide ~i~retlcs may decreasl' localized in one area of the brain. They result into a disturbance of
renal excretion and enhance lithium tOXICity .. function such as abnormal sensation or movement of the limb without
.:. Lithium may interfere with pressor effects of sympat~omlmet:l( loss of consciousness. Partial seizures are subdivided as follows;
agents and may decrease the effects of chlorpromazine Simple partial seizures (consciousness is not impaired)
.:. Tetracyclines, phenytoin, carbamazepine and methyldopa may Complex partial seizures (consciousness is impaired)
increase lithium toxicity . Partial seizures may become secondarily generalized seizures if the
.:. Concomitant use with haloperidol or other antipsychotic neuronal discharge spreads to involve the entire brain. :1.
agents may result in severe encephalopathy ·'i1lI
Generalized Seizures
.:. Use of lithium with SSRls may increase GI and CNS adverse
Generalized seizures are characterized by a neuronal discharge
effects . f
InvolVing the whole brain with loss of consciousness
.:. Indomethacin and other NSAIDs decrease renal excretion 0
They are sub-divided as follows:- i
lithium Lf
.:. Tonic-clonic seizures (grand mal)
.:. Myoclonic seizures III
Key issues to note . .:. Atonic seizures iIi
•:. The drug may be taken with food or milk t reduce GI.upset
.:. Absence seizures (petit mal)
.:. Lithium should be discontinued before electroconvulsive
therapy . Absence Seizures (Petit mal)
•:. Patient should maintain adequate water Intake . rhese are generalized seizures characterized by a sudden loss of
.:. Avoid large amounts of caffeine, which will interfere with (onsciousness lasting for a few seconds. It is usually accompanied by
drug's effectivenes 'Ilotor activity which may vary from eyelid blinking to more extensive
•:. The drug should not be stopped abruptly ( Ionic body movement. It is common in Children and juveniles.
Myoclonic Seizures
15.1.3 DRUGS USED IN THE TREATMEN~ OF EPILEPSY
Ihey are characterized by brief jerks in the limbs which may be single
Epilepsy is a disorder of brain function charactenzed by recurre~t
seizures that have a sudden onset. A patient should not be descnbe( I or multiple. The duration of the seizure is a few seconds. It mainly
occurs in Children and juveniles.
as having epilepsy until a second non-febrile seizure occurs
Atonic seizures
Seizure . II Atonic seizures are characterised by loss of postural tone; the head
Seizure is a paroxysmal discharge of cerebral neurons accompanlo( ly \.lSlS or the patient falls down.
a clinical phenomena apparent to the patient or to an observer. Generalized tonic-clonic seizures (Grand mal fits)
I hose are characterized by sudden attack with loss of consciousness
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 \
PRECISE PHARMACOLOGY
I
and violent body jerking lasting 3-5minutes. The patient regains Summary of choices of antiepileptic drugs
1\\\
consciousness spontaneously; and incontinence, tongue biting or other 'II[
Seizure type Treatment options
injuries may occur during the episode.
Partial seizures Carbamazepine, sodium
valproate, pregabalin,
Grand mal fits may be due to;
lamotrigine, Gabapentin,
.:. Family history of epilepsy
phenytoin
.:. Uncontrolled febrile convulsions in Children
Generahzed tOniC clOniC seIzures
.:. Head injuries
(grand mal) Carbamazepine, lamotrigine,
.:. Infections e.g. meningitis, HIV
Sodium valproate, phenytoin
.:. Birth trauma to an infant
Absence Seizure (petit mal) Ethosuximide, sodium
.:. Alcohol and drug abuse
valproate
Myoclonic SeIzures ISodium valproate, iii
Status Epilepticus
c10nazepam
It is a seizure lasting for more than 30 minutes or several fits following
Status epilepticus Diazepam, c1onazepam,
one another without restoration of consciousness in between the fits.
midazolam and phenytoin
Status epilepticus is a common complication of grand mal epilepsy and
it's a medical emergency. Note
Monotherapy is preferable to a multiple-drug regimen and treatment is
Management of status epilepticus
therefore initiated with a single drug, increasing the dose gradually Lintil
.:. Position the patient to avoid injury
seizures are brought under control or adverse effects become severe.
•:. Give oxygen to support respiration
If treatment with the first drug fails, it is preferable to try alternative
.:. If hypoglycaemia is suspected, give a bolus of SOml of 50%
single first-line antiepileptics before giving combinations of drugs.
glucose IV
.:. Consider giving parenteral thiamine if alcohol abuse is The change-over from one antiepileptic to another should be made
cautiously, withdrawing the first drug only when the new regimen has
suspected
been largely established Ii;
.:. Give anticonvulsants such as diazepam IV, lorazepam IV,
Drugs with different modes of action should be selected for combined
c1onazepam, midazolam
•:. Slow intravenous injection of Phenytoin may be given if therapy, to reduce the risk of additive adverse effects.
seizures recur or fail to respond to Diazepam 30 minutes Many antiepileptic drugs interact with each other therefore precautions
must be taken during prescribing.
after it began
.:. Phenytoin by Intravenous infusion should be given at a dos('
of I 5mg/kg body weight at a rate not greater than 50mg/ CARBAMAZEPINE iii
Available preparations: Tablets 100rng, 200mg
minute.
•:. Monitoring of blood pressure and ECG is necessary and Syrup 20mg/ml
phenytoin should be diluted with sodium chloride (norm;ll
saline) at a ratio of I mg of phenytoin: I ml of normal salillt'
I
iilll
Available brands: Tegretol®, Storilat®, Carbatol®, Carbadac®
Carbazina®

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 PRECISE L8GY 1111111] --..-m2&S_ pliJ4U13 PHARMACO 'lIij"
Pharmacokinetics 'II" Side Effects
It is absorbed slowly from the GIT, distributed widely throughout .:.
Nausea .:. Ataxia
the body, crosses the placenta and accumulates in fetal tiss~e. I~ i..
Ili\
, !II!
1111
Ii
".
.:.
Vomiting .:. Dizziness
metabolized by the liver to an active metabolite and is excreted In urlllC 1 'iiI I II .:.
Drowsiness .:. Dry mouth
.... and faeces
lillll\l1,
'I\.' .:.
Blurred vision .:. Headache
Indications .:.
Anorexia .:. Agitation
.:. Partial and secondary generalized tonic-clonic seizures .:.
Diarrhoea .:. Confusion
.:. Mixed partial or generalized seizure disorder .:.
Constipation .:. Impotence
.:. Trigeminal neuralgia .:.
Thrombocytopenia .:. Arthralgia ,11
.:. Prophylaxis in bipolar disorder .:. .:.
Stevens-Johnson syndrome Gynaecomastia
.:. Neuropathic pain
.:. Alcohol withdrawal
[)rug interactions
Contraindications .:. Clarithromycin, erythromycin, cimetidine, isoniazid may
.:•.~ Hypersensitivity to carbamazepine and TCAs inhibit hepatic metabolism of carbamazepine with resultant
.:. ". History of Bone marrow depression increase of its serum concentration and toxicity
.:. jlf! Porphyria .:. Rifampicin, phenytoin and phenobarbital may decrease serum
concentrations of carbamazepine \1
Dose .:. Antimalarial drugs may antagonize the activity ,of
Epilepsy: Initially 100-200mg 1-2 times daily, increased gradually ah,·,
carbamazepine
2weeks to the usual dose 400-1200mg daily in divided doses. In SOl1l"
.:. Use with alcohol and other CNS drugs may pontentiate
cases up to 1.6-2g daily may be needed
adverse effects of carbamazepine
Elderly: Initially 50mg twice daily then increase to 400-1200mg daily .:. Use with verapamil may significantly increase the serum levels
Children I month -12years: Initially 5mg/kg at night or 2.5mg/kgtwII II of carbamazepine
daily increased as necessary by 2.5-5mg/kg every 3-7~ays. Mainten,:u,1I .:. Carbamazepine may decrease the effectiveness of theophylline
dose 5mg/kg 2-3times daily. Doses up to 20mg/~g dally ~ay ~e usc(1 and oral contraceptives
Trigeminal neuralgia: Initially IOOmg 1-2 times dally, Incre;\""d .:. Carbamazepine may increase the metabolism of warfarin,
IiII
gradually according to response to 200mg 3-4 times daily. Up to I tId valproic acid, haloperidol and phenytoin
daily may be required in some cases. . ., .
Prophylaxis of bipolar disorder unresponsive to lithium: (mll,llly I(.,y issues to note
400mg daily in divided doses increased until symptoms are controlled .:. Take carbamazepine with food to prevent stomach upsets
Usual range 400-600mg daily, Max 1.6 g daily .:. Swallow controlled release tablets whole, do not chew or
Neuropathic pain: Initially I OOmg twice daily increased gradually 1111111 crash them
pain is relieved. Maintenance dose 200 - 600mg daily. Do not ex, "fl41 .:. Grapefruit juice may increase the absorption and blood
1.2 g daily. concentration of carbamazepine
.:- The drug is structurally siiTlilar to TCAs; some risk of activating

-479- -480-
 QMB~t< PHARMACOLOGY] PRECISE PHARMACOLOGY
2 Dose
OlS confusion or agitation in elderly patients
latent psyc h0 S , , Oral
exists Adult: Initially 150-300mg daily as a single dose or in 2 divided doses
.:. Avoid alcohol during thera~y d im air ability to perform increased gradually according to response, to the usual dose 200-500
.:. The drug may ~~use drowsl~e~:;ss or ~hysica\ coordination mgdaily.
activities reqUlrtng mental a e h d photosensitivity reactions Children: Initially 5mg/kg daily in 2 divided doses usual dose range 4-
.:. The drug may cause dry mout an 8mg/kg daily, max 300mg daily.
Arrhythmias:
PHENYTOIN Adults: Loading dose 250mg 4 times a day for I day, then 250mg/day
Tablets IOOmg
Available preparations:
Injection SOmg/ml for 2days, maintenance dose 300-400mg/day 1-4 times a day
,.: Side effects
Phenyto-S®, Epanutin®
Available brands: .:. Gastric intolerance Nausea
.:. Drowsiness .:. Nystagmus
Pharmacoldnetics th small intestine, distributed widely .:. Confusion .:. Vomiting
It is absorbed slowly from , b h liver to inactive metabo\it(~~. .:. Slurred speech .:. Diplopia
throughout the body, metabohzed Yt e .:. Gum hyperplasia .:. Behavioral disturbance
and excreted in urine. -:- Headache .:. Tremors
.:. Sedation .:. Anorexia
.:. Insomnia .:. Constipation
Indications -:. Blurred vision .:. Blood disorders
.:. Generalized tonic clonic seizures .:. Skin rashes .:. Coarse facies
.:. Partial seizures .:. Acne .:. Fever
.:. Status epilepticus .:. Hirsutism
, I
.:. Cardiac arrhythmias Orug Interactions
.:. Trigeminal neuralgia , or sevel I' .:. Alcohol and other CNS depressants may increase CNS
.:. Control of seizures associated wIth neurosurgery depression
traumatic injury to the head .:- Anticoagulants, cimetidine, fluoxetine, fluconazole,
ketoconazole, isoniazid and sulphonamides may increase
Contraindications . phenytoin blood concentration and risk of toxicity
•:. Hypersensitivity to phenytoin or other hydantolnS ·It Lidocaine, propranolol may increase cardiac depressant effects
.:. Sinus Bradycardia , caused by phenytoin
.:. Avoid parenteral use in sinus Bradycardia > Phenytoin may decrease the effects of oral contraceptives,
corticosteroids, haloperidol, frusemide, doxycycline, etc
.:. Sino-atrial block
I' Therapeutic effects of phenytoin may be decreased by
.:. 2nd and 3rd degree heart block
barbiturates, carbamazepine, ethanol, folic acid, antacids,
.:. Stokes - Adam's syndrome (IV)
charcoal and pyridoxine among others
.:. Hepatitis

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 " "'' '

p
• •• • • • • • • •1 '7 Q:JiH~ilq:G':J~j'~tBnIIIf\'1
Key issues to note . oin should be Children onder 12 years: with body weight over 20kg: initially 400mg
••• To ensure consistent absorption, phenyt I
• administered at the same time with regards to mea s GI daily in divided doses increased according to response, usual range 20-
30mg/kg daily, max. 3Smg/kg daily
.:. Phenytoin. may be taken with food or milk to decrease
upset
Children <:: 20kg: Initially 20mg/kg daily in divided doses
.:. Avoid alcohol during therapy . .
.:. Abrupt withdrawal may precipitate status e~lleptlcus Side effects
.:. Advise the patient to maintain good oral hygiene .:. Nausea
.:. Vomiting Tremor
.:. Ataxia
SODIUM VALPROATE .:. Increased appetite
.:. Abdominal cramps Oedema
Available preparations: Tablets 200mg, 300mg
.:. Sedation Diarrhoea
Syrup 200mg / Sml
.:. Weight gain
.:. Thrombocytopenia
Available brands: Epilim®, Petilin®, Valparin chrono® .:. Behavioural disturbance Gastric irritation
i~~ .:. Hyperammonaemia .:. Transient hair loss
Indications . DrOWSiness
0

.:. Menstrual disturbances

.:. Generalized tonic clonic seizures
.:. Partial seizures Drug Interactions
.:. Atonic seizures .:. Sodiu rn valproate increases plasma concentrations of
.:. Absence seizures Phenobarb, primidone, phenytoin, zidovudine
.:. Myoclonic seizures 0

.:. Aspirin may increase the effect of Sodium valproate

.:. Acute manic phase of bipolar disorder
.:. SOdium vafproate absorption may be reduced by
.:. Prophylaxis of migraine cnolestyramine
Contraindications .:. Cirnetidine and erythromYcin may increase the effect of
.:. Hypersensitivity to sodium valproate 0 sodium valproate
.:. Family history of severe hepatic dysfunction
.:. COl)colllitant use with c10llazepam may cause absence seizures
.:. Pregnancy
.:. Antacids ma increase the Oral absorption of sodium valproate
.:. Active liver disease
.:. Porphyria Key issueao note
.:. Pancreatitis
.:. AVoid alcohol during therapy

Dose d 2 dO oded doses preferably after food, .:. The drug may cause drOWSiness and impair ability to perform
~ of 2 Sg daily usual
01 0
Adult: Initially 600mg al y In IVI
increased by 200mg daily every 3days to a m . , act~ities requiring mental alertness or physical Coordination
maintenance dose 1-2g daily. .:. Thedru,g should not be Withdrawn abruptly

ETHOSUXIM. DE
Available ,repa.rations:
Capsules 2S0mg
Syrup 2S0mg/S m l
-483-
-484-
 , ' , PRE
PRECISE PHARMACOLOGY
Available brands: Zarontin®
.:. Haloperidol may change the frequency or pattern of seizure
Pharmacol<inetics activity
Ethosuximide is rapidly and completely absorbed from the ~IT, . Key issues to note
distributed widely throughout the body, metabolized ~xten.slvely. In .:. The drug may be administered with food or milk to prevent GI
the liver to several inactive metabolites, and excreted In urine with distress
small amounts in the faeces. .:. Abrupt withdrawal may precipitate petit mal seizures
Indications .:. Avoid alcoholic beverages during therapy
.:. Absence Seizures .:. The drug may cause drowsiness and impair ability to perform
.:. Myoclonic seizures activities requiring mental alertness

Contraindications GABAPENTIN
.:. Hyper sensitivity to Ethosuximide Available preparations: Capsules 100mg, 400mg
~~ . .
Adult and Children over 6 years: Initially 250mg tWice dally, Available brands: Neurontin®
increased by 250mg at intervals of 4-7days to the usual dose of 500-
750mg twice daily, up to 2g daily may be given . . Pharmacol<inetis
Children up to 6 years: Initially 5mg/kg (max I g) tWice dally Gabapentin is rapidly absorbed after oral administration, but
increased gradually over 2-3weeks up to maintenance dose of 10- bioavailability decreases with increasing doses. It is distributed to body
20mg/kg twice daily. tissues including breast milk and excreted unchanged in urine and
faeces.
Side effects
.:.Anorexia .:. Hiccup Indications
.:. Nausea .:. Drowsiness .:. Partial Seizures with or without secondary generalization
.:.Vomiting .:. Dizziness .:. Neuropathic pain
.:. Epigastric pain .:. Ataxia .:. Trigeminal neuralgia
.:.Weight loss .:. Headache Contraindications
.:.Abdominal pain .:. Mild euphoria .:. Hypersensitivity to gabapentin
.:. Fatigue .:. Depression
.:. Photophobia .:. Agranulocytosis
Dose
.:. Increased libido .:. Aplastic anaemia Epilepsy
.:.Gum hyperplasia Adult: 300mg on the I st day, then 300mg twice daily on 2nd day, then
300mg 3 times daily on the 3rd day, or initially 300mg 3 times daily on
Drug Interactions day I, then increased according to response in steps of 300mg daily in
.:. Alcohol and other CNS depressants causes additive CNS 3 divided doses to a max of 2.4g daily
depression and sedation .. Children 2-12 years: I Omg/kg day I, then I Omg/kg twice daily on
.:. Phenytoin, cabamazepine and phenobarbital may Increase day 2 then 10mg/kg 3 times daily on day 3, increased to the usual
hepatic metabolism of ethosuximide II III! maintenance dose of I 0-20mg /kg 3times daily.

-485- -486-
 PRECISE PHARMACOLOGY I
al giJjYtiIU:ti';J\1'~tBIJ(IId
Neuropathic pain
.:. Generalized tonic clonic seizures
Adults and Children over 18 years: 300mg on day I then 300mg .:. Partial seizures
twice daily on day 2 then 300mg 3 times daily on day 3, or initially
.:. Neonatal seizures
300mg 3 times daily on day I,then increased according to respon;e in
.:. Febrile convulsions
steps of 300mg daily to a max of I.8g daily. .:. Status epilepticus
Side effects Contraindications
.:. Diarrhoea .:. Tremors
.:. Dry mouth .:. Drowsiness .:. Hypersensitivity to phenobarbitone
.:. Absence seizures
.:. Dyspepsia .:. Amnesia .:. Porphyria
.:. Peripheral oedema .:. Ataxia .:. Respiratory depression
.:. Nausea and vomiting .:. Fatigue .:. Severe liver impairment
.:. Dizziness .:. Somnolence Dose
.:. Weight gain .:. Anxiety
.:. Skin rash .:. Diplopia Generalized tonic clonic seizures, partial seizures:
.:. Nystagmus
.:. Paraesthesia
.:. Pharyngitis
.:. Arthralgia
.:. Weakness
Adult: 60- I80mg once daily at night
Children: 5-8mg/kg daily
Febrile convulsions
\ \

Children: up to 8mg/kg daily

Drug Interactions Side effects
.:. Antacids containing aluminum and magnesium reduce .:. Sedation
absorption of Gabapentin from the GIT .:. Ataxia Mental depression
.:. Alcohol and other CNS depressants causes additive CNS .:. Nystagmus .:. Allergic skin reaction
depression and sedation .:. Somnolence Confusion
Constipation
Key issues to note .:. Respiratory depression
Hypotension
.:. Avoid alcoholic beverages during therapy .:. Behavioural disturbance
Drowsiness
.:. The drug should not be withdrawn abruptly .:. Megaloblastic anaemia
Slurred speech
.:. The drug may cause drowsiness and impair ability to perf01111 Drug Interactions
activities requiring mental alertness
.:. Phenobarbitone may increase the metabolism of
PHENOBARBITONE carbamazepine
Available preparations: Tablets 30mg .:. Phe~obarbit~ne may decrease the effect of digoxin,
Available brands: B-tone® corticosteroids, oral anticoagulants, tricyclic antidepressants
oral contraceptives and metronidazole '
Pharmacokinetics IIIII .> The sedative effect of phenobarbitone is enhanced by other
Phenobarbitone is well absorbed after oral administration, distril>llIlill I
!II:,-
,I I
CNS depressants including alcohol
widely to body tissues, metabolized by the liver and excreted ill III Inil lit '
!II'"
-:. Sodiu~ ~alproate increases the blood concentration and risk
of tOXICIty of phenobarbitone
Indications

-487-
-488-
 7' _ _ &&1.
Key issues to note , h Side Effects
. h r b erages dunng t erapy .:. Dizziness
.:. Avoid alco 0 IC ev . . bTty to perform
.:. The drug may cause drowsiness and Impair a II .. .:. Somnolence Dry mouth

rug rehqu\~n;O~~:~i:~~:r:~s
.:. Ataxia Constipation
.:. activdities
The s ou abruptly after prolonged Peripheral oedema
.:. Weight gain
use .:. Flatulence Euphoria
Drowsiness
.:. Memory impairment
PREGABALIN .:. Speech disorder Vomiting
Available preparations: Capsules 2Smg, 7Smg, ISOmg .:. Irritability Confusion
Fatigue
.:. Increased appetite
.
Available bran d s.. Lyrica® Diplopia
.:. Reduced libido
.:. Blurred vision Vertigo
Pharmacokinetics . 1\ but the rate of absorption is
It is rapidly absorb:d wh~nhgflve~ ~;~~ergoes negligible metabolism Drug interactions
decreased when given Wit 00. I
and is excreted in urine as unchanged drug, Alcohol, barbiturates, narcotics analgesics and other sedative
.:.
drugs may increase sedative effects of pregabalin
Key issues to note
Indication~ . . Wit
.:. PartIal seizures 'h or WI'thout secondary generalization
.:. Advise the patient not to stop the drug abruptly but to
.:. Neuropathic pain taperthe dose over a period of one week
.:. Generalized anxiety disorder .:. Pregablin is not recommended in children below 18 years
.:. Pregab/in may cause drowsiness and impair ability to perform
Contraindications , activities requiring mental alertness
.:. Hypersensitivity to pregabalin
.:. Breast feeding 15./.4 ANXIOlYTICS, SEDATIVES AND HYPNOTICS
AnXiety is an emotional condition characterised by feelings such as
<II ,prehension and fear accompanied by symptoms such as tachycardia,
Dose d 'I ' 2-3 divided doses increased if Increased respiration, sweating, and tremor,
Partial Seizures: ISOmg al y In d iI in 2-3 divided doses, incrc,I',I'
necessary after 3-7days to 300mg a y 600 daily Olugs used in the treatment of anxiety include:-
further I ne~essa. •
'f ry after 7days to max. mg . .:. Benzodiazepines
dail in 2-3 divided doses increased If
Neuropathic pain. ISOmg y d 'I ' 2-3 divided doses incrc.I....d .:. Antidepressants (Anxiety frequently co-exists with depression)
necessary after 3-7days to 300mg al y I~OO daily
.:. Beta blockers (may help to control physical symptoms such as
further if necessa?, after ~~ays to max'dail ~g2-3 divided doses tremor)
Generalized anxiety: Inltlal.'y ISOmgf
increased at I week interval In steps 0
Isb mg
daily max 600mg (l.llly
, Note:
in 2-3 divided doses. ',' Antidepressants can initially exacerbate anxiety (their
therapeutic response takes atleast 2weeks) therefore combined
therapy with benzodiazepines may be required initially
<- Benzodiazepines should be used for a maximum of 4 weeks
-489-
-490-
 ••••••••• ,. " " , •• " , , •• , ' j . ] '",u"'UUIlIIIIlUIIIIIIIIlIllIIIlIlIlIUIJIIIUlIIIJIIIIIJIIIIIIlIlUlllllllljjIUI!!!]! Ii::: ;11:

,I" , PRECISE~BL8GY ",.' , , ' I" I'" '" '" , ", ' ' ",', , I"'; PRECI' HARMACOLOGY

and the dose should be gradually reduced after the first 2weeks Pharmacokinetics
to avoid the risk of dependence. Diazepam is rapidly absorbed from the GIT follOWing o~al
administration, distributed Widely throughout the body, metabolized
Insomnia
in the liver to the active metabolite, excreted in urine and small
Insomnia is the inability to achieve or maintain sleep. It often leaves
amount in faeces.
sufferers feeling unrefreshed by sleep and may lead to impaired
daytime performance. Indications
Insomnia is classified as follows:- .:. Status epileptics
Transient insomnia .:. Febrile convulsions
It may occur in those who normally sleep well and may be due to .:. Convulsions due to poisoning
environmental stress such as noise, shift work or jet lag. It may also be .:. Anxiety disorders
associated with acute disorders. .:. Insomnia
.:. Control of muscle spasms
Short-term insomnia
.:. Management of alcohol withdrawal
It is often related to an emotional problem e.g. on going personal
stress or medical illness such as acute pain. Contraindications
.:. Hypersensitivity to diazepam
Chronic insomnia
.:. Respiratory depression l
Most cases of chronic insomnia are caused by psychiatric disorders
.:. Severe hepatic impairment
such as depression, anxiety, dementia, psychosis or substance abuse,
.:. Acute pulmonary insufficiency
or physical causes such as pain or pruritus.
.:. Sleep apnoea
Drugs used in the treatment of insomnia include:- .:. Comatose patients
.:. Benzodiazepines .:. Acute narrow angle glaucoma
.:. Antidepressants .:. Acute alcohol intoxication
.:. Infants less than I month
BENZODIAZEPINES
This class includes: - Dose
.:. Diazepam .:. C10nazepam Oral
.:. Midazolam .:. Nitrazepam Anxiety: 2-1 Omg 2-4 times daily
.:. Bromazepam .:. Chlordiazepoxide Insomnia associated with anxiety: 5-15mg at bed time
.:. Alprazolam .:. Lorazepam Muscle spasms: 2-1 Omg 2-4times a day
DIAZEPAM acute alcohol withdrawal: 10mg 2-4 times for the first 24 hours,
reduce to 5mg 3-4 times on the next day as required
Available preparations: Tablets 5mg
Severe acute anxiety, control of acute panic attacks, acute
RectallOmg
alcohol withdrawal, muscle spasms:
Injection IOmg/2ml
By 1M or slow IV injection: IOmg repeated if necessary after not less
Available brands: Valium®, Cozepam®, Solina® than 4hours
Status epileptics: by slow IV at a rate of 5mg/ min
Adult: I 0-20mg repeated if necessary after 30-60 minutes.

-491- -492-

"!'i!!III'IIIII!I!_mllllll111!i l .IIII!'lllll!I!HIIi! • • • •I!illlllllllllllllllllllllllillililii!i _

s •• a zSI'
Children: 200-300mcg/kg or I mg /year of age
PRECI~11~:!:lilMM"Wrl I

.:.
': I '"," ,'~",,': "I, I I' I' ,:

Diazepam should not be discontinued suddenly instead

PRECISE PHARMACOLOGY

Seizures associated with poisoning: by slow IV at a rate of Smg decrease the dosage slowly over 8-12 weeks after long term
/l11 in; Adult: IO-20mg therapy
By rectum as a rectal solution ClONAZEPAM
Adult and Children over 3years: IOmg repeat the dose after
Available preparations: Tablets 2mg
5111inutes if necessary
Children 1-3years and elderly: 5mg. repeat the dose after Sminutes if Injection I mg/ml

necessary Available brands: Rivotril®

Side effects Pharmacol<inetics

.:. Drowsiness .:. Ataxia C10nazepam is well absorbed from the GIl; distributed widely
.:. Sedation Headache Ithroughout the body, extensively metabolized by the liver to several
.:. Dependence Confusion metabolites and excreted in urine.
.:. Muscle weakness •:. Vertigo
Skin rash Iindications
.:. Hypotension
Tremor .:. Myoclonic seizures .:. Absence seizures
.:. Visual disturbance
Blood disorders .:. Panic disorders .:. Status epilepticus
.:. Changes in libido
.:. Urinary retention or incontinence .:. Amnesia .:. Acute manic episodes
.:. Hypersensitivity reactions Contraindications
.:. Hypersensitivity to the drug
Drug Interactions
.:. Acute pulmonary insufficiency
.:. Alcohol and other eNS depressants may increase CNS
.:. Chronic respiratory disease
depression caused by diazepam
.:. Severe liver disease
.:. Antacids may decrease the rate of absorption of diazepam
.:. Narrow angle glaucoma
.:. Heavy smoking accelerates diazepam metabolism thus
lowering clinical effectiveness Dose
.:. Oral contraceptives may impair the metabolism of diazepam Oral: I mg (elderly SOOmcg), initially at night for 4 nights increased
according to the response over 2-4 weeks to usual maintenance dose
.:. Cimetidine, isoniazid, erythromycin may inhibit the break
of 4-8mg
down of diazepam leading to increased levels in blood
Children:
.:. Diazepam may inhibit the therapeutic effect of levodopa
5-12years: initially SOOmcg/day increased if necessary to daily
maintenance dose of 3-6mg
{ey issues to note I-Syears: initially 2~Omcg/day increased if necessary to daily
.:. Administer the drug with food or water but not grape fruit maintenance dose of 1-3mg
juice Up to I year: initially 2S0mcg increased if necessary to a
.:. Avoid alcohol and caffeine during therapy maintenance dose of 0.5-1 mg
.:. The drug may cause drowsiness and impair ability to perform Status epileptics: intravenous injection into large vein over at least
activities requiring mental alertness 2minutes, I mg repeated if necessary

-493- -494-
 •
, PRECISE PHARMA PRECISE PHARMACOLOGY
Children all ages: 500mcg Available brands: Dormicum®, Sedoz®
Panic disorders: 250mcg twice daily, this may be increased after 3
Pharmacokinetics
days to a total of I mg daily max. dose 4mg daily.
Midazolam is well absorbed following 1M administration, widely
Side effects distributed throughout the body, metabolized in the liver and
.:. Drowsiness Dry mouth excreted in urine.
.:. Fatigue Constipation Indications
.:. Dizziness Diarrhoea .:. Anxiety
.:. Ataxia Palpitations
.:. Premedication before induction of anaesthesia
.:. Irritability Confusion
.:. Induction and maintenance of anaesthesia
.:. Behavioral disturbance .:. Amnesia
.:. Patients in intensive care who require continuous sedation
.:. Change in appetite Dependence
.:. Sexual dysfunction Restlessness Contraindications
.:. Urinary incontinence .:. Known hypersensitivity to benzodiazepines
Drug Interactions . . " .:. Acute alcohol intoxication
.:. Alcohol, antidepressants, antihistamines and 0plold analgesl( ", .:. Acute angle closure glaucoma
re may result in additive CNS depression when given with .:. Severe respiratory depression
c10nazepam .:. Myasthenia gravis
.:. Azole antifungals may increase blood concentration and the .:. Coma
potential for c10nazepam toxicity .:. Hypotension or shock
.:. Hepatic enzyme inducers, such as carbamazepine, " Dose
phenobarbital, or phenytoin, may accelerate the metabolisill Insomnia: oral: 7.5 - 15mg at night
of c10nazepam Sedation: by IV injection over 30seconds: 2mg (elderly 1-1.5mg)
.:. Concomitant use with sodium valproate may induce absell( ,- followed after 2minutes by increment of 0.5-1 mg if sedation is not
seizures 'I(lequate.
Premedication before an operation:
lKey issues to note
.:. Abrupt withdrawal of c10nazepam may precipitate status
By 1M injection: 70-1 OOmcg/kg 30-60minutes before surgery. Usual
dose 5mg (2.5mg in elderly)
epilepticus after long term use therefore dosage should be'
Induction by slow IV injection: 200-300mcg Ikg (elderly 100-
lowered gradually 200mcg/kg)
.:. Avoid alcohol during therapy with c1onazepam.
Children over 7years: 150mcg/kg
.:. Advise the patient to avoid tasks that require mental alertllu'I'
Intensive Care patients: Loading dose of 30-300mcg I kg may be
until degree of sedative effect is determined
I(lven by intravenous infusion over 5 minutes to induce sedation.
MIDAZOLAM Side effects
Available preparations: Injection I mg/ml, 15mg/3ml, 5mg/ ')'"'
.:. Decreased respiratory rate .:. Dizziness
Tablets 7.5mg .:. Drowsiness .:. Ataxia
.:. Nausea and vomiting .:. Hypotension

-495- -496-
 , , , PRECISE ARMACOlOGY , ',' ' , PRECISE PHARMACOLOGY

.:. Confusion .:. Coughing .:. Breast feeding

.:. Headache .:. Hiccups .:. Chronic psychosis
.:. .:. Euphoria .:. Respiratory depression
.:.
Slurred speech
Tenderness at 1M injection site .:. Hallucination .:. Acute alcohol intoxication

Drug Interactions Dose

.:. Midazolam may potentiate the effects of alcohol, Anxiety: 10mg 3 times daily, increased if necessary to 60-1 OOmg daily
antihistamines, narcotics or antidepressants in divided doses.
.:. Isoniazid may decrease the metabolism of midazolam Muscle Spasms: 10 - 30mg before retiring to bed.
•:. Midazolam may decrease the needed dose of inhaled Alcohol withdrawal: 25-1 OOmg repeated every 4-6 hours up to a
anaesthetics by depressing respiratory drive max. of 300mg daily. The dose is reduced and discontinued after 4-1 0
days
Key issues to note
Insomnia: I 0-30mg taken before bedtime
.:. Advise the patient to avoid tasks that require mental alertness
Side effects
until the drug's effects have worn off
.:. Drowsiness Bradycardia
.:. Avoid alcohol during therapy with midazolam.
.:. Somnolence Dry mouth
.:. Ataxia Headache
CHLORDIAZEPOXIDE .:. Dizziness Skin rash
Available preparations: Tablets 5mg, 10mg, 25mg
.:. Confusion .:. Vertigo
Available brands: Librium® .:. Decreased libido Fatigue
.:. Urinary incontinence Constipation
Combinations: Epirax® (c1idinum bromide/chlordiazepoxide) 2.5/5
Drug interactions
Pharmacokinetics
.:. Chlordiazepoxide may increase or decrease the effects of
Chlordiazepoxide is absorbed from the GIl"; distributed widely
some anticonvulsant drugs
throughout the body, metabolized in the liver to several active
.:. Alcohol and other CNS depressants may increase CNS
metabolites and excreted in urine.
depression caused by chlordiazepoxide
Indications .:. Azole antifungals may increase the serum concentration of
.:. Anxiety Chlordiazepoxide and increase the risk of toxicity
.:. Relief of muscle spasms .:. Cimetidine increases serum concentration of chlordiazepoxide
.:. Alcohol withdrawal symptoms .:. Heavy smoking accelerates chlordiazepoxide's metabolism,
.:. Tension headache thus lowering clinical effectiveness
.:. Tremors .:. Oral contraceptives may impair the metabolism of
.:. Insomnia chlordiazepoxide
.:. Antacids may delay the absorption of chlordiazepoxide
Contraindications
.:. Concomitant use with levodopa may decrease the therapeutic
.:. Knwon hypersensitivity to chlordiazepoxide
effects of levodopa
.:. Acute pulmonary insufficiency
.:. Benzodiazepines may decrease serum levels of haloperidol
.:. Pregnancy

-497- -498-
 lfi.iDIARMACl!llOGY P~~PHARMACOl.GY

Key issues to note .:. Confusion Fatigue

.:. Warn the patient that sudden changes in position may cause .:. Nausea and vomiting Skin rashes
dizziness Drug interactions
.:. The drug should not be discontinued abruptly after longterm .:. Alcohol and other CNS depressants may potentiate sedative
use effect caused by alprazolam.
ALPRAZOLAM .:. Ketoconazole, itraconazole may inhibit metabolism and
Available preparations: Tablets O.5mg, O.25mg increase serum concentration of alprazolam
.:. Cimetidine increases serum concentration of alprazolam
Available brands: Xanax® .:. Heavy smoking accelerates alprazolam's metabolism, thus
Pharmacokinetics lowering clinical effectiveness
It is well absorbed after oral administration, widely distributed .:. Benzodiazepines may decrease serum levels of haloperidol
throughout the body, metabolized in the liver and excreted in urine. Key issues to note ~
Indications .:. Patients receiving prolonged therapy with high doses should be
.:. Anxiety weaned from the drug gradually to prevent withdrawal
.:. I~ Alcohol withdrawal symptoms
• ~Ji,p'
••• anlc artac ks .:. Warn the patient that sudden changes in position may cause
~.
.:.' Premenstrual syndrome dizziness
Contraindications .:. The drug may cause drowsiness and impair ability to perform
.:. Hypersensitivity to alprazolam activities requiring mental alertness
.:. Patients with pre-existing CNS depression or coma .:. Avoid alcohol during therapy and limit caffeine
.:. Acute narrow angle glaucoma BROMAZEPAM
.:. Pregnancy Available preparations: Tablets 1.5mg, 3mg
.:. Lactation
.:. Severe hepatic impairment Available brands: Lexotanil®
II
.:. Respiratory depression Iindications
.:. Acute alcohol intoxication .:. Anxiety
Dose
':ontraindications
Anxiety:
Adult: O.25-0.5mg 3 times daily, increased where necessary to a tot .11 .:. Known hypersensitivity to benzodiazepines
.:. Severe respiratory insufficiency
dose of 3 or 4 mg /day
Panic attacks: O.5mg 3 times a day, max. I Omg daily .:. Sleep apnoea syndrome
Premenstrual syndrome: O.25mg 3 times a day .:. Severe hepatic impairment
Dose
Side effects
.:. Dizziness .:. Headache 1.5-3mg up to 3 times daily
.:. Drowsiness .:. Blurred vision
.:. Sedation .:. Constipation
•:. Vertigo .:. Muscle weakn('·.·.

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 PRECISE PHARMACOLOGY
, , ,""" I '" I' " , , ' , I , PRECISE PHARMACOLOGY
Side effects disease and are effective in the treatment of drug induced
.:. Sedation .:. Headache
II, Parkinsonism.
.:. Dizziness .:. Fatigue
.:. Drowsiness .:. Dependence 1 ," BROMOCRIPTINE
.:. Hypotension .:. Confusion' 1
,11 Available preparations: Tablets 2.5mg
.:. Respiratory depression .:. Poor concentration I
Available brands: Lactodel®, Parlodel®, Dopagon®,
Drug interactions Brameston®
.:. Alcohol and CNS depressants may increase CNS depression Pharmacokinetics
caused by bromazepam Bromocriptine is poorly absorbed when given orally, undergoes first-
.:. Warfarin pass metabolism. It is metabolized completely in the liver and majorly
excreted through bile.
15.1.5 DRUGS USED IN THE TREATMENT OF
PARKINSONISM Indications
Parkinson's disease is a neurodegenerative disorder characterized .:. Parkinson's disease .:. Prolactinomas
by tremor, muscle rigidity, slowed movement and postural instability .:. Suppression of lactation .:. Female infertility
as a result of an imbalance between dopamine and acetylcholine .:. Puerperal breast engorgement .:. Amenorrhoea
neurotransmitters in the striatum. .:. Male hyperprolactineamia .:. Acromegaly
.:. Premenstrual symptoms .:. Benign breast diseases
Drugs used in the treatment of Parkinson's disease aim at restoring
the natural balance between dopamine deficiency and relative Contraindications
cholinergic excess in the brain. .:. Patients hypersensitive to ergot alkaloids
.:. Pregnancy
Classification of drugs used for Parkinson's disease .:. Severe ischemic heart disease
Dopaminergics .:. Uncontrolled hypertension
These drugs increase or enhance the action of dopamine in the brain
Examples Dose
.:. Bromocriptine Parkinson's disease and infertility; 1.25mg at night for 7 days
.:. Carbidopa increase to 2.5mg for the second week, 2.5mg twice daily for the
.:. Levodopa third week, and then, 2.5mg 3 times daily for the fourth week. Then
.:. Cabergoline increasing by 2.5 mg every 3-14 days according to response to a usual
range of I0-40mg daily taken with food
Antimuscarinics Suppression of lactation: 2.5mg daily for 2-3 days increased to
These drugs inhibit the action of acetylcholine in the brain. 2.5mg twice daily for 2 weeks
Examples Amenorrhoea and benign breast disease: initially 1.25mg once
.:. Benzhexol daily at bed time, gradually increased to 2.5mg 2-3 times daily
.:. Benztropine mesylate Side effects
Antimuscarinics are often effective in the early stages of Parkinson's .:. Dizziness Dry mouth
.:. Headache Confusion

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 PRECISE PHARMACOLOGY I I 'II I I '" r

I ,I, "',."",',, , ,,,,.. PRECISE PHARMAC[IRiM'II

.:. Constipation .:. Leg cramps
.:. Allergic skin reactions .:. Fatigue
Indications
.:. Parkinson's disease
.:. Cold fingers and toes .:. Nausea
.:. Postural hypotension .:. Hair loss Contraindications
.:. Light headedness .:. Abdominal cramps .:. Closed angle glaucoma
.:. Vomiting .:. Insomnia .:. Hypersensitivity to any of the ingredients
.:. Nasal congestion .:. Bronchial asthma
.:. Severe cardiovascular disease
Drug interactions
.:. Undiagnosed skin lesions or history of melanoma
.:. Anti psychotic drugs may oppose the action of bromocriptine
and increase the risk of parkinsonism Dose
.:. Erythromycin and other macrolide antibiotics may lead to Ini~ially 5?-1 OOmg of levodopa with I 0-12.Smg of carbidopa 3-4times
increased levels of bromocriptine and the risk of adverse dally. (as ~ -I tablet of sinemet I 10, 3-4 times daily). Increased by SO-
effects I OOmg dall~ or on alternate days according to response up to 800mg
.:.~.. Domperidone and metoclopromide may reduce the levodopa with 80-1 OOmg carbidopa in divided doses
iii
i.t hypoprolactinaemic effects of bromocriptine Side effects
.:. Alcohol intolerance may result when high doses of .:. Nausea
Dry mouth
bromocriptine are administered together with alcohol .:. Dizziness
Depression
Key issues to note .:. Palpitations Headache
.:. Side effects may be minimised by gradual introduction of the .:. Dark urine
Fluid retention
drug .:. Abnormal movements Tongue irritation
.:. The drug may be administered with meals to minimise GI .:. Visual abnormalities Muscle twitching
distress .:. Nervousness / agitation
.:. Take precautions while driving or operating machines since
dizinnes or drowsiness may occur at the beginning of therapy Drug Interactions
.:. Advise patient to limit alcohol use during treatment .:. Pyridoxine reverses effect of levodopa
.:. Inform the patient that it may take 6-8 weeks or longer for .:. Absorption of levodopa may be reduced by iron
menses to be re-instated .:. Anti psychotic drugs may reduce the effect of levodopa
.:. Antacids may increase the absorption of levodopa
LEVODOPA WITH CARBIDOPA
Available preparations: Tablets Key issues to note
.:. Gastric irritation may be reduced by taking the drug after food
Available brands: Sinemet® (Ievodopa/carbidopa) 100/ I 0
.:. :reatment should be started with low doses, then gradually
Pharmacokinetics Increased according to the response
levodopa is fairly well absorbed when given orally, though food .:. inform the patient that therapeutic response may be slow II
reduces rate and extent of its absorption. Carbidopa enhances .:. Warn the patient of the possible diziness and orthostatic
levodopa bioavailability. It is metabolized in the liver to dopamine allil
excreted in urine.
I!:. J
i i ',

'II .:
hypotension especially at the begining of therapy

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-504-
 ,
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CABERGOLINE .:. Hypoprolactinaemic effect of cabergoline may be antagonised

Available preparations: Tablets 0.5mg, 4mg by metodopramide.
Available brands: Dostinex® Key issues to note
.:. Pregnancy should be ruled out or exduded before
Indications
carbegoline is administered
.:. Parkinson's disease
.:. Care should be taken when giving cabergoline with drugs that
.:. Suppression of lactation
lower blood pressure
.:. Disorders associated with hyperprolactinaemia (amenorrhoea,
.:. Warn the patient of the side effects such as somnolence
oligomenorrhoea, galactorrhoea)
and sudden onset of sleep which may interfere with the
Contraindications performance of activities requiring mental alertness
.:. Hepatic insufficiency
.:. Toxaemia of pregnancy BENZHEXOL
.:. Hypersensitivity to any ergot alkaloid Available preparations: Tablets 2mg, Smg
Dose Available brands: Artane®
Parkinson's disease: Img as a single daily dose may be increased in
Pharmacokinetics
increments of 0.5 or Img at intervals of 7 or 14 days.
It is rapidly absorbed after oral administration, crosses the blood brain
The recommended therapeutic dose range is 2-6 mg daily.
barrier and excreted in urine as unchanged drug.
Suppression of lactation: 250mcg 2 times a day for 2 days
Inhibition of lactation: Img single dose during the first postpartum Indications
day .:. Parkinson's disease
.:. Drug induced extra pyramidal symptoms
Side effects
.:. Dyspepsia .:. Vertigo
.:. Palpitation .:. Nausea Contraindications
.:. Constipation .:. Breast pain .:. Closed angle glaucoma
.:. Breast pain .:. Angina .:. Chronic pulmonary disease
.:. Sleeplessness .:. Headache .:. Myasthenia gravis
.:. Peripheral oedema .:. Thyrotoxicosis
.:. Epigastric and abdominal pain .:. Urinary obstruction
.:. Hypersensitivity to the drug
Drug interactions .:. GI obstruction
.:. Hypoprolactinaemic and anti-parkinsonian effects of
cabergoline antagonised by anti psychotics. Dose
.:. Plasma concentration of cabergoline is increased by macrolide Initially 1-2mg daily, with increment of 2mg every 3-5 days as
.:. Hypoprolactinaemic effect of cabergoline may be antagonised required, maintenance dose of 5-15mg daily in 3 -4 divided doses
by domperidone. max.20mg daily.

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 : " PRECISE' OLOGY ,
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Side effects
,
Idi
Positive symptoms Negative symptoms
i
.:. Dry mouth .:. Constipation ;i .:. Delusions .:. Lack of drive
.:. Tachycardia .:. Euphoria q
i .:. Hallucinations .:. Apathy
.:. Nausea .:. Vomiting
I
.:. Thought disorders .:. Social withdrawal
.:. .:. .:. Disorganized behaviours .:. poor self care
Dizziness Blurred vision
ill i!1
.:. Agitation .:. poverty of speech
Drug interactions Positive symptoms are seen as exaggeration of normal function and
.:. There is increased risk of antimuscarinic side effects when are common in the acute phase,
benzhexol is given with antihistamines Negative symptoms are viewed as loss of normal function and are
•:. Concomitant use with haloperidol or phenothiazines may prominent in the chronic phase.
decrease the antipsychotic effectiveness of these drugs Most drugs are effective against positive symptoms except atypical
antipsychotics such as olanzepine which are effective against both
.:. Alcohol and other CNS depressants may increase the sedative
positive and negative symptoms.
effect of benzhexol
.:. Efficacy of levodopa may be enhanced when given with Drugs used in the treatment of schizophrenia can be classified as
benzhexol either typical (first generation) or atypical (second generation)
•:. Antacids and antidiarrhoeals may decrease the absorption of antipsychotics.
benzhexol Classification of antipsychotic drugs and their target symptoms
Key issues to note
Class Drug Target symptoms
.:. Warn the patient of the possible side effects such as dizziness
Phenothiazines Chlorpromazine Hallucinations
and blurred vision which may affect the ability'to drive
(typical) Fluphenazine Delusion
.:. Inform the patient that anticholinergic symptoms frequently
Trifluoperazine Irrational behaviour
diminish with continued therapy
Promethazine
.:. Patients with prostatic hypertrophy should be observed for
Thioridazine
signs of urinary retention
Butyrophenone Haloperidol Elated mood
15.1.6 ANTI PSYCHOTICS (NEUROLEPTIC) DRUGS (typical) Droperidol Expansive self image
Schizophrenia Grandiose delusion
Schizophrenia is a chronic psychotic illness characterized by a
disintegration of the process of thinking, contact with reality, and Atypical antipsychotic Resperidone Hallucinations
emotional responsiveness. C10zapine Delusions
It is more common in males and usually begins in late adolescence to Olanzapine
the early twenties.
Note
Clinical features of schizophrenia are often presented as positive or
.:. Drug treatment must be started as soon as possible for better
negative symptoms;
results
.:. Acute psychotic symptoms such as hallucination or

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 PRECISE PHARMACOLOGY , ,', ':' ;', ':, ":" ':' ',' ':",':" t: ,'::, I,:: :,,! PRECISE PHARMACOLOGY

delusions can be controlled using drugs such as haloperidol or response to a maintenance dose of 75 - 300mg daily
chlorpromazine Psychotic patients may require up to I OOOmg daily or more.
.:. Positive symptoms tend to respond better to drugs than Children:
negative symptoms 6-12years: third -half adult dose
.:. Treatment for schizophrenia is not curative and long term 1-5years: 500mcg/kg every 4-6hours
maintenance therapy (2-5years) is usually required to prevent By deep 1M injection: 25-50mg every 6-8hours
relapse 6-12years: 500mcglkg every 6-8hours (max 75mg daily)
1-5years: 500mcglkg every 6-8hours (max 40mg daily)
CHLORPROMAZINE
Intractable Hiccups: 25-50mg 3-4 times daily, by mouth for 2 -3
Available preparations: Tablets 25mg, 100mg
days then 25-50 mg may be given intramuscularly
Injection 25mg / ml
Side effects
Available brands: Largactil® .:. Sedation .:. '\I Depression

.:. Tardive dyskinesia .:. Apathy

Pharmacokinetics
.:. Galactorrhoea .:. Impotence
It is rapidly absorbed following oral administration but bioavailability is
.:. Blurred vision .:. Dry mouth
low due to extensive first-pass metabolism in the liver and gut walls. It
.:. Protrusion of the tongue .:. Tremors
is widely distributed into the body, including breast milk, metabolized
.:. Convulsions .:. Constipation
extensively in the liver and excreted in urine.
.:. EEG changes .:. Weight gain
Indications .:. Hypotension .:. Gynaecomastia
.:. Acute and chronic Schizophrenia .:. Acute Mania .:. Menstrual disturbance .:. Photo sensitization
.:. Psychomotor agitation .:. Violent behaviour
Drug interactions
.:. Nausea and vomiting .:. Severe anxiety
.:. Chlorpromazine may reduce the effect of drugs for
.:. Intractable hiccups
parkinsonism
.:. Adjunct in the treatment of
.:. All sedative drugs are likely to increase the sedative property
tetanus in adults and children
of chlorpromazine
Contraindications .:. Anticholinergics may intensify the anti cholinergic properties of
.:. Impaired consciousness due to CNS depression chlorpromazine
.:. Bone marrow depression .:. Beta blockers may inhibit chlorpromazine metabolism,
.:. Patients allergic to chlorpromazine increasing its plasma levels and toxicity
.:. Phaeochromocytoma .:. Chlorpromazine may antagonize therapeutic effect of
.:. Severe hepatic impairment bromocriptine on prolactin secretion
.:. Glaucoma .:. Chlorpromazine may inhibit metabolism and increase toxicity
Dose of phenytoin
Schizophrenia, mania, psychomotor agitation, severe anxiety .:. Chlorpromazine may inhibit blood pressure response to
and violent behaviour: centrally acting antihypertensives such as methyldopa
Initially 25mg 3times daily or 75mg at night, adjusted according to

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 Fa 1771lli! -- PRECISEIQ:M:IMMI10GY I . ,', ! ,I , , PRECISE PHARMACIJLlilGY

Key issues to note 5-12years: 75-150mg daily in severe cases up to 300mg daily.
.:. Avoid alcohol during therapy with chlorpromazine 1-5years; I mg /kg daily
.:. The patient should avoid sun exposure to prevent
Side effects
photosensitivity reactions
.:. Hypotension .:. Ventricular tachycardia
.:. Chlorpromazine should not be stopped suddenly
.:. Sudden death Dry mouth
THIORIDAZINE .:. Drowsiness Blurred vision
Available preparations: Tablets 25mg, 50mg, IOOmg .:. Constipation Nasal congestion
.:. Urine retention Peripheral oedema
Available brands: Mellaril® .:. Retrograde ejaculation
Pharmacokinetics Drug interactions
Thioridazine is rapidly absorbed following oral administration,
.:. Alcohol or other CNS depressants may increase respiratory
distributed widely into the body including breast milk. It is extensively
depression caused by thioridazine
metabolized in the liver to the active metabolite and excreted in urine.
.:. Antihypertensives may increase the hypotensive effects of
'L
Indications thioridazine
.:., schizophrenia .:. Thioridazine may decrease the effect of levodopa
.:. Mania and hypomania .:. Lithium may decrease the absorption of thioridazine and
.:. Behavioural disorders in epileptic children produce adverse neurological effects
.:. Anxiety .:. Tricyclic antidepressants may increase the anticholinergic and
.:. Agitation and restlessness in the elderly sedative effects of thioridazine
.:. Dementia .:. Beta blockers may inhibit thioridazine metabolism, increasing
plasma levels and toxicity
Contraindications
.:. Thioridazine may inhibit metabolism and increase toxicity of
.:. Angle-closure glaucoma
phenytoin
.:. Cardiac arrhythmias
.:. Patients allergic to thioridazine Key issues to note
.:. Hepatic impairment .:. Ejaculation problem may respond to reduction in dosage but
.:. Blood dyscrasias change to another drug may be necessary
.:. Severe CNS depression .:. Administer the drug with food to minimise GIT upset
.:. The drug is associated with high incidence of sedation,
Dose
anticholinergic effect and orthostatic hypotension
Schizophrenia, mania and other psychosis:
.:. The patient should avoid sun exposure to prevent
Adult: Initially 25-1 OOmg 3 times daily increased gradually according
photosensitivity reactions
to response up to 800mg daily
.:. Thioridazine should not be stopped suddenly
Short term adjunctive management of severe anxiety and
agitation and restlessness in the elderly: 25-1 OOmg daily
FLUPHENAZINE
Children (severe mental or behavioural problems only)
Available preparations: Injection 25mg/ml, 50mg/ml

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Pharmacokinetics t'l
; Ii
I TRIFLUOPERAZINE
Fluphenazine is rapidly absorbed following oral administration, Available preparations: Tablet 5mg
widely distributed into the body, including breast milk, metabolized Injection
extensively in the liver and excreted in urine. Available brands: Stelazine®

Indications Pharmacokinetics
.:. Schizophrenia Trifluoperazine is rapidly absorbed following oral administration,
.:. Severe anxiety widely distributed into the body, including breast milk, metabolized
•:. Mania extensively in the liver and excreted in urine and some in faeces.
.:. Behavioural disturbances
Indications
Contraindications .:. Schizophrenia .:. Severe anxiety
.:. Severely depressed patients .:. Manic-depressive illness .:. Toxic psychosis
.:. Comatose states .:. Disturbed behaviour .:. Nausea and vomiting
.:. Severe hepatic disease Contraindications
.:.!t, Blood dyscrasias .:. Pre-existing CNS depression
.:. Renal/heart failure .:. Known hypersensitivity to trifluoperazine
.:. Bone marrow depression
Dose .:. Liver disease
(fluphenazine decanoate) 1M 12.5mg (6.25mg in the elderly) then after .:. Comatose states
4-7days, 12.5-IOOmg repeated at intervals of 14-35days. Dose
Side effects Schizophrenia:
.:. Sedation Dry mouth Adults and children over 12 years: Initially 5mg twice daily or IOmg
.:. Hypotension Blurred vision daily in modified release form increased by Smg after I week at
.:. Constipation Dizziness intervals of 3 days according to the response. Severe psychosis daily
.:. Urine retention Somnolence doses of 40mg or more have be given
.:. Peripheral oedema Nasal congestion Children up to 12years: Initially up to Smg daily in divided doses
Drug interactions adjusted according to response, age and body weight
.:. Alcohol or other CNS depressants may increase hypotensive, Severe anxiety:
CNS and respiratory depressants effect of fluphenazine Adult: 2-4mg daily in divided doses increased if necessary to 6mg daily
.:. Fluphenazine may decrease the effect of levodopa Children
.:. Lithium may decrease the absorption of fluphenazine and
6-12years: up to 4mg daily
produce adverse neurological effect
3-Syears: up to I mg daily
.:. Tricyclic antidepressants may increase anticholinergic and
sedative effect caused by fluphenazine
Nausea and vomiting:
•:. Beta blockers may inhibit fluphenazine metabolism, increasing Adult: I or 2mg twice daily up to max.6 mg daily.
its plasma levels and toxicity Children 3-5 years: I mg daily in divided doses
.:. Fluphenazine may antagonize therapeutic effect of 6-12years: 2mg daily up to 4 mg daily
bromocriptine on prolactin secretion

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 PRECISE PHARMAC I I

Side effects distributed widely into the body, with high concentrations in adipose
.:. Sedation .:. Urticaria tissue. It is metabolized by the liver and excreted in urine and a small
.:. Hypothermia .:. Hypotension amount in faeces.
.:. Dizziness •:. Gait disturbance
.:. Urinary incontinence .:. Drowsiness'" Indications
.:. Severe form of liver damage .:. Anorexia .:. Schizophrenia .:. Mania
.:. Prolonged QT interval .:. Blurred vision .:. Behaviour disturbance .:. Severe anxiety
.:. Muscle weakness .:. Nausea and vomiting .:. Intractable hiccups

Drug interactions
Contraindications
.:. Antiacids reduce oral absorption of trifluoperazine
.:. Trifluoperazine may inhibit metabolism and increase toxicity .:. CNS depression Bone-marrow depression
.:. Comatose states Parkinson's disease
of phenytoin
.:. Trifluoperazine may inhibit blood pressure response to .:. Severe hepatic disease
centrally acting antihypertensives such as methyldopa .:. Known hypersensitivity to haloperidol
.:. Beta blockers may inhibit trifluoperazine metabolism,
increasing its plasma levels and toxicity Dose
.:. Trifluoperazine may antagonize therapeutic effect of Orally:
bromocriptine on prolactin secretion Schizophrenia and other psychosis, mania, psychomotor
Key issues to note agitation, violent behaviour and severe anxiety (adjunct)
.:. Administer the 1M injection deep in the upper outer quadrant Adult: Initially O.S-Smg 2-3 times daily increased as needed up to
of the buttock. Massaging the area after administration may 20mg/day, maintenance usually 2-1 Omg/day
prevent formation of abscess Acute psychosis: 2-1 Omg 1M 6-8houlry interval until symptoms are
.:. Chewing gum may help to relieve the dry mouth caused by controlled
the drug Long term therapy: IO-20mg up to max of I OOmg deep 1M of
.:. Monitor the patient regularly, atleast every 6 months for decanoate injection may be given
abnormal movements Nausea and vomiting: O.S-2mg daily by 1M injection
.:. The patient should avoid sun exposure to prevent Intractable hiccups: Orally O.Smg 3 times daily adjusted according
photosensitivity reactions to response
.:. Avoid alcohol and other medications that cause sedation
Side effects
HALOPERIDOL
.:. Dry mouth .:. Weight gain
.:. Lethargy .:. Sedation
Available preparations: Tablets 5 mg, IOmg,
Injection Smg/ml, SOmg/ml
.:. Restlessness of akathisia .:. Constipation
.:. Muscle stiffness .:. Hypotension
Available brands:
decanoas®
Haldol®, Haloxen®, Haldol
.:. Muscle cramping .:. Blurred vision
.:. I ncreased appetite .:. Tinnitus
Pharmacokinetics .:. Swelling of female breasts .:. Depression
Haloperidol is relatively well absorbed following oral adminstration, .:. Decreased sexual function .:. Peripheral oedema

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 PRECISE 1~:rMMMH!HDI . PREC
Drug interactions tissues including breast milk, extensively metabolized by the liver to
.:. Alcohol and other CNS depressants may increase CNS active metabolites and excreted mainly in urine and small amount in
depression faeces
.:. Rifampicin accelerates the metabolism of haloperidol resulting Indications
into reduced plasma concentration .. .:. Schizophrenia
.:. Haloperidol enhances the hypotensive effect of prazosin .:. Acute manic episodes
.:. Haloperidol enhances sedative effect of c1onazepam, codeine
Contraindications
and diazepam
.:. Breast feeding
.:. Carbamazepine accelerates the metabolism of haloperidol
.:. Haloperidol may inhibit blood pressure response to centrally .:. Known hypersensitivity to risperidone
acting antihypertensives such as methyldopa Dose
.:. Beta blockers may inhibit haloperidol metabolism, increasing Psychosis: 2mg in 1-2 divided doses on first day, then 4mg in 1-2
plasma levels and toxicity divided doses on the second day, 6mg in 1-2 divided doses on the
.:.... Haloperidol may antagonize therapeutic effect of third day, Usual dose range is 4-8mg daily, doses above IOmg daily
.~ bromocriptine on prolactin secretion only if benefit considered outweighing risk. max 16mg daily
.:. I Haloperidol may inhibit metabolism and increase toxicity of E.lderly: initially O.5mg twice daily, increased in steps of O.5mg twice
phenytoin daily to 1-2mg twice daily.
Key issues to note Mania: initially 2mg once daily increased if necessary in steps of I mg
.:. Tardive dyskinesia may occur after prolonged use and may daily. Usual dose range is 1-6 mg daily
disappear spontaneously or persist for life
Side effects
.:. Protect the drug from light, slight yellowing of the injection is
.:. Agitation Fatigue
common and does not affect potency
.:. Anxiety Insomnia
.:. Advise the patient to report side effects such as extrapyramicbI .:. Dyspepsia Headache
reactions .:. Abdominal pain Nausea
.:. Elderly patients usually require lower initial doses and a more .:. Urinary incontinence Constipation
gradual dosage adjustment .:. Sexual dysfunction including priapism .:. Dizziness
.:. The drug is not recommended for children under 3 years
because they are prone to extrapyramidal reactions Drug interactions
.:. Avoid alcohol and other medications that cause sedation .:. Risperidone may enhance the CNS depressant effect of
alcohol
.:. Risperidone may antagonize the actions of levodopa or other
RISPERIDONE
dopaminergic drugs
Available preparations: Tablets I mg, 2mg
.:. Fluoxetine may increase the plasma concentration of
risperidone
Available brands: Risperdal® .:. Carbamazepine may decrease the antipsychotic effect of
risperidone
Pharmacokinetics
It is well absorbed following oral administration, distributed to body

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 PRECISE PHARMACOLOGY I

Key issues to note .:. Elevated plasma glucose .:. Nervousness

.:. The drug may cause dizziness or drowsiness and impair ability .:. Oedema .:. Constipation
to perform activities that require mental alertness .:. Orthostatic hypotension .:. Dizziness
.:. Longterm usefulness of risperidone should be periodically,re- .:. Speech difficulties .:. Increased appetite
evaluated
.:. Avoid exposure to sunlight to avoid sunburn Drug interactions
.:. Inform the patient of the possible orthostatic hypotension and .:. CNS depressant effects of alcohol may be enhanced by

.
advise them to rise slowly from lying or sitting position olanzapine
.:. Additive hypotension may occur when olanzapine is given
OLANZAPINE
Available preparations: Tablets 5mg, IOmg together with antihypertensive
.:. Olanzapine may antagonize the effects of levodopa or other
Available brands: Oleanz®, Zyprexa®, Olandus®
dopamine agonists
Pharmacokinetics .:. Ciprofloxacin may increase the olanzapine blood concentration
Olanzapine is well absorbed after oral administration, undergoes .:. Olanzapine may inhibit the metabolism of imipramine and
extensive first-pass metabolism, metabolized by the liver and theophylline
excreted in urine and faeces.
.:. The clearance of olanzapine is increased by tobacco smoking
Indications and carbamazepine
.:. Schizophrenia Key issues to note
.:. Combination therapy for mania .:. Olanzapine may cause hyperglycemia, therefore monitoring of
.:. Control of agitation and disturbed behaviour in schizophrenia blood sugar in diabetic patients is required
or mania .:. Olanzapine should be given with caution in patients with
Contraindications prostatic hypertrophy, diabetes mellitus and those with bone
.:. Breast feeding and pregnancy·:· Narrow angle glaucoma marrow depression
.:. Acute myocardial infarction Unstable angina .:. The drug may cause dizziness or drowsiness and impair ability
.:. Severe hypotension Sick sinus syndrome to perform activities that require mental alertness
.:. Recent heart surgery .:. Monitor the patient for orthostatic hypotension.
•:. Known hypersensitivity to olanzapine
Dose
Schizophrenia: I Omg daily adjusted to tlote usual range of 5-20mg
daily.
Mania: I Smg daily, adjust to the usual range S-20mg daily
Side effects
.:. Somnolence Dry mouth
.:. Weight gain Insomnia
.:. Hyperprolactinaemia Headache

-519- -520-
 Q#n~E PHARMACOLOGY I
PARACETAMOL
CHAPTER SIXTEEN Available preparations: Tablets 500mg
ANALGESICS Syrup 120mg/5ml
Pain is an unpleasant sensation ranging from mild discomfort to Suppositories I 25mg, 250mg
organized distress, associated with real or potential tissue damage.
Pain may be classified as acute or chronic in nature Available brands: Panadol®, Kamadol®, Cetamol®, Rectol®,
Calpol®, Cosmol®, Curamol®, Paratal®,
Acute pain
It is usually associated with trauma or disease and has a well define( I Pharmacokinetics
location, character and timing. Paracetamol is rapidly and completely absorbed from the GIT,
It is accompanied by symptoms such as tachycardia, hypertensioll, metabolized in the liver and excreted in urine
sweating and mydriasis
Chronic pain Indications
This is pain lasting more than a few months. It may not be associatc( I .:. Acute migraine .:. Tension headache
with trauma or disease or may persist after initial injury has healed. .:. Fever .:. Post immunization fever
Localization, character and timing are more vague in chronic pain thall .:. Dysmenorrhoea .:. Headache
in acute pain.
Patients with chronic pain experience physical, psychological, social, Contraindications
and functional deterioration which contributes towards exacerbatioll .:. Known hypersensitivity to paracetamol
ofthe pain.
Drugs used in the treatment of pain are divided into two:- Dose
.:. Non -opioid analgesics Mild to moderate pain
.:. Opioid analgesi!=s Adult: 500mg-1 OOOmg every 4-6 hours max dose is 4g daily
Children:
16.1.1 NON-OPIOD ANALGESICS 6-12years: 250-500mg every 4-6 hours'
These drugs are suitable for pain in musculoskeletal conditions. They 1-5years: I 25-250mg every 4-6 hours
are the drugs of choice in the treatment of mild to moderate pain. 3 months to I year: 60-120mg every 4-6 hours
They are sometimes combined with opioids to potentiate the effect of
each drug e.g. Co-codamol (Paracetamol plus codeine)
Non opioid analgesics are suitable for use in both acute and chronic
It By rectum:
Adult: 500-1 OOOmg every 4-6 hours
Children:
6-12years: 250-500 every 4-6 hours
pain due to their lack of abuse property.
1-5 years: 125mg -250mg every 4-6hours
Examples
.:. Paracetamol Aspirin Side effects
.:. Diclofenac Indomethacin Paracetamol is well tolerated but rare side effects include:-
.:. Ibuprofen Mefenamic acid .:. Blood disorder
.:. Piroxicam .:. Rashes

-521- -522-

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,...----------------PMRitlECmISEPHARMAcou0'1 PRECISE PHARMA I I

.:. Acute Pancreatitis .:. Prophylaxis in myocardial infarction /ischemic heart disease
.:. Liver damage following over dosage
.:. Hypotension Contraindications
Drug interactions .:. Breast feeding .:. Active peptic ulcer
.:. The absorption of paracetamol may be accelerated by drugs .:. Gout Haemophilia
such as metoclopramide .:. Pregnancy
.:. Caffeine may enhance the therapeutic effect of paracetamol .:. Children and adolescents under 16 years
.:. Cholestyramine reduces the absorption of paracetamol and Dose
may reduce its effectiveness when given at the same time. 300 -900mg every 4 to 6 hours after food
.:. Excretion of paracetamol may be affected and plasma Prevention of blood clots: 75 -300mg daily
concentrations altered when given with probenecid
.:. Antacids and food delay and decrease the absorption of Side effects
sparacetamol .:. Gastrointestinal irritation Increased bleeding time
.:. Bronchospasm Skin reaction
Key issues to note .:. Headache Tinnitus
.:. Paracetamol should not be taken together with NSAIDs on a .:. Gastro intestinal bleeding Dizziness
J
regular basis
.:. Warn the patient to avaoid taking tetracycline antibiotics Drug interactions
within I hour after taking buffered paracetamol effervescent .:. Aspirin may increase the risk of bleeding when given
granules c1opidogrel
.:. Use the drug cautiously in the presence of alcoholism, .:. Aspirin may reduce the effect of drugs for gout
hepatic disease, viral infection, renal impairment and .:. Aspirin enhances anticoagulant effect of heparin.
cardiovascular disease •:. Concurrent use of aspirin with other GI irritating drugs such
as corticosteroids, other NSAIDs, alcohol may potentiate the
ASPIRIN aspirin's GI adverse effects
Available preparations: Tablets 75mg, IOOmg, ISOmg, 300mg .:. The absorption of aspirin may reduced by kaolin
Available brands: Aspirin®, Ascad®, Ecorin®, Aspirem® .:. Concomitant use of aspirin with drugs such as frusemide,
aminoglycoside antibiotics, may potentiate ototoxic effects
Pharmacokinetics
Aspirin is rapidly and completely absorbed from the GIT, .dist~ibuted
Key issues to note
widely into most body tissues and fluids, hydrolyze~ p~rtlally I~ the

It
.:. Moisture may cause aspirin to lose potency. Store in a cool,
GIT to salicylic acid with almost complete metabolism In the liver and
dry place, and avoid using if tablets smell like vinegar
excreted in urine as salicylate and its metabolites. .:. Enteric-coated products are absorbed slowly and are not
Indications suitable for acute therapy
.:. Acute migraine headache .:. Tension headache .:. The drug may be taken after a meal to minimize GI irritation
.:. Rheumatoid arthritis .:. Osteoarthritis .:. Patients who are hypersensitive to other NSAIDs are likely to
.:. Dysmenorrhoea .:. Tendonitis develop similar reactions to aspirin
.:. Thromboembolic disorders .:. Fever

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r=- _ _ _ _ _ _....PRECISE Ig:rMWIQIIND

16.1.2 OPIOD ANALGESICS Dose

Opiod refers to all compounds related to opium. Opiod analgesics Relief of pain
are the l1)ost effective analgesics and are used in the management of Adult: 30-60mg every 4-6 hours when necessary max dose 240mg
severe pa.in. .. daily
They are divided into two: Children: 1-12years: 0.5-1 mg/kg every 4-6hours
.:. Weak opioid analgesics such as codeine, dihydrocodeine Diarrhoea
.:. Strong opioid analgesics such as morphine, pethidine, Adults: 30mg 3-4 times daily
methadone
Side effects
.:. Constipation .:. Dizziness
Mode of action .:. Dry mouth .:. Sweating
They relieve pain by mimicing the action of endogenous opiod
.:. Nausea and vomiting .:. Headache
peptides, primarily at mu receptors. .:. Facial flushing
Their ability to produce a state of relaxation and euphoria helps to .:. Difficult with micturation
relieve tne stress that accompanies severe pain.
Drug interactions
.:. Alcohol and other CNS depressants potentiate the CNS
CODEltiE
depressing effects of codeine
Availabl~ preparations: Tablets 30mg
.:. Drug accumulation and enhanced effects may result from
concomitant use with other drugs extensively metabolized by
Pharmatokinetics the liver such as rifampin, phenytoin
Codeine is well absorbed after oral administration, distributed widely .:. Severe cardiovascular depression may result from
throughout the body; crosses the placenta and enters breast milk. It is concomitant use with general anaesthetics
metaboli~ed mainly in the liver and excreted mainly in urine.
key issues to note
Indicati()ns .:. Increase fluids and fibre intake to avoid constipation
.:. f'1ild to moderate pain .:. Avoid alcohol during therapy with codeine
.:. C:ough suppression .:. Avoid abrupt discontinuation after prolonged use
.:. t)iarrhoea .:. Codeine is not recommended for treatment of productive
cough
Contrait)dications .:. Codeine may be administered with food to minimise nausea
.:. ~espiratory depression and GI upset
.:. C)bstructive air way disease MORPHINE
.:. I--Iypersensitivity to codeine Available preparations: Oral solution Smg ISml, SOmg/Sml
.:. A.cute alcoholism Injection 10mg/ml, ISmg/ml
.:. ~ised intracranial pressure or head injury
.:. ~isk of paralytic ileus

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 PRECISEIQ:!j1M!il~o[OGY I
Pharmacokinetics 1-2years: Initially 200-400mcg/kg every 4hours adjusted according to
Morphine is absorbed variably from the GIT, distributed widely
through the body, metabolized primarily in the liver and excreted in
urine and bile.
Indications
.:. Post operative pain
, response
1-12months: Initially 80mcg/kg every 4hours
Myocardial infarction: By slow IV injection (2mg/ minute), IOmg
followed by a further 5-1 Omg if necessary. Elderly or debilitated
patients, give a half a dose
Acute pulmonary oedema: By slow IV injection (2mg/minute)
.:. Myocardial infarction
.:. Premedication before surgery 5-IOmg
.:. Severe pain
.:. Sickle cell crisis Side effects
.:. Acute pulmonary oedema .:. Nausea and vomiting .:. Euphoria
•:. Chronic pain (cancer) .:. Difficulty with micturation .:. Headache
Contraindications
.:. Constipation .:. Bradycardia
.:. Acute respiratory depression
.:. Postural hypotension .:. Facial flushing
.:. Known hypersensitivity to morphine
.:. Dependency .:. Drowsiness
.:. Acute alcoholism .:. Respiratory depression .:. Dry mouth
.:. Head injury .:. Anorexia .:. Palpitations
.:. Acute abdominal pain .:. Decreased libido .:. Sweating
.:. Raised intracranial pressure .:. Vertigo .:. Skin rash
.:. Avoid injection in phaeochromocytoma .:. Urticaria .:. Hallucinations
Dose
Acute pain, postoperative pain: Drug interactions
Oral: 5-20mg every 4 hours .:. Morphine increases the sedative effect of antidepressant drugs,
By SIC or 1M injection anti psychotics and sedative anti histamines
Adult: I Omg every 4 hours if necessary .:. Severe cardiovascular depression may occur when morphine is
Neonate: 150mcg Ikg every 6hours used with general anaesthetics
6-12 years: 5-1 Omg every 4 hours .:. Drug accumulation and enhanced effects may result from
1-5years: 2.5-5mg every 4 hours concomitant use with other drugs extensively metabolized by
I month -I 2months: 200mcg/kg every 6hours
the liver such as rifampin, phenytoin
Chronic pain: Oral ISC or 1M:
Adult: I O-15mg every 4 hours. Dose may be increased according to
Key issues to note
the response
.:. Avoid alcohol during therapy
.:. Morphine may cause low blood pressure or blurred vision
Children:
2-12years: Initially 200-500mcg/kg every 4hours adjusted according to I,'. therefore patient should take care while climbing stairs
response and changing position

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 PREClsEI~:'MM'QII!liGY] PRECISE PHARMACOLOGY I
.:.
.:.
In case of overdose, naloxone may be used
Warn the patient that prolonged use of the drug may result
Side effects
.:.
.:.
Nausea and vomiting
Drowsiness
.
.:
.:.
Constipation
Spasm of urinary tract
into physical depedence
.:. .:.
.:.
•:.
Avoid abrupt discontinuation after prolonged use
Urinary retention may occur in patients with prostatic .:.
.:.
Palpitations
Postural hypotension
Sweating
.
.:
.:.
Headache
Confusion
Skin rash
hypertrophy
.:. Dry mouth
~;
.:. Anorexia
PETHIDINE .:. .:.
Available preparations: Injection 50mg/ml, 100mg/ml .:.
.:.
Decreased libido
Hallucinations
Urticaria
..
.:
.:
Euphoria
Respiratory depression
Facial flushing
Indications
•:. Pre-operative medication .
Drug interactions
.:. Acute analgesia .:. Concurrent administration of pethidine and phenothiazines
.:. Post operative pain may produce severe hypotensive episodes and may
.:. Moderate to severe acute pain prolong respiratory depression due to pethidine
.:. Obstetric analgesia .:. Alcohol and other CNS depressants potentiate the respiratory
Contraindications and CNS depressing effects of pethidine
.:. Severe renal impairment .:. Cimetidine may decrease the elimination of pethidine and
.:. Acute respiratory depression increase the risk of toxic effects such as CNS depression
.:. Acute alcoholism Key issues to note
.:. Head injury .:. Prolonged use of pethidine may result in physical dependence
.:. Avoid injection in phaeochromocytoma .:. Lowest effective doses are recommended especially during
.:. Severe liver disease labor
.:. Raised intracranial pressure
.:. Knownypersensitivity to pethidine TRAMADOL
Available preparations: Tablets/Capsules 50mg, 100mg
Dose Injection 100mg/2ml
Acute pain
Adult: SC or 1M injection; 50-150mg repeated after 4 hours Available brands: Tramal®, Trabilin®, Tramazac®, Domadol®,
Children: O.5-2mg/kg every 4 hours Indications
Obstetric analgesia: SC or 1M injection, 50-1 OOmg repeated 1-3 .:. Moderate to severe pain
hours later if necessary max dose is 400mg in a day .:. Postoperative pain
Post operative pain: SC/IM injection .:. Neuropathic pain
Adult: 25-1 OOmg repeated every 2-3 hours if necessary .:. Cancer pain
Children: O.5-2mg/kg every 2 to 3 hours .:. Low back pain
.:. Pain associated with orthopaedic disorders

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 <.

, :':, ,'I' " I I', '" PRECISE PHARMACOLOGY

PRECISE PHARMACOLOGY

Contraindications 16.1.3 DRUGS USED IN THE TREATMENT OF MIGRAINE

.:. Known hypersensitivity to tramadol Migraine is a recurring severe headache usually unilateral
.:. Acute intoxication with alcohol characterised by visual disturbance and vomiting.
•:. Severe renal impairment Migraine headache is classified into two basing on whether it is
associated with presence or absence of aura symptoms:-
Dose .:. Migraine headache with aura
Oral: .:. Migraine headache without aura
Adults and Children over 12 years: 50-1 OOmg every 4-6 hours whcll
necessary max 400mg daily. Migraine with aura
Injection: by IVII M 50-1 OOmg every 4-6hours up to a total daily dos(' Headache in migraine with aura is preceded by other symptoms like:
of 600mg. given slowly (2-3 minutes) by I.V partial visual loss, seeing stars and numbness on one side of the body
Operative pain: Initially 100mg, then 50mg every 10-20 minutes The above symptoms are then followed by unilateral headache which
if necessary during the first hour to a total max. of 250mg including may be accompanied by nausea, vomiting and photo phobia and
initial dose, then 50-1 OOmg every 4-6hours max. 600mg daily normally lasts 4 to 72 hours.
Side effects Migraine without aura
.:. Headache Dizziness This type of migraine headache is not associated with pre-warning
'I
.:. Abdominal discomfort Hypotension symptoms.
"!I
1

I
.:. Tiredness Confusion Drugs used in the treatment of migraine either abort the attack of
.:. Urticaria Dry mouth migraine or prevent migraine attacks.
•:. Constipation Hallucination Drugs for acute attack include:-
11 .:. Fatigue Nausea and vomiting .:. Simple analgesics or NSAIDs;
I .:. Diarrhea Sweating .:. Ergotamine
.:. Weakness .:. Triptans e.g. Sumatriptan
Drug interactions Drugs used for prophylaxis of migraine include;
.:. Concomitant administration of tramadol with alcohol may .:. Beta blockers e.g. Propranolol, atenolol
potentiate CNS depressant effects .:. Tricyclic antidepressants
.:. Concurrent administration of carbamazepine with tramadol .:. Pizotifen
results into decreased serum concentration of tramadol .:. Sodium valproate
key issues to note
.:. Avoid rapid IV injection since it is associated with a higher ERGOTAMINE
Available preparations: Tablets Img, 2 mg
incidence of side effects
.:. Inform the patient that tramadol causes dizziness and Combinations: Migril® (Ergotamine 2rrrgJ c.ycIizine 5()rng' caffeine
drowsiness which may impair the ability to perform activities Iii 100mg)
that require mental alertness Cafergot® (Ergotamine Img/ caffeine 100mg)
.:. Avoid alcohol and other medications that cause sedation
.:. Do not chew or crush extended release tablets

II!
-531- -532-
 , I " P'RECISE PHARMAC I

Pharmacokinetics .:. Ergotamine should not be given until at least 6 hours after
Ergotamine is variably absorbed after oral administration, but caffeine stopping a serotonin (S-HT I) agonist such as sumatriptan
facilitaties absorption. It is widely distributed throughout the body, .:. There is an increased risk of blood clotting in women taking
extensively metabolized in the liver and excreted mainly in faeces. oral contraceptives with ergotamine
• .:. Erythromycin, c1arithromycin may increase adverse effects of
Indications ergotamine when given together
Key issues to note
.:. Acute migraine attacks
.:. Ergotamine should not be used for prophylaxis of migraine
.:. Cluster headache
.:. Stop medication immediately if numbness and tingling in the
i, extremities or angina pain develops
Contraindications .:. Discontinuation after regular normal dosage may result in
!I"!II
:!!!1
.:. Peripheral vascular disease Porphyria rebound headache or an increase in duration or frequency of
.:. Hyperthyroidism Severe sepsis headache
IiiI
.:. Pregnancy .:. Dependence can develop insidiously when ergotamine is
'! Breast feeding
used for more than 2 days each week even if proper dosage

I .:. wHepatic and renal impairment

.:. Coronary heart disease .:.
recommendations are observed
Ergotamine is most effective when used as soon as symptoms

Ir .:. Inadequately controlled hypertension

.:. Hypersensitivity to ergotamine or other ingredients
Dose
Cafergot: 1-2 tablets at onset max 4 tablets in 24 hours, not to be
repeated at intervals of less than 4 days max. 8 tablets in a week.
.:.
.:.
begin
.:. Advise the patient to be in a quiet, dark environment to relax
after a dose of ergotamine is administered
Avoid alcoholic beverages and smoking
Warn the patient to avoid prolonged exposure to very cold
temperatures
J
~;I' Migril: I tablet at on set, followed after 30minutes by 1/2 -I tablet
repeated every 30 minutes if necessary. Max 4 tablets per attack and 6 CYPROHEPTADINE
!I
Available preparations: Tablets4mg
tablets in I week

l I'

Side effects
.:. .:.
Available brands:
Syrup 2mg/Sml

Periactin®, Oraxin®, Toractin®, Cetpro®

Nausea and vomiting Abdominal pain Indications
.:. Weakness and muscle pains .:. Diarrhoea .:. Migraine headache
.:. Dizziness .:. Leg pain .:. Allergic rhinitis
.:. Cold fingers /toes .:. Myocardial ischemia .:. Appetite stimulant
.:. Increased headache .:. Vertigo .:. Vascular cluster headache
.:. Pruritus
Contraindications
Drug interactions .:. Known hypersensitivity to cyproheptadine
.:. The vasoconstrictor effects of ergotamine are enhanced by .:. Acute asthmatic attacks
sympathomimetics such as adrenaline .:. Lactation

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 ~PHARMACgLOGY p , l' I' '" i', ',', ',: PRECISE PHARMACOLOGY

Dose " '\11 Available brands: Lioresal®, Baclofen®

i ,11,Ii
Migraine: 4mg may be repeated after 30minutes if necessary. I
, Pharmacokinetics
!
Maihtenance dose; 4mg every 4 - 6 hours Baclofen is rapidly and extensively absorbed from the GIT, widely
Allergic conditions: 4mg 3 times daily up to 32 mg daily may distributed throughout the body, with small amounts crossing the
occasionally be necessary blood brain barrier. A small amount of the drug is metabolized in
Children the liver and is excreted in urine majorly as unchanged drug or as
7-14 years: 4mg 2-3 times daily up to max of.16mg daily metabolites.
2-6y€ars: 2mg 2-3 times daily max. 12mg dally Indications
.:. Chronic severe spasticity associated with multiple sclerosis,
Side effects spinal cord lesions and cerebral palsy
.:... Sedation .:. Drowsiness
.:. Trigeminal neuralgia
.:... Headache .:. Excitability
.:... Disturbed coordination .:. Hypotension Contraindications
.:... Dry mouth .:. Constipation .:. Active peptic ulcer disease
.:. Urticaria .:. Blurred vision .:. Hypersensitivity to baclofen
.:. Fatigue .:. Tremors
Dose
.:. Appetite stimulation .:. Confusion
Adults: 5mg 3 times daily (preferably with or after food),
.:. Ataxia .:. Palpitations
gradually increased up to a max. I OOmg daily.( Stop treatment if no :11I
.:. Tachycardia .:. Weight gain
improvement within 6 weeks).
I?rLl~ interactions . . . Children:
.:... Additive CNS depression occurs when cyproheptadme IS given
Over 10 years: 0.75-2mg/kg daily up to max. 2.5mg/kg daily OR 2.5mg
together with other CNS depressants such as alcohol
4 times daily increased gradually according to the age.
I
I 6.1 _4 SKELETAL MUSCLE RELAXANTS
rAusc:: Ie spasm is an involuntary contraction of muscle or group ?~
Maintenance:
6-10 years: 30-60mg daily
2-6 years: 20-30mg daily I
,I

,I

It
,.r'usC: Ie resulting from acute or chronic pain, trauma or muscle inJury. 1-2 years: I 0-20mg daily
I1rug~ used in the treatment of muscle spasms can either act on the
Side effects
UNS or directly on the muscles. .:. Nausea Confusion II' · ' \ I

~fan--,ples .:. Dizziness Hypotension

.:. Baclofen .:. Depression .:. Ataxia
.:. Diazepam til
.:. Vomiting Constipation
.:. Chlorzoxazone .:. Urinary frequency Visual disturbance
.:. Orphenadrine .:. Light headedness Muscular pain and weakness
eJC"OFEN .:. Fatigue Headache
A.rail ;;;able preparations: Tablets IOmg .:. Dry mouth .:. Ataxia
.:. Insomnia

-535- -536-
 PR «liSE PHARMAclemGY I . . , . PRECISE PHARMACOLOGY
Drug interactions .:. Myalgia
.:. Additive CNS depression occurs when baclofen is given with .:. Tension headache
other CNS depressants such as alcohol, sedative hypnotics .:. Torticollis
.:. Lithium may enhance the muscle relaxant effect og bacl~fen .:. Reflex muscles spasm associated with rheumatic disease
when given together. Contraindications
.:. Baclofen may enhance the hypotensive effect of beta .:. Impaired liver function
blocker .:. Hypersensitivity to any of the ingredients
.:. Baclofen may enhance the hypotensive effect of methyldopa
.:. Concomitant use with TCAs may cause CNS and respiratory Dose
depression and hypotension 1-2 capsules (2S0mg -7S0mg) 3-4 times daily after meals, depending
on the severity.
IKey issues to note
.:. Inform the patient of possible side effects such as drowsiness Side effects
and dizziness and advise them to avoid activities that require
.:. Drowsiness .:. Dizziness
mental alertness
.:. Light headedness .:. Malaise
Abrupt withdraw of the drug may cause visual hallucinations,
.:. Headache .:. Skin rash
paranoid and seizures, therefore taper the dose within 1-2
.:. Urticaria .:. Restlessness
weeks Drug interactions
.:. Avoid alcohol and other medications that cause CNS .:. Concomitant use with other CNS depressants produces
depression further CNS depression
.:. Caution the patient against taking any nonprescription drug .:. Concomitant use with TCAs may cause CNS and respiratory
without medical approval depression and hypotension
CHLORZOXAZONE Key issues to note
Available preparations: Capsules/Tablets .:. Inform the patient of possible side effects such as drowsiness
Combinations: Myolgin®(chlorzoxazone 2S0mg/paracetamol and dizziness and advise them to avoid activities that require
300mg) mental alertness
Myospaz® (chlorzoxazone 2S0mg, paracetamol .:. Avoid alcohol and other medications that cause CNS
SOOmg) depression
Pharmacokinetics .:. Tell the patient that the urine may turn orange or reddish
Chlorzoxazone is rapidly and completely absorbed from the GIT, purple, but this is a harmless effect
widely distributed in the body, metabolized in the liver and excreted .:. Tell the patient not to stop taking the medication without
in urine. instructions from the clinician
.:. The drug should be stored away from direct heat or light
Indications
.:. Sprains and strains ORPHENADRINE
.:. Traumatic muscles spasm Available preparations: Tablets
.:. Lumbago

-537- -538-
 .' ,PRECtijPHARMACOLOGY ~i!$B~nPHARMACOLOGY I
Combinations: Duragesic®(orphenadrine 35mgl Key issues to note
paracetamol450mg) .:. Tell the patient to relieve the dry mouth with ice chips,
sugarless gum
Pharmacokinetics .:. Inform the patient of possible side effects such as drowsiness
Orphenadrine is rapidly absorbed from the GIT, widely distributed and dizziness and advise them to avoid activities that require
mental alertness
throughout the body, almost completely metabolized in the liver and
excreted in urine. .:. The, drug should be stored away from direct heat or light
.:. Avoid alcohol and other medications that cause CNS
Indications depression
.:. Skeletal muscle spasm
.:. Parkinsonism
.:. Intractable hiccup
.:. Management of leg cramps
.:. Other painful conditions associated with skeletal muscles
spasm
Contraindications
.:. Known hypersensitivity to any of the ingredients
.:. Bladder neck obstruction
.:. Peptic ulcer disease
.:. Glaucoma
.:. Myasthenia gravis
.:. Prostate hypertrophy
.:. Pyloric or duodenal obstruction
Dose
2 tablets 2-3 times daily
Side effects
.:. Drowsiness .:. Dizziness
.:. Irritability .:. Epigastric distress
.:. Constipation .:. Blurred vision
.:. Headache .:. Palpitations
.:. Dry mouth .:. Urinary retention
.:. Urticaria .:. Skin rash
Drug interactions
.:. Concomitant use with alcohol, tricyclic anti depressants and
antipsychotic drugs may produce additive CNS effects

-539- -540-

o;o;'i~lllIrrrl
 • ' , ' " • H .' : •• I i. .,' "., PRECISE PHARMACOLOGY
.:. Primary dysmenorrhoea
.:. Secondary dysmenorrhoea
CHAPTER SEVENTEEN
DRUGS USED IN THE TREATMENT OF OBSTETRIC Primary dysmenorrhoea
AND GYNAECOLOGICAL DISORDERS ".
Primary Dysmenorrhoea usually begins with the first menstrual period
and it is characterized by cramping lower abdominal pain, nausea,
17.1.1 DRUGS FOR MENSTRUAL DISORDERS vomiting, headache and faintness.
The main disorders associated with menstruation that may require
The cause is thought to be due to excessive prostaglandin production
treatment include:- that causes the uterus to contract painfully.
.:. Amenorrhoea
Drugs used in the treatment of primary dysmenorrhoea inhibit either
•:. Dysmenorrhoea ovulation or prostaglandin production .
.:. Menorrhagia Examples
.:. Pre-menstrual syndrome
.:. NSAIDs such as mefenamic acid, ibuprofen, indomethacin,
.:. Menopause naproxen, piroxicam, and diclofenac
.:. Oral contraceptives
AMENORRHOEA
Patients who fail to respond to NSAIDS may be given
Amenorrhoea is the absence of menstruation. A break in menstruation
progestogens (norethisterone)
of 6 months or more is considered pathological in an adult woman who II. .:. Antispasmodics
is not pregnant, lactating or has reached menopause.
Drugs such as hyoscine and drotaverin may be used for the relief
Amenorrhea may be classified as;
... of spasm associated with dysmenorrhoea
•:. Primary amenorrhoea
.:. Secondary amenorrhoea Secondary dysmenorrhoea
Secondary dysmenorrhoea usually affects older women who complain
Primary amenorrhoea of congested ache with lower abdominal cramps which usually starts a
It occurs when a female fails to have her first menstrual cycle by age of
few days before menstruation. It is associated with various disorders
16 years in the presence of normal secondary sexual characteristics.
such endometriosis, pelvic inflammatory disease, fibroids or the
Secondary amenorrhoea presence of an IUD.
Secondary amenorrhoea is the absence of menses for 6 m~nths OJ
Treatment is aimed at rectifying the underlying cause.
more in a woman whose normal menstruation has been established.
Management MENORRHAGIA
Menorrhagia is excessive menstrual bleeding. It may be associated
.:. Identification and correction of any underlying disorder
with pelvic disorders such as fibroids, use of copper intra uterine
devices, complication of pregnancy, malignant tumours or dysfunctional
DYSMENORRHOEA bleeding.
Dysmenorrhoea is a painful menstruation that prevents normal activity
Menorrhagia may lead to iron deficiency anaemia as well as impairing
and requires medication. the quality of life of the patient.
Dysmenorrhoea may be classified as;

-541-
-542-
 PRECISE IQ:MiJMlSrI!oIifl QimlSE PHARMACOLOGY I

Drugs used in the treatment of menorrhagia include;- NORETHISTERONE

.:. Combined oral contraceptives Available preparations: Tablets 5mg
.:. Mefenamic acid
.:. Norethisterone Available brands: Regulate-N®, Primolut-N®
.:. Medroxyprogesterone
.:. Tranexamic acid Indications
Premenstrual syndrome .:. Dysfunctional uterine bleeding .:. Endometriosis
iI
It is a cyclic recurrence of psychological and physical symptoms thai .:. Premenstrual syndrome .:. Dysmenorrhoea
affect women in the days before menstruation.
:I II .:. Delay of menstruation .:. Contraception
:
I, I'
~

The symptoms include; Increased irritability, depression. anxiety. ,

bloating, headache and breast tenderness :I Contraindications

1'1'
:1 .:. Pregnancy
Drugs used in the treatment of Premenstrual syndrome include:- .:. Severe liver impairment
.:. Calcium supplements .:. Pyridoxine (vitamin B6) .:. Previous or existing liver tumors
.:. Bromocriptine .:. Spironolactone .:. Severe arterial disease
.:. Mefenamic Acid .:. Fluoxetine .:. Undiagnosed vaginal bleeding
.:. Paroxetine .:. Atenolol .:. Porphyria
Note .:. Hypersensitivity to norethisterone
Bromocriptine, mefenamic acid and spironolactone suppress physicll Dose
symptoms. Fluoxetine, paroxetine and atenolol mostly suppres'. Dysfunctional bleeding
psychological symptoms. 1:1: To stop bleeding: 5mg 3 times daily for IOdays.
! ,
To prevent bleeding: 5mg twice daily from day 19-26 of the cycle.
MENOPAUSE Dysmenorrhoea: 5mg 3 times daily from day 5-24 for 3-4 cycles.
Menopause is the occurrence of no menstrual periods for one yeal Endometriosis: I O-15mg daily for 4-6 months or longer starting on
after the age of 40 years or permanent cessation of ovulation after loss day 5 of cycle (if spotting occurs increase dose to 20-2Smg daily, reduce
of ovarian activity. once bleeding has stopped.
Signs and symptoms Delay of menstruation: Smg 3times daily starting 3 days before
.:. Atrophic vaginitis .:. Dyspareunia anticipated onset of menstruation. (Menstruation occurs 2-3 days after
.:. Complete cessation of menses .:. Heavier bleeding stopping).
•:. Osteoporosis .:. Anxiety Premenstrual syndrome: Smg 2-3 times daily from day I 9-26 for
.:. Depression .:. Insomnia seven cycles .
•:. Inability to concentrate .:. Irritability
.:. Decreased libido .:. Urinary incontinence Side effects
•:. Hot flashes .:. Night sweats .:. Nausea .:. Weight gain
.:. Headache .:. Tiredness .:. Dizziness .:. Depression
Treatment involves use of hormone replacement therapy and vagiml .:. Headache ~.:. Insomnia
lubricants.
II""
.:. Menstrual disturbance

-543- -544-
DYDROGESTERONE Side effects
Available preparations: Tablets 10mg .:. Nausea .:. Weight gain
.:. Dizziness .:. Depression
Available brands: Duphaston® .:. Headache .:. Insomnia
.:. Menstrual disturbance
Indications
17.1.2 DRUGS FOR INFERTILITY
.:. Endometriosis Infertility
Infertility refers to inability of a woman to conceive or in a man to
.:. Dysfunctional uterine bleeding Dysmenorrhoea
induce conception. The most common cause of infertility is the failure
•:. Premenstrual syndrome .:. Amenorrhoea
of either ovulation in females or spermatogenesis in males.
.:. Habitual and threatened abortion .:. Irregular cycles
In females infertility may also be due to obstruction of the fallopian
.:. Hormone replacement therapy
tubes or diseases of the lining of the uterus (endometrium)

Contraindications Drugs used in treatment of infertility include:-

.:•.1:1 Severe liver impairment .:. Clomifene
.::;;~; Previous or existing liver tumors .:. Bromocriptine
.:. Severe arterial disease .:. Tamoxifen
.:. Undiagnosed vaginal bleeding
.:. Porphyria CLOMIFENE
.:. Known hypersensitivity to dydrogesterone Available preparations: Tablets 50mg

Dose Available brands: Clomid®, Clominol®

Endometriosis: 10mg 2-3 times daily from day 5-25 of cycle or i:
continuously I" Pharmacokinetics
Dysfunctional bleeding It is readily absorbed from the GIT, metabolized by the liver and
To stop bleeding: 10mg twice daily (together with an oestrogen) for excreted in faeces.
5-7 days
To prevent bleeding: I Omg twice daily (together with an oestrogen) Indications
from day 11-25 of cycle .:. Anovulatory infertility
Dysmenorrhoea: I Omg twice daily from day 5-25 of cycle Contraindications
Amenorrhoea: 10mg twice daily from day I 1-25 of cycle with .:. Liver disease
oestrogen therapy from day 1-25 of cycle .:. Ovarian cysts
Premenstrual syndrome: I Omg twice daily from day 12-26 of cycle .:. Hormone dependent tumours
Irregular cycles: I Omg twice daily from day I 1-25 of cycle .:. Known hypersensitivity to c10mifene
Habitual abortion: 10mg twice daily from day 11-25 of cycle until .:. Pregnancy (exclude before treatment)
conception, then continuously until week 20 of pregnancy .:. Undiagnosed abnormal uterine bleeding

-545- -546-
 ill . , ' GIWlISE PHARMACOLOGY
II

Indications
Dose .:. Hyper prolactanaemic infertility
Adult: SOmg daily for Sdays, starting within Sdays of on set of .:. Suppression of lactation
menstruation (preferably on the second day) or at any time if cycles .:. Hypogonadism
have ceased • .:. Galactorrhoea syndrome
If ovulation does not occur, a second course of IOOmg daily for Sdays .:. Benign breast disease
may be given starting as early as 30days after the previous one. Contraindications
In general 3 courses of therapy are adequate to assess whether ovulation .:. Hypersensitivity to bromocriptine
is obtainable. .:. Toxaemia of pregnancy
.:. Hypertension in postpartum women
Side effects .:. Peripheral vascular disease
.:. Visual disturbance .:. Hot flushes
.:. Abdominal discomfort .:. Abnormal uterine bleeding Dose
.:. Headache .:. Inter menstrual spotting
.:. Insomnia .:. Endometriosis
Initially 1.2Smg at bed time increased gradually to the usual dose of
2.Smg 3 times a day with food increased if necessary to a max. dose
.:. Ovarian hyperstimulation .:. Dizziness 30mgdaily.
.:. Hair loss .:. Nausea and vomiting Usual dose in infertility without Hyperprolactinaemia: 2.Smg
.:. Breast tenderness .:. Weight gain twice daily
.:. Depression .:. Menorrhagia Prevention or suppression of lactation: 2.Smg on day one
(prevention) or daily for 2-3days (suppression) then 2.Smg twice daily
Key issues to note for 14days
.:. Advise the patient of the possibility of multiple births. The risk
increases with higher doses Side effects
.:. Since the drug may cause dizziness or visual disturbances, warn .:. Nausea Constipation
the patient to avoid harzadous tasks until the response to the .:. Headache Drowsiness
drug is known .:. Nasal congestion Hypotension
.:. Fatigue Dizziness
BROMOCRIPTINE .:. Dry mouth .:. Abdominal cramps
Available preparations: Tablets 2.Smg .:. Diarrhoea
Drug interactions
Available brands: Lactodel®, Dopagon®, Parlodel®, Brameston® .:. Erythromycin may increase the plasma concetration of and
risk of toxicity of bromocriptine.
Pharmacokinetics Hypoprolactinaemic and anti parkinsonian effect of
Bromocriptine is poorly absorbed from the GIT, undergoes first-pas\ bromocriptine is antagonised by anti psychotics.
metabolism, metabolized completely in the liver and excreted in Hypoproctinaemic effect of bromocriptine is antaginsed by
faeces. domperidone

-547- -548-
 PRECISE PHARMACO , "", ': : :1,':, 'I 'I," ,':: ':" I II. ' '" PRECISE PHARMACOLOGY
.:. Hypoproctinaemic effect of bromocriptine is antaginsed by Side ~ffects
metoclopramide. .:. Hot flushes .:. Vaginal bleeding and discharge
.:. Headache .:. Light-headedness
Key issues to note .. .:. Depression .:. Confusion
.:. Bromocriptine may be administered with meals to minimise GI .:. Thrombosis .:. Photosensitivity
distress .:. Nausea and vomiting .:. Blurred vision
.:. Avoid alcohol use during therapy with bromocriptine .:. Anorexia
.:. Advise the patient that it may take 6-8 weeks or longer
for menses to be reinstated and for galactorrhea to be Key iSsues to note
suppressed .:. Adverse effects may be controlled by dosage reduction
.:. The drug's CNS effects may impair ability to perform tasks .:. Use cautiously in pre-existing leucopenia and
that require alertness and co-ordination thrombocytopenia
.:. Tell the patient to call promptly if vomiting occurs shortly after
TAMOXIFEN a dose is taken
Available preparations: Tablets 10mg, 20mg 17.1·3 DRUGS USED IN TREATMENT OF PRE-ECLAMPSIA
AND ECLAMPSIA
I[
Available brands: Nolvadex®
Pre-eclampsia is a condition that develops late in pregnancy after
20 w~ek of gestation characterised by hypertension, proteinuria and
th
Pharmacokinetics
oedema of legs, hands and face.
Tamoxifen is well absorbed after oral administration, distributed widely
into total body water, metabolized extensively in the liver and excreted Severe pre-eclampsia (BP > 16°/110 mmHg) may result into morbidity
primarily in faeces. and mOrtality for the mother or baby. It can lead to poor intra uterine
growth and early delivery.
Indications
.:. Anovulatory infertility
Eclampsia
.:. Breast cancer
This is the occurrence of seizures or coma in a mother with pre-
Contl"aindications eclampsia occurring at greater than 20 weeks of gestation or less than
•:. Pregnancy 48 houl's postpartum. Eclampsia is a threat to both mother and baby
and mUSt be treated immediately.
Dose Drugs Used in eclampsia include:
Anovulatory infertility: 20mg daily on days 2, 3, 4 and 5 of cycle; .:. Magnesium sulphate
if necessary the daily dose may be increased to 40mg then 80mg for .:. HydralaZine
subsequent courses.
MAGNI;:SIUM SULPHATE
Breast cancer: 20mg daily
Available preparations: Injection 50%
Indica~ions
.:. Eclampsia (prevention of recurrent seizures)

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 , :', ,':, '; 1,,1,,', ,: "r: ,':' ,: , " PRECISE PHARMACO GY

.:. Severe pre-eclampsia 17.1.4 DRUG USED IN LABOUR

.:. Hypomagnesaemia
Drugs used to delay premature labour
Contraindications Premature labour is the onset of labour before the expected date,
.:. Heart block .:. Severe renal failure resulting in delivery of an inmature infant. Risk factors for premature
.:. Hypermagnesaemia .:. Myocardial damage labour include:-
.:. Respiratory depression .:. Intestinal obstruction .:. Infections
.:. Appendicitis
.:. Premature rupture of the membrane
Dose .:. Cervical incompetence
By intravenous injection .:. Multiple pregnancies
Start with a loading dose of 4g by IV infusion 0.9% Sodium Chloride
over IS to 20 minutes. Then administer maintenance dose of Ig Ways of preventing premature labour
per hour by continous IV infusion for at least 24 hours upto the last .:. Cervical cerclage (for cervical incompetence)
seizure. .:. Treatment of infection
b~ Or .:. Postpone delivery by use of drugs (tocolysis)
Start 'ith a loading dose of 4g by IV infusion in 0.9% Sodium Chloride
Uterine stimulants
over IS to 20 minutes. Then administer by 1M 109 (Sg in ,each buttock)
These drugs inhibit uterine motility by decreasing the frequency and
followed by Sg every 4 hours for at least 24 hours after delivery or the
strength of contractions.
last seizure.
Examples
Side effects .:. Salbutamol
.:. Nausea and vomiting .:. Thirst .:. Nifedipine
.:. Flushing of skin .:. Hypotension .:. Magnesium sulphate
.:. Respiratory depression .:. Confusion Note
.:. Coma .:. Muscles weakness Delay in premature labour is likely to succeed if only the cervical dilation
.:. Arrhythmias Loss of tendon reflexes is <4cm.
Drug interactions Tocolysis is rarely necessary after 34 weeks gestation.
.:. Magnesium sulphate potentiates the effects of calcium channel Delay in premature labour should not be performed in the following
blockers and neuromuscular blockers cases:-
.:. Concomitant use with alcohol and other CNS depressants .:. Toxaecemia of pregnancy
may increase the CNS depressant effects of magnesium .:. Foetal death
sulphate .:. Intra uterine infection
Key issues to note .:. When the membranes have ruptured
.:. IV bolus must be injected slowly to avoid respiratory or cardiac .:. Antepartum haemorrhage
arrest
SALBUTAMOL
.:. Discontinue the drug as soon as the needed effect is achieved
Available preparations: Tablets 4mg
.:. When giving repeated doses, test knee jerk reflex before each
solution for injection SOmcg Iml
dose; if absent, discontinue magnesium

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 · HARMACOlOGY , ' " ,,: : ',' .':.', :". .:1" • ,;:1 .::,,,,,,, ." PRECISE PHARMACOLOGY

Available brands: Ventolin®, Kamvent® .:. Oral therapy is associated with fewer side effects
.:. Patients should be carefully monitored
Indications
.:. Uncomplicated premature labour between 24-33weeks of NIFEDIPINE
....
gestation Available preparations: Tablets IOmg, 20mg
.:. Asthma
Contraindications Available brands: Adalat®, Nifelat®, Depin®, Calcigard®
.:. Cardiac disease Indications
.:. Antepartum haemorrhage .:. Threatened or established pre-term labour (less than 34 week-
.:. Intrauterine infection
gestation)
.:. Intrauterine fetal death
.:. Ruptured membrane Contraindications
.:. Cord compression .:. Maternal conditions e.g. hypotension, cardiac disease
.:. Eclampsia and Pre-eclampsia .:. Any condition that would make prolongation of pregnancy
.:•. ' Placenta praevia hazardous
.:. i,l First and second trimester of pregnancy
:: .:. Fetal death
it .:. Intrauterine infection
Dose
Premature labour Dose
By intravenous infusion: Initially IOmcg /minute, gradually increased Initially conventional tablet 20mg, repeat the dose after 30 minutes if
according to response at IOminutes intervals until contractions diminish, utljl,rine contractions persist
then increase rate until contractions have ceased, max 45mcg/min. Crush or chew the first 2 doses to increase the rate of absorption
Maintain rate for I hour then gradually reduce If contractions continue after 3 hours, give 20mg every 3-8 hours until
By intravenous or intramuscular injection: IOO-2S0mcg repeated contractions cease, max 160mg per day.
according to response, then orally 4mg every 6-8hours. Maintenance, after 72 hours if necessary give daily dose required to
Do not use for more than 48hours. stop contraction as controlled release tablet in 2-3 divided doses daily
until 34 weeks gestation
Side effects
.:. Hypokalaemia .:. Nausea Side effects
.:. Vomiting .:. Flushing .:. Dizziness
.:. Sweating .:. Headache .:. Headache
~ ~emo~ ~ Palpitations .:. Flushing
.:. Hypotension .:. Urticaria .:. Oedema of the ankle
.:. Pulmonary oedema .:. Muscle cramps .:. Fatigue
.:. Maternal and fetal tachycardia
.:. Increased tendency to uterine bleeding Oxytocic drugs
These drugs include:-
Key issues to note .:. Ergometrine
.:. Treatment is usually started with IV infusion, which may be
.:. Oxytocin
substituted subsequently with oral therapy

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 , PRECISE llilmO " ":' ",.' ;',,', ': : , " PRECISE PHARMACOLO

Oxytocin stimulates the contractioons during the active management Drug interactions
of labour. Its is also used in combination with ergometrine during the 3 .:. The vasoconstrictor effects of ergometrine are enhanced by
stage of labour to reduce the risk of postpartum haemorrhage. sympathomimetic
Key issues to note
ERGOMETRINE .:. Before administration of the drug, always check that expulsion
Available preparations: Tablets O.12Smg of the placenta is complete, no multiple pregnancy and do not
Injection 200mcg/ml, O.5mg/ml administer before the birth of the last child
Ergomin® .:. Do not combine the drug with another ergot derivative
Available brands:
.:. Do not administer to patients WIth hypersensitivity to,
carbergoline, bromocriptine or ergotamine
Indications
.:. Prevention and treatment of post partum haemorrhage
.:. Treatment of post abortion haemorrhage in emergency OXYTOCIN
Available preparations: Solution for injection I 0 IU/ml
situations
Contraindications
.:. Induction of labour ,I Pharmacokinetics
I Absorption is immediate following IV injection, the drug is distributed
.:. I st and 2nd stages of labour
.:. Severe hypertension throughout the extracellular fluid, small amounts may enter the fetal
.:. Impaired respiratory function circulation. It is metabolized rapidly in the kidneys and the liver. Only
•:. Severe renal and hepatic impairment Ii small amounts are excreted in urine as oxytocin.
.:. Severe cardiac disease Ii
Indications
.:. Sepsis
.:. Pre-eclampsia and eclampsia .:. Induction and augmentation of labour
.:. Prevention of postpartum haemorrhage
.:. Vascular disease
.:. Treatment of postpartum haemorrhage
.:. Incomplete or missed abortion
Dose
Prevention and treatment of haemorrhage: IV 250-S00mcg, to be .:. Active management of 3rd stage of labour
repeated every 2-4 hours if necessary '!It
Contraindications
Side effects
.:. Nausea and vomiting .:. Headache .:. Hypertonic uterine contractions
.:. Dizziness .:. Abdominal pain .:. Any condition where spontaneous labour or vaginal delivery are
.:. Chest pain .:. Palpitations liable to harm either the mother or the fetus
.:. Myocardial infarction .:. Hypertension II .:. Mechanical obstruction to delivery
.:. _Bradycardia .:. Tinnitus il .:. Avoid prolonged administration in oxytocin resistance uterine
.:. Dyspnoea .:. Stroke
I"' inertia
.:. Pulmonary oedema .:. Transient hypertension
I -556-
-555-
/
 " ' I I I' 'Ii ' I
, ", PftECfDpHAftMACOLOGY , , I " PRECISE PHARMACOLOGY

.:. Severe pre-eclampsia toxaemia .:. Oxytocin may delay the induction of thiopental anesthesia
.:. Severe cardiac disease Key issues to note
.:. Fetal distress .:. Administer by IV infusion not IV bolus injection
Dose .:. Oxytocin may produce an antidiuretic effect, monitor fluid
Induction/augumentation of labour intake and output
Dilute SIU in SOOml of solution for infusion, initially 5 drops/min, i i .:. The drug is not recommended for routine 1M use.
then increase the rate by 5 drops/min every 30minutes until efficient .:. Have magnesium sulphate available for relaxation of the
contractions are obtained. Do not exceed 60 drops/min myometrium
Prevention of post partum haemorrhage after delivery of Prostaglandin derivatives
,.
placenta These drugs include:-
By slow intravenous injection,S units (if infusion used for induction .:. Misoprostol
or enhancement of labour, increase rate during third stage and for next .:. Dinoprostone
few hours).
MISOPROSTOL
Available preparations: Tablets 200mcg
Treatment of postpartum haemorrhage
By slow intravenous injection 5 -10 units, followed in severe cases Available brands: Kontrac®, Cytotec®
by intravenous infusion 5 - 30 units in SOOml infusion fluid at a rate Pharmacokinetics
sufficient to control uterine atony. Misoprostol is rapidly absorbed after oral adminl'stration, higly bound
Side effects to plasma proteins, rapidly de-esterified to misoprostol acid, the
•:. Uterine spasm biologically active metabolite and excreted mainly in urine.
.:. Uterine hyperstimulation Indications
.:. Fetal bradycardia Feotal arrhythmias .:. Inductio~f labour
.:. Nausea Vomiting .:. Gastric,and duodenal ulceration
.:. Headache Rashes .:. Prevention of NSAID induced ulcer
.:. Hypotension Contraindications
.:. Water intoxication associated with high doses .:. Pregnancy
.:. Hypersensitivity to misoprostol
Drug interactions Dose
.:. Oxytocin may enhance the vasopressor effects of
Induction of labour: 100mcg inserted into the vagina every 12 hours
sympathomimetics Prevention of NSAID induced ulceration: 200mcg 4 times a day
.:. Halothane may enhance the hypotensive effect of oxytocin aile I with food for duration of NSAID therapy
reduce its oxytocic effect Side effects
.:. Prostaglandins and oxytocin may potentiate the effects of eacll .:. Diarrhoea Stomach pain
other on the uterus .:. Dyspepsia Constipation

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 PRE B~1Ig:rMMi'B[I'Her'
7

e-PRECISE PHARMACOLOGY I
.:. Abnormal vaginal bleeding .:. Skin rash .:. Untreated pelvic infection .:. Fetal malpresentation
.:. Nausea .:. Flatulence .:. Hypersensitivity to dinoprostone
.:. Headache .:. Vomiting .:. Unexplained vaginal bleeding during pregnancy

Drug interactions .. Dose

.:. Magnesium antacids enhance diarrhoea associated with Induction of labour: 3mg inserted high into posterior fornix followed
misoprostol after 6-8 hours by 3mg if labour is not established. Max 6mg
.:. Misoprostollevels are diminished by concomitant
Side effects 1'1
administration with food or antacids
.:. Nausea and vomiting Diarrhoea
.:. Misoprostol decreases the bioavailability of aspirin
.:. Abdominal pain Dizziness
Key issues to note .:. Hypotension Fetal distress
.:. Extreme caution must be taken where a uterine scar is present .:. Shivering Bronchospasm
e.g. previous caesarean section .:. Back pain Rash
.:. Concurrent use with oxytocin requires careful monitoring .:. Flushing Headache
because of the risk of uterine rupture .:. Severe uterine contractions Fever
.:. Incidence of diarrhoea may be lessened by taking the drug .:. Rapid cervical dilation Maternal hypertension
right after meals
.:. Avoid magnesium-containing antacids Drug interactions
DINOPROSTONE .:. Dinoprostone enhances the effects of oxytocin and other
Available preparations: Vaginal tablets 3mg oxytocics on the uterus
Available brands: Prostin E2®
Key issues to note
Pharmacoldnetics .:. Instruct the patient to remai'iin prone position for 10 minutes
Following vaginal insertion, it is diffused slowly into the maternal blood,
after insertion
there is also some local absorption into the uterus through the cervix.
.:. Dinoprostone-induced fever is transient and self-limiting.
It is distributed widely in the mother, metabolized in the lungs, liver,
Sponge baths or increased fluid intake usually correct this
kidneys, spleen and other maternal tissues and excreted primarily in
problem ..
urine, with small amounts in faeces.
.:. Give the drug with caution in patients with a history of asthma
Indications or epilepsy
.:. Induction or augmentation of labour
.:. Missed abortion
17.1.5 DRUGS AFFECTING LACTATION
Contraindications Drugs used to inhibit lactation include:-
.:. Active cardiac disease .:. Pulmonary disease .:. Bromocriptine
.:. Hepatic disease .:. Renal disease .:. Cabergoline
.:. Ruptured membranes .:. Fetal distress
.:. Multiple pregnancies .:. History of caesarean sectioll

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 "
I

•
I'

I
BROMOCRIPTINE Contraindications
Bromocriptine is a dopamine D2-agonist which inhibits the secretion of .:. Hypersensitivity to any ergot alkaloid
prolactin from the anterior pituitary. .:. Toxaemia of pregnancy
.:. Post partum hypertension
I Ii:i
I

Indications .:. Severe hepatic insufficiency

.:. Suppression of lactation i
I Dose
,
.:. Galactorrhoea ; L Inhibition of lactation I-mg as a single dose on the first day
! ~
.:. Amenorrhoea postpartum.
.:. Infertility associated with Hyperprolactinaemia Suppression of established lactation 250 micrograms every 12
:
: 'I'
i hours for 2 days.
Contraindications
Side effects
.:. Hypersensitivity to ergot alkaloids .:. Nausea and vomiting Abdominal pain
.:. Toxaemia of pregnancy .:. Dyspepsia Constipation
·:·.ll Uncontrolled hypertension .:. Vertigo Drowsiness
Dose .:. Headache Depression
Suppression of lactation: 2.5mg twice daily for 2 weeks starting not .:. Sleep disturbance
before 4 hours after parturition.
17.1.6 DRUGS USED IN THE TREATMENT OF ... 'i
Amenorrhoea/Galactorrhoea: Initially 1.25mg once daily at bedtime, ENDOMETRIOSIS
gradually increase to 2.5mg 2-3 times daily. Endometriosis is a medical condition characterized by growth of
Side effects endometrial tissue outside the uterine cavity. It affects women in their
•:. Nausea reproductive years.
.:. Postural hypotension Patients may be a symptomatic or have pelvic pain, menstrual changes,
.:. Drowsiness bowel symptoms or infertility
.:. Dizziness Drugs used in the treatment of endometriosis include;
.:. Danazol
CABERGOLINE .:. NSAIDS
Available preparations:. Tablets 0.5 mg .:. Progesterone
.:. Combined oral contraceptives
Available brands: Dostinex®
DANAZOL
Available preparations: Capsules 50mg, IOOmg, 200mg
Indications
.:. Suppression of lactation after still birth and when Available brands: Gonablok®
breastfeeding is contraindicated Pharmacokinetics
.:. Parkinson's disease It is well absorbed following oral administration, extensively metabolized

-561- -562-
 IIIII"III"""""'l"","'''''''I!I!'

, ~RECISE PHARMACClUIGY .' " ,I , I ";" 'ii" II I: I", I ,: 'I ':\ , :,' PRECIhi]PHARMACOLOGY

in the liver and excreted in urine. Drug interactions

.:. Warfarin anticoagulant effects may be enhanced by danazol
Indications
II' .:. Danazol may increase the effect of carbamazepine
.:. Endometriosis I
.:. Danazol may cause decreases in blood glucose levels, which
.:. Benign fibrocystic breast disease
may require adjustment of insulin or oral hypoglycaemic drugs
.:. Dysfunctional uterine bleeding
.:. Prevention of hereditary angioedema Key issues to note
.:. Gynaecomastia in males .:. The drug should not be discontinued without consulting the
.:. Pre-menstrual syndrome prescriber
.:. Therapy may take up to several months for full benefit
Contraindications
depending on the purpose of treatment
.:. Markedly impaired renal, hepatic or cardiac function
.:. The drug may cause photosensitivity, therefore avoid direct
.:. Undiagnosed abnormal vaginal bleeding
exposure to sunlight It
.:. Pregnancy and lactation
.:. To treat endometrios and fibrocystic breast di~ease, danaZol
.:. Porphyria
therapy should begin during menstruation
.:. Androgen tumor
.:. Advise the patient to report voice changes
.:. History of thromboembolic disease
.:. Advise female patients that amenorrhea usually occurs after 6-
Dose 8 weeks of therapy
Endometriosis: 100 -400mg twice daily for 3-9months •:. Avoid administration of danazol with a fatty meal •
Benign breast disorder: 50-200mg twice daily, adjusted according to .:. Use nonhormonal contraceptive measures and discontinue the
response for 3-6months drug if you suspect pregnancy
Dysfunctional uterine bleeding: 200mg daily for 3 -6months
Hereditary angioedema: 200mg 2-3 times daily reduced according 17.1.7 DRUGS FOR CONTRACEPTION
to patient response Contraception refers to the various methods used to prevent pregnancy.
Gynaecomastia: 200mg daily increased after 2months to 400mg daily These methods can be either medical or non medical and may be used
if no response occurs by men, women or both.
Side effects Common methods of contraception include:-
.:. Acne .:. Oily skin .:. Abstinence
.:. Weight gain .:. Mild hirsutism .:. Barrier methods (male and female condoms)
.:. Nausea .:. Skin rash .:. Intra uterine devices (IUD)
.:. Menstrual disturbance .:. Hot flashes .:. Hormonal contraceptives
.:. Changes in libido .:. Oedema .:. Female or male sterilization
.:. Hair loss .:. Headache .:. Emergency contraceptives
.:. Backache .:. Tremors
.:. Amenorrhea .:. Sweating The above methods may prevent ovulation, fertilization of the ovum or
.:. Vaginal dryness and irritation .:. Deepening of the voice implantation of the fertilized ovum

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 , I PRECISE PHARMACOLOG I I PRECISE PHARMAC:iII!IiI

Oral Contraceptives Side effects

Oral contraceptives are divided into two .:. Break through bleeding .:. Nausea and vomiting
.:. Combined oral contraceptives .:. Changes in weight .:. Depression
.:. The progestogen only pill .:. Changes in libido .:. Acne
.:. Venous thromboembolism .:. Cervical cancer
Combined oral contraceptives .:. Fluid retention .:. Headache
Oral combined contraceptives contain low doses of oestrogen and .:. Amenorrhoea .:. Stroke
progesterone. They are the most widely used contraceptives and havIl .:. Photosensitivity .:. Increased'blood pressure
the lowest failure rate in terms of unwanted pregnancies. .:. Breast enlargement and tenderness
They are suitable for women who regularly experience exceptiomlly Examples of combined oral contraceptives
'1
painful, heavy or prolonged periods.
MICROGYNON®/NEW FEM®
Composition: Levonorgestrel O.ISmg
Mode of action Ethinylestradiol O.03mg
They inhibit ovulation, reduce receptivity of endometrium 1.1)
Ferrous fumarate 7Smg (7 brown tablets)
implantation and thicken cervical mucus to form a barrier to sperm, Dose: I tablet daily for 28 days starting on day I of the menstruation
cycle with the active tablets
Indications
.:. Contraception PILL PLAN®
.:. Dysfunctional uterine bleeding Composition: Norgestrel O.3mg
.:. Dysmenorrhoea Ethinylestradiol O.03mg
.:. Endometriosis Ferrous fumarate 7Smg (7 brown tablets)
.:. Premenstrual syndrome Dose
.:. Menorrhagia I tablet daily for 28 days starting on day one of menstruation cycle with
the active tablets.
Contraindications
LO-FEMENAL®
.:. Pregnancy
Composition NorgestrelO.3mg
.:. History of thromboembolic disorder
Ethinylestradiol O.03mg
.:. Pulmonary hypertension
Ferrous fumarate 7Smg (7 brown tablets)
.:. Active vi ral hepatitis
.:. Unexplained uterine bleeding Dose: I tablet daily starting on day I of the menstruation cycle with
.:. History of breast or hepatic Cancer the active tablets
.:. Migraine
Progestogen only pills
.:. Atrial fibrillation
They are often recommended for women who react to oestrogen in
.:. Severe cirrhosis

-565- -566-

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__ 7_;;".'.'.7•••:•.".] ....1 1 r:;;;r;;;;]]ii!':r:rr:::rr;:r::'IilI/:; 'PPiiirirWiii::_
 , ' PREC[§)PHARMACOLOGY - _ _I Of PHARMACOLOGY I
the combined pill or where combined pills are not suitable because of SOFTSURE®
the age or medical history. They may be used by breastfeeding mothers Composition: Levonorgestrel O.03mg
since they do not affect the quantity and quality of the milk produced.
Progestogen only pills have a higher failure rate compared to com.bined Dose: I tablet daily at the same time each day
pills and must be taken at the same time each day for maximum
contraceptive effect. Emergency contraceptives
Mode of action Emergency contraceptives are effective ifthe dose is taken ideally within
Progestogen thickens the cervical mucus which impedes the passage 12 hours but not later than 72 hours of unprotected intercourse.
of sperm, disrupts the menstrual cycle including preventing release of Examples:-
the eggs from the ovaries and changes the endometrium reducing the .:. Postinor®
potential for implantation.
Indications POSTINOR-2®
.:. Contraception Composition Levonorgestrel O.75mg
,I
I'
.:. Emergency contraception
.:. Endometriosis Dose
.:. Menstrual disorders 1.5mg (2 tablets) as a single dose as soon as possible within 12 hours
Contraindications but not later than 72 hours.
.:. Pregnancy
.:.
~I
Undiagnosed vaginal bleeding Parenteral Progestogen Only Contraceptives
,I
.:. Porphyria They provide reliable suppression of ovulation by suppressing the
Ii:
.:. Active viral hepatitis luteinising hormone.
'III
.:. Breast or liver cancer
:11
.:. Severe arterial disease Indications ilj

.:. Severe cirrhosis .:. Contraception

II
iii
Side effects
.:. Nausea .:. Vomiting Side effects
.:. Spotting .:. Weight gain. .:. Menstrual irregularities .:• Prolonged bleeding
.:. Dizziness .:. Headache .:. Spotting .:. Amenorrhoea
.:. Breast discomfort .:. Prolonged bleeding .:. Breast tenderness .:.
.:. Depression .:. Acne .:. Loss of bone mineral density
Weight gain

.:. Amenorrhoea
OVRETTE® Contraindications
Composition: Norgestrel O.075mg .:. History of breast cancer
Dose: I tablet daily starting on the day I of the menstruation cycle .:. Pregnancy

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1111IIIIIII1I111111111111111111
 t i
Examples
.:. Medroxyprogesterone CHAPTER EIGHTEEN
DRUGS FOR UROLOGIC DISORDERS
MEDROXYPROGESTERONE
URINARY INCONTINENCE
Available preparations: I SOmg Iml
Urinary incontinence is the involuntary loss of urine. It is a distressing
problem which may have a profound impact on the quality of life of the
Available brands: Depo-provera, Injecta plan
patient.
Types of urinary incontinence
Dose .:. Stress incontinence
By deep intramuscular injection I SOmg within the first 5 days of the .:. Urge incontinence
Cycle repeated every after 12 weeks. (3 months) .:. Overflow incontinence

Stress incontinence
It is the involuntary loss of urine with physical activities that increase
abdorminal pressure in the absence of dextrusor contraction or an
overdistended bladder.
It's common in women and the patient usually has urethral sphincter
incompetence

Urge incontinence
It is the involuntary loss of urine associated with an abrupt and strong
desire to void. It's also known as unstable bladder or detrusor instability
and it is the most common in elderly.
Overflow incontinence
It is loss of urine resulting from over distention of the bladder with
resultant overflow of the urine. Patients with this kind of incontinence
suffer from a continuous or frequent dribbling of urine.. Most patients
are elderly men with urethral blockage due to benign prostatic
hyperplasia.
URINARY RETENTION
It is the lack of ability to urinate and is a common complication of benign
prostatic hyperplasia.
It is characterized by poor urinary stream with intermittence, straining,
a sense of incomplete voiding and urgency.
Treatment involves catheterization and drug treatment depends on the
cause.

-569- -570-
 , ~ISE PHARMACOLOGY

18.1.1 BENIGN PROSTATIC HYPERPLASIA (BPH) .:. Known hypersensitivity to the drug
This refers to benign enlargement of the prostate gland which gives rise .:. Partial or complete gastrointestinal tract obstruction
to symptoms. It is a natural occurrence with advancing age and sexual
activity does not play any role in its etiology. Dose
Initially 2.S-Smg 2-3 times daily increased if necessary to Smg 4 times
Signs and symptoms
daily.
•:. Hesitancy
Elderly: Initially 2.Smg twice daily increased to Smg twice daily if
.:. Incomplete voiding
necessary.
.:. Dribbling after urination
Children over 7years (nocturnal enuresis): Initially 2.Smg twice
.:. Nocturia
daily increased to Smg 2-3 times daily according to response (the last
.:. Frequency and urgency
dose given before bed time).

Drugs used in the management of benign Prostatic Hyperplasia

Side effects
include:-
.:. Alfuzosin .:. Facial flushing .:. Dry mouth
.:.'" Oxybutynin
If.
.:. Prazosin .:. Constipation .:. Dizziness
.:. Doxazosin
.:. Finasteride .:. Blurred vision .:. Skin rash
.:. Terazosin
.:. Dry eyes .:. Impotence
.:. Insomnia
OXYBUTYNIN
Drug interactions
Available preparations: Tablets 2.Smg, Smg
.:. Oxybutynin intensifies the anti muscarinic effects of atropine
Available brands: Cystrin® and related compounds
Pharmacokinetics .:. Concomitant use of itraconazole and ketoconazole with
Oxybutynin is rapidly absorbed after oral administration, metabolized oxybutynin results in moderate increase of serum concentration
by the liver and excreted principally in urine. of oxybutynin
.:. Additive sedation may occur when oxybutynin is given
Indications I'i:
together with alcohol and other CNS depressants
.:. Urinary frequency
.:. Urinary urgency
Key issues to note
.:. Urinary incontinence
.:. Food may slightly delay absorption of oxybutynin
.:. Neurogenic bladder instability
.:. Nocturnal enuresis associated with over active bladder .:. The drug may cause drowsiness and impair ability to perform
activities that require mental alertness
.:. Avoid prolonged exposure to hot environment
Contraindications
.:. Breast feeding
ALFUZOSIN
.:. Myasthenia gravis
Available preparations: Tablets IOmg
.:. Glaucoma
.:. Severe ulcerative colitis
Available brands: Xatral LP®
.:. Obstructive uropathy

-571- -572-

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" ", , , t " , : " :,:' ,d' i, '~PHARMACOLOGY . , PRECISE PHARMACOLOGY

Pharmacokinetics FINASTERIDE
It is fairly absorbed from the GIT, metabolized in the liver and excretml Available preparations: Tablets Smg
in urine and faeces.
Available brands: Proscar®, Finast®
Indications
.:. Benign Prostatic hyperplasia Pharmacokinetics
.:. Adjuvant treatment to catheter in acute urinary retention Finasteride is relatively well absorbed from the GIT, highly bound to
associated with BPH plasma proteins, crosses the blood brain barrier, extensively metabolized
by the liver and excreted in faeces and urine.
Contraindications Indications
.:. Known hypersensitivity to alfuzosin .:. Benign prostatic hyperplasia
.:. Severe liver and kidney impairment .:. Androgenetic alopecia in men (male pattern baldness)
.:. Orthostatic hypotension
.:. Micturition syncope Contraindications
Dose .:. Women
2.Smg 3 times daily, maxi Omg daily. Elderly; initially 2.Smg twice (Lilly .:. Children and adoloscents
Modified release preparation: IOmg once daily .:. Known hypersensitivity to finasteride
Adjuvant treatment to catheter in acute urinary retentiOlI
associated with BPH: I Omg once daily for 3 -4 days Dose
BPH: Smg daily
Side effects Male pattern baldness: I mg daily for 3 months or more
.:. Light headedness .:. Nausea
.:. Stomach pain .:. Drowsiness Side effects
.:. Skin rash .:. Chest pain .:. Decreased libido .:. Impotence
.:. Headache .:. Fatigue .:. Allergic reaction .:. Testicular pain
.:. Dizziness .:. Diarrhoea .:. Decreased volume of ejaculate
.:. Flushes .:. Breast tenderness and enlargement

Drug interactions Key issues to note

.:. Cimetidine may increase alfuzosin blood concentration .:. Inform the patient that clinical response is not immediate
.:. Ketoconazole, itraconazole and ritonavir may increase .:. Condoms should be used if the female partner is at risk of
alfuzosin serum levels pregnancy
Key issues to note .:. Withdrawal of drug for hair loss leads to reversal within 12
.:. The first dose should be given at bed time to minimise postlll ,II months
hypotension .:. Finasteride may decrease the volume of ejaculate but does
.:. The dose may need to be reduced in patients with hepatic all' I not impair normal sexual function
renal impairment, and elderly

-573- -574-

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18.1.2 DRUGS FOR ERECTILE DYSFUNCTION

.:. Unstable angina and myocardial infarction
Erectile dysfunction, commonly known as impotence, is the persistent Dose
inability of a man to achieve or sustain an erection which is adequate in
Adults over 18years: Initially SOmg I hour before sexual intercourse,
terms of hardness and duration for sexual intercourse.
the dose may be increased or decreased depending on response. Max
It may be classified as primary or secondary erectile dysfunction." dose I OOmg daily.
Elderly: 25mg one hour before sexual intercourse.
Primary erectile dysfunction
In this type of impotence, the patient has never been able to attain and Side effects
maintain an erection for sexual intercourse. ·:·Headache .:. Hypotension
Secondary erectile dysfunction
,
.:. Tachycardia .:. Diarrhoea
I! 'I' I .:. Dyspepsia .:.
It is where impotence occurs in a man who has a past history of
satisfactory sexual performance.
'I
.:. Flushing .:.
Skin rash
Pain and redness of the eyes
.:. Visual disturbance .:. Dizziness
Drugs commonly used include;-
.:. Nasal congestion .:. Vomiting
.:. Sildenafil .:. Muscle pain .:. Priapism
.:. Tadalafil +:. Sudden cardiac death
SILDENAFIL Drug interactions
Available preparations: Tablets SOmg, IOOm'g
.:. Cimetidine, erythromycin, ketoconazole, and itraconazole may
increase sildenafil plasma concentration
Available brands: Viagra®, Kamagra®, Canova®
.:. Sildenafil may potentiate the hypotensive effects of Nitrates
Penegra®, Androz®
.:. Concomitant use with alpha-blockers may lead to hypotension
Pharmacokinetics
.:. Concurrent use with heparin may have an additive effect on
Sildenafil is rapidly absorbed from the GIT, but a high-fat meal decreases bleeding time
the absorption. It is distributed into most tissues, metabolized in the
.:. Sildenafil potentiates the effect of other antihypertensives
liver and excreted in faeces and urine.
.:. Use of sildenafil with vitamin K antagonists may increase the
Indications risk of bleeding
.:. Erectile dysfunction
.:. Pulmonary hypertension Key issues to note
Contraindications .:. A smaller dose is required to maintain adequate erection
.:. Concurrent use of sodium nitroprusside or nitrate .:. Regular medical review during treatment is necessary
.:. Hereditary degenerative retinal disorders .:. Discourage social use by men who do not have erectile
.:. Patients in whom vasodilation or sexual activity is unadvisable dysfunction problem since they may have a greater risk of
.:. Hypotension priapism
.:. Recent stroke .:. Avoid grapefruit juice
.:. Patients with anatomical or haematological disorders which .:. Do not combine sildenafil with other approaches to treating
may predispose them to priapism erectile dysfunction without consulting a clinician

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TADALAFIL .:. Erythromycin, c1arithromycin. ritonavir, ketoconazole,

Available preparations: Tablets IOmg, 20mg itraconazole, indinavir and saquinavir may increase tadalafil
plasma concentration
Available brands: Megali®. Cialis®, Apcalis®. Saheal®
Key issues to note
Pharmacokinetics .:. Efficacy may persist up to 36hours after using tadalafil and it
Tadalafil is rapidly absorbed from the GIT, highly protein boubd, should not be taken more than once in 24hours
metabolized in the liver and excreted in faeces and urine. .:. Sexual stimulation is required for an erection to occur after
Indications taking tadalafil
.:. Erectile dysfunction

Contraindications
.:. Severe hepatic impairment
.:. Hypersensitivity to tadalafil
.:. Concurrent use of nitrates in any form
.:. Moderate heart failure
.:. Uncontrolled hypertension
.:. Uncontrolled arrhythmias
.:. Patients in whom vasodilation or sexual activity is unadvisable
.:. Unstable angina and myocardial infarction

Dose
IOmg at least 30minutes before sexual intercourse, with or without
food. The daily dose may be increased to 20mg depending on the
response.
I,
i
Side effects
.:. Headache Dyspepsia
.:. Nasal congestion Flushing
.:. Palpitation Back pain
.:. Myalgia Dizziness
.:. Abnormal vision .:. Tachycardia
Drug interactions
.:. Alcohol increases the risk of orthostatic hypotension
.:. Tadalafil potentiates hypotensive effects of alpha blockers,
nitrates

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 , " " ' I ,'" ' 'i' ,I' ",I: ,I,'" ". '.::m:IIiISE PHARMACOLOGY

Pharmacokinetics
Allopurinol is well absorbed from the gastrointestinal tract after oral
CHAPTER NINETEEN administration, metabolised in the liver to active form and excreted in
MUSCULO-SKELETAL DISORDERS faeces and and a small percentage of unchanged drug in urine.

- 19.1.1 DRUGS FOR GOUT Indications

.:. Prophylaxis of gout
Gout is a metabolic disease characterized by inflammation and pain in
the affected joints due to increased levels of uric acid in the blood.
I .:. Hyperuricaemia associated with acute uric acid nephropathy
Gout arthritis may be due to the diminished renal excretion of uric acid .:. Prophylaxis before cancer chemotherapy
or increased production of uric acid I
"
"
I
Contraindications
',., ~ !
Management of Gout arthritis .:. Acute attacks of gout
Acute gout .:. Known hypersensitivity to allopurinol
NSAIDs in high doses are drugs of first choice. Dose
These include:-
Initially I OOmg daily gradually increased by I OOmg according to plasma
.:.~'0, Diclofenac
or urinary uric acid concentration. Usual maintenance dose
.:.i; Indomethacin I 00-200mg daily in mild condition
.:. Naproxen
300-600mg daily in moderately severe conditions
Other drugs used during acute attack 700-900mg daily in severe conditions
.:. Colchicine Doses above 300mg should be taken in divided doses
.:. Systemic corticosteroids Prevention of uric acid nephropathy associated with cancer
chemotherapy
Note
600-900mg daily for 2-3 days before starting the cancer treatment (high
Aspirin is not recommended in the treatment of gout since it increases
fluid intake is necessary)
the plasma uric acid concentration.
Children: I 0-20mg /kg daily up to a max of 400mg daily.
Chronic gout Side effects
Prevention of gout attack .:. Skin rash
.:. Allopurinol I Ii Nausea and vomiting
I .:. Headache Drowsiness
.:. Colchicine
.:. Visual disturbance .:. Abdominal pain
.:. Probenecid
.:. Diarrhoea Malaise
These drugs inhibit the production of uric acid or enhance its urinary .:. Vertigo
excretion. They should not be started during acute attack because they
may prolong the existing attack Drug interactions
.:. Aluminium-containing antacids decrease absorption of
ALLOPURINOL
allopurinol
Available preparations: Tablets 100mg, 300mg
.:. Allopurinol increases the risk of toxicity when given together
Available brands: Stradumel®, Zynol®, Zyloric® with captopril especially in renal impairement.

-579- -580-
 PREC~~HARMACOLOGY
, I
.:. Use of allopurinol with ampicillin or amoxicillin may increase 'I'i
j Dose
the incidence of skin rash Treatment of gout: Initially I mg then O.Smg every 2-3hours until
.:. Allopurinol may increase risk of osteomalacia in patients pain relief is obtained or vomiting! diarrhoea occurs (6mg per course
receiving phenytoin or phenobarbital which should not be repeated until at least 3 days)
.:. Allopurinol may enhance the anticoagulant effect of coumarins Prevention of gout attack during initial treatment with
allopurinol: O.5mg 2-3 times daily
Key issue to note
.:. Taking allopurinol with food reduces gastric irritation Side effects
.:. Treatment should be withdrawn if a skin rash or fever appears .:. Nausea and vomiting Abdominal pain
as these symptoms may precede a serious hypersensitivity .:. Diarrhoea Renal damage
reaction .:. Muscle weakness. Hepatic damage
•:. Doses should be reduced in renal impairment to avoid .:. Gastro intestinal haemorrhage .:• Skin rash
toxicity
.:. Patients with gout may experience an increase in acute attacks Drug interactions
rllon beginning treatment with allopurinol although attacks usually .:. Colchicine induces reversible malabsorption of vitamin B 12
subside after several months .:. Colchicine increase sensitivity to CNS depressants
.:. Advise the patient to drink plenty of fluids while taking his drug .:. Erythromycin, c1arithromycin increase the toxicity of
.:. Avoid alcohol during therapy with allopurinol colchicine
.:. Alcohol may inhibit the action of colchicine
COLCHICINE
Available preparations: Tablets O.5mg Key issues to note
.:. Prolonged prophylactic therapy is not recommended
Available brands: Zolzine®
.:. Adjust dosage carefully to avoid precipitating diarrhoea or
Pharmacokinetics other adverse effects
Colchicine is readily absorbed orally, rapidly distributed into various .:. Avoid alcohol during therapy with colchicine
tissues, partially deacetylated in the liver and mainly excreted in faeces .:. If the colchicine is used for acute gout, discontinue once the
with small amounts excreted in the urine. pain is relieved or vomiting or diarrhoea occurs
.:. To avoid cumulat!ve toxicity, a course of oral colchicine should
Indications not be repeated for at least 3 days
.:. Acute gout
.:. Prophylaxis of acute attacks especially during the first few 19.1.2 DRUGS USED IN THE TREATMENT OF RHEUMATOID
months of treatment with allopurinol ARTHRITIS
Contraindications Rheumatoid arthritis is a chronic autoimmune disease characterized
.:. Blood dyscrasias by pain, stiffness and swelling of the joints. It may present as an acute
.:. Severe cardiac disorder polyarthritis or as fleeting joint pains progressing over a period of
.:. Severe renal disorder months.
•:. Known hypersensitivity to colchicine
Drugs used in the treatment of rheumatoid arthritis include:-

-581- -582-
 E PRECISE PHARMACOLOGY] gj!3CISE PHAR MjteOLOGY I
II:
.:. Disease modifying anti rheumatic drugs like methotrexate, .:. Visual disturbance
!II!
hydroxychloroquine, corticosteroids, sulfasalazine .:. Pruritus of palm, sole and scalp
.:. NSAIDS
Drug interactions
Note ~ .:. Concomitant administration with kaolin or magnesium
'" Disease modifying drugs are used in an attempt to modify the course trisilicate may decrease absorption of hydroxychloroquine
of the disease. They should be started early in the course of the disease .:. Use with digoxin may increase serum digoxin levels
before joint damage starts. Their full therapeutic response occurs
Key issues to note
between 4-6months.
.:. To prevent drug-induced dermatoses, warn the patient to
avoid excessive exposure to the sun
HYDROXYCHLOROQUINE
Available preparation: Tablets 200mg .:. Give hydroxychloroquine immediately after meals on the same
day each week to minimize gastric distress
Available brands: Plaquenil®
III' METHOTREXATE
Pharmacokinetics Available preparations: Tablets 2.5mg
Hydroxychloroquine is readily and almost completely absorbed from Ii' Injection 25mg/ml
I,
the GIT, concentrates in the liver, spleen, kidneys, heart and brain, II
I

metabolized in the liver and excreted in urine; unabsorbed drug is I~ Available brands: Texol®
Pharmacokinetics
excreted in faeces.
Absorption across the GIT is dose related, that is, when given in lower
Indications doses it is rapidly absorbed but higher doses are less well absorbed.
.:. Rheumatoid arthritis It is distributed to tissues and extracellular fluids, metabolized in the
.:. Discoid lupus erythematosus liver and excreted primarily in the urine, with small amounts in faeces.
1!'
Indications
Contraindications
.:. Long term therapy for Children .:. Severe active rheumatoid arthritis
.:. Malignant disease
.:. Pregnancy
.:. Hypersensitivity to hydroxychloroquine .:. Crohn's disease
.:. Neurological disorders Contraindications
.:. Hepatic impairment .:. Pregnancy
.:. Breast feeding
Dose
Adults: Initially 400mg daily for 5-1 Odays gradually decreased to a .:. Immunodeficiency syndromes
.:. Active infection
maintenance dose of 200-400mg daily
.:. Hepatic impairment
Side effects
.:. Headache .:. Anorexia Dose
.:. Fatigue .:. Nausea Rheumatoid arthritis: Oral; 7.5mg once weekly as a single dose or in
.:. Personality changes .:. Vomiting 3 divided doses of 2.5mg given at 12hourly interval, max. weekly dose
20mg

-583- -584-

, • , III 1111
,._--
giUijlSE PHARMACOLOGY I :I: " I:,: I:: I ,I: II' ":,,1 'I' :, i ,::, ',':1 :: ',i:; ,"':!,i PREC PHARMACOLOGY
Side effects Selective NSAIDS
.:. .:.
.:.
.:.
Bone marrow depression
Gastrointestinal disturbance .:.
.:.
Liver damage
Renal failure
These drugs selectively block cyclooxygenase 2 (COX 2) and are well
tolerated compared to the non-selective NSAIDS.
Skin reaction Osteoporosis Examples
.:. Myalgia .:. Arthralgia .:. Aceclofenac
.:. Ocular irritation .:. Precipitation of diabetes .:. Meloxicam
Drug interactions .:. Celecoxib
.:. Alcohol enhances the hepatotoxicity caused by methotrexate DICLOFENAC
.:. Phenytoin, co-trimoxazole may give additive antifolate activity Available preparations: Tablets 50mg, 75mg SR, 100mg
and increase the risk of methotrexate toxicity Capsules 100mg SR
Key issues to note Injection 75mg/3ml
.:. Full blood count, urea and liver function tests should be carried Suppositories 50mg, 100mg
out prior to and during treatment Topical gel
·:·:tFolinic acid is required for rescue procedures
.:.!~ Patients with hyperuricaemia should maintain adequate fluid Available brands: Olfen®, Diclo-denk®, Voltaren®,
intake and alkalinization of urine 'j, Diclomol®, Soludol®, Cataflam®, Diclomax®,
Combination: Panoxen (Diclofenac 50mg + Paracetamol 500mg)
NON STEROIDAL ANTI-INFLAMMATORY DRUGS(NSAIDs) Diclomol plus (Diclofenac 50mg + Paracetamol
Most of the drugs in this class produce three useful effects, that is, 500mg)
suppression of inflammation, relief of pain and reduction of fever. All
these responses are produced by inhibition of cyclooxygenase enzyme, Ii Pharmacokinetics
which is responsible for the synthesis of prostaglandins and related Diclofenac is rapidly absorbed when given orally although the rate but
compounds. This same mechanism underlies their side effects of gastric not the extent is decreased by food. It undergoes first-pass metabolism
ulceration, bleeding and acute renal failure. and almost 50% is available in unchanged form. It is metabolised in the
liver and excreted in urine and bile.
NSAIDs are classified as:-
.:. Non selective NSAIDS Indications
.:. Selective NSAIDS
.:. Rheumatoid arthritis .:. Post operative pain
.:. Osteoarthritis .:. Renal colic pain
Non selective NSAIDS
.:. Dysmenorrhoea .:. Ankylosing spondylitis
These drugs block both cyclooxygenase I and 2 (COX-I and COX- 2)
.:. Bursitis .:. Tendonitis
Examples
.:. Sprain and strains .:. Acute gout
.:. Diclofena Ibuprofen
.:. Migraine
.:. Mefenamic acid Acetyl salicylic acid Contraindications
.:. Indomethacin Naproxen .:. Active peptic ulcer
.:. Piroxicam Tenoxicam .:. Known hypersensitivity to diclofenac or other NSAIDS
.:. Porphyria

-585- -586-
m' 7 PRECISE PHARMACOLOGY I
II I It ,

,,
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: PRECISE
.:. Pregnancy Key issues to note
.:. Proctitis or haemorrhoids (suppositories contraindicated) .:. Administration of diclofenac with food is recommended as this
.:. Severe heart failure may buffer the GI irritant effects of the drug
Dose .:. Avoid alcohol during therapy as it may aggravate GI irritation
Adult: .:. Dehydration during therapy markedly enhances the risk of
Oral 50mg 3 times daily or 75-1 OOmg SR daily is indicated for long term re~al. damage, therefore advise the patient to ensure adequate
flUid mtake to protect renal function
therapy.
.:. Symptoms of infection may be masked by use of diclofenac
Rectal suppository I OOmg once daily at night,
Acute pain 1M injection 75mg once daily or twice daily in severe cases IBUPROFEN
for a max of 2 days. Available preparations: Tablets 200mg, 400mg
Children: Syrup IOOmg/5ml
Uuvenile arthritis.) Topical gel
Oral or by rectum: 1-3mg Ikg daily in divided doses.
Available brands: Ibumex®, Brufen®, Marcofen®, Fenbid®,
6-12years (postoperative).
Brumed®, Betafen®, Agofen®, Flamifen®,
By rectum: 1-3mg/kg daily in divided doses for a max of 4 days.
Side effects
Combinations: Brustan®(lbuprofen 400mg + paracetamol 300mg)
Ibex®(lbuprofen 200mg + Paracetamol 325mg +
.:. Headache Abdominal cramps
caffeine 30mg)
.:. Peptic ulcer Nausea
Pharmacokinetics
.:. Skin rash Dizziness
Ibuprofen is rapidly absorbed when taken orally and the rate of
.:. GIT bleeding Constipation
absorption is reduced by food, It is metabolized in the liver and
.:. Wheezing
excreted in urine mainly as inactive metabolites.
Drug interactions Indications
.:. Diclofenac may antagonise the hypotensive effect of .:. Rheumatoid arthritis Osteoarthritis
antihypertensive and diuretics .:. Headache .:. Juvenile arthritis
.:. Diclofenac may increase the risk of bleeding when given together .:. Fever and pain Gout arthritis
with heparin, oral anticoagulants and thrombolytics .:. Vascular headache Sprains and strains
.:. Concomitant use with digoxin and methotrexate may increase .:. Dysmenorrhoea Dental pain
the toxicity of these drugs .:. Post operative pain Migraine
.:. Concurrent administration of diclofenac and aspirin lowers the Contraindications
plasma levels of diclofenac .:. History of hypersensitivity to aspirin
.:. Concurrent use of diclofenac with potassium-sparing diuretics .:. GIT bleeding disorder
may increase serum potassium levels .:. Active peptic ulcer
.:. Concurrent use with other NSAIDs may produce additive .:. Chronic inflammation of GI tract
potential for ulcerogenicity and other adverse effects
Dose
•:. Concomitant use with corticosteroids may enhance the Adult 200-400mg 3-4 times a day up to a max of 2400mg.
potential toxicity of both medications Children > 6 months.

-587- -588-
 , PREC ~UHARMACOI!iliil " ,
,: ," ,,' ',,:, ';1:' 1" I 'I PREC' I : : u ~liIl0GY
For pain and fever; 5-1 Omg /kg / dose 3-4 times a day.
Juvenile arthritis: I Omg /kg! dose 3-4 times a day.
'1ranfib-MF®(mefenamic acid 250mg!tranexamic acid
SOOmg)
Topical gel: Rub to the affected area 4 times a day.
Side effects Pharmacokinet'l (;s
.:. Heart burn Ringing in the ears Mefenamic acid i . .
S rapidly absorbed from the gastrointestinal tract and
0

, .
.:. Skin rash Constipation IS extensively
' . . boun d . It .IS metab 0 I'Ise dOh
prOteln I'
In t elver an d excrete d
.:. Pruritus Nausea and vomiting In unne.
•:. Dizziness Abdominal pain
Indications
.:. Flatulence
.:. Dysmenorrhoea .:. Osteoarthritis
Drug interactions .:. Rheumat()'d I arth n'fIS .:. Fever in Children
.:. Ibuprofen may increase the blood levels of lithium, digoxin .:. ~venile ic:liopathic arthritis .:. Headache
and methotrexate .:. enorrnClgia .:. Post operative pain
•:. Ibuprofen may decrease the hypotensive effects of .:. Dental PClin
antihypertensives and diuretics
.:. Bleeding problems may occur if ibuprofen is used with other I,
Contraindicati()tl
•
••• Inflamm s
drugs that inhibit platelet aggregation such as dipyrimandole,
P . Cltory bowel disease
other NSAIDs Ii .:.
eptlc ul<::er
.:. Concomitant use with alcohol and steroids may cause .:.
Neonates
increased GI adverse effects .:. Pregnan<::y (3rd trimester)
.:. Aspirin may decrease the bioavailability of ibuprofen
.:. Antacids may decrease the absorption of ibuprofen Dose
Adult: 250-500..... 3 d'l f e d
Ch'ld g times al yater 100 •
0

Key issues to note

.:. Administration with food is recommended as this may buffer 7 d I ren ove~ 6 months: 25mg!kg in divided doses for not more than
ays except In j lJvenile arthritis.
the GI irritant effects of the drug
.:. Avoid alcohol during therapy as it may aggravate GI irritation Side effects
.:. Dehydration during therapy markedly enhances the risk of renal .:. Diarrho~~
Drowsiness
damage, therefore advise the patient to ensure adequate .:. Skin rast)
Nausea and vomiting
fluid intake to protect renal function .:. IHeamolY1::ic anaemia Thrombocytopenia
.:. Symptoms of infection may be masked by use of ibuprofen .:. ndigesti~n
Abdominal pain
MEFENAMIC ACID Drug interacti~Itl
Available preparations: Tablets 500mg •
••• Mefena~. s
- • IIC aCid reduces the hypotensive effect of
0

Capsules 250mg, 500mg

antihyp~.....
• ~enslve an d d'luretlc
0 'd rugs
Suspension I 25mg!5ml .:. M efe
na~ic acid may raise blood levels of lithium, digoxin and
Available brands: Ponstan®, Meftal®, Mefenam®, Alfoxasan®, M ethot'-~xate
.:. Bleeding......
.....ro bl ems may occur IOf melenamlC
C •
aCi°d .IS used
Combinations: Meftal forte®(mefenamic acid 500mg!paracetamol
with ott).......
d' , ""r d rugs t hat In h'b' I Iet aggregation suc h as
I It pate
450mg)
0 0

IpynmC\.l1dole and other NSAIDs

-589-
-590-

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•.1••••
 II

.:.
'__mp ••"
Concomitant use with alcohol and steroids may cause
increased GI adverse effects
--
Note: Take the drug with or shortly after food

Side effects
Key issues to note .:. Headache .:. Vertigo
.:. For acute pain therapy, mefenamic acid should not be used .:. GIT bleeding .:. Light headedness
longer than I week to avoid adverse effects of prolonged use .:. Drowsiness .:. Insomnia
.:. Warn the patient that drowsiness may occur and to avoid .:. Nausea and vomiting .:. Dizziness
hazardous activities that require alertness .:. Diarrhoea .:. Peptic ulcer
.:. Administration with food is recommended as this may decrease .:. Depression .:. Tinnitus
the GI effects of the drug .:. Blurred vision .:. Hypertension
.:. Symptoms of infection may be masked by use of mefenamic .:. Heart burn and epigastriac pain .:. Anorexia
acid .:. Confusion

INDOMETHACIN Drug interactions

Available preparation: Capsules 25mg .:. Indomethacin may increase the blood concentration of
aminoglycosides in neonates
Available brands: Indocid®, Indox® Indoren®, Kam indo®, Indos® .:. Indomethacin may increase the effect of heparin, oral anti
Pharmacokinetics coagulant and thrombolytics
Indomethacin is rapidly and completely absorbed after oral .:. Indomethacin may decrease the effect of antihypertensives and
administration; highly protein bound, metabolized in the liver and diuretics
excreted mainly in urine, with some biliary excretion. .:. Probenecid may increase indomethacin blood concentration

Indications Key issues to note

.:. Rheumatoid arthritis .:. Osteoarthritis .:. Warn the patient that drowsiness may occur and to avoid
.:. Post operative pain. .:. Ankylosing spondylitis hazard,fPus activities that require al.ertness
.:. Juvenile arthritis .:. Tendonitis .:. Administration with food is recommended as this may reduce
.:. Dysmenorrhoea .:. Acute gout the GI side effects of the drug
.:. Closure of ductus arteriosus .:. Bursitis .:. Symptoms of infection may be masked by use of indomethacin

Contraindications NAPROXEN
.:. Known hypersensitivity to Indomethacin Available preparations: Tablets 500mg
.:. Active GIT bleeding Gel 10%
.:. Active peptic ulcer
Available brands: Naprox®, Napreben®
Dose
Adult: 25 -50mg 2-4 times daily Pharmacokinetics
Children: 1-4mg / kg daily in 2- 4 divided doses Naproxen is readily absorbed from the gastrointestinal tract and protein
binding is 99%. It is metabolised in the liver by demethylation and
conjugation and excreted in urine.

-591- -592-
 PftECIS LOGY

Indications .:. Naproxen may decrease the effect of antihypertensives and

.:. Rheumatoid arthritis .:. Osteoarth ritis diuretics
.:. Ankylosing spondylits .:. Post operative pain
.:. Dysmenorrhoea .:. Headache
Key issues to note
.:. Migraine .:. Acute gout .:. Use lowest possible effective dose
.:. Juvenile arthritis .:. Bursitis .:. Relief usually begins within 2 weeks after beginning therapy
.:. Tendinitis .:. Vascular headache with naproxen
.:. Caution the patient to avoid concomitant use of non
Contraindications prescription drugs
.:. Hypersensitivity to aspirin, naproxen or other NSAIDS .:. Administration with food is recommended as this may decrease
.:. Active peptic ulcer the GI irritant effects of the drug
.:. Pregnancy
.:. Lactation PIROXICAM
Available preparations: Capsules 20mg
Dose
Injection 20mg/ml
Rheumatic disease: 2S0-S00mg twice daily in 1-2 divided doses
Juvenile arthritis: I Omg/kg daily in 2 divided doses Available brands: Piricam®, Mobidin®, Feldene®, Angomove®,
Acute gout: 7S0mg initially then 2S0mg every 8 hours until attack has
Pharmacokinetics
passed.
Piroxicam is well absorbed from the gastrointestinal tract, metabolised
Dysmenorrhoea and acute musculoskeletal disorders: SOOmg
in the liver by hydroxylation and conjugation and excreted mainly in the
stat, followed by 2S0mg every 8 hours.
urine and small amount in faeces.
Side effects
Indications
.:. Nausea .:. Constipation
.:. Dizziness .:.
.:.
Somnolence
.:. Rheumatoid arthritis .:. Acute gout
.:. Indigestion Abdominal pain
.:. ,,,.Juvenile chronic arthritis .:. Ankylosing spondylitis
.:. Heart burn .:. Headache .:. Osteoarthritis .:. Post operative pain
.:. Diarrhoea .:. Soft tissue disorders .:. Dysmenorrhoea
cii
Drug interactions Contraindications
.:. Naproxen may decrease the renal excretion of Iitihium and .:. Active peptic ulcer
methotrexate .:. Known hypersensitivity to aspirin or piroxicam
.:. Concomitant use of naproxen with anticoagualants and .:. History of recurrent ulceration
thrombolytic drugs may potentiate anticoagualant effects Dose
.:. Concomitant use with alcohol and steroids may cause Rheumatic disease: Initially 20mg daily, maintenance 20-40mg daily in
increased GI adverse effects
single or divided doses
.:. Concurrent use with other NSAIDs may produce additive
Acute Gout: 40mg initially 40mg daily in single or divided doses for
potential for ulcerogenicity and other adverse effects
4-6days
.:. Concurrent administration of naproxen and aspirin lowers
Acute musculoskeletal disorders: 40mg daily in single or divided
the plasma levels of naproxen
doses for 2 days, then 20mg daily for 7-14 days

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 ~~~~~~~-~~--~~~~~~-~~~~~~~~-~----------

, PRECISE PHARMACOLOGY PRECISE PHARMACOLOGY

Side effects
.:. Post traumatic pain .:. Dysmenorrhoea
.:. Dyspepsia .:. Constipation .:. Strains, sprains and other soft-tissue injuries
.:. Abdominal pain .:. Flatulence
.:. Skin reaction .:. Nausea Contraindications
.:. Dizziness .:. Diarrhoea .:. Known hypersensitivity to tenoxicam or other NSAIDS
.:. Malaise .:. Tinnitus .:. Active peptic ulcer
.:. Pregnancy (3 rd trimester)
Drug interactions .:. GIT bleeding
.:. Piroxicam may increase the effect of heparin, oral anti
coagulant and thrombolytics Dose
.:. Aspirin may decrease the bioavailability of piroxicam 20mg once daily for 7-14days
.:. Concomitant use with alcohol and steroids may cause
Side effects
increased GI adverse effects
.:. Piroxicam increases the risk of hyperkalemia caused by
.:. Heart burn .:. Nausea
potassium-sparing diuretics
.:. Vomiting .:. Diarrhoea
.:. Piroxicam increases the toxicity of aminoglycosides by
.:. Constipation .:. Oedema
.:. A plastic anaemia .:. Headache
•:.
reducing their clearance
Piroxicam reduces anthypertensive effect of ACE Inhibitors,
.:. Skin rashes .:. Visual disturbance

alpha blockers and angiotensin II antagonists

.:. Gastralgia .:. Jaundice
MELOXICAM
Key issues to note
Available preparations: Tablets 7.Smg, ISmg
.:. Administration with food is recommended as this may
decrease the GI irritant effects of the drug Available brands: M-cam®, Mobic®, Mel-OD®, Melonax®,
.:. Avoid alcohol Melox®
.:. Avoid exposure to sunlight to minimise photosensitivity .... Pharmacokinetics
.:. Piroxicam should be given with caution in patients with Meloxicam is well absorbed when given orally and 99% is bound to
hypertension plasma proteins. It is extensively metabolised mainly by oxidation and
TENOXICAM excreted in urine and faeces.
Available preparations: Capsules 20mg Indications
.:. Rheumatoid arthritis
Available preparations: Soral®
.:. Acute exacerbations of osteoarthritis
Pharmacokinetics .:. Juvenile rheumatoid arthritis
Tenoxicam is well absorbed after oral administration but presence of .:. Ankylosing spondylitis
food in the GIT delays its absorption. It is completely metabolised to
Contraindications
inactive metabolites which are excreted mainly in the urine.
.:. Active peptic ulcers .:. Known hypersensitivity
Indications .:. Bleeding disorders .:. Pregnancy
.:. Osteoarthritis .:. Rheumatoid arthritis .:. Severe heart failure
.:. Acute gout .:. Post-operative pain .:. Severe hepatic and renal impairment

-595- -596-

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Key issues to note .:. Peripheral oedema .:. Dizziness

.:. Acedofenac should be given with caution in patients with .:. Insomnia .:. Skin rash
broncho-asthma
.:. Administration with food is recommended as this may reduce Drug interactions
GI irritation. .:. Celecoxib reduces anthypertensive effect of ACE Inhibitors,
.:. Avoid alcohol during therapy with aceclofenac diuretics and angiotensin II antagonists
.:. Celecoxib may increase the effect of heparin, oral anti
CELECOXIB coagulant and thrombolytics
Available preparations: Capsules IOOmg, 200mg Key issues to note
Available brands: Zycel® .:. Celecoxib may mask fever and other signs of inflammation
.:. Celecoxib should be given with caution in patients with
Pharmacokinetics hypertension and oedema
Celecoxib is well absorbed from the gastrointestinal tract, but food
delays its absorption and about 97% is bound to plasma proteins. It
""I
is metabolised in the liver and excreted mainly as metabolites in the
faeces and urine.
Indications
.:. Osteoarthritis .:. Rheumatoid arthritis
.:. Acute pain .:. Dysmenorrhoea

Contraindications
.:. Severe hepatic impairment .:. Severe heart failure
.:. Inflammatory bowel disease .:. Pregnancy and lactation
.:. Active peptic ulcer
.:. History of hypersensitivity to sulfonamides

Dose
Osteoarthritis: 200mg daily in 1-2 divided doses, increased if necessary
to max. 200mg twice daily
Rheumatoid arthritis: IOOmg twice daily, increased if necessary to
200mg twice daily
Elderly: 200mg daily in 2 divided doses, max. 200mg twice daily
Children: Not recommended
Pain and Dysmenorrhoea: Initially 400mg followed by 200mg on the
first day, then 200mg twice daily.
Side effects
.:. Abdominal pain .:. Diarrhoea
.:. Dyspepsia .:. Nausea

-599- -600-

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Vinca alkaloids Vincristine

Vinblastine
CHAPTER TWENTY Platinum analogs Cisplatin
DRUGS USED IN THE TREATMENT OF CANCE,R ~.
Hormonal agents Tamoxifen
Oestrogen
Cancer is a disease characterized by a shift in the control mechanism
Others Hydroxyurea
that governs cell survival, proliferation and differentiation. Uncontrolled
Procarbazine
multiplication of cells leads to the formation of tumours that may be
benign or malignant. Benign tumours do not spread to other tissues BLEOMYCIN
while malignant tumours spread. Available preparations: Powder for Injection 15units/vial

Types of cancer Available brands: Blenoxane®

.:. Carcinoma, affects the skin and cells in the tissue lining internal Pharmacokinetics
~organs
1M administration results in lower serum levels than those occurring
.:. ':Sarcoma, affects muscles, bones and fibrous tissues after equivalent IV doses. It distributes widely into total body water,
.:. ~;" Leukaemia, affects white blood cells mainly in the skin, lungs, kidneys, peritoneum and lymphatic tissue. It
.:. Lymphoma, affects the lymph glands undergoes extensive tissue inactivation in the liver and kidney, bleomycin
Drugs used in the treatment of cancer either kill cancer cells or modify and its metabolites are excreted primarily in urine.
their growth. Indications
Classification of Anticancer drugs .:. Squamous cell carcinoma (head, neck, penis, cervix)
.:. Testicular carcinoma
Class Examples
.:. Non-Hodgkin's lymphoma
Antimetabolites Methotrexate
.:. Lymphosarcoma
5-f1uorouracil
Cytarabine Contraindications
6-mercaptopurine .:. Pregnancy
Antitumor antibiotics Bleomycin .:. Breast feeding
Dactinomycin .:. Previous allergic reaction
All<yalating agents Cyclophosphamide
Dose
Busulfan
Chlorambucil A test dose of 1-2units given 2-4hours prior to therapy is
Carmustine recommended
Dacarbazine 0.25 - 0.5unit/kg body weight or I 0-20unit/ M 2 body surface area given
Melphalan IV, 1M, or SC once or twice weekly.
Anthracyclines Daunorubicin Side effects
Doxorubicin
.:. Skin rash Redness of the skin
Idarubicin
........ .:. Striae Fever

-601- -602-

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II I j ~

.:. Acute anaphylactoid reaction .:. Anorexia .:. Pregnancy and lactation
.:. Urticaria .:. Pruritus .:. Persistent myelosuppression
.:. Hyperpigmentation .:. Stomatitis .:. Severe cardiac failure
.:. Hyperkeratosis .:. Weight loss .:. Recent mocardial infarction
.:. Progressive pulmonary fibrosis .:. Mucositis
~,

Dose
.:. Pneumonitis .:. Phlebitis
60-74mglM2 or I .2 -2.4mglkg once every 3 weeks as a single intravenous
.:. Vomiting
injection of a solution in sodium chloride 0.9% or glucose 5% over 3
Drug indications minutes or more.
.:. Cisplatin may decrease bleomycin clearance and increase the Children: 35-75mgl M2 as a single intravenous injection, once every 3
risk of bleomycin toxicity weeks
.:. Concomitant use may decrease serum levels of phenytoin and
Side effects
digoxin .:. .:.
Bone marrow depression Anorexia
Key issues to note .:. Hyperpigmentation of nail beds .:. Diarrhoea
.:. Increased pigmentation particularly affecting the flexures and .:. Irreversible CHF .:. Reversible alopecia
Ill)
tin' subcutaneous sclerotic plaques may occur .:. Nausea and vomiting .:. Stomatitis
.:. Fever and chills .:. Urticaria
DOXORUBICIN .:. Conjuctivitis .:. Lacrimation
Available preparations: Powder for Injection I Omg /vial, 50mg/vial
Drug interactions
Available brands: Doxorubin® .:. Cholestasis induced by mercaptopurine may be potentiated by
the concurrent administration of doxorubicin
Pharmacokinetics
.:. Concomitant use of daunoribicin or cyclophosphamide may
It distributes widely into body tissues, with the highest concentrations
potentiate the cardiotoxicity of doxorubicin through additive
found in the liver, heart, kidneys, skin andl>muscles; it does not cross
effects on the heart
the blood brain barrier. It is metabolized both in the liver and plasma;
.:. Serum digoxin, carbamazepine and phenytoin levels may be
excreted largely in faeces, with small amounts in urine.
decreased if used concomitantly with doxorubicin
Indications .:. Phenobarbitone increases elimination of doxorubicin
.:. Acute leukaemia .:. Lymphomas
.:. Breast carcinoma .:. Thyroid carcinoma Key issues to note
.:. Non hodgkin's lymphoma .:. Ovarian carcinoma .:., Notify the patient that the urine may turn red for the first 1-2
.:. Bone and soft tissue sarcomas .:. Hodgkin's disease days
.:. Kaposi's sarcoma in patients with AIDS .:. Doxorubicin may induce hyperuricaemia, therefore monitor
.:. Transitional cell bladder carcinoma patient's blood uric acid levels
.:. Encourage the patient to take adequate fluid intake to increase
Contraindications
.:. Hepatic dysfunction urine output and facilitate excretion of uric acid
.:. Cardiomyopathy .:. Advise the patient to call if fever, bleeding and sorethroat
occur

-603- -604-

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Avoid exposure to sunlight to prevent sun burns

·I' I
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I
Drug interactions
.:. Warn the patient that alopecia will occur. Expain that hair !llI!' .:. Cyclophosphamide used concurrently with daunorubicin may
growth should resume 2-5 months after drug is stopped result in increased cardiotoxicity
.:. Tell the patient not to receive any immunization during therapy .:. Antigout drugs may decrease the effects of daunorubicin
and for several weeks after .:. Concomitant use with other hepatotoxic drugs may potentiate
.:. Advise the patient to avoid exposure to people with infections the hepatotoxicity of daunorubicin
DAUNORUBICIN Key issues to note
Available preparations: Injection 20mg/vial .:. Notify the patient that the urine may turn red for the first 1-2
Available brands: Daunotec ® days
.:. Warn the patient that alopecia may occur, but it is usually
Pharmacokinetics
reversible
Daunorubicin distributes widely into body tissues, with the highest
.:. Encourage the patient to take adequate fluid intake to increase
concentrations found in the liver, heart, kidneys, spleen and lungs. It
urine output and facilitate excretion of uric acid
does not cross the blood brain barrier and is extensively metabolized in
.:. Advise the patient to call if fever, bleeding and sorethroat
the liver; excreted largely in faeces, with small amounts in urine.
occur
Indications .:. Warn the patient that nausea and vomiting may be severe and
.:. Acute leukaemia may last for 24-48 hours
.:. AIDS related kaposi's sarcoma .:. Advise the patient to avoid exposure to people with infections

Contraindications METHOTREXATE
.:. Pregnancy Available preparations: Tablets 2.5mg
.:. Breast feeding mothers Injection 25mg/ml
.:. Hypersensitivity to daunorubicin Available brand: Texol®
.:. Life threatening myelosuppression
.:. Pre-existing cardiac disease Indications
.:. Severe infections .:. Treatment and palliaton of solid tumours
.:. Hepatic or renal dysfunction .:. Burkitt's lymphoma
.:. Leukaemia
Dose: 30-60mg/M 2 IV daily on days I, 2, and 3 repeated every 3 - 4
.:. Psoriasis
weeks.
Contraindications
Side effects
.:. Known hypersensitivity to methotrexate
.:. Alopecia .:. Fever
.:. Pregnancy and lactation
.:. Nausea and vomiting .:. Chest pain
.:. Diarrhoea .:. Fatigue .:. Severe hepatic and renal impairment
.:. Stomatitis .:. Headache .:. Bone marrow suppresssion
.:. Abdominal pain .:. Constipation .:. Anaemia
.:. Insomnia .:. Neuropathies .:. Immunodeficiency syndromes
.:. Traverse pigmentation of finger nails .:. Active infection

-605- -606-

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Dose .:. Current radiotherapy to the liver

Leukaemia: IS-30mg/M2 orally, intramuscularly or intravenously; once .:. Known hypersensitivity to vincristine
a week.
Dose
Side effects . Adult: IV l.4mg/m 2 up to a max weekly dose of 2mg/m 2
.:.
Nausea and vomiting .:. Stomatitis Children: IV, 2mg/m 2 once a week
.:.
Diarrhoea .:. Anorexia Children < IOI<g: O.OSmg/kg once a week
.:.
Malaise .:. Headache
.:. .:. Side effects
Skin rash
.:. .:.
Dermatitis .:.
Hair loss .:. Stomatitis
Pruritus
.:.
Blurred vision
Dizziness .:.
Constipation .:. Abdominal cramps
.:.
Diarrhoea .:. Skin rash
Drug interactions .:.
Headache .:. Jaw pain
•:. Concomitant use with probenecid and salicylates increase the .:.
Hoarseness .:. Diplopia
therapeutic and toxic effects of methotrexate by inhibiting its .:.
Nausea and vomiting .:. Abdominal distention
renal clearance .:.
Urinary tract disturbance .:. Peripheral neuropathy
.:. Alcohol enhances the hepatotoxicity caused by methotrexate
Drug interactions
.:. Phenytoin, co-trimoxazole may give additive antifolate activity
.:. Vincristine may decrease digoxin plasma levels and renal
and increase the risk of methotrexate toxicity
excretion
Key issues to note .:. Vincristine may reduce phenytoin plasma levels
.:. Full blood count, urea and liver function tests should be
Key issues to note
carried out prior to and during treatment
.:. Allopurinol may be given to prevent uric acid nephropathy
.:. Folinic acid is required for rescue procedures
.:. Stool softeners should be used for constipation prophylaxis
.:. Patients with hyperuricaemia should maintain adequate fluid
.:. Vincristine is a tissue irritant, care should be taken to avoid
intake and alkalinization of urine
extravasation
VINCRISTINE
CYCLOPHOSPHAMIDE
Available preparations: Solution for injection I mg/ml, 0.1 mg/ml
Available preparations: Tablets SOmg
Available brands: Cristol® Injection SOOmg, 1000mg
Indications Available brands: Endoxana® .
.:. Leukaemias Pharmacokinetics
.:. Lymphomas It is almost completely from the GIT, distributed throughout the body,
.:. Some solid tumours metabolized to its active form in the liver and excreted primarily in
Contraindications urine.
.:. Demyelination form of Charcot -Marie -tooth syndrome Indications
.:. Pregnancy .:. Pulmonary carcinoma
.:. Breast feed ing mothers .:. Ovarian carcinoma

-607- -608-

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.:.
.:.
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Breast carcinoma
Leukemia's
Burkitt's lymphomas
,, ,

.:.
.:.
.:.
PRECISE I'HARMAC[l

Mammary carcinoma
Neuroblastoma
Rheumatoid arthritis
I '

- .:.

.:.
WCISE PHAR MIQI!'oWI

Take tablets peferably on an empty stomach but if GIT upset

is severe, take with food
Contraceptive measures are recommended during therapy
.:. Malignant lymphogranulomatosis for both men and women
.:. Advise the patient to call if fever, bleeding, shortness of
Contraindications
breath, lack of menstrual flow and sorethroat occur
.:. Pregnancy and lactation ;;1'

.:. Haemorrhagic cystitis

TAMOXIFEN
.:. Hypersensitivity to Cyclophosphamide
Available preparations: Tablets IOmg, 20mg
.:. Severe bone marrow suppression

Dose Available brands: Nolvadex®

Adults
Pharmacokinetics
oral: 1-5mg/kg/day
Tamoxifen is well absorbed after oral administration, distributed widely
IV: I O~ 15 mg/kg every 7-10 das or 3-5 mg/kg twice weekly
into total body water, metabolized extensively in the liver and excreted
Children
primarily in faeces
induction; oral/IV; 2-8mg/kg or 6-200mg/ M 2 /day
maintenance; 2-5mg/kg or SO-150mg/ M 2 twice weekly Indications
.:. Breast cancer
Side effects .:. Female infertility (induction of ovulation)
.:. Nausea and vomiting .:. Alopecia
.:. Anorexia .:. Stomatitis Contraindications
.:. Diarrhoea .:. Metallic taste .:. Known hypersensitivity to tamoxifen
.:. Headache .:. History of deep vein thrombosis or pulmonary embolism in
.:. Darkening of skin and finger nails high risk women
.:. Pregnancy
Drug interactions
.:. Allopurinol may increase myelo suppression Dose
.:. Concomitant use with barbiturates and phenytoin increases the Breast cancer: 20mg daily
rate of metabolism of cyclophosphamide to toxic metabolites Induction of ovulation (infertility): 20mg daily on days 2, 3, 4 and
.:. Digoxin serum levels may be reduced by cyclophosphamide 5 of cycle, if necessary the daily dose may be increased to 40mg then
.:. Antimicrobial effect of quinolones may be decreased by 80mg for subsequent courses
cyclophosphamide Side effects
.:. Anticoagulant effect of oral anticoagulants may be increased by .:. Hot flushes .:. Nausea
cyclophosphamide .:. Vomiting .:. Light headedness
Key issues to note .:. Bone pain .:. Confusion
.:. Warn the patient that alopecia may occur, but it is usually .:. Vaginal bleeding .:. Vaginal discharge
reversible .:. Headache .:. Decreased libido
.:. Weakness

-609- -610-
Drug interactions
.:. Estrogen may decrease the effect of tamoxifen
.:. Anticoagulant effect of oral anticoagulants may be increased CHAPTER TWENTY ONE
by tamoxifen 21.1.1 DRUGS USED IN ANAESTHESIA
.:. Bromocriptine may elevate serum levels of tamoxifen Anaesthesia is defined as the absence of feelings, sensation or pain.

Key issues to note Anaesthetics

.:. Adverse effects may be controlled by dosage reduction These are drugs that reduce or abolish sensation, affecting either the
.:. Use cautiously in pre-existing leucopenia and whole body (general anaesthetics) or a particular area or region (local
thrombocytopenia anaesthetics)
.:. Advise women not to become pregnant during therapy with
Local anaesthetics
tamoxifen
Local anaesthetics provide brief periods of anaesthesia in a small localized
area of the skin and adjacent tissues. They may be administered in two
ways; topically for surface aneasthesia and by injection for infiltration
anaesthesia.
Topical anaesthetics are usually applied to the skin or the mucous
membrane to relieve itching, insect bites, haemorrhoids, pruritus and
minor surgical procedures.
Infiltration anaesthesia may be achieved by injecting a local aneasthetic
into the immediate area of surgery. It is commonly used during dental
extraction and biopsies.
Examples
.:. Lidocaine (lignocaine)
.:. Bupivacaine
.:. Mepivacaine
Note
Lignocaine is sometimes combined with epinephrine (adrenaline),
a powerful vasoconstrictor, that decreases blood flow to the tissue
where it is injected. Adrenaline controls bleeding and also prolongs the
anaesthetic action of Lignocaine.

General Anaesthetics
General anaesthetic drugs are normally given IV or by inhalation to
produce rapid, reversible loss of consciousness and insensibility to
surgical stimuli.

-611- -612-

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Examples .:. Stroke
Inhaled anaesthetics .:. Known hypersensitivity to ketamine
.:. Halothane .:. Cerebral trauma
.:. Nitrous oxide .:. Eye injury
.:. Ether
Dose
Intravenous anaesthetics
.:. Ketamine Induction
.:. Midazolam Intravenous Injection: 1-4.5mg/kg (2mg/kg usually produce anaesthesia
.:. Propofol lasting 5 -10 minutes)
Intramuscular Injection: 6.5-13mg/kg, (duration of anaesthesia upto 25
KETAMINE minutes).
Ketamine is rapidly acting general anaesthetic that selectively blocks IN infusion: 0.5-2mg/kg initially then infuse at 10-45 mcg/kg Iminute
afferent impulses and interacts with CNS transmitters systems. adjust according to response.
This results into anaesthetic state characterized by profound analgesia
Maintenance
and normal pharyngeal- laryngeal reflexes.
Intravenously: Increments of half of full dose repeated as required.
Analgesic for painful procedures: IN 1-1.5mg/kg slowly over 2-5
Available preparations: Injection 50mg/ml
minutes. Give half dose every 10 minutes if required for prolonged
procedures.
Available brands: Ketajex®, Ketalar®
Administration instructions: Dilute dose with an equal volume of
water for injection, sodium chloride 0.9% or glucose 5% before I.V
Pharmacokinetics
injection.
Ketamine is rapidly and well absorbed after 1M injection, rapidly enters
Give I.V slowly, rapid administration may result in respiratory depression
the CNS, metabolized by the liver and excreted in urine.
and enhanced hypertensive response.
Indications Side effects
.:. Induction and maintenance of anaesthesia .:. Raised blood pressure and pulse rate
.:. Pain relief .:. Increased muscle tone
.:. Diagnostic manoeuvres and procedures not involving intense .:. Lacrimation
pain .:. Hypersalivation
.:. Raised intracranial pressure
Contraindications .:. Redness of the skin
.:. Thyrotoxicosis .:. Post operative nausea and vomiting
.:. Hypertension (including pre-eclampsia) .:. Pain on injection
.:. History of cerebrovascular accident .:. Irrational behavior during recovery
.:. Raised intracranial pressure Drug interactions
.:. Psychiatric disorders particularly hallucination .:. Inhalation anaesthetics such as other and halothane may
.:. Severe cardiac disease prolong the effeCt of ketamine and delay recovery
.:. Recent myocardial infarction

-613- -614-

·111111111111111111111111111,11111111111111111111111 _ _ _ _ _1111111111111111111111111111111111111 _
I " ' ','. "" I, :I ' 'IIIPRECISE PHARMACOLOGY

.:. Prolonged recovery occurs when barbiturates or opioids are Children over I month: Administer slowly 2.5mg/ kg up to 4mg/kg
given concurrently with ketamine Maintenance of anaesthesia
.:. Ketamine should not be used with ergometrine By IV infusion: 4-12mg/kg / hour
.:. Concomitant use with thyroid hormones may cause By IV injection: 25-50mg repeated according to response
hypertension and tachycardia Children over 3years: by IV infusion: 9-15mg/kg/hour
Sedation in intensive care
Key issues to note By IV infusion:
.:. Warn the patient t avoid tasks requiring motor coordination
Adult and Children over 17years: 0.3-4mg kg /hr
and/or mental alertness for 24 hours after anaesthesia Children below 17years: Not recommended
.:. Keep verbal, tactile and visual stimulation to a minimum during
Sedation for surgical and diagnostic procedures: By IV injection
induction and recovery over 1-5minutes 0.5-1 mg/kg
PROPOFOL Maintenance by IV infusion 1.5-4.5mg/kg/hour
Propofol is a short acting anaesthetic given intravenously for induction Administr~tion instructions: Inject bolus dose over 30-60 seconds
and maintenance of general anaesthesia or more slowly if patient is elderly or debilitated
Adhere strictly to aseptic technique (formulation is a good medium for
Available preparations: I % injection I Omg /ml
bacterial growth)
Propofol is physically incompatible with atracurium.
Available brands: Provive®
Flush I.V cannula with sodium chloride 0.9% after injecting each drug
Pharmacokinetics or use separate I.V access sites.
The drug is highly lipophilic and induces anaesthesia in about 30 minutes.
Side effects
it has a biphasic distribution phase; the rapid and the slower phase. It .:. .:.
Pulmonary oedema Pain on injection
is metabolized within the liver and tissues; and excreted through the .:. .:.
Apnoea Post operative fever
kidneys. .:. Hypotension .:. Bradycardia
Indications .:. Cough .:. Hiccup
.:. Induction of anaesthesia .:. Involuntary movements .:. Convulsions
•:. Maintenance of anaesthesia .:. Headache .:. Nausea
.:. Sedation in intensive care .:. Vomiting
.:. Sedation for surgical and diagnostic procedures
Drug interactions
Contra indications .:. Use of propofol with other CNS depressants may increase
.:. Known hypersensitivity to propofol the sedative effect
.:. Use for intensive care sedation in children less than 17 years .:. The dosage of propofol should be reduced if used with
Dose nitrous oxide or halogenated anaesthetics
Induction of anaesthesia: by IV injection or infusion .:. Theophylline may antagonize the CNS effects of propofol
9-55years: 1.5 -2.5mg/kg (less in patients over 50years) at a rate of 20- .:. Increased toxicity may occur with acetazolamide
40mg every 10 seconds until response .:. Propofol should not be mixed with other drugs or blood
products

-615- -616-
(

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Key issues to note 6months -5years: 50-1 OOmcg Ikg max is 6mg daily
.:. Occasionally, after short procedures resedation occurs; 6-12 years; 25-50 mcg/ kg max is I Omg daily
adequate recovery time before discharge in day-case surgery By intramuscular injections (I M):
is mandatory .. I to 15 years: 50-150 mcg Ikg max I Omg daily
.:. Local pain during IV injection may be minimised by usingthe Induction of anaesthesia: By slow IV injection 150-200 mcg/kg in
larger veins in the forearm and antecubital fossa premedicated patients 300-35mcg Ikg in those who have not received
premedication. Additional doses may be needed to complete induction
MIDAZOLAM up to 600 mcg/kg in resistant cases
It is a short acting benzodiazepine with general properties similar to Sedation in intensive care: By slow intravenous injection, initially 30-
diazepam except that it has a more potent amnestic action 300mcg/kg given in steps of I -2.5 mg every 2 minutes
Available preparations: Injection 5mg/5ml, 15mg/ 3ml By slow intravenous injection I intravenous infusion: 30-200mcg Ikg I
Tablets 7.5mg hour
Premedication
Available brands: Dormicum® By deep J M injection: 70-1 OOmcg/kg
,'"
Pharmacokinetics Elderly: 25-50mcg/kg 20 -60minutes before induction. Usual dose is
ij"
Midazolam is well absorbed after 1M administration, widely distributed 2- 3mg
into body tissues, crosses the plancenta and enters fetal circulation. It is Children 1-15 years: 80-200mcg/kg
metabolized in the liver and excreted in urine. Side effects
Indications .:. Hypotension .:. Tachycardia
.:. Sedation with amnesia Sedation in intensive care .:. Hiccup .:. Cough
Premedication .:. Pain at injection site .:. Thrombophlebitis
.:. Induction of anaesthesia
.:. Nausea and vomiting .:. Increased appetite
.:. Status epilepticus .:. Jaundice .:. Cardiac arrest
.:. Sedation in minor surgical or investigative procedures .:. Headache .:. Confusion
.:. Drowsiness .:. Ataxia
Contraindications .:. Retrograde amnesia .:. Pruritus
.:. Allergy to benzodiazepine
.:. Marked neuromuscular respiratory weakness Drug interactions
.:. Alcohol intoxication .:. Enhanced sedation or respiratory depression may occur when
.:. Severe hypotension or shock midazolam is given concurrently with alcohol, antipsychotic
.:. Existing CNS depression and antidepressants
.:. Narrow angle glaucoma .:. Midazolam may decrease the needed dose of inhaled
Dose anaesthetics by depressing respiratory drive
Sedation: By slow intravenous injection (2mgl minutes) initially 2-2.5mg .:. Isoniazid may decrease the metabolism of midazolam
increased if necessary in steps of I mg, usual range 3.5-7.5mg .:. Theophylline may antagonize the sedative effects of
Elderly: 0.5-1 mg increased if necessary in steps of 0.5-1 mg max midazolam
3.5mg .:. Carbamazepine and phenytoin may increase the hepatic
Children: by intravenous injection over 2-3 minutes metabolism of midazolam

-617- -618-

.. .m~mllllllllli
Key issues to note Note: It takes up to 5 minutes to attain surgical aneasthesia and
.:. Avoid alcohol and grapefruit juice while taking this drug halothane produces little or no excitement in the induction period .
•:. Individualize dosage; use smallest effective dose possible
Side effects
.:. Use with extreme caution and reduced dosage in elderly and
.:. Hypotension Cardiac arrhythmias
debilitated patients ..
.:. Nausea Vomiting
.:. Administer 1M dose deep into a large muscle mass to prevent
.:. Shivering Respiratory depression
tissue injury
.:. Malignant hyperthermia Liver necrosis
.:. Hypotension occurs most frequently in patients pre-medicated
.:. Hepatitis Bradycardia
with narcotics
.:. Do not use any solution that is discolored or contains a Drug interactions
precipitate .:. Increased risk of arrhythmias and hypotension occurs when
halothane is given concurrently with amitriptyline
HALOTHANE
.:. Enhanced hypotensive effects occurs when atenolol, captopril,
Halothane is a volatile, halogenated, liquid anaesthetic administered by
inhalation. Its widely used because its potent, non irritant and does not isorsobide dinitrate, nifedipine, propranolol, methyldopa,
hydralazine is given concurrently with halothane
induce cough.
.:. Enhanced sedative effect when c1onazepine, diazepam, chloral
Available preparations: volatile liquid hydrate is given together with halothane
Pharmacokinetics .:. Theophylline may potentiate the arrhytmic effect of halothane
Halothane produces smooth induction and a rapid onset of anaesthesia. .:. Longterm barbiturate or phenytoin treatment prior to
A small percentage is metabolized in the liver and remainder of the anaesthesia may increase the risk of halothane
drug is excreted unchanged in urine. hepatotoxicity

Indications LIDOCAINE
.:. Induction and maintenance of general aneasthesia Available preparations: Solution 1%, 2%
Topical gel 2-4%
Contraindications
.:. Pregnancy Combinations: Xylocaine® (Lidocaine + epinephrine)
Note
.:. Known hypersensitivity to halothane
.:. Porphyria Epinephrine is often added to delay absorption and thus reduce
.:. Family history of malignant hyperthermia anaesthetic systemic toxicity and keep it in contact with nerve fibres
Dose prolonging the duration of action.
Pharmacokinetics
Anaesthesia may be induced with 2-4 % v/v of halothane in oxygen or
mixture of nitrous oxide and oxygen It, is. effectively absorbed from the mucous membranes, widely
Induction may also be started at a concentration of 0.5% v/v and dlstnbuted through out the body, metabolized in the liver and excreted
in urine.
increased gradually to the required level.
Children: 1.5 -2 % is used Indications
Maintenance 0.5-2% .:. Infiltration anaesthesia
.:. Surface anaesthesia of mucous membrane

-619- -620-

. . . ._110011I11I111 _
 ~~ ~~~~~~~~~~~~~~~~~~~~~.~ .., _-_._-----

.:. Dental anaesthesia Key issues to note

.:. Ventricular arrhythmias .:. Doses should be reduced in acute and chronic hepatic
.:. Relief of pain in haemorrhoids diseases
Contraindications .:. If solutions discolor or precipitate they should be discarded
.:. Adjacent skin infection .:. Hypersensitivity
.:. Heart block .:. Hypovolaemia 21.1.2 DEPOLARIZING NEUROMUSCULAR BLOCKING
DRUGS
.:. Severe anaemia .:. Myasthenia gravis
.:. Spinal anaesthesia in dehydrated patients
Drugs in this class include:
Dose .:. Suxamethonium
Dental anaesthesia: using 2% solution with epinephrine .:. Atracurium
Adult: 20-1 OOmg (1-5ml) .:. Pancuronium
Local infiltration and peripheral nerve block: using I % solution
SUXAMETHONIUM
with the epinephrine
Available preparations: Injection 500mg, 50mg/ml
Adult: Up-to 400mg (up-to 40ml)
Note Pharmacokinetics
Use lower doses for elderly, epileptics or acutely ill patients. Suxamethonium is rapidly absorbed folloWing administration, rapidly
Do not use solution containing preservatives for spinal, epidural, hydrolysed in the plasma and tissues by pseudocholinesterase and
intravenous regional anaesthesia. excreted in urine.

Side effects Indications

.:. Dizziness .:. Light headedness .:. Skeletal muscle relaxation in anaesthesia including
.:. Tremors .:. Numbness endotracheal intubation, endoscopy and electroconvulsive
.:. Restlessness .:. Convulsions therapy
.:. Unconsciousness .:. Headache
.:. Blurred vision .:. Hypotension
Contraindications
.:. Myasthenia gravis
.:. Cardiac arrest .:. Backache
.:. Ocular surgery
Severe burns
.:. Sense of heat .:. Hypersensitivity reaction
.:. Hyperkalaemia
Liver disease
.:. Urinary retention
.:. Known hypersensitivity to suxamethonium
Drug interactions .:. Personal or family history of malignant hyperthermia
.:. Anti convulsants may increase cardiac depressant effect of
lidocaine Dose
.:. Cimetidine and beta blockers may increase plasma Intramuscular injection
concentration of lidocaine leading to increased risk of toxicity Children: 4mg/kg up to max. of 150 mg
.:. Use of opiod analgesics peri-operatively may have additive Infant: 4 -5 mg /kg
respiratory and cardiac depressant effects Intravenous injection
Adult and Children: initially I mg/kg; maintenance, usually 0.5- I mg/kg at

-621- -622-

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i 5-10 minute intervals

Infant: 2mg/kg
Dose
Surgery or intubations
I
I Intravenous infusion Adult and Children over I month: IV initially 300-600mcg/kg
!
Adult and Children: 2-5mg/kg of solution containing 1-2 mg Iml maintenance
III
IOO-200mcg/kg as required or by intravenous infusion: 5-1 Omcg/kg I
.~ Side effects
minute
.:. Postoperative muscle pain Excessive salivation
.:. Bradycardia Prolonged apnoea
Intensive care
.:. Increased intraocular pressure Hypotension Adult and Children or I month: IV injection. Initially 300-600mcg Ikg
.:. Arrhythmias Hyperkalaemia Intravenous infusion: 4.5-29.5mcg Ikg per minute. Usual dose 11-
.:. Intracranial Flushing 13mcg/kg/minute
.:. Skin rash Bronchospasm
.:. Transient rise in intragastric pressure .:. Urticaria Side effects
.:. Hypertension .:. Tachycardia
Drug interactions .:. .:.
Bronchospasm Skin rash
.:. ,lFIConcomitant use with aminoglycosides (gentamycin,
amikacin), oral contraceptive, lithium, quinine, may enhance or
.:. Flushing .:. Pruritus
prolong neuromuscular blocking effect of suxamethonium
.:. Urticaria .:. Respiratory depression
.:. Concomitant use with cardiac glycosides produces possible
cardiac arrhythmias Drug interactions
.:. Propofol competes for hydrolysis by pseudocholinesterase .:. Effects of atracurium may be enhanced by concomitant
and will prolong the action of suxamethonium use with c1indamycin, gentamycin, frusemide, lithium, quinine
and potassium depleting drugs
ATRACURIUM .:. Concomitant use of opioid analgesics and Atracurium may
Available preparations: Injection 2mg/ml
cause additive respiratory depression
Available brands: Nmbex® Key issues to note
Pharmacol<inetics .:. If bradycardia occurs during atracurium administration, treat
Atracurium is rapidly absorbed following IV administration, distributed by administration of IV atropine
into the extracellular space, rapidly metabolized by Hoffman elimination .:. Peripheral nerve stimulator may be used to detect residual
and excreted in urine and faeces. paralysis during recovery and to avoid atracurium
overdose
Indications
.:. Muscles relaxation in anaesthesia PANCURONIUM
.:. Muscle relaxation in intensive care Available preparations: Injection 4mg/2ml

Contraindications Pharmacol<inetics
.:. Known hypersensitivity to atracurium Pancuronium is rapidly absorbed following IV administration, small
.:. Myasthenia gravis amounts metabolized in the liver and mainly excreted unchanged in
.:. Severe electrolyte disturbance urine; with some biliary excretion .
•:. Asthma

-623- -624-

1111111111111111111111 "0111' _
r Indications
£ gr ill[ n PRECISE PHARMACOLOGY I

.:. Muscle relaxation in general (anaesthesia)

.:. Endotracheal intubations CHAPTER TWENTY TWO
.:. Muscle relaxation during intensive care VACCINES AND IMMUNOGLOBULINS

Contraindications
Vaccines are special preparations of antigenic materials that can be
.:. Known hypersensitivity to pancuronium
used to stimulate the development of antibodies and thus confer active
.:. Conditions in which tachycardia would be undesirable
immunity against a specific disease or a number of diseases.
•:. Concurrent use of depolarizing neuromuscular blockers e.g.
Vaccines may be single component or mixed combined vaccines.
suxamethonium
Dose Types of vaccines
Intubations by IV injection .:. Live attenuated vaccines
Adult: initially 50-1 OOmcg Ikg then I 0-20mcg Ikg as required .:. Killed or inactivated vaccines
Children: initially 60-1 OOmcg Ikg then I0-20mcg Ikg .:. Toxoid vaccines
Neonate: initially 30-40mcg Ikg then 10-20mcg/kg
Live attenuated: These vaccines contain live microbes that have
Intensive care IV: 60mcg/kg every 60-90 minutes
been weakened (attenuated). Live attenuated vaccines usually confer
Side effects immunity with a single dose which is of long duration. They may be
.:. Hypertension Tachycardia dangerous in recipients who are immunocompromised because these
.:. Excessive salivation Bronchospasm patients are unable to mount an effective immune response.
.:. Sweating Increased pulse rate Examples;
.:. Arrhythmias .:. Mumps vaccines Rubella vaccines
.:. Local skin reaction at the site of injection .:. Measles vaccines Chicken pox vaccines
.:. BCG vaccines
Drug interactions
.:. Concomitant use of pancuronium with aminoglycosides, Killed or inactivated vaccines
c1indamycin, quinine, frusemide and lithium may potentiate the This type of vaccines contain whole inactivated microbes. e.g. polio
effect of pancuronium vaccines. Inactivated vaccines may require a series of injections in order
.:. Concomitant use with opioid analgesics may increase to produce an adequate body response and in most cases booster doses
respiratory depression are required .
•:. Concurrent use with cardiac glycosides may increase the
Toxoids
incidence of arrhythmias
Toxoid vaccines use bacterial toxins that have been rendered harmless
Key issues to note Administration of the toxoid causes the recipient's immune system to
.:. Dosage should be reduced when ether or other inhalation manufacture antitoxins directed angaint the bacterial toxins.
anaesthetics that enhance neuromuscular blockade are Examples
used .:. Tetanus toxoid

-625- -626-
 [CISE PHARMACIIl!r1D
IMMUNITY Drug interactions
Immunity is the body's ability to resist infections afforded by the .:. Concomitant administration with immunosuppressant drugs
presence of circulating antibodies and white blood cells.
Key issues to note
Types of immunity .:. Live polio vaccine loses potency once the container has been
.:. Active immunity opened, therefore discard any unused preparation
.:. Passive immunity .:. Breastfeeding does not interfere with immunization even
though polio antibodies may be excreted in breast milk
Active immunity
.:. If the vaccine is vomited repeat the dose immediately
Active immunity is induced by the administration of microorganisms
.:. A child who has previously had polio should never the less be
or their products which act as antigens to induce the body to produce
immunized to offer complete protection
antibodies.
Passive immunity MEASLES VACCINE
Passive immunity is obtained by injecting preparations made from the Available preparations: Injection powder for solution (live
plasma of immune individuals with adequate levels of antibodies to the attenuated measles virus)
disease for which protection is sought. Treatment should be given
Available brands: Sii® measles vaccine live
as soon as possible after exposure for effective results. This type of
immunity lasts for only a few weeks. Indications
.:. Active immunization against measles
POLIOMYELITIS VACCINE
Available preparations: Oral suspension of live attenuated Contraindications
poliomyelitis virus .:. Hypersensitivity to any antibiotic present in the vaccine
.:. Hypersensitivity to eggs
Indications
.:. Active immunization against poliomyelitis Dose
O.5ml SC at 9 months (left upper arm)
Contraindications
.:. Hypersensitivity to any of the ingredients Side effects
.:. Patients with diarrhoea or vomiting .:. Fever .:. Headache
.:. Immunocompromised patients .:. Malaise .:. Rashes
.:. Pregnancy .:. Thrombocytopenia

Dose Key issues to note

2 drops at birth .:. Vaccination is recommended in all children at age of 9 months
2 drops at 6 weeks .:. Maternal antibodies may interfere with an effective immune
2 drops at 10 weeks response to the vaccine if given in the first 6 months of life
2 drops at 14 weeks .:. The vaccine may be give at 6 months incase there is an
outbreak in the community
Side effects
.:. Vaccination should not be given to patients with untreated
Rarely seen
active tuberculosis

-627- -628-

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 PRlIISE PHARMACOL8GY

MEASLES, MUMPS AND RUBELLA VACCINE (MMR Dose

VACCINE) 0.05ml intradermally in the right upper arm (infants less than 12
Available preparations: Injection of live attenuated measles, months)
mumps and Rubella virus 0.1 ml intradermal on the right upper arm (adults and Children greater
Available brands: Sii® measles, mumps and rubella vaccine than 12 months)
Trimovax®. Priovix® Side effects
Indications .:. Keloid formation .:. Lymphadenitis
.:. Active immunization against measles, mumps and rubella .:. Localized necrotic ulceration .:. Anaphylaxis
.:. Disseminated BCG infection in immuno suppressed patients
Contraindications
.:. Pregnancy Drug interactions
.:. Hypersensitivity to any antibacterial such as neomycin or .:. Concomitant administration with immuno suppressant drugs
kanamycin used in the manufacturing process
.:. Immuno suppressed patients DIPHTHERIA, PERTUSSIS AND TETANUS (DPT) VACCINE
Available preparations: Powder for injection
Dose
By deep SC or by intramuscular injection 0.5mg (12-15 months) Available brands: Tripacel®,lnfantrix®

Side effects Indications

.:. Fever Malaise .:. Active immunization against diphtheria, tetanus and pertussis
.:. Parotid swelling Rashes Dose
Drug interactions Infant: 0.5ml by intramuscular or deep SC injection at 6, 10 and 14
.:. Concomitant administration with immuno suppressants drugs weeks
BCGVACCINE Side effects
Available preparations: Powder for injection of live bacteria of .:. Irritability .:. Restlessness
a strain derived from the bacillus of calmette and Guerin .:. Limb swelling .:. Malaise
Indications .:. Peripheral neuropathy .:. Myalgia
.:. Active immunization against tuberculosis .:. Urticaria .:. Headache
.:. Fever .:. Loss of appetite
Contraindications
.:. Generalized oedema TETANUS TOXOID VACCINE
.:. Immuno suppressed patients Available preparations: Injection
.:. Antimycobacterial treatment
.:. Previous TB infections Available brands: Sii® tetanus toxoid vaccine, Tetavax®
.:. Generalized skin diseases Indications
.:. Tuberculin reaction> 5mm .:. Active immunization against tetanus and neonatal tetanus
Dose

-629- -630-

1111111111111111
 7
Available brands: Stamaril®
Women 15-45 years of age including pregnant women: O.sml deep Sc
or intramuscular injection at first contact or as early as possible during Indications

I
pregnancy (TTl) .:. Active immunization against yellow fever
TT2 (0.5ml) at least 4 weeks after TTl or during subsequent
Contraindications
pregnancy .:. Immuno suppressed patients
TT3 (0.5ml) at least 6 months after TT2 or during the subsequent
.:. Known hypersensitivity to any of the ingredients
pregnancy .:. Infants under 4 months of age
TT4 (0.5 ml) at least I year after TT3 or during subsequent pregnancy
.:. Hypersensitivity to eggs
TTs (O.sml) at least I year after TT4 or during subsequent pregnancy
Note: To achieve life long protection against tetanus, 5 doses of TT are Dose
required Infants at 9 months: O.sml by SC injection
Immunization of travelers and others at risk:
Side effects Adult and Children over 9 months: O.sml
.:. Peripheral neuropathy Infants 4-9 months: O.5ml only if risk of yellow fever is unavoidable.
~
ANTI TETANUS IMMUNOGLOBULIN Side effects
Available preparations: Injection ,sOOiu .:. Headache Myalgia
.:. Fever Influenza like symptoms
Available brands: Tetanea® .:. Weakness Nausea
.:. Diarrhoea
Indications
.:. Passive immunization against tetanus as part of the Drug interactions
management of tetanus prone wounds .:. Concomitan~ administration with immunosuppressant drugs
Chol~ra vaccine should not be given together with yellow fever
Dose
Adult and Children: Iml by 1M injection. Give additional dose if wound vaccine
is older than 12hours or heavily contaminated
TYPHOID VACCINE
Side effects I Available preparations: Injection VI capsular
.:. Local reactions Polysaccharide typhoid 25 m~ /
.:. Fever
.:. Pain and tenderness at site of injection
.:. Headache
I
I Available brands:
O.sml
Typhim Vi®, Typherix®
ill Indications
Drug interactions .:. Active immunization against typhoid
.:. Live vaccines
YELLOW FEVER
\1Ii, Available preparations: Injection powder + solvent of live
1'1 attenuated virus

'1'1 -631-
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Contraindications Contraindications
.:. Immunosuppressed patients .:. Severe allergic reaction to any of the ingredients
.:. Febrile illness Dose
.:. Known hypersensitivity to any of the ingredients Adult and children> 2 years: O.5ml deep Sc or 1M as a single dose

Dose Side effects

Adultand children> 2 years: By deep Sc (subcutaneous) or intramuscular .:. Fever
05tnl with booster doses every 3 years for those at continued risk .:. Myalgia
.:. Pain and erythema at injection site
Side effects Key issues to note
.:. Headache Nausea .:. Re-vacination is recommended every 5-10 years in high risk
.:. Allergic reaction Malaise patients
.:. Myalgia Swelling and pain
.:. J Fever MENINGOCOCCAL VACCINE
,It
Available preparations: Injection
Key issues to note
.:. Typhoid fever prevention becomes effective after 2-3 weeks Bivalent vaccine from group A and C
after injection Tetravalet vaccine from groups A, C,
.:. Typhoid is rare in children under 2 years therefore to YandWI35
immunize in this age group should be based on the risk of Available brands: Meningo A + C®, Mencevax ACWY®
exposure
.:. The vaccine offers protection for a minimum duration of 3 Indications
.:. Active immunization against Neisseria meningitides infections
years ~i
such as meningitis and septicaemia
PNEUMOCOCCAL VACCINE Contraindications
Available preparations: Injection in form of 23 valent .:. Allergy to diphtheria toxoid
polysaccharide vaccine .:. Febrile €onditions
25mcg IO.5ml
Dose
Available brands: Pneumo 23® Adult and Children> 2 years of age
Bivalent: O.5ml deep Sc or 1M injection as a single dose
Indications
Immunization against pneumococcal infections in:- Tetravalent: O.5ml deep Sc injection as a single dose.
.:. Sickle cell disease in Children> 2 years of age Side effects
.:. Immuno compromised patients> 5 years at increased risk of .:. Allergic reaction
pneumococcal infection. .:. Anaphylaxis
.:. Erythema

-633- 634-
 " " '" ,"'" 'PRECISE PHARMACOLOGY
.:. Pre-exposure prophylaxis in persons at high risk of being bitten
Key issues to note
.:. Do not use in children under 2 years except in epidemic by rabid animals
situations Contraindications
.:. Known hypersensitivity to any of the ingredients
CHOLERA VACCINE •
Available preparations: Oral vaccine containing live attenuated or Dose
inactivated Pre-exposure prophylaxis: I ml by deep subcutaneous or
Dukoral® intramuscular injection on days 0, 7, and 28;
Available brands:
Post exposure treatment: I ml by deep subcutaneous or intramuscular
Indications injection on days 0, 3, 7, 14, and 30
.:. Immunization for travellers> 2years of age at high risk of
cholera infections Side effects "
.:. Pain at injection site .:. Nausea

.
Contraindications
.:. '"' History of hypersensitivity to any of the ingredients
·:·'1.:
'
Acute GIT or febrile
W·
.:. Fever
.:. Erythema at injection site
.:. Malaise
.:.
.:.
.:.
Myalgia
Headache
Hypersensitivity reaction
Dose
Children 2 - 6 years: 3 doses given at interval of atleast I week. Give a HEPATITIS .B VACCINE
booster after 6 months if still at risk Available preparations: Injection containing inactivated
Adult and Children > 6 years of age: 2 doses given at I week a part. hepatitis B surface antigen
Given a booster after 2 years if still at risk
Available brands: Euvax B adult®, Euvax B paed®, Engerix B®
Side effects
Indications
.:. Abdominal discomfort .:. Diarrhoea
.:. Fever .:. Active immunization against Hepatitis B infection
.:. Headache
Contraindications
Key issues to note
.:. History of hypersensitivity
.:. Avoid food and drinks I hour before and after taking the
vaccine Dose
Adult and Children over 15 years: I ml with an interval of I month
RABIES VACCINE between the I st and 2nd dose and 5 months between the 2nd and 3rd
Available preparations: Injection 2.5 IU/dose doses. Total of 3 doses
Children below 15 years: 0.5ml with I month between the I st and
Available brands: Sii rabivax®, Lyssavac n berna®, Verorab®
2nd dose, and 5 months between the 2nd and 3rd dose
Indications Infants: 0.5ml intramuscular injection at 6 weeks, 10 weeks, and 14
.:. Active immunization against rabies weeks of age.
•:. Post exposure treatment to prevent rabies in patients who
have been bitten by rabid animals

-636-
I -635-
II
WllllllllllllllIllllllll IIII
Side effects Note: Subcutaneous route may be used for patients with bleeding
.:. Abdominal pain .:. GIT disturbance disorders.
.:. Sleep disturbance .:. Lymphadenopathy
.:. Muscle and joint pains .:. Dizziness Side effects
.:. Peripheral .:. Malaise .:. Headache .:. Malaise
.:. Neuropathy .:. Myalgia .:. Fatigue .:. Myalgia
.:. Loss of appetite .:. Nausea
Key issues to note .:. Urticaria .:. Skin rash
.:. Immunocompromised patients may need further dose .:. Fever

HEPATITIS A VACCINE
ANTI- D (RHO) IMMUNOGLOBULIN
Available preparations: Injection containing suspension of
A Rhesus negative mother may develop antibodies against Rho antigen
formaldehyde inactivated hepatitis
red cells when she carries a Rhesus positive fetus and fetal red cells
Avirus 80U PD, 160U AD
enter her circulation during child birth, abortion or miscarriage.
Rho Immunoglobulin is used to prevent non sensitized mothers from
Available brands: Avaxim®, Havrix®
producing antibodies which may cause heaemolytic disease of the new
Indications
born.
Active immunization against hepatitis A infection in the following
groups:- Available preparations: Injection
.:. Laboratory workers Indications
.:. Patients with haemophilia .:. Prevention of rhesus D sensitization in females who are rhesus
.:. Patients with severe liver disease D negative
.:. Individuals who change sexual partners frequently
.:. Travellers to high risk areas Contraindications
.:. Parenteral drug abusers .:. Rhesus positive individuals
.:. Isolated immunoglobulin A deficiency
Contraindications Dose iii
.:. Severe febrile infections Following birth of rhesus positive infant; SOOunits deep 1M immediately
.:. Acute or chronic diseases or within 72hours.
Following still birth; 2S0units per episode immediately or within
Dose 72hours
By intramuscular injection Antenatal prophylaxis: SOOunits given at vyveeks 28 and 34 of
Adult and Children above 16 years: O.Sml as a single dose pregnancy.
Booster dose of O.Sml is given 6-12 months after initial dose A further dose is still needed immediately or within 72 hours of
Further booster doses of O.Sml every 10 years delivery
Children under 16 years of age: Not recommended

-637- -638-

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 PRECISE PHARMACOlO
SUMMARY OF IMMUNIZATION SCHEDULE IN UGANDA
Side effects VACCINE PROTECTS HOW GIVEN
.:. Local tenderness and stiffnes .:. Fever AGAINST
.:. Nausea .:. Vomiting
AT birth BCG Tuberculosis Right upper
.:. Back pain .:. Abdominal pain
arm
.:. Myalgia .:. Malaise
.:. Sweating .:. Skin rash Polio 0 Polio Mouth drops
AT 6 weeks Polio 1 Polio Mouth drops
Drug interactions DPT Heb B+ - Diphtherial Left upper
.:. Live vacci nes Hib 1 tetanusl thigh
whooping
coughl
hepatitis B I
haemophilus
influenza type
B
At 10 weeks Polio 2 Polio Mouth drops
DPT-Heb B Diphtherial Left upper
-+Hib 2 tetanusl thigh
whooping
coughl
hepatitis B I
haemophilus
influenza type
B
At 14 weeks Polio 3 Polio Mouth drops
DPT-Heb B Diphtherial Left upper
-+Hib 3 tetanusl thigh
whooping
coughl hepatitis
B/Haemophilus
~
influenza type
B 'j '"
9 months Measles Measles Left upper arm '"

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