Table Of ContentPeter I. Folb
Drug Safety
in Clinical Practice
With 24 Figures
Springer-Verlag
Berlin Heidelberg NewY ork Tokyo
1984
Peter I. Folb, MD, FRCP
Professor of Pharmacology,
University of Cape Town Medical School;
Chief Physician, Groote Schuur Hospital,
Cape Town.
Library of Congress Cataloging in Publication Data
Folb, Peter 1., 1938- . Drug safety in clinical practice.
Bibliography: p. Includes index. 1. Drugs - Safety measures. 2. Drugs - Side
effects. 1. Title RM301.F57 1983 615'.704283-17156
ISBN-13: 978-3-540-12811-3 e-ISBN-13: 978-1-4471-1351-5
001: 10.1007/978-1-4471-1351-5
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Preface
Drugs may cause disease, or they may aggravate the morbidity of
the condition for which they are prescribed, and certain patients
may for one or other reason be particularly liable to drug injury.
The inextricable relationships between the toxic profiles of drugs,
the natural history of the diseases for which they are given, and
the adverse drug effects that may develop in the course of such
diseases are of considerable interest. It is the study of these rather
neglected aspects of pharmacology and therapeutics which has
formed the basis of this book.
An explanation is required of the approach and the style which
have been followed. The monograph does not purport to be
comprehensive. Only important drug groups which are commonly
used in practice are considered. Emphasis has been placed on
achieving maximum benefit and safety of the appropriate drugs in
the management of common illnesses. When treatment fails, either
ab initio or subsequent to an initial response, the risk-benefit
relationship of drugs inevitably alters. For this reason the main
factors responsible for treatment failure have been considered, with
special attention to the possible contribution of or implications for
drug therapy in such a situation. Finally, proposals have been put
forward for improving the diagnosis and reporting of adverse drug
effects.
In order to be practical and, as far as possible, constructive it
has been necessary for me to "take a position" on numerous issues.
In many instances I have expressed a point of view based on my
understanding of authoritative literature (cited at the end of each
section) and such clinical experience as I may have gained or have
accrued from colleagues. There is a danger that this approach will
be seen as somewhat categorical. I hope, however, that it may
be understood as an attempt to depart from the descriptive and
encyclopaedic approach which has tended to characterise medical
writing in this particular field.
My colleagues John Straughan and Ashley Robins have in
particular given me helpful advice, and I am grateful to Michael
Jackson of Springer-Verlag who has guided the original idea behind
VI Preface
the book to fruition. Renee Gelbart and June Chambers have given
me much assistance in the compilation of material. Elise Fuller
helped with the illustrations. The Medicines Safety Centre of the
University of Cape Town Medical School, jointly sponsored by
Ciba Geigy, has been a source of valuable information.
The South African Medical Research Council and the University
of Cape Town have supported my researches into mechanisms
and models of drug-induced damage, and this help is gratefully
acknowledged.
Cape Town, 1983 Peter I. Folb
Contents
1 Drugs in Common Use .................................................... 1
1.1 Antibiotics ................................................................. 1
Topical antibiotics; beta-Iactamases; side-effects;
renal elimination; hepatic disease and failure
1.2 Antihistamines ........................................................... 9
Use in the common cold and upper respiratory tract
infections; special problems; interaction with other
drugs; adverse effects on the nervous system; topical
use; acute poisoning
1.3 Histamine2-Receptor Blocking Agents ....................... 13
Cimetidine; ranitidine
1.4 Antacids .................................................................... 16
Aluminium toxicity; chronic aluminium toxicity;
bismuth encephalopathy and neuropathy
1.5 Laxatives ................................................................... 19
Safety profiles; cathartic syndrome; chronic
hypokalaemia; mineral oil deposits; phenolphthalein
1.6 Antidiarrhoeal Agents ............................................... 22
Kaolin; pectin; bismuth, anticholinergics; opiates;
diphenoxylate and atropine; iodochlorhydroxyquin;
antidiarrhoeallantibiotic combinations
1.7 Aspirin and the Acidic Non-steroidal
Anti-inflammatory Agents ......................................... 25
Gastrointestinal injury; sensitivity reactions;
analgesic nephropathy; redistributional drug
interactions; general considerations for use in
chronic rheumatic conditions
1.8 Digitalis ..................................................................... 30
Clinical signs of digitalis toxicity; early recognition
of cardiotoxicity; contraindications to digitalis
therapy; massive digitalis intoxication; digoxin and
quinidine
viii Contents
1.9 Sympathomimetic Drugs .......................................... 33
Adrenaline; ephedrine; phenylpropanolamine;
noradrenaline; isoprenaline; betarselective agents;
dopamine and dobutamine; clonidine '
1.10 Alpha-Adrenoreceptor Blocking Agents .................. 37
Phenoxybenzamine; prazosin; indoramin
1.11 Beta-Adrenoreceptor Blocking Agents ..................... 39
1.12 Potassium Supplements ........................................... 40
1.13 Nitrates ................................................................... 41
Adverse Effects; Tolerance
1.14 Calcium Antagonists ............................................... 42
Verapamil; nifedipine; perhexilene; prenylamine;
diltiazem
1.15 Benzodiazepines ...................................................... 44
Guidelines for use; dependence
1.16 Tricyclic Antidepressants ......................................... 46
Cardiotoxicity; postural hypotension; anticholinergic
effects; epilepsy; acute withdrawal effects
1.17 Methylphenidate ........ ............................................. 49
1.18 Anorectic Agents ..................................................... 50
Sympathomimetic amines; safety; fenfluramine;
phenylpropanolamine; comparative
pharmacological effects
1.19 Addition of Drugs to Intravenous Fluids ................ 55
1.20 Parenteral Nutrition ................................................ 57
Micronutrient deficiencies; metabolic bone disease;
hepatic dysfunction; fat overload syndrome
1.21 Topical Corticosteroids ........................................... 61
Potency; activity; local toxicity; systemic toxicity;
minimising risks of adverse effects; use in
ophthalmology
1.22 Methylene Blue ................ ...... .... ....... .... .................. 65
Use in methaemoglobinaemia; toxicity
1.23 Vitamins .................................................................. 66
Vitamin A (retinol): requirements;
hypervitaminosis A
Vitamin B12 and folic acid
Vitami~ C: antiscorbutic activity; toxicity
Vitamin D: Normal requirements; individual
susceptibility; hypervitaminosis D
Vitamin K: adverse effects; treatment of
hypoprothrombinaemia
Contents IX
2 Drug Safety in Some Common Medical Conditions . 73
2.1 Heart Failure .... .............. ...... ............ .... ........ ........... 73
Excessive diuresis; diuretic escape; hypokalaemia;
digitalis toxicity; myocardial ischaemia; adverse
drug-drug interactions; lack of response to therapy
2.2 Hypertension ............. .............. ................................ 77
Stepped approach to drug treatment; captopril;
methyldopa; beta-adrenoreceptor blocking agents;
frusemide; prazosin; minoxidil; drug treatment in
the elderly
2.3 Cough .......... .................................... ........................ 84
Codeine; mucolytic agents; antihistamines
2.4 Bronchial Asthma .................................................... 87
Methylxanthines; combination anti-asthmatic
preparations
2.5 Tuberculosis and Other Mycobacterial Infections 91
Drugs of choice; treatment failure; toxicity profiles;
renal failure; hepatotoxicity; pregnancy
2.6 Fungal Infections ..................................................... 96
Amphotericin B; 5-fluorocytosine
2.7 Malaria .................................................................... 98
Cerebral malaria; adverse effects of antimalarial
agents; prophylaxis in pregnancy
2.8 Urinary Tract Infections .......................................... 101
Antimicrobial therapy of uncomplicated infections;
repeated infections; catheter-associated infections;
treatment in renal failure; nalidixic acid;
nitrofurantoin
2.9 Cancer Chemotherapy ............................................. 106
Resistance to cytotoxic agents; general guidelines
2.1 0 Iron-Deficiency Anaemia ...... ...... ............ ................. 112
Contra indications to iron; failed response; choice of
an oral iron preparation; adverse effects of oral
therapy; hazards of parenteral therapy; iron
supplements
2.11 Diabetes Mellitus .................................................... 115
Insulin allergy; insulin lipoatrophy and
lipohypertrophy; insulin resistance; insulin
hypoglycaemic reactions; the Somogyi effect; beta
adrenoreceptor blocking drugs and blood sugar
control; sulphonylureas; lactic acidosis;
chlorpropamide-alcohol flush
2.12 Gout ........................................................................ 125
Colchicine; indomethacin; uricosuric agents;
allopurinol
x Contents
2.13 Myasthenia Gravis .................................................. 129
Anticholinesterases; atropine; corticosteroids;
other drugs affecting the myoneuronal junction
3 Patients at Special Risk .................................................... 135
3.1 Pregnant Women ..................................................... 135
Drug injury to the fetus: drug usage in pregnancy
Drug treatment of important medical conditions in
pregnancy: severe vomiting and hyperemesis
gravidarum; epilepsy; rheumatic conditions;
tuberculosis; ulcerative colitis; anticoagulation;
depression
3.2 Breast-Feeding mothers ............................................ 141
3.3 The Elderly .............................................................. 144
Disinhibition reactions; neuropsychiatric
syndromes; tranquilliser dependence;
anticholinergic syndrome; hypoglycaemic
syndromes; ocular effects; special issues in drug
treatment; guidelines
3.4 Motor Vehicle Drivers ............................................. 149
3.5 Porphyrics ................................................................ 150
Clinical guidelines; management of an acute
attack; prediction
4 Drug Irijuries .................................................................... 155
4.1 Drug Fever ............................................................... 155
Causes; pathogenesis; clinical features;
predisposing factors; diagnosis; management;
Herxheimer reaction; malignant hyperthermia;
neuroleptic malignant syndrome
4.2 Anaphylaxis and Anaphylactoid Reactions ............. 159
Pathogenesis; symptomatology; prediction and
prevention; differential diagnosis; Hoigne's
syndrome; serum sickness reactions; classification
of allergic drug reactions
4.3 Drug-Induced Diseases of the Skin .......................... 168
Diagnosis and natural history; management of
hypersensitivity
4.4 Drug-Induced Vasculitis .......................................... 171
Clinical features; allopurinol hypersensitivity
4.5 Drug-Induced Vomiting ........................................... 173
Metoclopramide; cannabinoids
4.6 Central Anticholinergic Syndromes ......................... 175
Toxic confusional state; disorders of temperature
control; neuroleptic malignant syndrome;
physostigmine
Contents Xl
4.7 Drug-Induced Ototoxicity....................................... 178
Diagnosis; aminoglycosides; salicylates; non-steroidal
anti-inflammatory agents; antimalarials; loop
diuretics
5 Diagnosing Adverse Drug Reactions ........................... ..... 181
Classification; probability of association; severity;
Berkson's bias
Subject Index ....................................................................... 187
