A Manual of Adverse Drug Interactions

J.P. Griffin, P.F. D'Arcy

• Publisher: Elsevier Science
• Year: 1997
• ISBN:
  9780080525839
• Edition: 5
• Topic: Medicina
• Subtopic: Farmacología

For twenty years this book, now in its 5th edition, has provided information on adverse drug interactions that is unrivalled in coverage and scholarship.

Adverse drug reactions, many of them ascribable to interactions with other drugs or with chemical substances in food or the environment, are thought to cause or complicate one in twenty of hospital admissions.

The book is conveniently divided into two parts: Part 1 comments on drug interactions and their mechanisms, on a pharmacokinetic and pharmacodynamic level, while Part 2 consists of drug interaction tables, divided and subdivided into categories of disorders, and the drugs used in the treatment of these disorders.

If safety in drugs is to improve, education of prescribers is vitally important. This book, with its up-to-date and coordinated approach, serves that purpose well. The real threat, as the authors remind us, is the ignorance of practitioners, not the drug itself. The volume is therefore an essential addition to the shelves of those responsible for the prescription of drugs, in order to prevent a potential backlash when used in combination with other drugs or chemical substances.

Part 1

Commentary on Drug Interactions and their Mechanisms

INTRODUCTION: A WIDENING PROBLEM

Over 20 years ago, an editorial on drug interactions in the Lancet (19 April 1975) said that the “publication of huge lists and tables will induce in doctors a drug-interaction-anxiety syndrome and lead to therapeutic paralysis”. This prediction has not come about, although the problem of drug interactions is still with us and the spectrum is widening as new drugs are introduced. Indeed it could be said that the nature of the problem has also widened for in the intervening years drug interactions have come to embrace interactions with food and with herbal medicines as well as the more numerous and better recognized drug–drug interactions.

There is little doubt that drug–drug interactions can often be serious, even life-threatening. They can also be very expensive, and evidence from the Medical Defence Unions’ Reports of over 10 years ago reveals that one case which settled for £44 000 was due to phenylbutazone-induced potentiation of warfarin which was followed by an intraspinal haemorrhage resulting in an incomplete tetraplegia at the level of C7. It is interesting in this case that the solicitor’s letter stated that “Butazolidin is a well known potentiator of coumarin anticoagulants of which warfarin is one” … “the prescribing of Butazolidin for a patient known to be taking warfarin routinely was a breach of your professional duty to him”.

Knowledge of the ‘state of the art’ has much advanced since the 1980s and what were then novel and scientifically interesting interactions are now established and well-recorded interactions in standard books of reference. Knowledge has advanced but there has been little progress in the way in which it is generated.

SOURCES OF INFORMATION: Most reports of drug–drug- or drug–food interaction arise primarily from experience in the clinic. Some of these are anecdotal and may not be reported again, whilst others represent the first warning signs of a wider cohort of cases that is yet to be realised. Their purpose is to report the interaction and explain its hazard so that others can avoid it occurring; however, few of these reports are able to indicate the precise mechanism of the interaction.

Generally, animal experiments have not contributed much of substance to knowledge about interactions. Admittedly, the early work of Conney and his associates (1956, 1957) in rats did much to explore the nature and organization of enzyme systems in liver microsomes, but it was the human studies of Levy (1970) and Neuvonen et al., (1970) that provided the now classical evidence that the salts of divalent or trivalent metals formed non-absorbable complexes with tetracyclines and reduced their absorption, resulting in sub-therapeutic levels in the plasma. It was observation in patients that gave the first indication that concomitant medication could antagonize the efficacy of oral contraceptives (Dossetor, 1975). It was in tuberculosis patients that the apparent interaction between PAS and rifampicin was first recognized and later to be explained that the interaction was not due to PAS but to the bentonite content of its granules (Boman et al., 1971). One of us (PFD’A) was reminded of this latter interaction in recent months when a lady in Belfast who had been a TB patient at that time and had been receiving rifampicin and PAS, mentioned that without warning or explanation her treatment had been changed to rifampicin plus isoniazid.

One of the advantages of the attention that has been focused on adverse drug interactions over the past 20 years or so is that many drug–drug and drug–food interactions are now predictable and many of the unwanted consequences of using drug combinations can be avoided by simply adjusting the dosage of one or more of the interactants. As a result of this, there has been a considerable improvement in the safety and efficacy of therapy with drug combinations.

However, the focus on drug interactions has always been more on their hazards than their advantages. This is the correct orientation since the vast majority of interactions are hazardous. An awareness of the possible hazards of medication and possible interactions between drugs on the part of those who use them, doctors and other health professionals, can only result in better therapy with benefit to the patient in terms of both safety and efficacy. Many excellent publications have explored the nature of drug interactions and their message has filtered down to the patient level being expressed by the maxim ‘do not use two drugs when one will do’.

THE LITERATURE ON DRUG INTERACTIONS: The literature on drug interactions tends to be very non-specific and in the last 20 years or so it has be...