There are two types of adverse drug reactions (ADRs). Type A are common, predictable, usually dose-dependent and appear as excessive manifestations of the normal pharmacology/toxicology of the drug; they are seldom fatal. Type B are uncommon, unpredictable, often independent of dose and usually represent abnormal manifestations of the drug's pharmacology/toxicology; they involve relatively high rates of serious morbidity and mortality.
ADRs frequently mimic ordinary diseases and, if they are uncommon, may easily be overlooked. They tend to affect the skin, haematopoietic system and lining of the gut (situations in which there is rapid cell multiplication) or the liver or kidneys (where drugs are detoxified and excreted). These special sites are frequently involved in iatrogenic (doctor-induced), type B illnesses, such as toxic epidermal necrolysis, aplastic anaemia, pseudomembranous colitis, drug-induced hepatitis or nephritis.
A high index of suspicion is needed if ADRs are to be successfully diagnosed. The clinician always has to think: "Could this be drug-induced—is this an ADR?'' The question is important, for withdrawal of the cause of an ADR is usually essential.
Iatrogenic ADRs are usually uncommon or rare—and this adds to the difficulty of diagnosis. Some are avoidable, such as skin rashes in patients with glandular fever given ampicillin. Some are accidental, such as the non-iatrogenic disaster of an asthmatic given a beta-adrenergic blocking agent by another member of the family. It is a truism that the detection of common or uncommon ADRs requires vigilance. Many of the known serious ADRs have been recognized by astute clinicians with a high level of awareness—and such awareness is likely to be just as important, as new methods of pharmacovigilance are developed, as it has been in the past.
Linked with this problem of diagnosing ADRs is the problem of understanding them. Why does one patient in 10 000 get some bizarre Type B reaction—and the rest of this cohort not get it? Clearly our increasing knowledge of clinical pharmacology, drug metabolism and genetics will contribute to our understanding of these things— and these subjects are explored in many of the chapters in this book.
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