Adverse drug reactions constitute a major morbidity, causing deaths in some cases. About 6% of all hospital admissions are related to ADRs and about half of these are avoidable. There is also a substantial diagnostic problem since there is a limited way in which the body may respond patho-physiologically. This means that ADRs often masquerade as other diseases. Commonly reported ADRs are given in Table 1.

In some instances ADRs may be more specifically related to drug or chemical exposure: some examples of these are shown in Table 2. From this latter table note that there are some very common problems with a relatively lower drug relatedness at the bottom, but these constitute a numerically higher public health risk.

It follows from this that practising clinicians must always consider adverse drug reactions as part of their clinical diagnosis. The causal relationship of a drug to a clinical event may be far from easy to distinguish from other (disease) candidates in the differential diagnosis.

There are some general points for any doctor to bear in mind before prescribing, related to safety:

• The skill of therapeutics is to anticipate, and then use drugs in a way that minimizes risk.

• Drugs are capable of modifying fundamental biological processes profoundly, and their use is associated with the risk of adverse drug reactions.

• Always consider the risks and benefits of using any drug. Think also about all of the costs of using that drug. Compare it with other treatments for the same indication. Then decide which is best to use for your particular patient.

• Remember that it is the patient stands to gain the benefits, but also runs the risks! The benefit of your specialised knowledge of both the patient and the drug must be shared as completely as possible.

• All drug effects are the result of complex interaction between the drug, the patient and the illness. Extrinsic factors, such as speed of administration intravenously, diet, chemical exposures (including other drugs) and many other factors, can also modify drug response.

• Important general predisposing factors to adverse reactions include an excessive amount of the drug due to non-individualised dosage, altered responsiveness to drugs at extremes of age, previous history of allergy or reaction to drugs.

• Pregnancy and labour are also times of altered drug responsiveness: the fetus has special susceptibility to some adverse drug reactions though may be immune to others, for example due to the drug not passing the placenta.

• The incidence of adverse reactions increases with the number of drugs. A minority of adverse effects of drugs can be attributed to drug interaction, but some important adverse interactions are predictable and can be avoided. In the WHO global database of individual case safety reports (ICSR), only about 0.7% of possible adverse events which might be due to interactions between drugs known to share the same CYP enzyme are recorded as possibly due to interaction by the reporter, therefore missing a possible important signal. It should be noted, however, that many interactions have been reported in the literature without much evidence (see Chapter 15).

• Adverse drug reactions should be avoided, managed by dose reduction or withdrawal of the offending drug, replacement with another if necessary, but not treated by with other drugs unless essential.

• The clinician has a responsibility to recognise the possibility of an adverse drug reaction and include it as part of the differential diagnosis or problem list.

• The clinician must report clinically important adverse drug effects to a committee or registry, which have responsibility for deciding on drug formularies (local or national) and for advice on therapeutics.