SIDE EFFECTS

The term side effects, or “adverse drug reactions” embodies a wide variety of toxic drug reactions that occur in numerous types of treatment. Assessing the incidence and consequences of side effects is extremely difficult, as causeand-effect relationships are often difficult or impossible to prove.

The ultimate proof, which may be unobtainable in cases of severe reactions, depends on disappearance of the effect on withdrawal of the suspected drug (although some severe reactions are irreversible) and reappearance on the administration of the drug.

It is also difficult to select a control population in a clinical setting to differentiate drug-related symptoms and signs from those that are non-drug-related; thus, there is a wide variation in the methods used to collect data on side effects of drugs.

Some studies of side effects rely on reactions reported voluntarily by doctors; others involve selected patient groups; information from patients may also be collected by direct questioning or by patients volunteering information.

There is also a potential for both under- and overestimating the incidence of side effects of drugs. Perhaps 2 to 3 percent of admissions to hospital are due to drug reactions (excluding deliberate overdose or drug abuse), and among patients already in hospital, the incidence of mild to severe side effects may be as high as 8 to 10 percent.

These data are difficult to interpret in terms of cause-and-effect, mortality and physical damage. The incidence of drug-related deaths is unknown, but probably only a few deaths in medical units are drug-related, and these are often in patients with serious diseases that warrant such risks.

The most commonly reported causes of drug-related deaths are:

- Gastro-intestinal hemorrhage and peptic ulceration, caused by corticosteroids, aspirin and other anti-inflammatory drugs.

- Other hemorrhages, caused by anticoagulants (which reduce blood clotting) or cytostatic agents (anti-cancer drugs).

- Aplastic anemia, caused by chloramphenicol, phenylbutazone, gold salts or cytostatic agents.
- Damage to the liver, caused by paracetamol, chlorpromazine or isoniazid.

- Failure of the function of the kidney, caused by analgesics (painkillers).

- Infections, caused by corticosteroids or cytostatic drugs.
- Anaphylaxis, caused by penicillin or its derivatives or by antisera. Although individuals vary considerably in their responsiveness to a particular drug effect, most toxic effects are related to the amount of drug taken. Previous contact with the drug is not necessary for the development of toxic reactions.

Side effects may be wanted under certain circumstances. For example, antihistamines given for hay fever may cause drowsiness as a side effect, but drowsiness may be a wanted effect when an antihistamine is given as a mild sleep remedy.