Many unwanted effects of drugs are medically trivial, and in order to avoid inflating the figures of drug-induced disease, it is convenient to retain the term side-effects for minor effects of type A events/effects (p. 139).
The term adverse reaction should be confined to: harmful or seriously unpleasant effects occurring at doses intended for therapeutic (including prophylactic or diagnostic) effect and which call for reduction of dose or withdrawal of the drug and /or forecast hazard from future administration; it is effects of this order that are of importance in evaluating drug-induced disease in the community.
Toxicity implies a direct action of the drug, often at high dose, damaging cells, e.g. liver damage from paracetamol overdose, eighth cranial nerve damage from gentamicin. All drugs, for practical purposes, are toxic in overdose and overdose can be absolute or relative; in the latter case an ordinary dose may be administered but may be toxic due to an underlying abnormality in the patient, e.g. disease of the kidney. Mutagenicity, carcinogenicity and teratogenicity (see index) are special cases of toxicity.
Secondary effects are the indirect consequences of a primary drug action. Examples are: vitamin deficiency or opportunistic infection which may occur in patients whose normal bowel flora has been altered by antibiotics; diuretic-induced hypokalaemia causing digoxin intolerance.
Intolerance means a low threshold to the normal pharmacodynamic action of a drug. Individuals vary greatly in their susceptibility to drugs, those at one extreme of the normal distribution curve being intolerant of the drugs, those at the other, tolerant.
Idiosyncrasy (see Pharmacogenetics) implies an inherent qualitative abnormal reaction to a drug, usually due to genetic abnormality, e.g. porphyria.
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