Metabolic changes over a long period may induce disease, e.g. thiazide diuretics (diabetes mellitus), adrenocortical hormones (osteoporosis), phenytoin (osteomalacia). Drugs may also enhance their own metabolism, and that of other drugs (enzyme induction).
Specific cell injury or cell functional disorder occur with individual drugs or drug classes, e.g. tardive dyskinesia (dopamine receptor blockers), retinal damage (chloroquine, phenothiazines), retroperitoneal fibrosis (methysergide), NSAIDs (nephropathy). Cancer may occur, e.g. with oestrogens (endometrium) and with immunosuppressive (anticancer) drugs.
Drug holidays. This term means the deliberate interruption of long-term therapy with the objective of restoring sensitivity (which has been lost) or to reduce the risk of toxicity. Plainly the need for holidays is a substantial disadvantage for any drug. The principal example is methysergide for refractory migraine (see Index). Patients sometimes initiate their own drug holidays (see Patient compliance).
Dangers of intercurrent illness. These are particularly notable with anticoagulants, adrenal steroids and immunosuppressives.
Dangers of interactions with other drugs or food:
see index, food, interactions, individual drugs.
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