Effects of prolonged administration chronic organ toxicity

While the majority of adverse events occur within days or weeks after a drug is administered, some reactions develop only after months or years of exposure. In general, pharmacovigilance programmes reveal such effects; once recognised, they demand careful monitoring during chronic drug therapy for their occurrence may carry serious consequences for the patient (and the nonvigilant doctor, medico-legally). Descriptions of such (types C and D) reactions appear with the accounts of relevant drugs; some examples are:

Eye. Toxic cataract can be due to chloroquine and related drugs, adrenal steroids (topical and systemic), phenothiazines and alkylating agents. Corneal opacities occur with phenothiazines and chloroquine. Retinal injury occurs with thioridazine (particularly, of the antipsychotics), chloroquine and indomethacin.

Nervous system. Tardive dyskinesias occur with neuroleptics; polyneuritis with metronidazole; optic neuritis with ethambutol.

Lung. Amiodarone may cause pulmonary fibrosis. Sulphasalazine is associated with fibrosing alveolitis.

Kidney. Gold salts may cause nephropathy; see also Analgesic nephropathy (p. 284).

Liver. Methotrexate may cause liver damage and hepatic fibrosis; (see also alcohol p. 184).

Carcinogenesis: see also Preclinical testing (p. 45). Mechanisms of carcinogenesis are complex; prediction from animal tests is uncertain and causal

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