Saint John s Wort
ethanol (chronic use)
Enzyme induction is relevant to drug therapy for the following reasons:
• Clinically important drug interactions may result, e.g. in failure of oral contraceptives, loss of anticoagulant control, failure of cytotoxic chemotherapy.
• Disease may result. Antiepilepsy drugs increase the breakdown of dietary and endogenously formed vitamin D, producing an inactive metabolite — in effect a vitamin D deficiency state, which can result in osteomalacia. The accompanying hypocalcaemia can increase the tendency to fits and a convulsion may lead to fracture of the demineralised bones.
• Tolerance to drug therapy may result in and provide an explanation for suboptimal treatment, e.g. with an antiepilepsy drug.
• Variability in response to drugs is increased. Enzyme induction caused by heavy alcohol drinking or heavy smoking may be an unrecognised cause for failure of an individual to achieve the expected response to a normal dose of a drug, e.g. warfarin, theophylline. • Drug toxicity may be more likely A patient who becomes enzyme-induced by taking rifampicin is more likely to develop liver toxicity after paracetamol overdose by increased production of a hepatotoxic metabolite. (Such a patient will also present with a deceptively low plasma concentration of paracetamol due to accelerated metabolism, see p. 287)
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