Cigarettes and drug therapy: pharmacokinetic and pharmacodynamic considerations.

Cigarette smoking-induced alterations in drug absorption, distribution, metabolism, excretion, and effectiveness are reviewed. Drug therapy can be affected pharmacokinetically by polyaromatic hydrocarbons and pharmacodynamically by nicotine. Pentazocine and phenylbutazone show increased metabolism in smokers and may have to be given in higher dosages. Smokers experience less pain relief with propoxyphene than do nonsmokers. Codeine, meperidine, and morphine are unaffected pharmacokinetically, and the effect on acetaminophen is probably not clinically important. Carbamazepine, phenytoin, and phenobarbital are not influenced. Heparin metabolism is elevated in smokers; this effect may necessitate modest increases in dosage. Warfarin clearance is increased, but this is not associated with a change in prothrombin time. Pindolol and propranolol are unaffected pharmacokinetically, but direct effects of nicotine may interfere with blood pressure control. Smoking transiently diminishes the diuretic effect of furosemide, inconsistently affects protein binding of lidocaine, and has no effect on prednisone, prednisolone, or dexamethasone. The metabolism of estrogens to less active metabolites is increased. Smoking is associated with decreased subcutaneous absorption of insulin and increased dosage requirements. Healing of GI ulcers with histamine H2-receptor antagonists may be compromised in smokers; sucralfate is probably more useful. Imipramine, benzodiazepines, chlorpromazine, and glutethimide may be influenced, and theophylline metabolism is accelerated. Cigarette smoking can affect the pharmacokinetic and pharmacodynamic properties of many drugs.