title: Recent developments in the study of the effects of cigarette smoking on clinical pharmacokinetics and clinical pharmacodynamics.
abstract: With the ever-increasing population of cigarette smokers, the potential for cigarette smoke to affect drug therapy both pharmacokinetically and pharmacodynamically is significant. The overriding pharmacokinetic effect is increased drug metabolism through the induction of liver enzymes. The constituents of tobacco smoke, primarily nicotine, have their own pharmacological effects which may potentiate or antagonise the desired pharmacological effect of a particular drug, thereby affecting its efficacy. Furthermore, end-organ responsiveness may also be altered by tobacco. These latter 2 aspects constitute altered clinical pharmacodynamics. Approximately 30 drugs have been evaluated in terms of cigarette smoking. Induction of liver enzymes has been shown to increase the metabolism of imipramine, meprobamate, oestrogens, pentazocine, phenylbutazone, theophylline and warfarin. Nicotine has been shown to inhibit diuresis, alter ulcer healing, impair subcutaneous absorption, affect protein binding and stimulate catecholamine release; these effects have been evaluated in terms of therapy with frusemide (furosemide), histamine H2-antagonists, insulin, lignocaine (lidocaine) and beta-blockers, respectively. The interactions have not been correlated with clinical significance in all cases. Diminished end-organ responsiveness may account for reduced drowsiness in smokers receiving chlorpromazine and benzodiazepines, compared with non-smokers. Smoking has been associated with diminished pain tolerance, requiring increased dosages of morphine, pethidine (meperidine) and propoxyphene. Enzyme-inducers such as carbamazepine, phenytoin and phenobarbitone appear to be minimally affected by cigarette smoke, perhaps because hepatic enzymes are already maximally stimulated. Codeine, corticosteroids and nortriptyline do not appear to be affected by cigarette smoke. The bioavailability of glutethimide is higher in smokers, but this has not been associated with greater efficacy. The effect of smoking on paracetamol (acetaminophen) has been variable, depending on the extent of smoking, and does not appear to be of clinical significance.
authors.affiliation: Department of Family Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: L G
authors.initials: LG
authors.lastname: Miller
mesh_terms: D000818:Animals; D004358:Drug Therapy; D006801:Humans; D010599:Pharmacokinetics; D012907:Smoking / Q000378:metabolism*