Smoking in patients receiving psychotropic medications - A pharmacokineticperspective

Many psychiatric patients smoke, and are believed to be heavier smokers tha n those without psychiatric disorders. Cigarette smoking is one of the envi ronmental factors that contributes to interindividual variations in respons e to an administered drug. Polycyclic aromatic hydrocarbons (PAHs) present in cigarette smoke induce hepatic aryl hydrocarbon hydroxylases, thereby in creasing metabolic clearance of drugs that are substrates for these enzymes . PAHs have been shown to induce 3 hepatic cytochrome P450 (CYP) isozymes, primarily CYP1A1, 1A2 and 2E1. Drug therapy can also be affected pharmacody namically by nicotine. The most common effect of smoking on drug dispositio n in humans is an increase in biotransformation rate, consistent with induc tion of drug-metabolising enzymes. Induction of hepatic enzymes has been sh own to increase the metabolism and to decrease the plasma concentrations of imipramine, clomipramine, fluvoxamine and trazodone. The effect of smoking on the plasma concentrations of amitriptyline and nortriptyline is variabl e. Amfebutamone (bupropion) does not appear to be affected by cigarette smo king. Smoking is associated with increased clearance of tiotixene, fluphena zine, haloperidol and olanzapine. Plasma concentrations of chlorpromazine a nd clozapine are reduced by cigarette smoking. Clinically, reduced drowsine ss in smokers receiving chlorpromazine, and benzodiazepines, compared with nonsmokers has been reported. Increased clearance of the benzodiazepines al prazolam, lorazepam, oxazepam, diazepam and demethyl-diazepam is found in c igarette smokers, whereas chlordiazepoxide does not appear to be affected b y smoking. Carbamazepine appears to be minimally affected by cigarette smok e, perhaps because hepatic enzymes are already stimulated by its own autoin ductive properties. Cigarette smoking can affect the pharmacokinetic and ph armacodynamic properties of many psychotropic drugs. Clinicians should cons ider smoking as an important factor in the disposition of these drugs.