Drug Interactions with Tobacco Smoking

Abstract

Cigarette smoking remains highly prevalent in most countries. It can affect drug therapy by both pharmacokinetic and pharmacodynamic mechanisms. Enzymes induced by tobacco smoking may also increase the risk of cancer by enhancing the metabolic activation of carcinogens. Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for the induction of cytochrome P450 (CYP) 1A1, CYP1A2 and possibly CYP2E1, CYP1A1 is primarily an extrahepatic enzyme found in lung and placenta. There are genetic polymorphisms in the inducibility of CYP1A1, with some evidence that high inducibility is more common in patients with lung cancer. CYP1A2 is a hepatic enzyme responsible for the metabolism of a number of drugs and activation of some procarcinogens. Caffeine demethylation, using blood clearance or urine metabolite data, has been used as an in vivo marker of CYP1A2 activity, clearly demonstrating an effect of cigarette smoking, CYP2E1 metabolises a number of drugs as well as activating some carcinogens. Our laboratory has found in an intraindividual study that cigarette smoking significantly enhances CYP2E1 activity as measured by the clearance of chlorzoxazone. In animal studies, nicotine induces the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown. Similarly, although inhibitory effects of the smoke constituents carbon monoxide and cadmium on CYP enzymes have been observed in vitro and in animal studies, the relevance of this inhibition to humans has not yet been established. The mechanism involved in most interactions between cigarette smoking and drugs involves the induction of metabolism. Drugs for which induced metabolism because of cigarette smoking may have clinical consequence include theophylline, caffeine, tacrine, imipramine, haloperidol, pentazocine, propranolol, flecainide and estradiol. Cigarette smoking results in faster clearance of heparin, possibly related to smoking-related activation of thrombosis with enhanced heparin binding to antithrombin III. Cutaneous vasoconstriction by nicotine may slow the rate of insulin absorption after subcutaneous administration. Pharmacodynamic interactions have also been described. Cigarette smoking is associated with a lesser magnitude of blood pressure and heart rate lowering during treatment with beta-blockers, less sedation from benzodiazepines and less analgesia from some opioids, most likely reflecting the effects of the stimulant actions of nicotine. The impact of cigarette smoking needs to be considered in planning and assessing responses to drug therapy. Cigarette smoking should be specifically studied in clinical trials of new drugs.

Effects of nicotine on cytochrome P450 2A6 and 2E1 activities

“…Cigarette smoking accelerates the metabolism of certain drugs, particularly those primarily metabolized by cytochrome P450 1A2 (CYP1A2) and, to a lesser extent, CYP2E1 and some UDP-glucuronosyltransferases [1,2]. The induction of CYP1A2 is mediated via binding of polycyclic aromatic hydrocarbons of the tobacco smoke to the aryl hydrocarbon receptor with consequent transcriptional activation of CYP1A2 gene, whereas the mechanism of CYP2E1 induction is usually the stabilization of CYP2E1 mRNA and protein [3].…”

Tobacco Use and Its Treatment Among Young People in Mental Health Settings: A Qualitative Analysis

“…Tobacco use can complicate psychiatric treatment, increasing the metabolism of some antipsychotic and antidepressant medications (Zevin & Benowitz, 1999). In prospective studies, tobacco use is one of the strongest predictors of suicidal behavior in youth and adults, even after controlling for depressive symptoms, other substance use, and prior suicidal behavior (Breslau, Schultz, Johnson, Peterson, & Davis, 2005;Oquendo et al, 2004).…”

Nicotine and symptoms of schizophrenia: the 2017 picture

“…This topic began to be deliberated upon in the 1970s and 1980s. Another relevant aspect was eventually found to be the fact that the aromatic hydrocarbons in cigarette smoke induce catabolic cytochrome enzymes (Zevin andBenowitz 1999, Desai et al 2001). As such, heavy cigarette smokers -those who smoke more than ten cigarettes per day -require higher doses of psychotropic drugs.…”