Cigarette Smoking and Clinically Significant Drug Interactions

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Abstract
Objective: To review clinically significant drug interactions associated with cigarette smoking. Data Sources: Data from scientific literature were identified by using a MEDLINE search. Data were extracted, evaluated, and summarized for this review. Study Selection: Findings and experiences were selected from clinical, epidemiologic, and pharmacokinetic studies; review articles; case studies; abstracts; letters to the editor; and proceedings. Data Extraction: Data from human studies published in English were evaluated. Only interactions deemed clinically significant are included in this review. Conclusions derived from review articles on the subject of smoking and drug interactions also were used. Data Synthesis: Cigarette smoking can affect drug therapy via pharmacokinetic and pharmacodynamic mechanisms. Pharmacokinetic drug interactions are presented for theophylline, tacrine, insulin, flecainide, propoxyphene, propranolol, diazepam, and chlordiazepoxide. Pharmacodynamic interactions are described for antihypertensive and antianginal agents, antilipidemics, oral contraceptives, and histamine2-receptor antagonists. Conclusions: Cigarette smoking can reduce the efficacy of certain drugs or make drug therapy more unpredictable. Pharmacokinetic interactions may cause smokers to require a larger dosage of certain drugs through an increase in plasma clearance, a decrease in absorption, an induction of cytochrome P450 enzymes, or a combination of these factors. Pharmacodynamic interactions may increase the risk of adverse events in smokers with cardiovascular or peptic ulcer disease, and in women who smoke and use oral contraceptives. Healthcare professionals should pay special attention to patients with these profiles and should try to prevent cigarette smoking or encourage patients to discontinue this addictive habit.