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LISA A. KROON, PHARM.D., is Associate Professor of Clinical Pharmacy, Department of Clinical Pharmacy, School of Pharmacy, University of California San Francisco, 3333 California Street, Suite 420, Box 0613, San Francisco, CA 94118 (kroonl{at}pharmacy.ucsf.edu).

Purpose. The mechanisms for drug interactions with smoking and clinically significant pharmacokinetic and pharmacodynamic drug interactions with smoking are reviewed. Summary. Polycyclic aromatic hydrocarbons (PAHs) are some of the major lung carcinogens found in tobacco smoke. PAHs are potent inducers of the hepatic cytochrome P-450 (CYP) isoenzymes 1A1, 1A2, and, possibly, 2E1. After a person quits smoking, an important consideration is how quickly the induction of CYP1A2 dissipates. The primary pharmacokinetic interactions with smoking occur with drugs that are CYP1A2 substrates, such as caffeine, clozapine, fluvoxamine, olanzapine, tacrine, and theophylline. Inhaled insulin’s pharmacokinetic profile is significantly affected, peaking faster and reaching higher concentrations in smokers compared with nonsmokers, achieving significantly faster onset and higher insulin levels. The primary pharmacodynamic drug interactions with smoking are hormonal contraceptives and inhaled corticosteroids. The most clinically significant interaction occurs with combined hormonal contraceptives. The use of hormonal contraceptives of any kind in women who are 35 years or older and smoke 15 or more cigarettes daily is considered contraindicated because of the increased risk of serious cardiovascular adverse effects. The efficacy of inhaled corticosteroids may be reduced in patients with asthma who smoke. Conclusion. Numerous drug interactions exist with smoking. Therefore, smokers taking a medication that interacts with smoking may require higher dosages than nonsmokers. Conversely, upon smoking cessation, smokers may require a reduction in the dosage of an interacting medication. Index terms: Contraceptives; Dosage; Drug interactions; Insulin; Insulins; Pharmacodynamics; Pharmacokinetics; Smoking; Steroids, cortico-; Toxicity

 

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