Microsoft word - 03 drug interactions with smoking.doc

DRUG INTERACTIONS WITH SMOKING
Many interactions between tobacco smoke and medications have been identified. Note that it is the tobacco smoke—not the
nicotine—that causes these drug interactions. Tobacco smoke may interact with medications through pharmacokinetic or
pharmacodynamic mechanisms. Pharmacokinetic interactions affect the absorption, distribution, metabolism, or elimination of other
drugs, potential y causing an altered pharmacologic response. The majority of pharmacokinetic interactions are the result of induction
of hepatic cytochrome P450 enzymes (primarily CYP1A2). Pharmacodynamic interactions alter the expected response or actions of
other drugs. The amount of tobacco smoking needed to have an effect has not been established and the assumption is that any
smoker is susceptible to the same degree of interaction. The most clinically significant interactions are depicted in the shaded rows.
DRUG/CLASS
MECHANISM OF INTERACTION AND EFFECTS
Pharmacokinetic Interactions
ƒ Plasma concentrations decreased up to 50% among tobacco smokers. ƒ Increased metabolism (induction of CYP1A2); clearance increased by 56%. ƒ Caffeine levels may increase after cessation. ƒ Decreased area under the curve (AUC) (36%) and serum concentrations (24%). ƒ Smokers may experience less sedation and hypotension and require higher dosages. ƒ Increased metabolism (induction of CYP1A2); plasma concentrations decreased 28%. ƒ Clearance increased by 61%; trough serum concentrations decreased by 25%. ƒ Smokers may require higher dosages. ƒ Increased metabolism (induction of CYP1A2); clearance increased by 24%; AUC decreased 31%; decreased plasma concentrations (32%). ƒ Dosage modifications not routinely recommended but smokers may require higher dosages. ƒ Clearance increased by 44%; serum concentrations decreased by 70%. ƒ Mechanism unknown but increased clearance and decreased half-life are observed. ƒ Smokers may require higher dosages. ƒ Insulin absorption may be decreased secondary to peripheral vasoconstriction; smoking may cause release of endogenous substances that antagonize the effects of insulin. ƒ Likely not clinically significant. Smokers may require higher dosages. ƒ Clearance (via oxidation and glucuronidation) increased by 25%; half-life decreased by 36%. ƒ Increased metabolism (induction of CYP1A2); clearance increased by 98%; serum ƒ Dosage modifications not routinely recommended but smokers may require higher dosages. ƒ Clearance (via side chain oxidation and glucuronidation) increased by 77%. ƒ Increased metabolism (induction of CYP1A2); half-life decreased by 50%; serum concentrations ƒ Increased metabolism (induction of CYP1A2); clearance increased by 58–100%; half-life ƒ Levels should be monitored if smoking is initiated, discontinued, or changed. ƒ Passive smoking (second-hand smoke) also increases the clearance. ƒ Maintenance doses are considerably higher in smokers. Tricyclic antidepressants ƒ Possible interaction with tricyclic antidepressants in the direction of decreased blood levels, but (e.g., imipramine, the clinical importance is not established. Pharmacodynamic Interactions
ƒ May be caused by central nervous system stimulation by nicotine. ƒ Less effective antihypertensive and heart rate control effects. ƒ May be caused by nicotine-mediated sympathetic activation; smokers may require higher ƒ Decreased analgesic effect; smoking may increase the metabolism of propoxyphene by 15– 20% and pentazocine by 40%. Mechanism unknown. ƒ Smokers may require higher opioid doses for pain relief. ƒ Increased risk of cardiovascular adverse effects (e.g., stroke, myocardial infarction, thromboembolism) in women who smoke and use oral contraceptives. ƒ Risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite Adapted from Zevin S, Benowitz NL. Drug interactions with tobacco smoking. Clin Pharmacokinet 1999;36:425–438. Copyright 1999-2006 The Regents of the University of California, University of Southern California, and Western University of Health Sciences. All rights reserved.

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