The chemicals in tobacco smoke may interact with medications through pharmacokinetic or pharmacodynamics mechanisms.1, 2
The chemical compounds in tobacco smoke—known as polycyclic aromatic hydrocarbons— induce hepatic (liver) enzymes: cytochrome (CYP) P450 iso-enzymes. 1A2 is the most clinically significant as many medications are substrates of 1A2.3, 4 Induction of these enzymes may result in an increase in metabolism of many medications (that are substrates) and cause a subsequent decrease in blood concentration levels.1 Stopping smoking results in the opposite effect—a decrease in metabolism of certain medications and an increase in blood concentration levels.1
Nicotine in nicotine replacement therapy (or nicotine e-cigarettes) does not influence CYP activity.5 Examples of medications that are CYP substrates include clozapine and olanzapine (antipsychotic medications),4 warfarin (an anticoagulant that helps prevent blood clots),6 and theophylline (which treats lung diseases).7
Pharmacodynamic interactions with smoking are largely due to nicotine. Nicotine can counter the pharmacological actions of certain medications because it activates the sympathetic nervous system.1, 2 Examples of medications affected by pharmacodynamic interactions due to smoking include beta-blockers (which reduce blood pressure) and benzodiazepines (which are often used to treat anxiety and sleep).2
As the effects of smoking (and stopping smoking) on some medications can cause changes in therapeutic response and the risk of adverse effects, people taking medications should be regularly monitored with regard to smoking status, extent of cigarette consumption and the doses of relevant medications adjusted accordingly.5
See Section 3.15.2 for additional discussion of the interaction between smoking and medications, and Section 9A.3 for an overview of how smoking and smoking cessation can affect psychiatric medications. Pharmacotherapies for smoking cessation are covered in detail in Section 7.16.
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1. Kroon LA. Drug interactions with smoking. American Journal of Health System Pharmacy, 2007; 64(18):1917-21. Available from: https://doi.org/10.2146/ajhp060414
2. Zevin S and Benowitz NL. Drug interactions with tobacco smoking: An update. Clinical Pharmacokinetics, 1999; 36(6):425-38. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10427467
3. Zhou S-F, Yang L-P, Zhou Z-W, Liu Y-H, and Chan E. Insights into the Substrate Specificity, Inhibitors, Regulation, and Polymorphisms and the Clinical Impact of Human Cytochrome P450 1A2. The AAPS Journal, 2009; 11(3):481-94. Available from: https://doi.org/10.1208/s12248-009-9127-y
4. Boksa P. Smoking, psychiatric illness and the brain. Journal of Psychiatry & Neuroscience, 2017; 42(3):147–9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28440208
5. Lucas C and Martin J. Smoking and drug interactions. Australian Prescriber, 2021; 36:102-4. Available from: https://www.nps.org.au/australian-prescriber/articles/smoking-and-drug-interactions
6. Nathisuwan S, Dilokthornsakul P, Chaiyakunapruk N, Morarai T, Yodting T, et al. Assessing Evidence of Interaction Between Smoking and Warfarin: A Systematic Review and Meta-analysis. Chest, 2011; 139(5):1130-9. Available from: https://doi.org/10.1378/chest.10-0777
7. Baxter K and Preston C. Stockley’s Drug Interactions, 2020, Pharmaceutical Press: London. Available from: www.medicinescomplete.com.