Nicotine and Tobacco

Roughly one-quarter of adults in the United States smoke tobacco products. Further, millions of smokers use nicotine replacement therapies (NRTs) as aids to quit smoking. NRTs are available in several forms including oral forms (gum, lozenge), transdermal patch, nasal spray, and vapor inhaler. Because of the high prevalence of smoking and use of NRTs, it is important that clinicians be aware of potential drug interactions that may occur. Nicotine and tobacco constituents may influence metabolic rates by induction or inhibition of enzyme systems. Nicotine is mainly metabolized in the liver to cotinine by the enzyme CYP2A6. Cigarette smoke contains literally thousands of compounds, among which polycyclic aromatic hydrocarbons (PAHs) are primarily responsible for its enzyme-inducing characteristics. PAHs have been shown to induce primarily three cytochrome P450 enzymes (e.g., CYP1A1, CYP1A2, and CYP2E1) as well as glucuronosyltransferases. Nicotine has been shown to interact with numerous drugs including alcohol, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, caffeine, carbon tetrachloride, cimetidine, cocaine, nitrates, opioids, and phencyclidine. Tobacco has been shown to interact with alcohol, analgesics/antipyretics, anticoagulants, antidepressants, antipsychotics, benzodiazepines, caffeine, carbamazepine, cardiovascular drugs, insulin, opioids, steroid hormones, tacrine, and theophylline. The only drug class contraindicated for smokers are combined oral contraceptives. Specifically, because of cardiovascular risk in smokers, combined oral contraceptives are considered contraindicated in heavy smokers who are older than 35 years. In addition, people who smoke, or people who stop smoking, may require dosage adjustments when using some medications including acetaminophen, caffeine, imipramine, oxazepam, pentazocine, propranolol, theophylline, insulin, adrenergic antagonists, and adrenergic agonists. This chapter will discuss the underlying evidence regarding these potential drug interactions.