Nicotine is a natural alkyloid that is a major component of cigarettes and is used therapeutically to help with smoking cessation. Nicotine has not been associated with liver test abnormalities or with clinically apparent hepatotoxicity.
Nicotine (nik' oh teen) is a liquid alkyloid that has a variety of activities in the body and central nervous system (CNS) acting largely as a stimulant via activation of nicotinic receptors. Nicotine is a CNS stimulant and has both stimulatory and depressant actions on autonomic ganglia. Use of nicotine in a program to stop smoking has been shown to increase the rate of smoking cessation in oral and transdermal forms. Nicotine is readily absorbed through the skin, mucous membranes and lungs. Oral nicotine can be taken as a gum (Nicorette: 2 or 4 mg each) or lozenge (2 or 4 mg) which is dissolved in the mouth and not swallowed or chewed. Nasal spray, inhaler (Nicotrol) and transdermal formulations (NicoDerm, Habitrol and others) are also used in smoking cessation programs. Most of these products are available over the counter, without prescription. The usually dose regimen varies by formulation and the dose is typically given in decreasing amounts with cigarette withdrawal. Cigarettes typically have 10-25 mg of nicotine each, and peak plasma nicotine levels are higher with cigarettes than with replacement products. Common side effects of nicotine include nausea, dyspepsia, nervousness, dizziness, headache, tachycardia and palpitations. Overdose of nicotine can cause mental confusion, faintness, hypotension, convulsions and respiratory failure.
Nicotine used in cigarette cessation programs has not been associated with serum enzyme elevations during therapy at rates greater than occurred with placebo. Medical uses of nicotine have not been associated with cases of clinically apparent liver injury.
Mechanism of Injury
Nicotine is metabolized extensively by many tissues including the liver and is rapidly excreted.
[Agents in clinical use to aid in smoking cessation and to treat nicotine withdrawal symptoms include bupropion, nicotine, and varenicline.]
REPRESENTATIVE TRADE NAMES
Nicotine – Generic, Commit®, Nicorette® (Oral); Habitrol® (Transdermal); Nicotrol® (Inhaler, Spray)
Substance Abuse Treatment Agents
Product labeling at DailyMed, National Library of Medicine, NIH
||CAS REGISTRY NUMBER
References Last Updated: 02 February 2014
Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999. (Expert review of hepatotoxicity published in 1999; nicotine is not discussed).
Hibbs RE, Zambon AC. Nicotine. Agents acting at the neuromuscular junction and autonomic ganglia. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the
pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp 270-2. (Textbook of pharmacology and therapeutics).
O'Brien CP. Nicotine. Drug addiction and drug abuse. In, Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006, pp. 615-7. (Textbook of pharmacology and therapeutics).
Molyneux A. Nicotine replacement therapy. BMJ 2004; 328: 454-6. PubMed Citation (Review of nicotine replacement therapy including mechanism of action, evidence of effectiveness, formulations, and safety; choice of product should be by patient preference; the products are safer than cigarettes and the only safety concerns relate to pregnant women and patients with heart disease).
Marsh HS, Dresler CM, Choi JH, Targett DA, Gamble ML, Strahs KR. Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: a 12-week, randomized, open-label study. Clin Ther 2005; 27: 1571-87. PubMed Citation (901 smokers with other medical conditions [mostly heart disease and diabetes] were treated with nicotine gum or lozenges for 12 weeks; nausea, hiccups and headache were the most common side effects; no mention of hepatotoxicity, but no instances of acute liver injury).
Dautzenberg B, Nides M, Kienzler JL, Callens A. Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges(Nicotinell). BMC Clin Pharmacol 2007; 7: 11. PubMed Citation (Use of nicotine lozenges even in higher than recommended amounts was not associated with any "clinically significant changes" in serum enzyme levels).
Shiffman S, Sweeney CT. Ten years after the Rx-to-OTC switch of nicotine replacement therapy: what have we learned about the benefits and risks of non-prescription availability? Health Policy 2008; 86: 17-26. PubMed Citation (Systematic review of literature and adverse event reporting on nicotine replacement therapy, which has been marketed "without incident as a non-prescription product in 33 countries...").
Moore D, Aveyard P, Connock M, Wang D, Fry-Smith A, Barton P. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. BMJ 2009; 338: b1024. PubMed Citation (Systematic review of literature on efficacy and safety of nicotine replacement therapy for smoking cessation; no serious adverse events were attributed to nicotine therapy; no mention of liver injury or ALT levels).
Ossip DJ, Abrams SM, Mahoney MC, Sall D, Cummings KM. Adverse effects with use of nicotine replacement therapy among quitline clients. Nicotine Tob Res 2009; 11: 408-17. PubMed Citation (Follow up interviews were conducted on 33,690 smokers who were given nicotine replacement therapy; 25% reported adverse events, but these were largely non-specific and mild without mention of liver injury).
Safety of smoking cessation drugs. Med Lett Drugs Ther 2009; 51(1319): 65. PubMed Citation (Concise review of safety of medications used for smoking cessation; nicotine replacement therapy is not discussed).
McNeil JJ, Piccenna L, Ioannides-Demos LL. Smoking cessation-recent advances. Cardiovasc Drugs Ther 2010; 24: 359-67. PubMed Citation (Review of mechanisms of action, efficacy and safety of smoking cessation therapies; hepatotoxicity is not discussed).
OTHER REFERENCE LINKS
Top of page