Smoking Cessation Agents
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Authored by: Tdwalsh 08:15, 25 September 2007 (PDT)
Contents |
Smoking Cessation
The risks of tobacco use are well documented. A study published in the British Medical Journal followed approximately 34,000 physicians between the years of 1951 and 2001 – this study showed that those who smoked were at an increased risk for cancer and vascular disease, as well as early mortality.[1] Fortunately, it appears that some of the damage done by smoking is reversible – data published in the American Journal of Public Health suggests that smoking cessation may increase a smoker’s lifespan by as much as 8.5 years in men or 7.7 years in women.[2] Sadly, smoking cessation is complicated by nicotine’s addictive effects. Nicotine withdrawal – which is characterized by symptoms such as insomnia, irritability, anxiety and cravings – usually starts between 4 to 6 hours after the last dose of the drug. (Nicotine’s T1/2 is around 2 hours.) Nicotine’s addiction potential appears to be related to its action at nicotinic acetylcholine receptors in the brain – when nicotine binds to these receptors, it triggers a cascade which culminates in the release of dopamine. (Dopamine release has been implicated as the cause of several types of drug dependence.) Certain behaviors (such as opening a package of cigarettes) can be so strongly linked to the chemically-rewarding behavior of tobacco use that they cause a release of dopamine even in the absence of nicotine.[3] Behavioral modification is an important part of any smoking cessation regimen, but pharmacologic aids also exist. These range from simple nicotine replacement therapy, to bupropion (which modulates dopamine levels), to varenicline (a partial agonist at nicotine receptors). While these drugs do not in any way ‘cure’ nicotine addiction, they do help alleviate withdrawal symptoms and reduce the urge to smoke. When a patient initiates a smoking cessation regimen, special care should be paid to his or her medication regimen. Nicotine affects the pharmacokinetics and pharmacodynamics of many drugs. Patients whose medication regimens have been tailored to account for their nicotine use should be watched for potential overdoses or underdoses which could result from the removal of nicotine.[4]
Description of Nicotine
Nicotine replacement therapy is available in numerous dosage forms – these include chewable gum, patches, intranasal spray and solution for inhalation. This therapy allows the patient to avoid withdrawal symptoms and cravings. As the treatment progresses, the dose is decreased – ideally, by the time nicotine replacement therapy is stopped, the patient is able to abstain from smoking. Though a significant risk of relapse still exists with nicotine replacement, it is much smaller compared to the risk of relapse when a smoker attempts to quit with no pharmacologic intervention.[5] Nicotine replacement therapy presents some possibility of toxicity. Possible side effects include headache, nausea, dizzness, or excessive salivation. (Cardiac toxicity has also been seen at high doses.) These side effects are dose-dependent.[6]
Description of Bupropion
The mechanism of action by which bupropion works (either in smoking cessation or in depression) is uncertain. The drug is known to inhibit dopamine re-uptake – this effect is presumably responsible for its actions in smokers.[7] Some care should be used when prescribing bupropion. The drug has been shown to decrease seizure threshold – seizure rate is roughly 0.1% with the 300 mg dose. (This effect is dose dependent.) Additionally, bupropion appears to have some potential to worsen depression or increase risk of suicide. This effect appears to be related to age, though – in clinical trials, bupropion increased suicides at a rate of 14 cases per 1,000 patients in patients below the age of 18. Between the ages of 18 and 24, however, the increase was only 5 cases per 1,000 patients. No increase in suicides was seen above the age of 24.[7]
Description of Varenicline
Varenicline is a selective α4β2 nicotinic acetylcholine receptor partial agonist. The dopamine release triggered by varenicline is smaller than that triggered by nicotine – this means that the drug helps to alleviate withdrawal symptoms, but does not trigger the kind of euphoria associated with nicotine. Varenicline also blocks nicotinic acetylcholine receptors from nicotine activation, which decreases the reward patients receive if they relapse back into tobacco use.[3] The most common adverse effect seen in clinical trials was nausea, which was seen in up to 30% of patients. (The drop-out rate due to nausea was only 3%.) This side effect it dose dependent, so patients who cannot tolerate it may benefit from a reduced dose. Taking varenicline with food may also help to ameliorate this problem.[8]
Description of Mecamylamine
Mecamylamine is nicotinic receptor antagonist. Though usually used to treat hypertension, it can also be used for smoking cessation. (The FDA has not approved the drug for this indication.) Not surprisingly, dizziness and/or hypotension were commonly reported with this drug. Various GI side-effects (such as nausea, vomiting, or constipation) have also been seen.[9]
Description of Clonidine
Clonidine, which is most often used as an antihypertensive, acts as an agonist at α-adrenoreceptors in the brain. This reduces the sympathetic action of the central nervous system, causing decreased vascular resistance, heart rate and blood pressure. Inhibition of sympathetic nervous system action may also explain clonidine’s ability to alleviate nicotine withdrawal symptoms.[10] Not surprisingly, commonly reported side effects of clonidine include dizziness and drowsiness (with 16% and 33% incidence respectively). Dry mouth was seen in nearly 40% of patients. These side effects are most likely dose related, and often diminish as the course of therapy continues.[10]
Description of Naltrexone
Naltrexone acts by blocking several types of opioid receptors, though it exhibits the highest affinity at mμ receptors. This blockade reduces or eliminates the rewarding effects of addictive drugs which act at opioid receptors. (Unlike other drugs indicated for use in addiction, naltrexone does not produce adverse effects if a patient uses it concomitantly with an opioid agonist.) Why naltrexone helps to alleviate nicotine’s withdrawal symptoms is unclear – the fact that it does, however, suggests that opioid receptors may play an as-yet-unknown role in nicotine addiction.[11][12] In clinical trials, the most commonly observed side effects included nausea, insomnia, headache and anxiety. These adverse reactions did not appear to be dose-dependent, but most patients considered them to be mild to moderate in severity.[11]
Medications in This Class
References
- ↑ Doll R, Peto R, Boreham J, and Sutherland I. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 2004 June 26; 328:1519-1533
- ↑ Taylor DH, Hasselblad V, Henley J, Thun MJ and Sloan FA. Benefits of smoking cessation for longevity. Am J Public Health 2002 June; 92(6):990-996.
- ↑ 3.0 3.1 Foulds J. The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. Int J of Clin Pract. 2006 May; 60(5):571-576.
- ↑ Zevin S and Benowitz NL. Drug interactions with tobacco smoking: and update. Clinical Pharmacokinetics. 1999 June; 36(6):425-438.
- ↑ Silagy C, Mant D, Fowler G, Lodge M. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet. 1994 January 15; 343(8890);139-142.
- ↑ Dale LC, Hurt RD, Offord KP, Lawson GM, Croghan IT, and Schroeder DR. High-dose nicotine patch therapy: percentage of replacement and smoking cessation. JAMA. 1995 November 1; 274(17):1353-1358.
- ↑ 7.0 7.1 Zyban (bupropion hydrochloride sustained-release tablets) prescribing information. Greenville, NC: GlaxoSmithKline. 2007 August.
- ↑ Chantix® (varenicline) package insert. New York, NY: Pfizer, Inc.; 2007 May.
- ↑ Inversine (mecamylamine) package insert. Winston-Salem, NC: Targacept Inc; 2002, July.
- ↑ 10.0 10.1 Catapres (clonidine hydrochloride) package insert. Mexico City, Mexico: Boehringer Ingelheim International GmbH; 2007 Jaunary 5.
- ↑ 11.0 11.1 Vivitrol (naltrexone for extended-release injectable suspension) package insert. Cambridge, MA: Alkermes, Inc.; 2006 April 5.
- ↑ Brauer LH, Behm FM, Westman EC, Patel P and Rose JE. Naltrexone blockade of nicotine effects in cigarette smokers. Psychopharmacology 1999 April; 143(4):339-346.
