Smoking cessation

This chapter will outline the epidemiology, pathophysiology, and treatment of cigarette smoking with particular emphasis on current pharmacotherapies including nortriptyline, clonidine, nicotine replacement, bupropion, and varenicline. Cigarette smoking is a chronic relapsing disorder with secondary complications including atherosclerotic cardiovascular disease, chronic obstructive pulmonary disease (COPD), and lung cancer. Nicotine as an addictive euphoriant is comparable to amphetamines, cocaine, or opiates. Nicotinic acetylcholine receptors in the central nervous system regulate downstream neurotransmitter release. Smoking leads to about one-third of deaths from coronary artery disease (CAD), the most common cause of morbidity and mortality in the developed world. Active and passive smoke exposure leads to increases in oxidative stress, vascular inflammation, blood coagulability, platelet aggregation, and thrombus formation as well as reduced oxygen delivery and coronary vasoconstriction. Heart disease risk drops off significantly after 1-2 years of cessation and normalizes at 3-5 years. Smoking abstinence rates at 6-12 months in motivated quitters without behavioral or pharmacologic therapy approach 3-5%. Because the subject characteristics and the support offered differ across clinical trials, the most conventional means to assess the effect of pharmacotherapy is the quit rate relative to placebo. When compared to placebo, pharmacotherapy doubles or triples quit rates achieved by nonpharmacological means. A number of novel smoking cessation pharmacotherapies have followed in the wake of recent insights into nicotine addiction. Several cannabinoid receptor antagonists are in development. One such cannabinoid receptor antagonist, rimonobant, demonstrated efficacy but did not lead to drug approval due to concerns of toxicity.