Smoking Cessation Pharmacology

Nicotine addiction involves complex neurobiological mechanisms centered on the mesolimbic dopamine reward pathway. Inhaled nicotine reaches the brain within 10-20 seconds, binding to nicotinic acetylcholine receptors (nAChRs) — primarily alpha4beta2 subtypes — on ventral tegmental area (VTA) neurons. Receptor activation causes dopamine release in the nucleus accumbens, producing the reinforcing effects of smoking. Chronic nicotine exposure upregulates nAChR density (neuroadaptation), such that receptor desensitization during abstinence produces withdrawal symptoms: irritability, anxiety, difficulty concentrating, increased appetite, depressed mood, and intense cravings. The Fagerström Test for Nicotine Dependence (FTND) quantifies physical dependence on a 0-10 scale, with the most predictive item being time to first cigarette after waking (<5 minutes indicates severe dependence). Nicotine has a half-life of approximately 2 hours, explaining the frequency of smoking behavior. Cotinine, the primary metabolite via CYP2A6, has a 16-hour half-life and serves as a biomarker for tobacco exposure. Withdrawal symptoms peak within 24-72 hours and gradually diminish over 2-4 weeks, though psychological cravings can persist for months. The 5 A's framework structures clinical intervention: Ask about tobacco use, Advise to quit, Assess willingness, Assist with...