Nicotine - Drug Monograph

Introduction

Nicotine is a naturally occurring alkaloid found primarily in tobacco plants (Nicotiana tabacum) that acts as a stimulant and parasympathomimetic agent. While most commonly associated with tobacco products, nicotine is also available in various pharmaceutical formulations as a smoking cessation aid. This monograph focuses on the pharmacological properties and clinical use of medicinal nicotine products.

Mechanism of Action

Nicotine exerts its effects primarily by binding to nicotinic acetylcholine receptors (nAChRs) in the central and peripheral nervous systems. This binding activates the receptors, leading to the release of various neurotransmitters including dopamine, norepinephrine, serotonin, and endorphins. The dopamine release in the mesolimbic pathway is particularly responsible for nicotine's reinforcing properties and addictive potential. Nicotine also stimulates the adrenal medulla, resulting in epinephrine release.

Indications

• FDA-approved: Smoking cessation aid to relieve nicotine withdrawal symptoms
• Off-label uses: May be considered for ulcerative colitis maintenance therapy (investigational)
• Nicotine replacement therapy (NRT) is indicated as part of a comprehensive smoking cessation program

Dosage and Administration

• Transdermal patch (7, 14, 21 mg/24h)
• Gum (2, 4 mg)
• Lozenge (2, 4 mg)
• Nasal spray (0.5 mg/spray)
• Inhaler (10 mg/cartridge)

• Patch: Apply one patch daily to non-hairy, clean, dry skin site
• Gum: Chew 1 piece every 1-2 hours (max 24 pieces/day)
• Lozenge: Dissolve 1 lozenge every 1-2 hours (max 20 lozenges/day)
• Nasal spray: 1-2 sprays/hour (max 40 sprays/day)
• Inhaler: 6-16 cartridges/day

• Hepatic impairment: Use with caution
• Renal impairment: No dosage adjustment required
• Geriatric: Use lowest effective dose
• Pediatric: Not recommended under age 18

Pharmacokinetics

• Absorption: Variable by formulation; buccal and transdermal routes avoid first-pass metabolism
• Distribution: Widely distributed; crosses blood-brain barrier and placenta
• Metabolism: Primarily hepatic via CYP2A6 to cotinine and other metabolites
• Elimination: Renal elimination (5-10% unchanged); half-life approximately 2 hours
• Protein binding: <5%

Contraindications

• Hypersensitivity to nicotine or any product components
• Immediate post-myocardial infarction period
• Life-threatening arrhythmias
• Severe or worsening angina pectoris
• Pregnancy and breastfeeding (unless benefit outweighs risk)

Warnings and Precautions

• Cardiovascular risk: Use with caution in patients with cardiovascular disease
• Addiction potential: Nicotine replacement products may lead to dependence
• GI effects: May exacerbate peptic ulcer disease, esophagitis, or GERD
• Diabetes: May cause catecholamine release and affect glucose metabolism
• Renal/hepatic impairment: Use with caution
• Non-smokers: Not recommended for use by non-tobacco users

Drug Interactions

• Smoking: Concurrent smoking may lead to nicotine toxicity
• CYP2A6 inducers: Rifampin, phenobarbital may decrease nicotine levels
• CYP2A6 inhibitors: Methoxsalen, tranylcypromine may increase nicotine levels
• Adenosine: Nicotine may antagonize effects
• Beta-blockers: Nicotine may decrease efficacy
• Theophylline: Smoking cessation may increase theophylline levels
• Insulin: Requirements may decrease after smoking cessation

Adverse Effects

• Local irritation (patch, gum, inhaler)
• Hiccups (gum, lozenge)
• Nausea, vomiting
• Headache
• Dizziness
• Insomnia, abnormal dreams

• Cardiovascular events (tachycardia, hypertension, arrhythmias)
• Nicotine toxicity/overdose
• Severe allergic reactions
• Worsening of peripheral vascular disease

Monitoring Parameters

• Vital signs (especially blood pressure and heart rate)
• Smoking cessation progress
• Signs of nicotine toxicity (nausea, vomiting, dizziness, tachycardia)
• Local application site reactions
• Cardiovascular symptoms in at-risk patients
• Adherence to therapy

Patient Education

• Use exactly as prescribed for smoking cessation only
• Do not use while continuing to smoke or use other tobacco products
• Proper administration technique varies by formulation
• Store safely away from children and pets (nicotine is highly toxic in overdose)
• Dispose of patches carefully (retain significant nicotine after use)
• Report chest pain, irregular heartbeat, or severe nausea immediately
• Combine with behavioral support for best cessation outcomes
• Gradually taper use rather than stopping abruptly

References

1. Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol. 2009;49:57-71. 2. FDA prescribing information for various nicotine replacement products. 3. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012;11:CD000146. 4. Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update. 5. Zevin S, Benowitz NL. Drug interactions with tobacco smoking. Clin Pharmacokinet. 1999;36(6):425-438. 6. Benowitz NL, Hukkanen J, Jacob P 3rd. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol. 2009;(192):29-60.