Nicotine Use Disorder Drugs

Core Concepts

Nicotine and the nicotinic acetylcholine receptor

Nicotine's target is the nAChR, an ion channel normally activated by acetylcholine. Nicotine binds these receptors — particularly the α4β2 subtype on dopamine neurons in the ventral tegmental area — and triggers dopamine release in the nucleus accumbens, the same reward pathway hijacked by other addictive substances. This dopamine surge is why smoking is reinforcing — and why quitting temporarily worsens concentration.

Two more facts anchor the pharmacology:

• Tolerance develops quickly. Receptors desensitize, so the smoker needs more nicotine for the same effect and feels withdrawal when levels drop (e.g., overnight).
• Nicotine is not the main killer. Tar, carbon monoxide, and carcinogens from combustion cause most tobacco-related disease. This is the rationale for NRT: deliver nicotine to relieve withdrawal while removing the smoke.

Nicotine replacement therapy (NRT)

NRT supplies nicotine by a cleaner route so the person can stop smoking without full withdrawal. Forms differ mainly in kinetics:

• Transdermal patch — slow, steady delivery over many hours; good baseline control but cannot be adjusted for acute cravings.
• Gum and lozenges — intermittent, user-controlled; good for breakthrough cravings but easy to misuse (gum should be "parked" between cheek and gum, not chewed like regular gum).
• Inhaler and nasal spray — faster absorption, closer to the ritual and speed of a cigarette; sprays can irritate the nose.

NRT is generally much safer than continuing to smoke because it eliminates combustion products. Nurses teach correct use per package directions and provider orders.

Varenicline: the partial-agonist strategy

Varenicline is a partial agonist at α4β2 nicotinic receptors — the same conceptual move used in opioid treatment. It does two things at once:

• Partial stimulation relieves craving and withdrawal, like a weak nicotine substitute.
• Receptor occupancy blocks nicotine from binding, so a lapse produces much less reward.

This "reduce the reward, reduce the withdrawal" combination makes varenicline one of the most effective single agents for cessation. It is started before the quit date so receptor levels build up; the schedule is prescribed and titrated, with psychiatric and cardiac considerations assessed by the care team.

Bupropion: a different mechanism

Bupropion reduces craving and withdrawal through a mechanism not fully understood but believed to involve inhibition of dopamine and norepinephrine reuptake, boosting these neurotransmitters in reward and attention circuits. It is also used as an antidepressant, but for cessation it is prescribed for that indication specifically. It is started about a week before the quit date (per prescriber order) to build steady-state levels. Because it lowers the seizure threshold, candidacy is a prescriber decision.

Withdrawal, relapse, and the chronic-disease view

Nicotine withdrawal peaks in the first days to weeks: craving, irritability, anxiety, poor concentration, insomnia, increased appetite. Relapse is common — most successful quitters needed multiple attempts — so treat it like other chronic disorders: sustained support, repeat counseling, re-prescribing when needed.

The nursing role: every encounter counts

A widely used framework is the 5 A's: Ask about tobacco use at every visit, Advise quitting in a clear personalized way, Assess readiness to change, Assist with counseling and pharmacotherapy, and Arrange follow-up. Nurses also educate about secondhand smoke risks and encourage smoke-free environments. Scope and available resources vary by setting and jurisdiction.

Safety note: This is an educational overview of drug classes and mechanisms. NRT products and cessation medications have specific indications, contraindications, and instructions determined by prescribers and product labeling — verify all dosing and use instructions against current references, the formulary, and prescriber orders.

Common Confusions