Nicotine is an extremely addictive substance, acting on the hypothalamic
center, which controls arousal, concentration, and stress reduction. Nicotine
releases dopamine and norepinephrine, resulting in increased energy and
euphoria, improved concentration, improved hand-eye coordination, and
anorexia. A true drug dependence develops and physiologic withdrawal
occurs after the patient stops using nicotine. Psychological dependence is
also likely to occur, with cravings to start using tobacco again. Nicotine
withdrawal symptoms are more likely if the patient smokes more than 10
cigarettes per day. "Nicotine withdrawal syndrome" is characterized by at
least five of the following within 24 hours: (1) dysmorphic or depressed
mood; (2) insomnia; (3) irritability, frustration or anger; (4) anxiety, restlessness,
or impatience; (5) difficulty concentrating; (6) decreased heart
rate; (7) increased appetite or weight gain.
Because of the addictive properties of nicotine, all patients willing to
quit should also be offered pharmacotherapy unless there is a contraindication.
Medications increase smoking cessation rates and reduce withdrawal
symptoms. The first-line pharmacotherapies recommended are
sustained-release bupropion hydrochloride, nicotine gum, nicotine inhaler,
nicotine nasal spray, and the nicotine patch. The choice of a first-line medication
is determined by the clinician's familiarity with the medication,
the patient's previous experience with the medication, specific contraindications,
and patient characteristics (such as history of depression or
concern about weight gain). Second-line therapies, such as clonidine
hydrochloride and nortriptyline hydrochloride, are suggested when patients
are unable to use first-line therapies because of contraindications or when
first-line therapies fail. A summary of recommended medications is listed
.• Nicotine replacement therapy (NRT): Smokers should quit smoking
entirely before beginning nicotine replacement and should not resume
smoking during therapy.
• Transdermal nicotine patch: Several different transdermal patches are
available, and all have lower doses used during tapering. Full-dose
patches are recommended for most smokers for the first 1-3 months,
followed by 1-2 tapering doses for 2-4 weeks each. The main side effect
is local irritation. The patch is preferred by many clinicians because of
ease of instruction in use and fewer compliance problems compared to
• Nicotine gum: 2- and 4-mg gum is available over the counter. Users
should not chew too rapidly, chewing for 20-30 minutes per piece.
Instruction in use requires considerable education. Side effects are primarily
local and include jaw fatigue, sore mouth and throat, upset stomach,
• Nicotine nasal spray: Patients administer one spray per nostril when
they feel the urge to smoke. Because the resulting blood nicotine levelis higher than that produced by the patch or gum, it may be more effeclive than other NRT delivery systems in highly addicted smokers. Side
effects are irritation of the nose causing burning, sneezing, and watery
eyes; tolerance to these effects usually develops in 1-2 days.
• Nicotine vapor inhaler: The inhaler is marketed in a cigarette-like plastic
device and has a unique role because it fulfills the "hand-mouth"
behavior of smoking. It can be used as frequently as desired. Nearly 80
puffs are required to achieve nicotine doses equivalent to a cigarette.
• Bupropion: Smokers are more likely than nonsmokers to have a history
of major depression; nicotine may act as an antidepressant in some
smokers. Bupropion, an antidepressant, is effective in some smokers. It
is dosed at 150-300 mg per day for 7 days before quitting, then at 300
mg per day for the next 6-12 weeks. Bupropion can also be used in conjunction
with a nicotine patch. In excessive doses, bupropion can cause
seizures and should not be used in patients with a history of seizures or