Pharmacotherapy

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

as follows:

First-line medications

.• 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.

• 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,

and hiccups.

• Nicotine nasal spray: Patients administer one spray per nostril when

they feel the urge to smoke. Because the resulting blood nicotine level

is 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

eating disorders.

Second-line medications

• Clonidine

• Nortriptyline