I Get By With a Little Help From My Friends: The
Pharmacotherapy of Smoking Cessation
by John A. Wolfe, RRT, CPFT
Seventy percent of adult smokers
want to quit, and many have made countless attempts, only to
be frustrated by repeated failures to remain smoke-free over
the long term. The highly addictive nature of nicotine is
augmented by the strong habitual association between smoking
and daily routines. The combination of physiological addiction
and psychological dependence aggravated by ready availability
creates a potent synergy. Pharmacotherapy for smoking
cessation has provided a critical lifeline, increasing both
long- and short-term success in transitioning to a smoke-free
The tobacco plant, Nicotiana tabacum, has
been cultivated in the Americas for thousands of years and was
exported to Europe almost immediately upon its discovery in
the so-called New World. The pleasurable effects of tobacco
chewing or smoking are attributable to nicotine (C10H14N2), a
naturally occurring alkaloid. Nicotine also represents the
addictive component of tobacco. Each cigarette contains 8 to
20 mg of nicotine, but only about 1 to 3 mg are actually
absorbed into the body. Experience has shown that so-called
“light” cigarettes, with lower measured tar and nicotine
levels, are by no means safer, and smokers typically alter
subtleties of their inhalation patterns to obtain and maintain
nicotine levels comparable to those of standard cigarettes.
Once inhaled, nicotine enters the bloodstream,
and the effects are evident in as little as 10 to 15 seconds.
It has a half-life of approximately 60 minutes, and is
primarily broken down by liver enzymes and excreted in the
urine as cotinine. Cotinine has a 24-hour half-life, and its
presence is frequently used for screening purposes, including
the screening of nonsmoking children of parents who smoke.
Pharmacotherapy for smoking cessation addresses the addictive
nature of nicotine either by providing direct nicotine
replacement in a much less unhealthy form than cigarettes and
chew, or by placating the effects of nicotine with an
alternative, nonaddictive substitute.
How Nicotine Works
Nicotine users often report that smoking
invigorates them, while simultaneously reporting that it has a
relaxing effect. The biphasic effect of the drug is not
unusual. Alcohol, for example, can have similar effects
depending on the amount consumed. The initial physiological
action causes a release of adrenaline, stimulating the
familiar “fight or flight” response and a corresponding
increase in blood pressure, heart rate, and rapid shallow
breathing, as the body prepares to escape from danger or
Nicotine stimulates the release of acetylcholine,
while also mimicking its action. Like acetylcholine, nicotine
affects the nervous system by stimulating activity at the
synapse where communication takes place between neurons, and
creating a burst of activity. Unlike acetylcholine, nicotine
activates cholinergic neurons in many regions of the brain
simultaneously. This promotes the release of dopamine, an
important neurotransmitter in the reward pathways of the
brain. It also stimulates the brain to produce more
endorphins. Nicotine stimulates the norepinephrine and
serotonin systems, enhancing concentration and memory and
decreasing anxiety. Users feel energized and satisfied and
they want more. The body quickly adapts to repeated nicotine
exposures, and the brain, in a sense, rewires itself to
compensate for the chemical imbalances imposed by the drug.
When nicotine is withdrawn, the physiological adaptations
remain, and the individual is left feeling extremely
uncomfortable. Cravings, anxiety, depression, and irritability
are all manifestations of nicotine withdrawal.
Although the health risks of smoking are well
documented and generally associated with other toxins in
tobacco, even small doses of nicotine are toxic, as evidenced
by its use as a commercial pesticide. Symptoms of nicotine
poisoning include nausea, vomiting, headaches, dyspnea, and
seizures. It can be lethal, even in small doses, and children
who ingest cigarettes are at the highest risk of toxicity.
Nicotine Replacement Therapy
Subsequent to a smoking ban instituted by the Royal
Swedish Navy, submarine crewmen were observed as being
ill-tempered and distracted as they coped with the affects of
nicotine withdrawal. The Swedish government requested
assistance from a pharmaceutical company, and in 1967 Ove
Ferno, a researcher at Pharmacia (now merged with Pfizer),
developed a nicotine replacement gum to placate the symptoms
of withdrawal. It was registered as a pharmaceutical and made
available to the general population in 1978. Nicotine
replacement therapy (NRT) was thus born. NRTs are now
available in numerous delivery formulations, and each has
specific and unique applications. NRTs help relieve nicotine
cravings without the carcinogens, carbon monoxide, and other
toxins found in cigarettes.
Providing nicotine replacement therapy is both a
science and an art. Although the benefits of NRTs are well
documented in peer-reviewed journals, achieving optimal
results is a challenge. Choosing the appropriate mix of NRTs
and other pharmaceutical options and integrating them with an
individualized quit plan is a skill that benefits from
experience. Unfortunately, many clinicians have neither the
inclination, the time, nor the training to work with the
patient to achieve the desired outcome. Only about half of
current smokers recall having been asked about their smoking
status, or being urged to quit by a doctor.1 And a
majority of US medical school graduates are not adequately
trained to treat nicotine dependence.2-4 Nursing
and respiratory therapy schools are just beginning to
integrate smoking cessation into the curriculum.
Nicotine gum is used in place of cigarettes as
soon as the patient stops smoking—10 to 15 pieces a day is
typical. It is essential that patients be instructed in
correct technique for using the gum to avoid releasing the
nicotine too rapidly. Nicotine inhalers utilize a plastic
cylinder containing a cartridge that delivers nicotine when
the user puffs on it. The cartridges last for about 20 minutes
of active puffing. It offers a convenient and feasible
alternative to cigarettes for patients who are not ready or
willing to abruptly quit. Nicotine lozenges release small
amounts (2 mg and 4 mg) of nicotine that is absorbed in the
mucosa of the mouth and gums. It should be allowed to dissolve
slowly—not chewed or swallowed. Nicotine nasal spray delivers
nicotine to the nasal membranes, and reaches the bloodstream
faster than any other NRT formulations.
The ubiquitous nicotine patch enables patients to
control cravings and withdrawal symptoms while they transition
to a nonsmoking status. It is commonly available in 5 mg, 10
mg, and 15 mg dosages, which are released over a 16- to
24-hour period and may or may not be removed at night
(depending on brand). The patch is composed of three layers: a
backing layer on top, a middle layer containing the
pharmaceutical, and a bottom layer that releases the drug into
the skin. Although treatment regimes vary, patients typically
begin by taking the largest dose for approximately 8 weeks,
while they deal with the psychosocial aspects of quitting.
They subsequently transition to the lower doses for 2 weeks at
a time, so that they are finished with the course of therapy
in about 3 months. Although the net amount of nicotine
delivered is less than with active smoking, the patient
experiences a steady dose of nicotine in the blood without the
swings in level associated with smoking. Itching and redness
are the most common side effects. Patch sites should be
As with cigars, cigarettes, and chew, NRTs should
not be used by pregnant or nursing mothers. Nicotine is
associated with increased miscarriage, it is known to be
harmful to fetal development, and it passes into breast milk.
Although NRTs can be combined with other forms of
pharmacotherapy, patients should obviously avoid smoking while
using the nicotine replacements. Unlike many other
pharmaceuticals, NRTs need to be used as part of a
comprehensive and ongoing care plan that includes counseling
Bupropion is primarily recognized as an
antidepressant, and was initially marketed for that purpose.
The mechanism of action is not well understood, but it is
theorized that its dopaminergic and noradrenergic actions
could be responsible for its efficacy in smoking cessation.
Repeated use of bupropion, even among patients who had
previously used bupropion in failed smoking cessation
attempts, can be successful. One study demonstrated that 27%
of participants receiving bupropion SR remained abstinent
compared with 5% of participants receiving
placebo.5 Patients should begin using bupropion 2
weeks before their quit date and continue using it for 6
months or more for best results. Experienced smoking cessation
counselors frequently endorse the use of bupropion in
conjunction with NRTs for maximum benefit.
Clonidine and Nortriptyline
Clonidine and nortriptyline are considered
second-line pharmaceuticals for use in smoking cessation.
Clonidine is primarily used to treat hypertension.
Nortriptyline is approved by the US Food and Drug
Administration (FDA) only as an antidepressant. Because
nortriptyline produces sedation, patients should be careful
when driving and using machinery.
Varenicline tartrate is a non-nicotine oral
medication that is being tested for its effectiveness and
safety in treating smoking addiction. It is not an NRT, but it
binds to nicotine receptors in the brain, just as nicotine
does, reducing the symptoms associated with withdrawal from
nicotine. Varenicline also dampens the effect of nicotine in
case a smoker has a relapse and smokes a cigarette.
Researchers hope that the dual action will make it a more
effective treatment for helping people quit smoking. The FDA
has granted a 6-month priority review for a New Drug
Application. The continuing studies on varenicline will
explore dosage, possible side effects, and optimal use of the
medication. Long-term success rates are the gold standard for
any smoking cessation aid, however, and varenicline remains
unproven in large groups over the long term.
exciting new drug that has been shown to reduce body weight
and improve cardiovascular risk factors in obese patients6 has
also showed promise for use in smoking cessation. Rimonabant
is a member of a new class of drugs called selective
cannabinoid-1 blockers. STudies with Rimonabant And Tobacco
USe (STRATUS-US), conducted at the University of Cincinnati
College of Medicine, showed rimonabant doubled the odds of
quitting smoking compared with placebo, markedly reduced
postcessation weight gain at 10 weeks, and was well
tolerated.7 However, when the FDA recently issued
approval for the drug in treating obesity, it excluded
approval for use in smoking cessation. The promise of a drug
that could be simultaneously efficacious in treating two major
cardiovascular risk factors—smoking and obesity—has naturally
created considerable anticipation. Long-term risk/benefits and
the ability of the drug to become the long-awaited “magic
bullet” for smoking cessation are far from being realized,
Pharmaceutical support for smoking cessation
continues to evolve, and the growing body of peer-reviewed
studies combined with practical experience has made treatment
options for nicotine addiction more flexible than ever.
Double-blind, placebo-controlled trials of pharmacological
cessation aids have revealed varying and conflicting degrees
of success. While patients and clinicians alike might wish for
a pharmaceutical solution to the complex process of smoking
cessation, a more sophisticated understanding of the problem
suggests there may never be an easy fix. In addition to
overcoming the powerful physical addiction of nicotine,
smokers are faced with essential social and psychological
hurdles that must be addressed. Long-term success includes
changing their mind-sets and self-identities from “smokers” to
“nonsmokers.” Pharmaceuticals are important tools but will
likely never replace the toolbox of resources required for
successful long-term smoking cessation.
John A. Wolfe, RRT, CPFT, is clinical
specialist, North Colorado Medical Center, Greeley
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