During much of the 20th century, cigarette smoking
was tacitly and even overtly romanticized. However, during the 1950s and
1960s, evidence supporting a link between smoking and negative health
consequences began to mount. In 1966, the surgeon general of the United States
required that all cigarette package labels contain a hazard warning. Today,
awareness of nicotine addiction continues to grow. Tobacco smoking is one of
the leading causes of morbidity and mortality in the U.S. Several
pharmacologic interventions are now available, and many are obtainable without
a prescription. Pharmacists are in a unique position to counsel and assist
patients who wish to stop smoking, and they can educate patients who smoke
about cessation methods and available pharmacologic interventions.
approximately half a million Americans die due to causes related to cigarette
smoking.1 Cigarette smoking is the leading cause of preventable
death in the U.S. It is a habit that typically starts at a young age, with
almost 90% of smokers reporting an initial encounter with smoking by age 18.
2 Approximately one out of five adults in the U.S. smokes cigarettes,
and of those who smoke, about 80% smoke daily.3 As awareness of the
dangers of smoking increases and as public attitudes regarding the
"attractiveness" of smoking shift, the prevalence of smoking will continue to
decline. According to a recent estimate, about 70% of smokers would like to
quit.4 Between 1993 and 2004, the prevalence of heavy smokers (>25
cigarettes/day) declined from 19.1% to 12.1%.5
According to the
World Health Organization, drug dependence is "a behavioral pattern in which
the use of a psychoactive drug is given a sharply higher priority over other
behaviors that once had significant value."5 Chronic use of
tobacco is easily consistent with this definition. The sustained use of
tobacco products is contingent on the pharmacologic activity of nicotine.
The molecular structure of the
naturally occurring alkaloid nicotine is similar to that of the endogenous
neurotransmitter acetylcholine. Nicotine binds to many of the same receptors
as does acetylcholine (via cholinergic receptors). Activation of these
cholinergic receptors promotes the release of a host of neurotransmitters and
hormones associated with the reinforcing effects of nicotine, including
acetylcholine, norepinephrine, dopamine, vasopressin, serotonin, and
beta-endorphin.6 Dopaminergic effects may be the most salient with
regard to the addictive nature of nicotine use. According to recent work from
the Institut Pasteur, nicotine stimulates nicotinic acetylcholine receptors
(nAChRs) on dopamine-releasing neurons. These dopamine-releasing neurons are
an integral part of the reward circuitry.7 It is possible
that two specific subunits on the surface of the nAChRs, alpha 7 and beta 2,
are necessary for the full sequence of events leading to nicotine
reinforcement. These findings may lead to new therapies and a better
understanding of nicotine addiction.
The daily cycle of nicotine
addiction begins with the first cigarette (or other tobacco form) of the day.
The initial daily dose produces significant pharmacologic effects, including a
sense of pleasure, arousal, and enhanced performance. At the same time,
tolerance begins to escalate.8 The smoker continues to smoke during
the day, nicotine accumulates, and tolerance continues to escalate; withdrawal
symptoms occur sooner and are more overt with each subsequent cigarette. As
the cycle progresses, people tend to smoke more in what is usually an
unconscious attempt to relieve the symptoms of withdrawal. However, sleep
provides a time of considerable resensitization to the effects of nicotine,
and, upon awakening, the cycle begins anew.
Effects of Nicotine Use
Nicotine use causes
ganglionic effects, including vasoconstriction, increased blood pressure, and
skeletal muscle relaxation.8 Nausea, increased intestinal activity,
pallor, and sweating may also be observed. Subjective reports of the effects
of nicotine include pleasure and a reduction in anger, depression, and
tension. Nicotine has been demonstrated to improve vigilance in repetitive
tasks and to augment selective attention.8 In an addicted
individual, nicotine withdrawal begins shortly after its last administration,
reaches maximal intensity after 24 to 48 hours, and subsides over a period of
several weeks. However, some symptoms may persist for months to years.
The chronic effects of tobacco
use are usually devastating. In 2004, the U.S. surgeon general reported that
virtually every organ system in the body is impacted by tobacco use.9
Chronic cigarette smoke, and even secondhand smoke, increases the risk of
lung cancer, other potentially fatal respiratory conditions, and
cardiovascular disease. Other adverse health consequences of smoking include
nonpulmonary cancers, reduced fertility in women, higher infant mortality
rates, osteoporosis, and poor surgical outcomes.9
Benefits of Smoking Cessation
effects of smoking cessation are measurable almost immediately. As soon as 20
minutes after the last cigarette, blood pressure decreases and peripheral
vasoconstriction is reduced, causing the temperature of the hands and feet to
return to normal.10 After eight hours, carbon monoxide levels drop
to normal. After just 24 hours, the chance of a heart attack is reduced.
After one to nine months, ciliary function in the lungs returns to normal;
this allows for appropriate clearance of mucus, which in turn clears the lungs
of excess mucus and particulate matter and reduces the chance for infection.
Coughing, sinus congestion, fatigue, and shortness of breath are also reduced.
Risk of coronary heart disease will drop to half of that of a smoker after one
year and to the level of a nonsmoker after 15 years. After five to 15 years,
risk of stroke is reduced to the level of a nonsmoker. After 10 years, risk of
cancer and cancer-related death is significantly lower. One study suggested
that an individual who quit smoking at age 30 could expect to live an average
of 10 years longer than one who continued to smoke.11
Approach to Treatment
pharmacist must remember that most attempts to stop using tobacco end in
relapse. The CDC reported that only about 5% of those who attempted cessation
were able to actually do so for three to 12 months.4 While even
short counseling periods with a clinician, as the sole intervention, are
associated with improved rates of cessation, the most effective approach is
multipronged. Since behavioral and social factors have a role in nicotine
addiction, in addition to pharmacologic factors, treatment modalities
addressing each of these factors is likely more effective and should include
pharmacologic therapy; counseling; support from family, friends, and
coworkers; and support from health care providers.
The CDC suggests that
"patients who are willing to quit should be provided with effective
intervention, including brief interventions by clinicians at every visit."
5 They recommend using the five A's: Ask about
tobacco use; Advise to quit; Assess willingness to make a quit
attempt; Assist in the quit attempt; and Arrange for a
follow-up. In addition, the CDC recommends pharmacotherapies for smoking
cessation, including prescription medications such as bupropion (Zyban),
nicotine nasal spray, nicotine inhaler, and the various forms of OTC nicotine
(patch, gum, and lozenge). One new prescription-only medication for smoking
cessation, Chantix (varenicline) was approved by the FDA after the above-cited
CDC recommendation was published and is an appropriate alternative. The CDC
also recommends that patients who are not ready to quit should be provided
with messages to increase the motivation to quit.
OTC products for smoking cessation constitute nicotine replacement therapy
(NRT) in the form of nicotine patches, gum, and lozenges (Table 1). NRT
should be used in conjunction with behavioral support. NRT produces less
severe physiologic alterations than tobacco-based systems and provides
patients with lower overall levels of nicotine than they would receive from
tobacco.12 NRTs are useful and beneficial in several ways. First,
they have little abuse potential, because they do not produce the same
pleasurable effects as tobacco products.13 Second, they do not
contain the carcinogens or other toxic gases contained in tobacco smoke. All
of the NRTs available provide a controlled dose of nicotine; reduce withdrawal
symptoms, including cravings; and allow the patient to gradually taper off
tobacco. Patients who use NRT are twice as likely to be successful in their
attempt to stop smoking as similar individuals treated with a placebo.13
While NRT is safer than
continuing to smoke, there are several warnings that should be considered.
First, patients should not continue to smoke while using NRT. The effects of
more than one delivery device for nicotine are additive, and the patient may
experience untoward effects due to high serum levels of nicotine. Second,
patients with serious underlying cardiovascular disease should be advised to
use NRT under the supervision of a primary care provider. Last, pregnant or
breast-feeding patients and those younger than 18 should use NRT only under
the supervision of a primary care provider. While in all of these situations
NRT probably has a much greater safety margin than does smoking, the current
labeling is worded in such a way that the pharmacist recommending one of these
products to one of the above-mentioned "high risk" patients could be exposing
him/herself to liability. However, there is currently a push from tobacco
researchers and policy makers to tone down the warnings on pharmaceutical
nicotine, which may eventually result in the removal of warnings targeting
pregnant or breast-feeding women and individuals younger than 18.14
Nicotine gum was the
first FDA-approved form of NRT. It was approved in 1984 as a prescription item
and in 1996 as an OTC product.12 Nicotine gum is a resin complex of
polacrilin and nicotine in a sugarless chewing-gum base.15 The
product is available in two dosage strengths: 2 and 4 mg.
Patients should not use more
than 24 pieces per day and should be told not to eat or drink 15 minutes prior
to or while chewing the gum. Also, patients should rinse their mouths out with
water prior to using this product if they have recently consumed acidic drinks
or foods (cola, fruit juices, coffee, wine, citrus fruits, tomatoes, or
vinegar-containing foods), since the pH shift caused by these substances may
interfere with the absorption of nicotine across the mucosal layer. The
patient should be instructed to
1. Chew the gum slowly until
noticing a peppery, minty, citrus taste or a tingling sensation in the mouth
(usually about 15 chews).13,15
2. When this occurs,
place the gum between the cheek and the gums (this allows for absorption).
3. After one or two
minutes, when the taste or tingling has stopped, resume chewing.
4. When the taste or
tingling sensation returns, place the gum in a different area between the gums
and the cheek.
5. Repeat steps 3 and 4
until the taste or tingling does not return (usually 30 minutes).
Problems encountered by
patients using nicotine gum include irritation of the mouth, fatigue of the
jaw, hypersalivation, hiccups, and dyspepsia. In addition, the gum's adhesive
properties make it likely that the gum will stick to fillings, bridges,
crowns, dentures, and braces.13 Furthermore, if the patient chews
the gum too fast or vigorously, he or she may experience dizziness, nausea,
vomiting, throat irritation, hiccups, or dyspepsia. Properly educating the
patient about the correct technique for chewing the gum could mitigate these
problems. If the gum sticks to or damages dental work, patients should be
advised to stop using the product, visit their dentist, and use an alternate
form of therapy, such as a patch or a lozenge.
In 1991 and 1992, the FDA approved four transdermal nicotine patches for
prescription-only use. In 1996, several transdermal nicotine patches were
approved for OTC use.
Patients electing to use the
patch should be instructed to apply the patch to a dry, clean, hairless area
on the upper body or upper part of the arm at about the same time each day.
13 The application site for the patch should be rotated daily, with each
site being used only once per week to avoid skin irritation. After use, a
slight redness at the site of the patch may occur. If erythema persists for
more than four days, or if swelling or a rash develops at the site, the
patient should be told to discontinue use of the patch and contact a health
care provider. Use of the product should also be discontinued and medical
attention sought if palpitations occur, or if the patient develops symptoms of
nicotine toxicity (i.e., nausea, vomiting, dizziness, diarrhea, sweating, or
weakness). Other adverse effects, which are uncommon but seem to be unique to
the transdermal patch, include insomnia, headache, and vivid or troublesome
dreams. These problems seem to be associated with the continuous release of
nicotine. If these problems are encountered and are intolerable, the patient
should be counseled to use an alternative form of NRT.
Like nicotine gum,
nicotine lozenges are a resin complex of nicotine and polacrilin. They are
sugar free and have a slight mint flavor. The lozenges should be allowed to
dissolve slowly in the mouth and should occasionally be rotated to different
areas in the mouth to avoid discomfort.13 The patient may
experience a warm, tingling sensation in the mouth. The lozenges typically
take about 30 minutes to dissolve and should not be chewed or swallowed. No
more than five lozenges should be used in a six-hour period, and no more than
20 should be used per day. Patients should follow the same guidelines
regarding use of the lozenges with food and beverages as they would with
nicotine gum.15 Nicotine lozenges are typically well tolerated but
may cause dyspepsia, nausea, headache, or flatulence. Side effects are more
common in patients who use too many lozenges.
and other forms of tobacco use are a major cause of morbidity and mortality in
the U.S. Chronic use of tobacco is due to nicotine addiction, and the addicted
patient must be motivated to quit before cessation attempts will be
successful. Motivation is sometimes created by education about the dangers of
nicotine addiction and the mere offer of help by someone with knowledge about
cessation methods, such as the pharmacist. Nicotine addiction is best treated
using a multimodal approach that includes counseling, support,
pharmacotherapy, and follow-up. While several prescription-only medications
for tobacco cessation are available, a number of effective OTC products are
also available. By counseling patients and recommending appropriate smoking
cessation products, the pharmacist can have an important role in improving the
quality and longevity of the lives of tobacco users who wish to quit.
Pharmacists wishing to set up pharmacy-based smoking cessation programs can
find helpful information at the University of California, San Francisco's
Rx for change Web site, located at rxforchange.ucsf.edu.16
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3. Johnston LD,
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