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Smoking Cessation
Smoking Cessation craving for nicotine.
27
In over 31 bupropion trials in which bupropion was
The health benefits of smoking cessation are well documented, but the sole agent used for cessation (compared with placebo on
many smokers are unable to quit. Smoking cessation at any age treatment), bupropion has been shown to increase cessation rates by up
provides both immediate and long-term health benefits.
5
Experience has to 40% after nine weeks.
17
In fact, bupropion alone, or in combination
shown that the most cost-effective tobacco control measures are with the nicotine patch, has been found to significantly increase
population-wide public policies such as bans on direct and indirect long-term cessation rates compared with NRT patches.
28
tobacco advertising, tobacco tax and price increases, smoke-free
environments in all public places and large, clear graphic health Varenicline
messages on tobacco packaging.
14
According to the international Varenicline (Champix) is a non-nicotine drug used to promote smoking
guidelines for the treatment of tobacco dependence,
13,15
every physician cessation. The mode of action of varenicline is as a partial agonist of the
should ask for and record the smoking habits of their patients. This α
4
β
2
neuronal nicotinic cholinergic receptors that is thought to mediate
information should be used to provide advice, counselling and the dependency effects of nicotine.
21,29
Varenicline aids smoking
pharmacotherapy on smoking cessation and to guide follow-up or cessation through two mechanisms: reducing craving and withdrawal
specialist referrals to intensive smoking cessation programmes. In symptoms during abstinence by acting as a weak agonist stimulating
addition, a European Respiratory Society (ERS) task force recently dopamine release in the mesolimbic region, and lowering the reward
published a document on smoking cessation treatment targeted at effects of nicotine by partially blocking the nicotine-mediated activation
patients with respiratory diseases.
16
of the dopaminergic system.
21
In a recent open-label, randomised trial it
was shown that patients using varenicline were 26.1% more likely to
Pharmacological Interventions abstain from smoking compared with 20.3% using a transdermal
To date, three pharmacological approaches have been approved for nicotine patch at 52 weeks.
30
smoking cessation: NRT, bupropion and varenicline. All three of these
drugs are effective aids for patients smoking more than 10 cigarettes per Genetic Epidemiology of Smoking Cessation
day. Second-line drugs that have demonstrated efficacy in clinical trials Despite the treatments available for tobacco dependence, there remain
but are not currently approved by regulatory authorities for smoking a considerable number of smokers who have difficulty achieving
cessation include nortriptyline, a tricyclic antidepressant,
17,18
and sustained abstinence from smoking. In addition to the environmental
clonidine, a β
2
-noradrenergic agonist.
19,20
Several novel therapies also factors (e.g. parental and peer influence, economic status, depression)
under investigation include Rimonabant, a cannaboid (CB-1) receptor that can affect the ability of an individual to cease smoking,
antagonist, nicotine vaccines, monoamine oxidase inhibitors to inhibit epidemiological studies of smoking cessation indicate that genetics
the metabolism of dopamine and selective nicotinic cholinergic receptor plays an important role.
31,32
In twin studies approximately 60–70% of the
antagonists.
19,21
A complete review of all potential pharmacological variability in nicotine dependence and smoking persistence is due to
interventions is beyond the scope of this article, thus currently approved genetic differences.
31,33–36
Nicotine dependence is inheritable in ways
smoking cessation therapies will be the focus. that substantially overlap with vulnerability to dependence on other
addictive substances.
37–40
It has also been demonstrated that the
Nicotine Replacement Therapy heritable influences on successful smoking cessation differ from
NRT aids in smoking cessation by replacing the nicotine-mediated those that influence aspects of nicotine dependence.
41
Therefore,
neuropharmacological effects achieved by smoking.
19
Forms of NRT understanding the mechanisms that influence an individual to achieve
available include nicotine dermal patches, chewing gum, nasal sprays, and sustain abstinence from smoking is essential.
inhalers, lozenges and sublingual tablets. All forms slowly deliver
nicotine and provide lower nicotine plasma levels than cigarette Candidate Gene Studies
smoking.
22
According to the latest Cochrane review on smoking Candidate gene studies are effective approaches to identifying genes
cessation and NRT, which included 123 trials with over 40,000 that produce small changes in risk for smoking phenotypes. However,
participants, NRT increases the chances of smoking cessation by these studies rely on what is already known about nicotine addition and
50–70% after at least six months compared with placebo or no NRT may overlook additional genes that could have an influential role.
control group.
23
None of the NRT formations has been reported to be Nicotine binds to neuronal nicotinic acetylcholine receptors (nAChRs)
superior, but evidence suggests that the nicotine dermal patch expressed on dopamine and gamma-amionbutyric acid (GABA)
combined with a fast-acting form of NRT such as gum, lozenge, inhaler neurons in the ventral tegmental area (VTA), resulting in dopamine
or nasal spray is more effective than any single NRT.
23
There is also release in the nucleus accumbens.
42,43
Therefore, candidate genes
evidence to suggest that NRT is not as beneficial in women as in men,
24
including nAChR subunits,
44–48
dopamine D2 receptors (DRD) 2
49–54
and
because women have significantly higher rates of nicotine metabolism, 4,
55
dopamine transporter (SLC6A3),
56,57
mu opioid receptor (OPRM1)
58–60
especially when using oral contraceptives.
25
and catecol-O-methyltransferase (COMT) enzyme
61
associated with
dopamine degradation have been extensively studied. Additional
Bupropion studies have also focused on nicotine metabolism by the P450 liver
Bupropion is a non-tricyclic antidepressant that was launched as a enzyme, CYP2A6 and smoking behaviour.
62–64
However, subsequent
smoking cessation aid in 1997 in the US and has now been approved in research has not always replicated many of these earlier findings.
65–67
over 50 countries. Bupropion acts as a norepinephrine and dopamine This represents additional limitations of candidate gene association
re-uptake inhibitor, with minimal effect on the re-uptake of seratonin and studies as false-positive results often occur in case-control studies due
no inhibitory effect on monoamine oxidase.
26
Bupropion acts to either small sample sizes for the genotype frequency being studied
independently of its antidepressant effect on smoking cessation by (small sample from a very heterogeneous population) or groups
reducing the activity of dopamine-releasing neurons, which is thought to consisting of individuals from genetically diverse backgrounds, which
deactivate the reward circuit associated with smoking and reduce makes replication of studies difficult.
38 EUROPEAN RESPIRATORY DISEASE
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