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Nicotine has an agonistic action at the nicotinic
receptor
sites in the cholinergic nervous system. It binds
with these receptors in a similar manner as acetylcholine
(ACh),
predominantly at the midbrain level, and influences various reflexes by excitation of chemoreceptors in the carotid
body.
The effects of nicotine are described in terms of a sense
of alertness, relaxation, pleasure, increased concentration,
and stimulation of the autonomic nervous system.
Prolonged use of nicotine causes a significant increase
in the number of nicotinic receptors, and in the
accumulation of ACh by enzymatic induction and/or repression
of choline acetyltransferase (CAT) and acetylcholinesterase
(AChE). The overall result is biochemical tolerance, and
physiological and psychological dependence.
During nicotine abstinence in chronic smokers, the
biochemical interpretation of withdrawal is through the
elimination of the nicotine blockade at nicotinic sites.
Withdrawal symptoms result from excessive ACh intersynaptic
stimulation of predominately muscarinic receptors in the
Nucleus Accumbens and Ventral Tegmental Area. The responses
may result in excitation or inhibition, and the clinical
symptoms can include decreased heart rate and blood
pressure, gastrointestinal disturbances, fatigue, nausea,
headache, and electroencephalogram changes, along with
increased irritability, nervousness, and decreased
concentration.
Injections of scopolamine and atropine provide effective
levels of anticholinergic activity to block the attachment
of ACh to these receptors, thereby reducing and eliminating
physical nicotine withdrawal symptoms during their most
pronounced period - the first 24 to 48 hours of abstinence.
Although nicotine is eliminated from the body by
urination in approximately three days, the normalization of
ACh concentrations to non-smoker status can take up to two
weeks. Consequently, oral and transdermal anticholinergic
treatment is prescribed during this two week period to
maintain lower, yet therapeutically effective, levels while
withdrawal symptoms subside.
Treatment is supported by an interactive program of
self-help behavioral changes to maintain nicotine abstinence
permanently.
Research on the efficacy of different smoking cessation
programs with no
follow-up behavioral modification assistance
indicates the following results immediately following
treatment regimen and after treatment:
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Anticholinergic Block Treatment
(one), (500 subjects)
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initial |
87% |
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at 12 months |
40% |
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Zyban, 8 week treatment (615
subjects) |
initial |
36% |
|
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at 12 months |
23% |
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Nicotine Patch , 8 week treatment
(244 subjects) |
initial |
<23% |
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at 12 months |
16% |
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Zyban & Patch, 8 week treatment (245
subjects) |
initial |
44% |
|
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at 12 months |
36% |
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Nortriptyline, 5 week treatment (68
patients) |
initial |
N/A |
|
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at 6 months |
21% |
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Placebo Group, 8 week treatment (615
subjects) |
initial |
19% |
|
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at 12 months |
15% |
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The authors of some of the above studies noted that
12-month results demonstrated the need for follow-up
emotional support, after initial success of smoking
cessation, to reduce recidivism. The challenge for motivated
smokers to remain smoke-free is to continue to pursue the
available support groups to which they are referred in order
to modify the emotional side of their smoking behavior.
References for the above data can be found
here.
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