The physiological effect of smoking
Intro:
Smoking cause addiction and the component that cause addiction in the cigarettes is nicotine, the
cigarettes contain 1 mg of nicotine in average. Nicotine is drug found in tobacco When you
smoke a cigarette it will enter your lungs and it will be absorbed by your blood stream and it will
reach your brain within 8 seconds, when it reaches your brain it will release adrenaline, the
release of adrenaline leads to increased heart rate, Nicotine also makes the pancreas produce less
insulin it will cause slight increase in blood sugar level, hypertension, restriction of blood vessels
and The electrical activity in your brain to change, it will cause the release of dopamine in
pleasure area of the brain These changes won’t be pleasant but your body will tolerate these
physiologic changes until you don’t notice them anymore. The way you get the drug into your
system have effect of how addictive you are, and inhaling tobacco smoke is one of the fastest
way to get it the drug into your system because it goes directly to your brain.
Mechanism of action:
Neuropharmacology
Nicotine diffuse through the brain tissue and bind to (nAChRs) which are ligand-gated ion
channels The nAChR complex is composed of five subunits and is found in both the peripheral
and central nervous when cholinergic agonist binds to the outside of the channel, the channel
gate opens, allowing the positive charge cations to enter, (sodium and calcium). These cations
further activate voltage-dependent calcium channels, allowing further calcium entry. Nicotine
increase the activity of prefrontal cortex, thalamus, and visual system, Stimulation of central
nAChRs by nicotine results in releasing variety of neurotransmitters like dopamine release in
mesolimbic area the corpus striatum, and the frontal cortex, other neurotransmitters will be
released like norepinephrine, acetylcholine, serotonin, γ-aminobutyric acid (GABA), glutamate,
and endorphins. The release of neurotransmitter occurs by modulation by presynaptic nAChRs,
but direct release can be occurring, with repeated exposure to nicotine some individual will
develop tolerance (neuroadaptation), there will be increase in nAChR binding sites at the same
time neuroadaptaion happen, this increase is believed to represent upregulation in response to
nicotine-mediated desensitization of receptors, this desensitization may play a role in nicotine
tolerance and dependence
Psychoactive Effects of Nicotine and Nicotine Withdrawal
In nicotine stimulate pleasure reduce anxiety and stress, smoking improves performance and
concentration when someone stop smoking nicotine withdrawal symptoms emerge which include
irritability, depressed mood, restlessness, difficulty concentrating, increased starvation and eating
insomnia, and craving for tobacco untreated smoker withdrawal can produces mood disturbances
close in intensity to those seen in psychiatric outpatients.
NICOTINE ADDICTION AND PSYCHIATRIC COMORBIDITY:
Tobacco addiction is seen more with people that have mental illness substance abuse disorders,
people that are diagnosed with schizophrenia, major depression, bipolar disorder, anxiety
disorder, panic attacks, attention deficit hyperactivity disorder, posttraumatic stress disorder,
alcohol abuse, and illicit drug abuse are shown more addiction and more likely to have more
severe addiction.
PHARMACODYNAMICS OF NICOTINE: CONTRIBUTIONS TO SMOKING-
RELATED DISEASE:
Nicotine is sympathomimetic drug that releases catecholamine, which increase cardiac output,
hypertension and constriction of the blood vessels, these various effects of nicotine on the
cardiovascular system could, in theory, promote atherogenesis and precipitate acute ischemic
events in people who have coronary artery disease. However, increased cardiovascular risk due
to nicotine medication does not appear to be a problem in people. Nicotine is not a direct
carcinogen, but there are concerns that it may be a tumor promoter. In animal studies, nicotine
can inhibit apoptosis, resulting in impaired killing of cancer cells, Nicotine also promotes
angiogenesis in animals, an effect which could lead to greater tumor invasion and metastasis
PHARMACOTHERAPY TO AID SMOKING CESSATION:
Currently, three classes of medications have been approved for smoking cessation: nicotine
replacement products (patch, gum, spray, inhaler, and lozenge), bupropion, and most recently,
varenicline
Nicotine Replacement Therapy
Nicotine medications act on nAChRs by replacing the effects of nicotine, these medications can
facilitate smoking in several ways. One of them is the relief of withdrawal symptoms when
someone stop smoking, a second mechanism of benefit is positive reinforcement which is related
to the rapidity of absorption and the peak nicotine level achieved in arterial blood by rapid
delivery formulations such as nicotine nasal spray gum, inhaler, and lozenge this allow the
smokers to dose their self with nicotine when they have the urge to smoke cigarettes, Nicotine
patches, on the other hand, deliver nicotine gradually and produce sustained nicotine levels
throughout the day, thus not providing much positive reinforcement. A third possible mechanism
of benefit is related to the ability of nicotine medications to desensitize nicotinic receptors it
reduces effect of nicotine from cigarettes
Bupropion
Bupropion was used and marked as an antidepressant medication before it was used widely for
smoking cessation. Bupropion increases brain levels of dopamine and norepinephrine which are
neurotransmitter can be produced during smoking, simulating the effects of nicotine on these
neurotransmitters Bupropion also has some nicotine receptor blocking activity, which could
contribute to reduced reinforcement from a cigarette in the case of a lapse
Varenicline
It both reduces craving for nicotine and decreases the pleasurable effects of cigarettes and other
tobacco products synthesized with the goal of developing a specific antagonist for the
α4 β2 nAChR, Varenicline produces less of a response than nicotine 50 percent but at the same
time blocks the effects of any nicotine added to the system. prolonged administration of
varenicline has been shown to reduce relapse in smokers who were abstinent 12 weeks after
initial therapy.
References:
1. The Health Consequences of Smoking: A Report of the Surgeon General. Washington, DC:
GPO; 2004. U. S. Dep. Health Hum. Serv. Public Health Serv.
2. Cent. Dis. Control Prev. 2002. Cigarette smoking among adults—United States. MMWR.
2000. pp. 637–660.
3. Gotti C, Zoli M, Clementi F. Brain nicotinic acetylcholine receptors: native subtypes and their
relevance. Trends Pharmacol. Sci. 2006; 27:482–491.
4. Maskos U, Molles BE, Pons S, Besson M, Guiard BP, et al. Nicotine reinforcement and
cognition restored by targeted expression of nicotinic receptors. Nature. 2005; 436:103–107
5. [Link]
[Link]
6. [Link]
7. Wang H, Sun X. Desensitized nicotinic receptors in brain. Brain Res. Brain Res. Rev. 2005; 48:420–
Prepared by: Aakef Mohammad Aakef
Supervised: by Dr. Abbas Burhan
Group: A
