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α4β2- nicotinic acetylcholine receptors have reinforcing effects of nicotine
Nicotine produces a sustained effect on dopamine release in the nucleus accumbens& induce motivational / reinforcing properties.
The influence of prefrontal cortex, amygdala, hippocampus ( through glutamate / GABA neurons) mediate the drive to take drugs+ influence of drug-associated cues &the memory of drug taking.
Medications that act on glutamate or GABA systems hold the promise of reducing drug cravings or avoiding relapse.
Enviromental determinants :
Advertising specially to thee youth.
Friend, Peer pressure.
Individual determinants :
Individuals are not at equal risk of tobacco dependence.
G enetic component: smoking behaviour; the initiation/ maintenance of smoking, the number of cigarettes smoked& the response to pharmacologic treatments.
A strong link exists between tobacco use & psychiatric disorders *2- 3, as schizophrenia, depression, drug addiction, suggests shared neurobiologic / behavioural abnormalities.
Tobacco may be used to improve the psychiatric condition or to reduce the side effects of some psychiatric medications,as tobacco smoke contains chemical substances other than nicotine that inhibit monoamine oxidase A/B in the brain mimic the effects of antidepressants, may explain the increased risk of depression for 6 months or longer following smoking cessation.
Management of tobacco dependence :
Adequate evaluation of the patient & environment.
Since 70% of smokers see a physician/year, physicians &health professionals (counsellors, nurses, dentists, pharmacists) have a substantial opportunity to influence smoking behaviour.
The essential features of smoking cessation treatment 5 As:
Ask about smoking at every opportunity
Advise all smokers to stop
Assess their willingness to stop
Assist the smoker to stop
Success is often obtained only after several attempts& HCWs should adopt the same attitude as with other chronic disorders & should provide support over a long period.
Management : overall
2 approaches proven effective:
Best results obtained when the 2 combined& pharmacotherapy increase chance of initiating / maintaining abstinence 23-fold& should be used more extensively.
Management : overall
Three 1 st -line drugs : NRT, bupropion, varenicline.
Smokers with moderate to severe tobacco dependence respond best to these 3 types of pharmacotherapy
No consensus on which type should be used first, except on the basis of the preference & presence of contraindications.
Whichever chosen, it should be used first as monotherapy , since there is no clear evidence for additive effects of combining pharmacotherapies.
Combinations can be tested if monotherapy is not effective .
Combinations of various NRTs (e.g., patch ,gum, patch / inhaler) tested& NRT/ bupropion.
Other medications (nortriptyline,clonidine, selegiline, rimonabant) increase rates of smoking cessation significantly
Only nortriptyline/clonidine could be considered as second-line medications in patients who do not respond to first-line medications.
Management : NRT
Reduces nicotine withdrawal symptoms&the desire to smoke.
Several products;patch, gum, nasal spray, inhaler, tablet , lozenge.
No difference demonstrated between products.
Ineffectiveness is often due to improper use or insufficient dosage.
The dosage should be adjusted if there are clinical signs of toxic effects( nausea insomnia, palpitations) or of insufficient dosage (i.e. severe withdrawal symptoms as irritability, restlessness, anxiety, increased appetite, depressed mood).
If a patient finds one type ineffective or intolerable, it is useful to try another.
Management : NRT
Typically, the dose is decreased progressively over 8–12 weeks.
For all NRT taken by mouth, acidic drinks as coffee/juice avoided for 15 minutes before use, since they can reduce nicotine absorption.
NRT well tolerated & does not increase the severity of CVD &can even be used several days after AMI.
These products can also be used safely by adolescents, although of-label &Nicotine patches may be more effective than nicotine gum.
The use of NRT during pregnancy is controversial, since the fetus may have harmful effects on the fetus; but is potentially less harmful to the fetus than tobacco smoke.
Antidepressant with a dopaminergic–noradrenergic profile.
The sustained-release formulation is effective.
Its effect is separate from its antidepressant effect, since it is effective even in non depressed.
It block nicotinic receptor function.
Can double the chance of smoking cessation, comparable to that of NRT.
Should start 1 week before their quit date.
The dose is 150 mg/d for the first 3 days then 150 mg twice daily.
Useful either as monotherapy or in combination with NRT&may be used to prevent relapse.
Sustained-release bupropion is effective&safe for use in medication-stabilized psy outpatients.
The most serious side effect is seizure (f 0.1%),insomnia.
Used cautiously in smokers with CVD.
A nicotinic receptor partial agonist, acting like an agonist or an antagonist depending on the state of activation of nicotinic receptors.
Through its intrinsic partial activation of the α4β2-nicotinic acetylcholine recs, elicits a moderate/ sustained increase in mesolimbic dopamine& counteract the low dopamine encountered in the absence of nicotine during smoking cessation attempts.
By competitively binding to α4β2-nicotinic acetylcholine receps, as a partial agonist, protects against nicotine-induced dopaminergic activation if the patient smokes&disrupt the reinforcing effects of nicotine& compensate for withdrawal symptoms.
A significant effect on smoking cessation rates, higher than bupropion ,but no direct comparison with NRT conducted.
Varenicline efficacious in preventing smoking relapse.
Started at 0.5 mg once daily for the first 3 days, 0.5 mg twice daily for the next 4 days then 1 mg twice daily, for a total duration of 12-24 weeks (lower dosage in kidney disease or dialysis).
The main side effect of varenicline therapy is nausea ,30%.