Prepared by: Dr. Mohammad Shaikhani

University of SulaimaniCollege of Medicine.

Dept of Medicine.

Introduction:Smoking is currently responsible for the death of 1/10 adults worldwide, or 5 million deaths /year. 50% of 650 million smokers today will eventually be killed by tobacco& this morbidity/mortality can be mostly avoided by quitingThe prevalence varies greatly around the world, from 18% - 30% 50% in China& on the rise in developing countries. Tobacco is one of the few causes of preventable death increasing globally.In West, progress made in decreasing tobacco use, cigarettes/day (15.4 vs 18.4 /day in 1990)& increasing smokers not smoking daily. Although the gap is narrowing, males continue to smoke more than females overall, but there is currently no significant sex-related difference in smoking prevalence among adolescents. The prevalence of tobacco use among females is increasing with alarming trend &health consequences are now at high rates, with lung cancer among women is now higher than breast cancer.

Determinants of tobacco use:Tobacco dependence results from several closely interrelated factors: Neurochemical Environmental Individual

Neurochemical determinants:Nicotine is the critical reinforcing component responsible for most of the effects in humans. α4β2- nicotinic acetylcholine receptors have reinforcing effects of nicotine, initially activate these receptors located on dopamine neurons in the ventral tegmental area; although rapidly desensitized, nicotine produces a sustained effect on dopamine release in the nucleus accumbens& this is critical to the drugs’ ability to induce motivational / reinforcing properties. Although the nucleus accumbens plays a pivotal role in drug-seeking behaviour, 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.

Neurochemical determinants:Tobacco withdrawal triggers unpleasant/stressful signs/symptoms ,as headache, nausea,constipation or diarrhea, falling heart rate /BP,fatigue, drowsiness or insomnia, irritability, difficulty concentrating,anxiety, depression, increased hunger /energy in-take, increased pleasantness of the taste of sweets& tobacco cravings. Most withdrawal signs/symptoms peak 48 hours after quitting smoking & disappear completely in 6 months.Switching to a cigarette with a reduced nicotine or ceasing the use of nicotine gum can also result in withdrawal syndrome. NRT decreases the intensity of withdrawal symptoms. As with other subs addictions, the behaviour of smokers is controlled by both positive reinforcement (desire to obtain nicotine) & negative reinforcement(desire to decrease withdrawal symptoms).The risk of abuse of NRT is low in naive pats&nicotine is addictive in humans only through tobacco as speed of nicotine delivery to the brain may be ideal to initiate dependence properties.

Enviromental determinants:Measures that limit the purchase of tobacco&exposure to tobacco smoke should be widely implemented/expanded to sustain the reduction of tobacco use. Comprehensive effective tobacco control measures include increased taxation, consumer regulations, dissemination of information about tobacco products, legislation against advertising/ sponsorship by tobacco companies, economic alternatives to tobacco production / smoking cessation programs&warnings on cigarette packaging.Individuals have also become particularly sensitive to environmental stimuli, or cues, that have acquired motivational salience through repeated associations with self-administered nicotine.Tobacco-seeking, craving/relapse are well known to be triggered by these environmental stimuli. The new regulations that restrict the use of tobacco in public places help to reduce the influence of these cues on behaviour &therefore help exsmokers to maintain their abstinence

Individual determinants:Individuals are not at equal risk of tobacco dependence. An important / significant genetic component play a role in several aspects of smoking behaviour, as 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. On the contrary 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 &o health professionals (counsellors, nurses, dentists, pharmacists) have a substantial opportunity to influence smoking behaviour.Other can also play an important role 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, arrange follow-up 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. Any new treatment phase should be considered a therapeutic trial & its efficacy re-evaluated regularly.

Management: overallHCWs should systematically ask about tobacco use& advise the patient about the risks &about the availability of effective strategies to quit.The next step is to assess the patient’s willingness to quit &if not motivated, effective approaches (e.g., motivational interviewing) developed to enhance the patient’s motivation to quit.For a patient who is motivated to quit, the goal of treatment is total abstinence, the only outcome associated with reduced health risks. The use of pharmacologic trs as partial substitutes to reduce tobacco consumption &morbidity or mortality (harm reduction).2 approaches proven effective for smoking cessation are pharmacotherapy / nonpharmacologic interventions&best results obtained when the 2 combined& pharmacotherapy increase chance of initiating / maintaining abstinence 23-fold& should be used more extensively.

Management: overallThree distinct types : 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: NRTAlleviates nicotine withdrawal symptoms Reduces 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: NRTTypically, 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.

BupropionAntidepressant 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, an effect that may be critical for smoking cessation. Use of bupropion 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.

VareniclineA 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%.

NPT:Majority of successful quits occur without direct medical assistance or without pharmacotherapy.NPT are feasible & should be encouraged, especially by people for whom medication use is problematic, as adolescents/ pregnant.Quitting attempts are encouraged by media or the quit advice. Advising to quit, even just once, helps to double quit rates. To initiate as many cessation attempts as possible, practitioners should advise all of their patients who smoke to quit. Also, by using general motivational techniques or motivational enhancement therapy, the clinician promotes the patient’s self-motivational statements& the patient gains greater awareness of the problems associated with smoking. During each patient contact, the clinician should ask about the person’s smoking status& provide information on available trts.

NPT:A variety of interventions efficacious, although may not be additive with pharmacologic interventions. A more intensive approach, as behavioural cognitive therapy, can be useful to help patients recognize, avoid , cope with difficult situations most likely to initiate smoking. Coping strategies also target maladaptive thoughts to prevent relapse.Hotlines/helplines. Social support from their family, friends ,coworkers to establish a smoke-free home.Increase their physical activity facilitate smoking cessation, most notably in women&limit the weight gain that frequently follows smoking cessation. Most smokers will gain fewer than 5 kg after quitting, negligible compared with the risks associated with continued smoking. Since smoking cessation is the priority, aggressive treatment to fight the weight gain (e.g strict dieting) are not recommended during a quit attempt,but once the patient has successfully quit smoking, dealt with later.

NPT:Most alternative therapies, as acupuncture, mesotherapy,hypnosis , auriculotherapy, have not been found to have favourable effect on smoking cessation outcomes.