Smoking Cessation

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Smoking Cessation Programs


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SMOKING CESSATION Dr. Riham Hazem Raafat Lecturer of Chest Diseases Ainshams University

The integrated approach to successful smoking cessation:

The integrated approach to successful smoking cessation P r o f e s si o n a l i nv o l v e m e n t B eha vi o u r a l support Proven p ha rm aco t he r ap y

Non-Phys io logical Reasons::

Non - Phys io logical Reas ons : Peer pressure Mass media Pleasure and relaxation Nature of work Improved thinking and performance Relief from negative moods (anxiety, stress, anger, irritability and depressed mood) Weight control Why Smokers Smoke?

Phys io logical Reasons ::

Phys io logical Reasons : Physical dependence on nicotine Relief from withdrawal symptoms

Effects of Nicotine Withdrawal:

Effects of Nicotine Withdrawal When nicotine level drop s , most smokers report physiological withdrawal symptoms : Anxiety Irritability Restlessness Difficulty in concentrating Stomach problems Craving (Nicotine Hunger) Drowsiness

Nicotine Circulation in the BODY:

N icot i n e C i r c u l a t i o n in t h e B ODY When the smoker inhales Nicotine first enters the lungs Quickly enter the pulmonary circulation and is pumped into the heart The heart pumps the nicotine-laden blood throughout the body Reaches the brain only 7 to 10 secs after inhalation

Effects on the Nervous System:

Effects on the Ne rvo us Sys tem Nicotine acts on the central and autonomic nervous systems by stimulating the brain’s nicotinic receptors Changes in mood, learning, concentration, alertness and performance Physical changes such as up-regulation of the brain (increase in no. of nicotine receptors) Change in metabolism and energy utilisation in the brain, similar to other addictive drugs


EEG changes Alteration of the endocrine system functioning These changes in the physical make-up and function of the brain and nervous system may contribute to the development of : Nicotine Tolerance Physical Dependence

Health Bene fits of CESSATION:

He alth Bene fits of CESSATION Within days of quitting, carbon monoxide from smoking begins to leave the body Within weeks, ex-smokers begin to breathe easier and enjoy improved senses of taste and smell One year after quitting, risk of death from coronary heart disease decrease by 50% and continues to decline with time


Risk of stroke and lung cancer are also reduced significantly over time Overall , fifteen years after quitting, the overall risk of death is about the same as for those who have never smoked . One-fourth of smokers die early because of smoking A 25 year-old heavy smoker’s life expectancy may be shortened by more than 25% compared to a non-smoker

Obstacles to Cessation:

Obs tacles to Ces s atio n Nicotine addiction Stress / anxiety Fear of gaining weight Peer pressure Many have tried and failed !




Dependence Occurs when body becomes accustomed to the presence of nicotine and is altered in such a way that it needs nicotine in order to function normally To feel stabilised, heavy smokers need to maintain a high level of nicotine in their brains and will unconsciously regulate their puff rate until this requirement is met Addiction and Dependence are used interchangeably despite that “dependence” does not incorporate the compulsive use aspect

Two Type s of Addiction:

Two Type s of Addiction Interplay of the two types of addiction that make smoking so addicting and so difficult to give up Ingestive addiction Process addiction

INGESTIVE Addiction:

INGESTIVE Addic tion Excessively and compulsively taking into the body artificially refined or produced mood-altering substances such as specific foods, drugs, gases, alcohol or tobacco PROCESS ADDICTION “Hooked” on a set of neutral actions, interactions, or behaviors that become overused to the point where they lose their original value, meaning and purpose Highly addictive - gambling, working, exercising, spending money, or eating

Physio logy of Nic o tine Addiction:

Phys io logy of Nic o tine Addic tion Cigarette smoking is being reinforced by both positive and negative processes Nicotine affects both reward & withdrawal pathways Dopaminergic effects in nucleus accumbens involved in reward Noradrenergic effects in locus ceruleus involved in withdrawal

Anatomy of Reward and Withdrawal:

Anatomy of Reward and Withdrawal Me s o l i m b i c Do p a m i n e S y s tem Nu c l e us A cc u m b e n s Prefrontal Cortex Locus Ceruleus

Phys iology of Addic tio n:

Phys iology of Addic tio n Dopaminergic pathway Also known as the reward pathway or mesolimbic pathway Between the ventral tegmental area to the nucleus accumbens These contain high density of nicotinic receptors Responsible for motivational behaviour - the need to reproduce and survive Produces pleasurable effects and positive reinforcement

The Reward Pathway:

Dopamine surge in the nucleus accumbens is thought to produce the same positive motivational state associated with food and sex The Reward Pathway


While all highly addictive drugs activate the mesolimbic pathway, nicotine is a particularly reinforcing drug because it is inhaled and nicotine levels in the brain rise very rapidly (within 10 secs), producing a more powerful effect than drugs taken orally

Smoker’s Withdrawal:

Smoke r ’ s Withdrawal Withdrawal is mediated by norepinephrine in the locus ceruleus Approximately 80% of individuals who quit smoking experience physiological withdrawal effects such as Increased taste of sweets Weight gain Gastrointestinal problems - constipation Increased hunger Irritability Difficulty concentrating Restlessness Cravings Anxiety Drowsiness


Withdrawal symptoms begin 6 to 12 hours after cessation Most intense within the first 3 days May last from a few days to many months About 25% of those who quit smoking relapse within 48 hours 50% relapse within the first 7 days 75% relapsed in 1 year

The Reality of Nico tine Addiction:

The Re ality of Nic o tine Addic tio n The smoker experience positive reinforcement every time he lights a cigarette and stimulates the reward pathway He also receives negative reinforcement through withdrawal symptoms and must light another cigarette to relieve them



Intervention S trate gies:

Inte rve ntio n S trate gies Non-pharmacological Self-help Behavioural Group support Hypnosis Acupuncture Pharmacological Nicotine replacement Bupropion Verinicline

Self-help Programmes:

Self - he lp Pro g ramme s Smoking Cessation Clinics Counselling support Behavioural programmes If the above programmes are inadequate, then pharmacological therapies are sought

“5 A’s ” for Smoking Cessation:

“ 5 A ’ s ” for Smoking Ces s atio n AS K ADVISE ASSESS ASSIST A R R A N G E Systematically identify ALL tobacco users at every visit Strongly urge all smokers to quit Asses smokers willingness to make a quit attempt Aid the patient with a quit plan Follow-up to monitor progress

Behavioural Pro g ramme s:

Behavioural Pro g ramme s Self-management strategies Aversion conditioning techniques Relapse-prevention methods Nicotine fading

Self-Manag ement S trate gies:

Self - Manag ement S trate gies Most commonly used Make smokers more aware of their smoking patterns and cues Self-monitoring Record when, where, and why they smoke Promote a behavioural change and design a treatment plan Done before quitting to reduce the strength of the smoking cue Stimul us control (Cue extinction) Avoiding dominant cues (talking on the phone, finishing a meal

Ave rs ion CO nditioning Techniques:

Ave rs ion C O nditioning Te chniques Should only be administered by trained smoking cessation specialists Used to decrease a smoker’s urge to smoke before quit dates or upon relapse Techniques include rapid smoking and satiation Rapid smoking : Smokers puff cigarettes every 6 to 8 seconds until the cigarette is gone or nausea occurs Satiation : Smokers double or triple their daily cigarette consumption for brief periods of time

Relapse -Pre ventio n Me tho ds:

Relaps e - Pre ventio n Me tho ds Designed to prevent smokers from returning to smoking behaviour Avoidance : Minimising exposure to temptations, e.g. stress, other smokers Coping Strategies : Techniques such as deep breathing or use of relaxation tapes, to deal with withdrawal symptoms Contingency management : Rewards and punishments

NICotine Fading:

N IC ot i n e F a d i n g Gradual reduction of nicotine intake : Tapering the number of cigarettes smoked Switching to brands containing less nicotine Disadvantage : Smokers can compensate by inhaling more deeply and longer Further reinforce each episode of smoking Results are inconsistent and thus not recommended for routine use

Gro up Smoking Cessatio n Pro g ramme s:

Gro up Smoking Ces s atio n Pro g ramme s Most smokers are unwilling to attend such programmes Option for smokers who have failed to respond to less intensive cessation methods Done in small group with multiple sessions Incorporate various types of behavioural approaches

Hypno s is and Acupunc ture:

Hypno s is and Acupunc ture Appeal to smokers who want rapid cessation with little effort Claims to have high cure rates up to 95% No clinical data to support efficacy of these methods

Nicotine Replacement The rapie s:

Nicotine Replacement The rapie s Gum Transdermal patches Nasal Spray Oral Inhaler Lozenges

Nico tine Gum:

N i c o t i n e G u m Administered on an as-desired basis Most people chew 8 to 15 pieces a day; Each piece is chewed for 20 to 30 mins Approximately 50% of nicotine is released Providing 8 to 15mg of nicotine per day from the 2- mg form and 16 to 30mg from 4-mg form Approx. one-third or one-half of the usual daily intake of a person who smokes 30 cigarettes daily Recommended use for 4 to 6 months and patients should be encouraged to wean from nicotine gum, but the optimal duration of use is unknown

Effic aCy of Nico tine Gum:

E f fic a C y o f N i c o ti n e G u m Successful only accompanied by intensive behavioural programmes Acidic drinks, such as coffee or soda, decrease acidity of saliva and may interfere with the effects of nicotine gum One should never smoke and chew

Safe ty and Adverse Effe c ts of Nico tine Gum:

S a f e ty a n d A d v e r se Effe c ts o f Nico tine Gum Flatulence Indigestion Nausea Unpleasant taste Hiccups Sore mouth, throat and jaw

Nico tine Patc hes:

Nico tine Patc hes Delivering a steady amount of nicotine to the body right through the skin (usually on an arm, abdomen) Easy to use Once a day (changing the location each time)


Start with TTS 30 or TTS 20 depending on no. of cigarettes smoked/day Those smoking >20 sticks/day start with TTS 30 Those smoking <20 sticks/day start with TTS 20 Use 30, 20 and 10 cm 2 to allow gradual withdrawal Use over 3-4 weeks treatment Treatment > 3 months and doses > 30 cm 2 have not been evaluated

Safe ty and ADVe rse Effect s of Nico tine Patches:

S a f e ty a n d A D V e r se Effect s o f Nico tine Patches Skin irritation at the patch site Insomnia Headache Cold and flu-like symptoms Nausea Myalgia Dizziness Less common : Sleep disturbance, GI side effects - diarrhoea, upset stomach

Safety of Replacement The rapie s:

Safe ty of Replacement The rapie s NRTs should be used with extra caution in patients with cardiovascular disease Smoking while using patch or gum therapy may increase the risk of cardiovascular and toxic effects of nicotine Patients should stop smoking completely when starting treatment In addition, many smokers see such therapy as simply prolonging their dependence or fear becoming dependent on the replacement itself


Works on the biology of nicotine addiction By enhancing dopamine levels in the reward pathway Affect noradrenergic neurons in the locus ceruleus to reduce craving and withdrawal symptoms Bupropion

Dos age & Adminis tratio n for Bupro pion:

Dos age & Adminis tratio n for Bupro pion Start with 150mg/day for the first 3 days Follow by a dose increase to 300mg/day given as 150mg b.d. (at 8-hourly interval) Maximum dose : 300 mg/day Doses above 300mg/day should not be used due to dose-dependent risk of seizures

Dos age & Adminis tratio n:

Dos age & Adminis tratio n     Patients should start taking bupropion BEFORE they quit smoking They should set a “target quit date” during the 2nd week of treatment with bupropion as it takes about 1 week to reach steady-state blood levels Treatment with bupropion should be continued for 7-12 weeks Dose tapering is not necessary when discontinuing bupropion Important that patients continue to receive counselling and support throughout treatment with bupropion, and for a period of time thereafter

Individualizatio n of The rapy:

Individualizatio n of The rapy Need for education/counseling/support Discontinue if patient has not made significant progress toward abstinence by the seventh week of therapy If unsuccessful, re-evaluate later for retrial of therapy Bupropion should be used as a part of a comprehensive smoking cessation treatment program

Bupropion in Clinical Practice:

Bupropion in Clinical Practice Bupropion is indicated for the treatment of nicotine dependence as an aid to smoking cessation in subjects aged 18 years and over . Adult smokers who are motivated to stop could benefit from treatment with bupropion . For the majority of patients, the recommended dosage is 150mg once daily for 3 days, increasing to 150mg twice daily.

Combination Therapy for the Heavily Addicted Smoker—Mayo Clinic Style:

Combination Therapy for the Heavily Addicted Smoker—Mayo Clinic Style Nicotine patch Strongest dose, can use more than one Shorter acting nicotine replacement Bupropion SR

Vareniciline (Champix):

Vareniciline (Champix) Indicated for smoking cessation in adults Oral administration (tablet) Non-nicotine A partial agonist selective for the α4β2 nicotinic acetylcholine receptor Dual action with dual benefits Partial agonist activity: Reduces craving and withdrawal symptoms Antagonist activity: Produces a reduction of the rewarding and reinforcing effects of smoking 1. Champix Prescribing Information


1. Coe JW et al. Presented at the 11th Annual Meeting and 7th European Conference of the Society for Research on Nicotine and Tobacco. 2005. Prague, Czech Republic. 2. Picciotto MR et al. Nicotine Tob Res. 1999; Suppl 2:S121-S125. Binding of nicotine at the  4  2 nicotinic receptor in the VTA is believed to cause release of dopamine at the nAcc Champix is an  4  2 nicotinic receptor partial agonist, a compound with dual agonist and antagonist activities. This is believed to result in both a lesser amount of dopamine release from the VTA at the nAcc as well as the prevention of nicotine binding at the  4  2 receptors. N i c o t i n e Ch a m p i x


Nicotine Part Ag Part ag  4  2 nAChR Dual action of a partial agonist A go n ist R es p o n se 100 % Nicotine Smoking No Partial Ag No Smoking Partial Ag Smoking + Partial Ag Antagonist 50% Potential to block reinforcing effects when smoking Partial Agonist 50% Potential to relieve craving and withdrawal when quitting Varenicline on nicotinic receptors and dopamine release

Varenicline (Champix®): Dosage:

Varenicline (Champix ® ): Dosage Treatment period is 12 weeks An additional course of 12 weeks of treatment may be considered for patients who have successfully quit at end of 12 weeks Varenicline is supplied for oral administration in 2 strengths: 0.5 and 1.0 mg; titration is as below: Days 1 – 3: 0.5 mg once daily Days 4 – 7: 0.5 mg twice daily Day 8 – End of treatment: 1 mg twice daily 1. Champix Prescribing Information

Pharmacokinetics of Varenicline:

Pharmacokinetics of Varenicline Half-life ~24 hours Cmax within 3 to 4 hours Steady state reached within 4 days Oral bioavailability unaffected by food 92% of drug is excreted unchanged No inhibition of cytochrome P450 enzymes No clinically meaningful drug interactions identified No dose restrictions in patients with hepatic insufficiency          Dose adjustment required for severe renal impairment, may be considered for moderate renal impairment  No dosage adjustment is necessary for elderly patients absent renal impairment 1. Champix Prescribing Information

Adverse Effects:

Adverse Effects During clinical trials, approximately 4000 individuals were exposed to varenicline Most frequently reported AEs (≥10%) associated with varenicline 1 mg vs placebo were:       Nausea Abnormal dreams Insomnia Headache  The percentage of participants who discontinued treatment due to adverse events receiving varenicline treatment was comparable; 11.4% vs 9.7% 1. Varenicline Prescribing Information

Contraindications & Interactions:

Contraindications & Interactions Contraindications: hypersensitivity to the active substance or to any of the excipients No clinically meaningful drug interactions have been identified with varenicline 1. Champix Prescribing Information


Pre c a u t i o ns There are no adequate data from the use of varenicline in pregnant women Varenicline should not be used during pregnancy It is unknown whether varenicline is excreted in human breast milk Animal studies suggest varenicline is excreted in breast milk A decision whether to discontinue varenicline or discontinue breastfeeding should consider the benefits of breastfeeding to the child and varenicline to the woman  Varenicline may have minor or moderate influence on the ability to drive and use machines 1. Champix Prescribing Information

Dose Adjustment in Special Populations:

Do s e A d j u s t me n t i n S pe ci a l Populations Patients with hepatic impairment No dosage adjustment necessary Patients with renal insufficiency    No dosage adjustment necessary for patients with mild to moderate renal impairment For patients with moderate renal impairment who experience adverse events that are not tolerable, dosing may be reduced to 1 mg once daily For patients with severe renal impairment, the recommended dose is 1 mg/d. Dosing should begin at 0.5 mg once daily for the first 3 days then increase to 1 mg once daily. In patients with end-stage renal disease, treatment is not recommended 1. Champix Prescribing Information

New Medications in the Pipeline:

New Medications in the Pipeline Rimonabant Cannabinoid receptor inhibitor Blocks reinforcing effects of nicotine Also suppresses appetite In phase III trials Not approved for smoking cessation by FDA  Nicotine Vaccine Produces antibodies to nicotine Reduces nicotine levels in animals CYP246 Inhibitors CYP246 is a hepatic enzyme that metabolizes nicotine Higher blood nicotine levels per cigarette smoked Could also increase potency of NRT

Smoking Cessation: A Very Powerful Intervention…:

Smoking Cessation: A Very Powerful Intervention… Intervention Reduction in Mortality Smoking Cessation 36% Statin Therapy 29% Beta-Blockers 23% ACE Inhibitors 23% Aspirin 15% Critchley JA, Capewell S. JAMA ;2003;290:86-97

Effects of Clinician Interventions:

0 10 20 30 No clinician Physician clinician Estimated abstinence at 5+ months 1.0 1.1 (0.9,1.3) 1.7 (1.3,2.1) 2.2 (1.5,3.2) n = 29 studies Self-help Non-physician clinician Type of clinician Fiore et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. USDHHS, PHS, 2000. Effects of Clinician Interventions Compared to smokers who receive no assistance from a clinician, smokers who receive such assistance are 1.7–2.2 times as likely to quit successfully for 5 or more months.

Power of Intervention:

Power of Intervention ⅓ to ½ of the 44.5 million smokers will die from the habit. Of the 31 million who want to quit, 10 to 15.5 million will die from smoking. Increasing the 2.5% cessation rate to 10% would save 1.2 million additional lives. If cessation rates rose to 15%, 1.9 million additional lives would be saved. No other health intervention could make such a difference!