SMOKING CESSATION WORKSHOP. Dr Mark Palayew December

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1 SMOKING CESSATION WORKSHOP Dr Mark Palayew December

2 Conflicts of Interest None

3 Case 1 Mr. T is a 55 year old smoker 2 packs/day He has been smoking continuously since age 16 When he wakes up at 3 AM he has 2 cigarettes before going back to sleep He then smokes upon awakening at 7 AM He had a recent ED visit for chest pain He has COPD on Tiotropium and Salbutomol PRN His wife is a non-smoker He works in a restaurant What other important question(s) should we ask him? What advice should we give him?

4 Case 2 Ms. P is a 40 year old single female She has smoked ½ ppd intermittently since age 20 She has her first cigarette with her coffee 1 hour after awakening She has a history of depression and is currently taking Paxil She has no other PMH She works in a library What other important question(s) should we ask her? What advice should we give her?

5 Case 3 Ms. L is a 24 year old lady smokes 15 cigs/day She started smoking at age 20 She smokes her first cigarette upon awakening Her partner is a non-smoker Her partner wants her to stop smoking She has no PMH and takes no medications or EtOH Ms. L is 12 weeks pregnant and wishes to quit smoking What advice should we give her?

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8 Quitting

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11 The Impact of Smoking on Canadians Almost 5 Million Canadians Smoke 1 Smoking is the #1 preventable cause of death in Canada. 2 22% of all deaths in Canada are attributable to smoking 2 More than 45,000 Canadians die due to smoking each year 2 Calculation based on data from the year Health Canada. Canadian Tobacco Use Monitoring Survey 2005, Summary of Annual Results. 2. Makomaski Illing EM, Kaiserman, Can J Public Health 2004;95:38-44.

12 Mechanism of Action of Nicotine in the Central Nervous System b2 b2 a4 b2 a4 Nicotine binds preferentially to nicotinic acetylcholine (nach) receptors in the central nervous system; the primary is the α4β2 nach receptor in the Ventral Tegmental Area (VTA) a4b2 Nicotinic After nicotine binds to the Receptor α4β2 nach receptor in the VTA, it results in a release of dopamine in the Nucleus Accumbens (nacc), which is believed to be linked to reward Foulds J. Int J Clin Pract 2006;60:

13 The Cycle of Nicotine Addiction Nicotine binding causes an increase in dopamine release 1 Dopamine gives feelings of pleasure and calmness 2 The dopamine decrease between cigarettes leads to withdrawal symptoms of irritability and stress 3,4 The smoker craves nicotine to release more dopamine to restore pleasure and calmness 2,3 Chronic exposure to nicotine causes desensitization and compensatory receptor upregulation 2,5 Withdrawal symptoms occur in the prolonged absence of nicotine (4-6h), as nicotine levels decrease, and receptors become resensitized 1 Nicotine Dopamine 1. Foulds J. Int J Clin Pract 2006;60: Fagerstrom K. Drugs 2002;62(Suppl2): Jarvis MJ. BMJ 2004; 328: Rigotti NA. N Engl J Med 2002;346: Dani JA, De Biasi M. Pharmacol Biochem Behav 2001;70:

14 Withdrawal Syndrome: a Combination of Physical and Psychological Conditions, Making Smoking Hard to Treat 1,2 Withdrawal Syndrome Irritability, frustration, or anger (<4 weeks) 2 Insomnia/sleep disturbance (<4 weeks) 2 Anxiety (may increase or decrease with quitting) 1,2 Restlessness or impatience (<4 weeks) 2 Increased appetite or weight gain (>10 weeks) 2 Dysphoric or depressed mood (<4 weeks) 2 Difficulty concentrating (<4 weeks) 2 1. Diagnostic and Statistical Manual of Mental Disorders, IV-TR. Washington, DC: APA; West RW et al. Fast Facts: Smoking Cessation. 1st ed. Oxford, United Kingdom. Health Press Limited, 2004.

15 Quitting Smoking: A Long and Difficult Journey The majority of smokers are motivated to quit 2 The Stages of Change Model 1 Most try to quit without pharmacological assistance 3 87% of current smokers have tried to quit smoking at least once before 4 19% of smokers report craving is the most common reason why quitting smoking is considered difficult 4 Adapted from Prochaska et al. 1 20% of smokers seek help Addiction leads to relapse 5 Most smokers make 5-7 attempts before succeeding 2 1. Prochaska JO et al. Am Psychol 1992;47: Hughes JR. CA Cancer J Clin 2000;50: Anthenelli RM. Clin Neurosci Res 2005;5: Pfizer Canada Inc., Data on file O'Donnell DE et al. Can Respir J 2004;11(SupplB):3B-59B. 6. Fiore MC et al. JAMA 2002;288: Only ~5% succeed without help 6

16 Fiore MC et al. Treating Tobacco Use and Dependence 2008 Update. Clinical Practice Guideline

17 Developing a Medication Treatment Plan

18 Baseline assessment of the smoking status: The Fagerström Test for Nicotine Dependence 1,2 Questions Answers Points 1. How soon after you wake up do you smoke your first cigarette? After 60 minutes minutes minutes 2 Within 5 minutes 3 2. Do you find it difficult to refrain from smoking in places where it is forbidden? Yes 1 No 0 3. Which cigarette would you hate most to give up? The 1st in the morning 1 All others 0 4. How many cigarettes per day do you smoke? 10 or less 0 5. Do you smoke more frequently during the first hours after awakening than during the rest of the day? or more 3 Yes 1 No 0 6. Do you smoke even if you are so ill that you are in bed most of the day? Yes 1 No 0 1. Heatherton TF et al. Br J Addict 1991;86: Heart and Stroke Foundation. The Fagerström Test for Nicotine Dependence. Dependence scores 0-2 Very low 6-7 High 3-4 Low 8-10 Very high 5 Medium

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22 Developing a Medication Treatment Plan

23 Developing a Medication Treatment Plan

24 Developing a Treatment Plan

25 Every which way to Quit Cold Turkey Plus Hypnosis Acupuncture Counseling Nicotine replacement Anti-depressants Varenicline

26 The 5 A s Ask Advise Assess Assist Arrange Followup JAMA 2000;283:

27 A Comprehensive Approach to Smoking Cessation Smoking addiction has two main components that need to be addressed: one related to the pharmacological action of inhaled nicotine and the other related to behavioural factors 1-3 Current pharmacotherapies approximately double the odds of quitting 4,5 Advice and behavioural support increase the chances of quitting successfully 4,5 Most effective methods of smoking cessation combine pharmacotherapy with advice and behavioural support 2,4 1. Jarvis MJ. BMJ 2004;328: Coleman T. BMJ 2004;328: Rigotti NA. N Engl J Med 2002;346: Hughes JR. CA Cancer J Clin 2000;50: O'Donnell DE et al. Can Respir J 2004;11(SupplB):3B-59B.

28 Nicotine Replacement Therapy (NRT): Nicotine Delivery by Cigarettes and NRT Products Plasma Nicotine Concentration (μg/l) Cigarette (nicotine delivery, 1-2 mg) Gum (nicotine delivery, 4 mg) Nasal spray (nicotine delivery, 1 mg) Transdermal patch Time post-administration (minutes) Sweeney CT et al. CNS Drugs 2001;15:

29 NICOTINE GUM AND CESSATION CMAJ (2)

30 TRANSDERMAL NICOTINE AND CESSATION CMAJ (2)

31 Efficacy of Nicotine Replacement Therapy (NRT) 1,2 Comparison Trials (n) Participants (n) Pooled OR (95% CI) Gum 52 17, ( ) Patch 37 16, ( ) Nasal spray ( ) Inhaler ( ) Tablets/lozenges ( ) Combination vs. single type ( ) Any NRT vs. control , ( ) OR= odds ratio 1. Silagy C et al. Cochrane Database Syst Rev 2004;(3):CD Stead L, Lancaster T. Int J Epidemiol 2005;34:

32 Bupropion SR and Nortriptyline for Tobacco Dependence Comparison Bupropion SR alone vs. Placebo Bupropion SR plus nicotine patch vs. placebo All bupropion SR vs. placebo Nortriptyline alone vs. placebo Nortriptyline plus nicotine patch vs. placebo Trials (n) Participants (n) Pooled OR (95% CI) ( ) ( ) ( ) ( ) ( ) All nortriptyline vs. placebo ( ) OR= odds ratio 1. Hughes J, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2004;(4):CD Hughes JR, Stead LF, Lancaster T. Nortriptyline for smoking cessation: a review. Nicotine Tob Res 2005;7:

33 BUPROPION AND CESSATION CMAJ (2)

34 VARENICLINE AND CESSATION CMAJ (2)

35 VARENICLINE VS. BUPROPION CMAJ (2)

36 CHAMPIX (Varenicline) Indication and Dosing Information Indicated for smoking cessation treatment in adults in conjunction with smoking cessation counselling Treatment period is 12 weeks An additional course of 12 weeks of treatment may be considered for patients who have successfully quit at the end of 12 weeks Varenicline is supplied for oral administration in 2 strengths: 0.5 and 1.0 mg To optimize therapy success, patients should be titrated up to the maximum recommended dose of 1 mg BID, using the following 1-week titration schedule: Days 1 3: Days 4 7: Day 8 End of treatment: 0.5 mg once daily 0.5 mg twice daily 1 mg twice daily CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007

37 Varenicline Summary An innovative smoking cessation therapy believed to have simultaneous partial agonist and antagonist activities at the a4b2 nach receptor 1 Clinical significance is not fully confirmed 1 Demonstrated significantly superior continuous quit rates for weeks 9 through 12 vs. bupropion SR (Zyban ) and placebo in 2 pivotal head-to-head clinical trials: 2,3 ~4X greater odds of quitting smoking with varenicline (CHAMPIX) vs. placebo (odds ratio=3.85, p<0.001; odds ratio=3.85, p<0.001) 2,3 ~2X greater odds of quitting smoking with varenicline (CHAMPIX) vs. bupropion SR (odds ratio=1.93, p<0.001; odds ratio=1.90, p<0.001) 2,3 Established safety and tolerability profile in approximately 2,300 treated smokers 1 Pr Zyban is a registered trademark of the GlaxoSmithKline Group of Companies and is used by Biovail under license. 1. CHAMPIX Product Monograph, Pfizer Canada Inc., January Gonzales D et al. JAMA 2006;296: Jorenby DE et al. JAMA 2006;296:56-63.

38 N Engl J Med 2011; 365: September 29,

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