Successful  SMOKING CESSATION Dr. Sallehudin Bin Abu Bakar MD (M’sia); MPH (Philippines); M.Epid.(Johns  Hopkins)
The integrated approach to successful smoking cessation Professional involvement Behavioural support Proven  pharmacotherapy
 
Non-Physiological Reasons for Smoking <ul><li>Peer pressure </li></ul><ul><li>Mass media </li></ul><ul><li>Pleasure and re...
Physiological Reasons for Smoking <ul><li>Physical dependence on nicotine </li></ul><ul><li>Relief from withdrawal symptom...
Effects of Nicotine Withdrawal <ul><li>When nicotine levels drop, most smokers report physiological withdrawal symptoms su...
Nicotine Circulation in the Body <ul><li>When the smoker inhales </li></ul><ul><ul><li>Nicotine first enters the lungs  </...
Effects on the Nervous System <ul><li>Nicotine acts on the  central and autonomic  nervous systems by stimulating the brai...
Effects on the Nervous System <ul><li>These changes in the physical make-up and functioning of the brain and nervous syste...
Health Benefits <ul><li>Within days of quitting, carbon monoxide from smoking begins to leave the body </li></ul><ul><li>W...
Health Benefit <ul><li>Overall, fifteen years after quitting, the overall risk of death is about the same as for those who...
Health Benefits <ul><li>One-fourth of smokers die early because of smoking </li></ul><ul><li>A 25 year-old heavy smoker’s ...
Smoking Finances <ul><li>Assuming a smoker spends RM8.00 a day on cigarettes (1 pack of 20’s), quitting will save RM2,920....
The Cessation Reality <ul><li>74% of current smokers want to quit </li></ul><ul><li>Only 25% of those who manage to quit r...
Obstacles to Cessation <ul><li>Nicotine addiction </li></ul><ul><li>Stress / anxiety </li></ul><ul><li>Fear of gaining wei...
 
Addiction Triangle Physical (Neurochemistry) Emotional (Psychological) Habitual (Routine) FACTORS AFFECTING ADDICTION
Nicotine Addiction <ul><li>Brain disease </li></ul><ul><li>Compulsive need for and use of a habit-forming substance charac...
Dependence <ul><li>Occurs when body becomes accustomed to the presence of nicotine and is altered in such a way that it ne...
Two Types of Addiction <ul><li>Interplay of the two types of addiction that  make smoking so addicting and so difficult to...
Ingestive Addiction <ul><li>Excessively and compulsively taking into the body artificially refined or produced mood-alteri...
Process Addiction <ul><li>“ Hooked” on a set of neutral actions, interactions, or behaviours that become overused to the p...
Physiology of Nicotine Addiction <ul><li>Cigarette smoking is being reinforced by both positive and negative processes </l...
Anatomy of Reward and Withdrawal <ul><ul><li>Mesolimbic Dopamine System </li></ul></ul><ul><ul><li>Nucleus Accumbens </li>...
Physiology of Addiction <ul><li>Dopaminergic pathway </li></ul><ul><li>Also known as the  reward pathway   or  mesolimbic ...
The Reward Pathway Dopamine surge in the  nucleus accumbens is thought to produce the same positive motivational state ass...
The Reward Pathway While all highly addictive drugs activate the mesolimbic pathway, nicotine is a particularly reinforcin...
Physiology of Nicotine Addiction <ul><li>The combination of heightened arousal with pleasure trigger creates a sense of cy...
Smoker’s Withdrawal <ul><li>Withdrawal is mediated by norepinephrine in the locus ceruleus </li></ul><ul><li>Approximately...
Smoker’s Withdrawal <ul><li>Withdrawal symptoms begin 6 to 12 hours after cessation </li></ul><ul><li>Most intense within ...
The Reality of Nicotine Addiction <ul><li>The smoker experience positive reinforcement every time he lights a cigarette an...
 
Healthcare Provider Strategies <ul><li>The Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guidelines...
“ 5 A’s” for Smoking Cessation <ul><li>ASK  1. Systematically identify ALL    tobacco users at every visit </li></ul><ul><...
Assisting Patient in Quitting <ul><li>Help the patient set a quit date and prepare for quitting </li></ul><ul><li>Encourag...
A Quit Plan <ul><li>Setting a quit date - within 2 weeks of the decision to quit </li></ul><ul><li>Should inform family, f...
Key Advice on Successful Quitting <ul><li>Abstinence - “Not even a single puff after quit date” </li></ul><ul><li>Alcohol ...
Patient Types <ul><li>5 Stages of smoking cessation readiness : </li></ul><ul><li>Pre-contemplation </li></ul><ul><ul><li>...
Patient Types <ul><li>Action </li></ul><ul><ul><li>Actively trying to quit or has recently quit </li></ul></ul><ul><ul><li...
Patient Types <ul><li>Relapse </li></ul><ul><ul><li>Very common and most difficult </li></ul></ul><ul><ul><li>Help patient...
 
Intervention Strategies <ul><li>Non-pharmacological </li></ul><ul><ul><li>Self-help </li></ul></ul><ul><ul><li>Behavioural...
Management <ul><li>Researchers and clinicians view nicotine addiction as a brain disease embedded in a social context </li...
 
Self-help Programmes <ul><li>Smoking Cessation Clinics </li></ul><ul><ul><li>Counselling support </li></ul></ul><ul><ul><l...
Behavioural Programmes <ul><li>Self-management strategies </li></ul><ul><li>Aversion conditioning techniques </li></ul><ul...
Self-Management Strategies <ul><li>Most commonly used </li></ul><ul><li>Make smokers more aware of their smoking patterns ...
Aversion Conditioning Techniques <ul><li>Should only be administered by trained smoking cessation specialists </li></ul><u...
Relapse-Prevention Methods <ul><li>Designed to prevent smokers from returning to smoking behaviour </li></ul><ul><li>Avoid...
Nicotine Fading <ul><li>Gradual reduction of nicotine intake : </li></ul><ul><ul><li>Tapering the number of cigarettes smo...
Group Smoking Cessation Programmes <ul><li>Most smokers are unwilling to attend such programmes </li></ul><ul><li>Option f...
Hypnosis and Acupuncture <ul><li>Appeal to smokers who want rapid cessation with little effort </li></ul><ul><li>Claims to...
 
Nicotine Replacement Therapies <ul><li>Gum </li></ul><ul><li>Transdermal patches </li></ul><ul><li>Nasal Spray </li></ul><...
Nicotine Gum <ul><li>Administered on an as-desired basis </li></ul><ul><li>Most people chew 8 to 15 pieces a day; Each pie...
Efficacy of Nicotine Gum <ul><li>Successful only accompanied by intensive behavioural programmes </li></ul><ul><li>Acidic ...
Safety and Adverse Effects of Nicotine Gum <ul><li>Flatulence </li></ul><ul><li>Indigestion </li></ul><ul><li>Nausea </li>...
Nicotine Patches <ul><li>Delivering a steady amount of nicotine to the body right through the skin (usually on an arm, abd...
<ul><li>Start with TTS 30 or TTS 20 depending on no. of cigarettes smoked/day </li></ul><ul><ul><li>Those smoking >20 stic...
Safety and Adverse Effects of Nicotine Patches <ul><li>Skin irritation at the patch site </li></ul><ul><li>Insomnia </li><...
Safety of Replacement Therapies <ul><li>NRTs should be used with extra caution in patients with cardiovascular disease </l...
<ul><li>Works on the biology of nicotine addiction </li></ul><ul><ul><li>By enhancing dopamine levels in the reward pathwa...
Dosage & Administration for Bupropion <ul><li>Start with 150mg/day for the first 3 days </li></ul><ul><li>Follow by a dose...
Dosage & Administration <ul><li>Patients should start taking bupropion  BEFORE  they quit smoking </li></ul><ul><li>They s...
Individualization of Therapy <ul><li>Need for education/counseling/support  </li></ul><ul><li>Discontinue if patient has n...
Bupropion in Clinical Practice <ul><li>Bupropion is indicated for the treatment of nicotine dependence as an aid to smokin...
Combination Therapy for the Heavily Addicted Smoker—Mayo Clinic Style <ul><li>Nicotine patch </li></ul><ul><ul><li>Stronge...
Varenicline Tartrate (Champix ® ) <ul><li>Indicated for smoking cessation in adults  </li></ul><ul><li>Oral administration...
Champix ®  (Varenicline): A Highly Selective   4  2 Receptor Partial Agonist 1. Coe JW et al. Presented at the 11th Annu...
Varenicline:   4  2 nAChR Partial Agonists  4  2 nAChR Dual action of a partial agonist Agonist Response 100% Smoking ...
Varenicline on nicotinic receptors and dopamine release
Varenicline (Champix ® ): Dosage <ul><li>Treatment period is 12 weeks </li></ul><ul><li>An additional course of 12 weeks o...
Pharmacokinetics of Varenicline <ul><li>Half-life ~24 hours </li></ul><ul><li>Cmax within 3 to 4 hours </li></ul><ul><li>S...
Adverse Effects <ul><li>During clinical trials, approximately 4000 individuals were exposed to varenicline </li></ul><ul><...
Contraindications & Interactions <ul><li>Contraindications:  </li></ul><ul><ul><li>hypersensitivity to the active substanc...
Precautions <ul><li>There are no adequate data from the use of varenicline in  pregnant women  </li></ul><ul><ul><li>Varen...
Dose Adjustment in Special Populations <ul><li>Patients with hepatic impairment </li></ul><ul><ul><li>No dosage adjustment...
Comparative Daily Costs of Pharmacotherapy Cost per day, in U.S. dollars $6.07 $5.81 $5.73 $5.26 $3.91 $3.67 $4.22 $4.26
New Medications in the Pipeline <ul><li>Rimonabant </li></ul><ul><ul><li>Cannabinoid receptor inhibitor </li></ul></ul><ul...
Smoking Cessation: A Very Powerful Intervention… Critchley JA, Capewell S.  JAMA ;2003;290:86-97 Intervention Reduction in...
Effects of Clinician Interventions 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...
Power of Intervention <ul><li>⅓   to ½ of the 44.5 million smokers will die from the habit. Of the 31 million who want to ...
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Updates On Smoking Cessation

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Updates On Smoking Cessation

  1. 1. Successful SMOKING CESSATION Dr. Sallehudin Bin Abu Bakar MD (M’sia); MPH (Philippines); M.Epid.(Johns Hopkins)
  2. 2. The integrated approach to successful smoking cessation Professional involvement Behavioural support Proven pharmacotherapy
  3. 4. Non-Physiological Reasons for Smoking <ul><li>Peer pressure </li></ul><ul><li>Mass media </li></ul><ul><li>Pleasure and relaxation </li></ul><ul><li>Nature of work </li></ul><ul><li>Improved thinking and performance </li></ul><ul><li>Relief from negative moods (anxiety, stress, anger, irritability and depressed mood) </li></ul><ul><li>Weight control </li></ul>
  4. 5. Physiological Reasons for Smoking <ul><li>Physical dependence on nicotine </li></ul><ul><li>Relief from withdrawal symptoms </li></ul>
  5. 6. Effects of Nicotine Withdrawal <ul><li>When nicotine levels drop, most smokers report physiological withdrawal symptoms such as : </li></ul><ul><ul><li>Anxiety </li></ul></ul><ul><ul><li>Irritability </li></ul></ul><ul><ul><li>Restlessness </li></ul></ul><ul><ul><li>Difficulty in concentrating </li></ul></ul><ul><ul><li>Stomach problems </li></ul></ul><ul><ul><li>Craving </li></ul></ul><ul><ul><li>Drowsiness </li></ul></ul>
  6. 7. Nicotine Circulation in the Body <ul><li>When the smoker inhales </li></ul><ul><ul><li>Nicotine first enters the lungs </li></ul></ul><ul><ul><li>Quickly enter the pulmonary circulation and is pumped into the heart </li></ul></ul><ul><ul><li>The heart pumps the nicotine-laden blood throughout the body </li></ul></ul><ul><ul><li>Reaches the brain only 7 to 10 secs after inhalation </li></ul></ul>
  7. 8. Effects on the Nervous System <ul><li>Nicotine acts on the central and autonomic nervous systems by stimulating the brain’s nicotinic receptors </li></ul><ul><li>Changes in mood, learning, concentration, alertness and performance </li></ul><ul><li>Physical changes such as up-regulation of the brain (increase in no. of nicotine receptors) </li></ul><ul><li>Change in metabolism and energy utilisation in the brain, similar to other addictive drugs </li></ul><ul><li>EEG changes </li></ul><ul><li>Alteration of the endocrine system functioning </li></ul>
  8. 9. Effects on the Nervous System <ul><li>These changes in the physical make-up and functioning of the brain and nervous system may contribute to the development of : </li></ul><ul><ul><li>Nicotine Tolerance </li></ul></ul><ul><ul><li>Physical Dependence </li></ul></ul>
  9. 10. Health Benefits <ul><li>Within days of quitting, carbon monoxide from smoking begins to leave the body </li></ul><ul><li>Within weeks, ex-smokers begin to breathe easier and enjoy improved senses of taste and smell </li></ul><ul><li>One year after quitting, risk of death from coronary heart disease decrease by 50% and continues to decline with time </li></ul><ul><li>Risk of stroke and lung cancer are also reduced significantly over time </li></ul>
  10. 11. Health Benefit <ul><li>Overall, fifteen years after quitting, the overall risk of death is about the same as for those who have never smoked. </li></ul>
  11. 12. Health Benefits <ul><li>One-fourth of smokers die early because of smoking </li></ul><ul><li>A 25 year-old heavy smoker’s life expectancy may be shortened by more than 25% compared to a non-smoker </li></ul>
  12. 13. Smoking Finances <ul><li>Assuming a smoker spends RM8.00 a day on cigarettes (1 pack of 20’s), quitting will save RM2,920.00 a year. </li></ul>
  13. 14. The Cessation Reality <ul><li>74% of current smokers want to quit </li></ul><ul><li>Only 25% of those who manage to quit remain abstinent for longer than 1 year </li></ul><ul><li>1.3 million (6.5%) experience long term success </li></ul>
  14. 15. Obstacles to Cessation <ul><li>Nicotine addiction </li></ul><ul><li>Stress / anxiety </li></ul><ul><li>Fear of gaining weight </li></ul><ul><li>Peer pressure </li></ul><ul><li>Many have tried and failed! </li></ul>
  15. 17. Addiction Triangle Physical (Neurochemistry) Emotional (Psychological) Habitual (Routine) FACTORS AFFECTING ADDICTION
  16. 18. Nicotine Addiction <ul><li>Brain disease </li></ul><ul><li>Compulsive need for and use of a habit-forming substance characterised by tolerance and by well-defined physiological symptoms upon withdrawal </li></ul>Cigarette Smoking Is An Addiction! Not Just A Bad Habit.
  17. 19. Dependence <ul><li>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 </li></ul><ul><li>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 </li></ul>Addiction and Dependence are used interchangeably despite that “dependence” does not incorporate the compulsive use aspect
  18. 20. Two Types of Addiction <ul><li>Interplay of the two types of addiction that make smoking so addicting and so difficult to give up </li></ul><ul><li>Ingestive addiction </li></ul><ul><li>Process addiction </li></ul>
  19. 21. Ingestive Addiction <ul><li>Excessively and compulsively taking into the body artificially refined or produced mood-altering substances such as specific foods, drugs, gases, alcohol or tobacco </li></ul>
  20. 22. Process Addiction <ul><li>“ Hooked” on a set of neutral actions, interactions, or behaviours that become overused to the point where they lose their original value, meaning and purpose </li></ul><ul><ul><li>Highly addictive - gambling, working, exercising, spending money, or eating </li></ul></ul>
  21. 23. Physiology of Nicotine Addiction <ul><li>Cigarette smoking is being reinforced by both positive and negative processes </li></ul><ul><li>Nicotine affects both reward and withdrawal pathways </li></ul><ul><ul><li>Dopaminergic effects in nucleus accumbens involved in reward </li></ul></ul><ul><ul><li>Noradrenergic effects in locus ceruleus involved in withdrawal </li></ul></ul>
  22. 24. Anatomy of Reward and Withdrawal <ul><ul><li>Mesolimbic Dopamine System </li></ul></ul><ul><ul><li>Nucleus Accumbens </li></ul></ul><ul><ul><li>Prefrontal Cortex </li></ul></ul><ul><ul><li>Locus Ceruleus </li></ul></ul>
  23. 25. Physiology of Addiction <ul><li>Dopaminergic pathway </li></ul><ul><li>Also known as the reward pathway or mesolimbic pathway </li></ul><ul><li>Between the ventral tegmental area to the nucleus accumbens </li></ul><ul><li>These contain high density of nicotinic receptors </li></ul><ul><li>Responsible for motivational behaviour - the need to reproduce and survive </li></ul><ul><li>Produces pleasurable effects and positive reinforcement </li></ul>
  24. 26. The Reward Pathway Dopamine surge in the nucleus accumbens is thought to produce the same positive motivational state associated with food and sex
  25. 27. 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
  26. 28. Physiology of Nicotine Addiction <ul><li>The combination of heightened arousal with pleasure trigger creates a sense of cyclical satisfaction </li></ul><ul><li>Each time a smoker smoke, these states are being reinforced. </li></ul>Reinforcing message “You will only continue to feel well if you continue smoking” is the foundation of lifelong nicotine addiction.
  27. 29. Smoker’s Withdrawal <ul><li>Withdrawal is mediated by norepinephrine in the locus ceruleus </li></ul><ul><li>Approximately 80% of individuals who quit smoking experience physiological withdrawal effects such as </li></ul><ul><ul><li>Irritability - Increased taste of sweets </li></ul></ul><ul><ul><li>Difficulty concentrating - Weight gain </li></ul></ul><ul><ul><li>Restlessness - Gastrointestinal problems </li></ul></ul><ul><ul><li>Cravings - constipation </li></ul></ul><ul><ul><li>Anxiety - Increased hunger </li></ul></ul><ul><ul><li>Drowsiness </li></ul></ul>
  28. 30. Smoker’s Withdrawal <ul><li>Withdrawal symptoms begin 6 to 12 hours after cessation </li></ul><ul><li>Most intense within the first 3 days </li></ul><ul><li>May last from a few days to many months </li></ul><ul><li>About 25% of those who quit smoking relapse within 48 hours </li></ul><ul><li>50% relapse within the first 7 days </li></ul><ul><li>75% relapsed in 1 year </li></ul>
  29. 31. The Reality of Nicotine Addiction <ul><li>The smoker experience positive reinforcement every time he lights a cigarette and stimulates the reward pathway </li></ul><ul><li>He also receives negative reinforcement through withdrawal symptoms and must light another cigarette to relieve them </li></ul>
  30. 33. Healthcare Provider Strategies <ul><li>The Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guidelines : </li></ul><ul><li>1. Every person who smokes should be offered smoking cessation treatment at every visit </li></ul><ul><li>2. Ask and record the tobacco use status of every patient </li></ul><ul><li>3. Clinician intervention, even as brief as 3 mins, is effective </li></ul><ul><li>4. The more intensive the treatment, the more effective it is in producing long-term abstinence from tobacco </li></ul><ul><li>5. Nicotine-replacement therapy, social support, and skills training are effective components of smoking cessation treatment </li></ul>
  31. 34. “ 5 A’s” for Smoking Cessation <ul><li>ASK 1. Systematically identify ALL tobacco users at every visit </li></ul><ul><li>ADVISE 2. Strongly urge all smokers to quit </li></ul><ul><li>ASSES 3. Asses smokers willingness to make a quit attempt </li></ul><ul><li>ASSIST 4. Aid the patient with a quit plan </li></ul><ul><li>ARRANGE 5. Follow-up to monitor progress </li></ul>
  32. 35. Assisting Patient in Quitting <ul><li>Help the patient set a quit date and prepare for quitting </li></ul><ul><li>Encourage pharmacotherapy except in special circumstances </li></ul><ul><li>Give key advice on successful quitting </li></ul><ul><li>Provide supplementary materials </li></ul>
  33. 36. A Quit Plan <ul><li>Setting a quit date - within 2 weeks of the decision to quit </li></ul><ul><li>Should inform family, friends, co-workers of quitting and request for understanding and support </li></ul><ul><li>Remove cigarettes from the environment and, prior to quitting, avoid smoking in places where they spend a lot of time, e.g. the car </li></ul><ul><li>Review previous quit attempts to determine what was helpful and what led to relapse </li></ul>
  34. 37. Key Advice on Successful Quitting <ul><li>Abstinence - “Not even a single puff after quit date” </li></ul><ul><li>Alcohol - associated with relapse </li></ul><ul><li>Other smokers in the household- developing specific plans to deal with their abstinence in a household where others still smoke </li></ul>
  35. 38. Patient Types <ul><li>5 Stages of smoking cessation readiness : </li></ul><ul><li>Pre-contemplation </li></ul><ul><ul><li>Not seriously considering quitting </li></ul></ul><ul><ul><li>Clinicians should put their effort towards motivating the patients to consider quitting </li></ul></ul><ul><li>Contemplation </li></ul><ul><ul><li>Seriously considering quitting </li></ul></ul><ul><ul><li>Clinician should help to develop a quit plan </li></ul></ul>
  36. 39. Patient Types <ul><li>Action </li></ul><ul><ul><li>Actively trying to quit or has recently quit </li></ul></ul><ul><ul><li>Clinicians should advise smokers on coping strategies to reduce withdrawal symptoms and at the same time discuss specific treatment options </li></ul></ul><ul><li>Maintenance </li></ul><ul><ul><li>Has quit and is attempting to avoid relapse </li></ul></ul><ul><ul><li>Clinicians should follow-up and advise them on relapse prevention strategies </li></ul></ul>
  37. 40. Patient Types <ul><li>Relapse </li></ul><ul><ul><li>Very common and most difficult </li></ul></ul><ul><ul><li>Help patients realise that relapse is part of cessation process not a failure </li></ul></ul><ul><ul><li>Able to learn from the causes of relapse </li></ul></ul><ul><ul><li>Develop a more intensive treatment on the next attempt </li></ul></ul>
  38. 42. Intervention Strategies <ul><li>Non-pharmacological </li></ul><ul><ul><li>Self-help </li></ul></ul><ul><ul><li>Behavioural </li></ul></ul><ul><ul><li>Group support </li></ul></ul><ul><ul><li>Hypnosis </li></ul></ul><ul><ul><li>Acupuncture </li></ul></ul><ul><li>Pharmacological </li></ul><ul><ul><li>Nicotine replacement </li></ul></ul><ul><ul><li>Bupropion </li></ul></ul><ul><ul><li>Verinicline </li></ul></ul>
  39. 43. Management <ul><li>Researchers and clinicians view nicotine addiction as a brain disease embedded in a social context </li></ul><ul><li>Effective treatment should incorporate both : </li></ul><ul><ul><li>Behavioural Therapy </li></ul></ul><ul><ul><li>Medication </li></ul></ul>
  40. 45. Self-help Programmes <ul><li>Smoking Cessation Clinics </li></ul><ul><ul><li>Counselling support </li></ul></ul><ul><ul><li>Behavioural programmes </li></ul></ul><ul><ul><li>If the above programmes are inadequate, then pharmacological therapies are sought </li></ul></ul>
  41. 46. Behavioural Programmes <ul><li>Self-management strategies </li></ul><ul><li>Aversion conditioning techniques </li></ul><ul><li>Relapse-prevention methods </li></ul><ul><li>Nicotine fading </li></ul>
  42. 47. Self-Management Strategies <ul><li>Most commonly used </li></ul><ul><li>Make smokers more aware of their smoking patterns and cues </li></ul><ul><li>Self-monitoring </li></ul><ul><ul><li>Record when, where, and why they smoke </li></ul></ul><ul><ul><li>Promote a behavioural change and design a treatment plan </li></ul></ul><ul><li>Stimulus control (Cue extinction) </li></ul><ul><ul><li>Done before quitting to reduce the strength of the smoking cue </li></ul></ul><ul><ul><li>Avoiding dominant cues (talking on the phone, finishing a meal </li></ul></ul>
  43. 48. Aversion Conditioning Techniques <ul><li>Should only be administered by trained smoking cessation specialists </li></ul><ul><li>Used to decrease a smoker’s urge to smoke before quit dates or upon relapse </li></ul><ul><li>Techniques include rapid smoking and satiation </li></ul><ul><li>Rapid smoking : </li></ul><ul><ul><li>Smokers puff cigarettes every 6 to 8 seconds until the cigarette is gone or nausea occurs </li></ul></ul><ul><li>Satiation : </li></ul><ul><ul><li>Smokers double or triple their daily cigarette consumption for brief periods of time </li></ul></ul>
  44. 49. Relapse-Prevention Methods <ul><li>Designed to prevent smokers from returning to smoking behaviour </li></ul><ul><li>Avoidance : </li></ul><ul><ul><li>Minimising exposure to temptations, e.g. stress, other smokers </li></ul></ul><ul><li>Coping Strategies : </li></ul><ul><ul><li>Techniques such as deep breathing or use of relaxation tapes, to deal with withdrawal symptoms </li></ul></ul><ul><li>Contingency management : </li></ul><ul><ul><li>Rewards and punishments </li></ul></ul>
  45. 50. Nicotine Fading <ul><li>Gradual reduction of nicotine intake : </li></ul><ul><ul><li>Tapering the number of cigarettes smoked </li></ul></ul><ul><ul><li>Switching to brands containing less nicotine </li></ul></ul><ul><li>Disadvantage : </li></ul><ul><ul><li>Smokers can compensate by inhaling more deeply and longer </li></ul></ul><ul><ul><li>Further reinforce each episode of smoking </li></ul></ul><ul><li>Results are inconsistent and thus not recommended for routine use </li></ul>
  46. 51. Group Smoking Cessation Programmes <ul><li>Most smokers are unwilling to attend such programmes </li></ul><ul><li>Option for smokers who have failed to respond to less intensive cessation methods </li></ul><ul><li>Done in small group with multiple sessions </li></ul><ul><li>Incorporate various types of behavioural approaches </li></ul>
  47. 52. Hypnosis and Acupuncture <ul><li>Appeal to smokers who want rapid cessation with little effort </li></ul><ul><li>Claims to have high cure rates up to 95% </li></ul><ul><li>No clinical data to support efficacy of these methods </li></ul>
  48. 54. Nicotine Replacement Therapies <ul><li>Gum </li></ul><ul><li>Transdermal patches </li></ul><ul><li>Nasal Spray </li></ul><ul><li>Oral Inhaler </li></ul><ul><li>Lozenges </li></ul>
  49. 55. Nicotine Gum <ul><li>Administered on an as-desired basis </li></ul><ul><li>Most people chew 8 to 15 pieces a day; Each piece is chewed for 20 to 30 mins </li></ul><ul><li>Approximately 50% of nicotine is released </li></ul><ul><li>Providing 8 to 15mg of nicotine per day from the 2-mg form and 16 to 30mg from 4-mg form </li></ul><ul><li>Approx. one-third or one-half of the usual daily intake of a person who smokes 30 cigarettes daily </li></ul><ul><li>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 </li></ul>
  50. 56. Efficacy of Nicotine Gum <ul><li>Successful only accompanied by intensive behavioural programmes </li></ul><ul><li>Acidic drinks, such as coffee or soda, decrease acidity of saliva and may interfere with the effects of nicotine gum </li></ul><ul><li>One should never smoke and chew </li></ul>
  51. 57. Safety and Adverse Effects of Nicotine Gum <ul><li>Flatulence </li></ul><ul><li>Indigestion </li></ul><ul><li>Nausea </li></ul><ul><li>Unpleasant taste </li></ul><ul><li>Hiccups </li></ul><ul><li>Sore mouth, throat and jaw </li></ul>
  52. 58. Nicotine Patches <ul><li>Delivering a steady amount of nicotine to the body right through the skin (usually on an arm, abdomen) </li></ul><ul><li>Easy to use </li></ul><ul><li>Once a day (changing the location each time) </li></ul>
  53. 59. <ul><li>Start with TTS 30 or TTS 20 depending on no. of cigarettes smoked/day </li></ul><ul><ul><li>Those smoking >20 sticks/day start with TTS 30 </li></ul></ul><ul><ul><li>Those smoking <20 sticks/day start with TTS 20 </li></ul></ul><ul><li>Use 30, 20 and 10 cm 2 to allow gradual withdrawal </li></ul><ul><li>Use over 3-4 weeks treatment </li></ul><ul><li>Treatment > 3 months and doses > 30 cm 2 have not been evaluated </li></ul>Nicotine Patches
  54. 60. Safety and Adverse Effects of Nicotine Patches <ul><li>Skin irritation at the patch site </li></ul><ul><li>Insomnia </li></ul><ul><li>Headache </li></ul><ul><li>Cold and flu-like symptoms </li></ul><ul><li>Nausea </li></ul><ul><li>Myalgia </li></ul><ul><li>Dizziness </li></ul><ul><li>Less common : Sleep disturbance, GI side effects - diarrhoea, upset stomach </li></ul>
  55. 61. Safety of Replacement Therapies <ul><li>NRTs should be used with extra caution in patients with cardiovascular disease </li></ul><ul><li>Smoking while using patch or gum therapy may increase the risk of cardiovascular and toxic effects of nicotine </li></ul><ul><li>Patients should stop smoking completely when starting treatment </li></ul><ul><li>In addition, many smokers see such therapy as simply prolonging their dependence or fear becoming dependent on the replacement itself </li></ul>
  56. 62. <ul><li>Works on the biology of nicotine addiction </li></ul><ul><ul><li>By enhancing dopamine levels in the reward pathway </li></ul></ul><ul><ul><li>Affect noradrenergic neurons in the locus ceruleus to reduce craving and withdrawal symptoms </li></ul></ul>Bupropion
  57. 63. Dosage & Administration for Bupropion <ul><li>Start with 150mg/day for the first 3 days </li></ul><ul><li>Follow by a dose increase to 300mg/day given as 150mg b.d. (at 8-hourly interval) </li></ul><ul><li>Maximum dose : 300 mg/day </li></ul><ul><li>Doses above 300mg/day should not be used due to dose-dependent risk of seizures </li></ul>
  58. 64. Dosage & Administration <ul><li>Patients should start taking bupropion BEFORE they quit smoking </li></ul><ul><li>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 </li></ul><ul><li>Treatment with bupropion should be continued for 7-12 weeks </li></ul><ul><li>Dose tapering is not necessary when discontinuing bupropion </li></ul><ul><li>Important that patients continue to receive counselling and support throughout treatment with bupropion, and for a period of time thereafter </li></ul>
  59. 65. Individualization of Therapy <ul><li>Need for education/counseling/support </li></ul><ul><li>Discontinue if patient has not made significant progress toward abstinence by the seventh week of therapy </li></ul><ul><li>If unsuccessful, re-evaluate later for retrial of therapy </li></ul><ul><li>Bupropion should be used as a part of a comprehensive smoking cessation treatment program </li></ul>
  60. 66. Bupropion in Clinical Practice <ul><li>Bupropion is indicated for the treatment of nicotine dependence as an aid to smoking cessation in subjects aged 18 years and over. </li></ul><ul><li>Adult smokers who are motivated to stop could benefit from treatment with bupropion. </li></ul><ul><li>For the majority of patients, the recommended dosage is 150mg once daily for 3 days, increasing to 150mg twice daily. </li></ul>
  61. 67. Combination Therapy for the Heavily Addicted Smoker—Mayo Clinic Style <ul><li>Nicotine patch </li></ul><ul><ul><li>Strongest dose, can use more than one </li></ul></ul><ul><li>Shorter acting nicotine replacement </li></ul><ul><li>Bupropion SR </li></ul>
  62. 68. Varenicline Tartrate (Champix ® ) <ul><li>Indicated for smoking cessation in adults </li></ul><ul><li>Oral administration (tablet) </li></ul><ul><li>Non-nicotine </li></ul><ul><li>a partial agonist selective for the α 4β2 nicotinic acetylcholine receptor </li></ul><ul><ul><li>Dual action with dual benefits </li></ul></ul><ul><ul><li>Partial agonist activity: </li></ul></ul><ul><ul><ul><li>Reduces craving and withdrawal symptoms </li></ul></ul></ul><ul><ul><li>Antagonist activity: </li></ul></ul><ul><ul><ul><li>Produces a reduction of the rewarding and reinforcing effects of smoking () </li></ul></ul></ul>1. Champix Prescribing Information
  63. 69. Champix ® (Varenicline): A Highly Selective  4  2 Receptor Partial Agonist 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. Nicotine Champix
  64. 70. Varenicline:  4  2 nAChR Partial Agonists  4  2 nAChR Dual action of a partial agonist Agonist Response 100% Smoking No Partial Ag No Smoking Partial Ag Smoking + Partial Ag Antagonist Partial Agonist Nicotine Part Ag Part ag Nicotine 50% Potential to block reinforcing effects when smoking 50% Potential to relieve craving and withdrawal when quitting
  65. 71. Varenicline on nicotinic receptors and dopamine release
  66. 72. Varenicline (Champix ® ): Dosage <ul><li>Treatment period is 12 weeks </li></ul><ul><li>An additional course of 12 weeks of treatment may be considered for patients who have successfully quit at end of 12 weeks </li></ul><ul><li>Varenicline is supplied for oral administration in 2 strengths: 0.5 and 1.0 mg; titration is as below: </li></ul>1. Champix Prescribing Information 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
  67. 73. Pharmacokinetics of Varenicline <ul><li>Half-life ~24 hours </li></ul><ul><li>Cmax within 3 to 4 hours </li></ul><ul><li>Steady state reached within 4 days </li></ul><ul><li>Oral bioavailability unaffected by food </li></ul><ul><li>92% of drug is excreted unchanged </li></ul><ul><li>No inhibition of cytochrome P450 enzymes </li></ul><ul><li>No clinically meaningful drug interactions identified </li></ul><ul><li>No dose restrictions in patients with hepatic insufficiency </li></ul><ul><li>Dose adjustment required for severe renal impairment, may be considered for moderate renal impairment </li></ul><ul><li>No dosage adjustment is necessary for elderly patients absent renal impairment </li></ul>1. Champix Prescribing Information
  68. 74. Adverse Effects <ul><li>During clinical trials, approximately 4000 individuals were exposed to varenicline </li></ul><ul><li>Most frequently reported AEs (≥10%) associated with varenicline 1 mg vs placebo were: </li></ul><ul><ul><li>Nausea </li></ul></ul><ul><ul><li>Abnormal dreams </li></ul></ul><ul><ul><li>Insomnia </li></ul></ul><ul><ul><li>Headache </li></ul></ul><ul><li>The percentage of participants who discontinued treatment due to adverse events receiving varenicline treatment was comparable; 11.4% vs 9.7% </li></ul>1. Varenicline Prescribing Information
  69. 75. Contraindications & Interactions <ul><li>Contraindications: </li></ul><ul><ul><li>hypersensitivity to the active substance or to any of the excipients </li></ul></ul><ul><li>No clinically meaningful drug interactions have been identified with varenicline </li></ul>1. Champix Prescribing Information
  70. 76. Precautions <ul><li>There are no adequate data from the use of varenicline in pregnant women </li></ul><ul><ul><li>Varenicline should not be used during pregnancy </li></ul></ul><ul><li>It is unknown whether varenicline is excreted in human breast milk </li></ul><ul><ul><li>Animal studies suggest varenicline is excreted in breast milk </li></ul></ul><ul><ul><li>A decision whether to discontinue varenicline or discontinue breastfeeding should consider the benefits of breastfeeding to the child and varenicline to the woman </li></ul></ul><ul><li>Varenicline may have minor or moderate influence on the ability to drive and use machines </li></ul><ul><ul><li>Patients are advised not to engage in potentially hazardous activities until it is known whether their ability to perform these activities is affected </li></ul></ul>1. Champix Prescribing Information
  71. 77. Dose Adjustment in Special Populations <ul><li>Patients with hepatic impairment </li></ul><ul><ul><li>No dosage adjustment necessary </li></ul></ul><ul><li>Patients with renal insufficiency </li></ul><ul><ul><li>No dosage adjustment necessary for patients with mild to moderate renal impairment </li></ul></ul><ul><ul><li>For patients with moderate renal impairment who experience adverse events that are not tolerable, dosing may be reduced to 1 mg once daily </li></ul></ul><ul><ul><li>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. </li></ul></ul><ul><ul><li>In patients with end-stage renal disease, treatment is not recommended </li></ul></ul>1. Champix Prescribing Information
  72. 78. Comparative Daily Costs of Pharmacotherapy Cost per day, in U.S. dollars $6.07 $5.81 $5.73 $5.26 $3.91 $3.67 $4.22 $4.26
  73. 79. New Medications in the Pipeline <ul><li>Rimonabant </li></ul><ul><ul><li>Cannabinoid receptor inhibitor </li></ul></ul><ul><ul><li>Blocks reinforcing effects of nicotine </li></ul></ul><ul><ul><li>Also suppresses appetite </li></ul></ul><ul><ul><li>In phase III trials </li></ul></ul><ul><ul><li>Not approved for smoking cessation by FDA </li></ul></ul><ul><li>Nicotine Vaccine </li></ul><ul><ul><li>Produces antibodies to nicotine </li></ul></ul><ul><ul><li>Reduces nicotine levels in animals </li></ul></ul><ul><li>CYP246 Inhibitors </li></ul><ul><ul><li>CYP246 is a hepatic enzyme that metabolizes nicotine </li></ul></ul><ul><ul><li>Higher blood nicotine levels per cigarette smoked </li></ul></ul><ul><ul><li>Could also increase potency of NRT </li></ul></ul>
  74. 80. Smoking Cessation: A Very Powerful Intervention… Critchley JA, Capewell S. JAMA ;2003;290:86-97 Intervention Reduction in Mortality Smoking Cessation 36% Statin Therapy 29% Beta-Blockers 23% ACE Inhibitors 23% Aspirin 15%
  75. 81. Effects of Clinician Interventions 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 Type of clinician Fiore et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. USDHHS, PHS, 2000. 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.
  76. 82. Power of Intervention <ul><li>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. </li></ul><ul><li>Increasing the 2.5% cessation rate to 10% would save 1.2 million additional lives. </li></ul><ul><li>If cessation rates rose to 15%, 1.9 million additional lives would be saved. </li></ul>No other health intervention could make such a difference!

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