1. Rx for CHANGE Tobacco Cessation in Respiratory Care

2. TRAINING OVERVIEW Epidemiology of Tobacco Use Impact of Tobacco Use on Respiratory Health Nicotine Pharmacology & Addiction Medications for Cessation Assisting Patients with Quitting

3. EPIDEMIOLOGY of TOBACCO USE

4. is the chief, single, avoidable cause of death in our society and the most important public health issue of our time.” C. Everett Koop, M.D., former U.S. Surgeon General “CIGARETTE SMOKING… All forms of tobacco are harmful.

5. TRENDS in ADULT SMOKING, by SEX—U.S., 1955–2013 Trends in cigarette current smoking among persons aged 18 or older Graph provided by the Centers for Disease Control and Prevention. 1955 Current Population Survey; 1965–2013 NHIS. Estimates since 1992 include some-day smoking. Percent 69% want to quit 53% tried to quit in the past year 53% tried to quit in the past year Males Females 20.5% 15.3% 17.8% of adults are current smokers Year

6. ANNUAL U.S. DEATHS ATTRIBUTABLE to SMOKING, 2005–2009 33% 27% 23% 9% 7% <1% Cardiovascular & metabolic diseases160,600 Lung cancer130,659 Pulmonary diseases113,100 Second-hand smoke41,280 Cancers other than lung36,000 Other1,633 Percent of all smoking- attributable deaths TOTAL: >480,000 deaths annually U.S. Department of Health and Human Services (USDHHS). (2014). The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General.

7. 2014 REPORT of the SURGEON GENERAL: HEALTH CONSEQUENCES OF SMOKING Cigarette smoking is causally linked to diseases of nearly all organs of the body, diminished health status, and harm to the fetus. Additionally, smoking has many adverse effects on the body, such as causing inflammation and impairing immune function. Exposure to second-hand smoke is causally linked to cancer, respiratory, and cardiovascular diseases, and to adverse effects on the health of infants and children. Disease risks from smoking by women have risen over the last 50 years and for many tobacco-related diseases are now equal to those for men. MAJOR DISEASE-RELATED CONCLUSIONS: U.S. Department of Health and Human Services (USDHHS). (2014). The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General.

8. HEALTH CONSEQUENCES of SMOKING Cancers Bladder/kidney/ureter Blood (acute myeloid leukemia) Cervix Colon/rectum Esophagus/stomach Liver Lung Oropharynx/larynx Pancreatic Pulmonary diseases Asthma COPD Pneumonia/tuberculosis Chronic respiratory symptoms Cardiovascular diseases Aortic aneurysm Coronary heart disease Cerebrovascular disease Peripheral vascular disease Reproductive effects Reduced fertility in women Poor pregnancy outcomes (e.g., congenital defects, low birth weight, preterm delivery) Infant mortality Other: cataract, diabetes (type 2), erectile dysfunction, impaired immune function, osteoporosis, periodontitis, postoperative complications, rheumatoid arthritis U.S. Department of Health and Human Services (USDHHS). (2014). The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General.

9. COMPOUNDS in TOBACCO SMOKE Carbon monoxide Hydrogen cyanide Ammonia Benzene Formaldehyde Nicotine Nitrosamines Lead Cadmium Polonium-210 An estimated 4,800 compounds in tobacco smoke, including 11 proven human carcinogens GasesParticles Nicotine is the addictive component of tobacco products, but it does NOT cause the ill health effects of tobacco use.

10. ELECTRONIC CIGARETTES (“e-cigarettes”) Battery-operated devices Known to contain nicotine (0–36 mg/ml), flavoring (e.g., tobacco, fruit, chocolate, mint, cola), propylene glycol, and glycerin Battery warms cartridge; user inhales nicotine vapor or “smoke” Heating element vaporizes liquid at temperatures of 65–120°C Not labeled with health warnings

11. Nicotine is highly addictive and can be harmful. Refill cartridges with high concentrations of nicotine are a poisoning risk, especially in children. Propylene glycol may cause respiratory irritation and increase the risk for asthma. Glycerin may cause lipoid pneumonia on inhalation. Carcinogenic substances are found in some aerosols. Use of e-cigarettes leads to emission of propylene glycol, particles, nicotine, and carcinogens into indoor air. Long-term safety of second-hand exposure to e-cigarette aerosols is unknown. ELECTRONIC CIGARETTES: Potential Health Risks

12. Can reduce the desire (craving) to smoke cigarettes and alleviate nicotine withdrawal symptoms Some smokers reduce the number of cigarettes smoked or quit smoking as a result of using e- e-cigarettes Have not been proven effective as an aid for sustained smoking cessation Concern about “gateway” to tobacco use in adolescents ELECTRONIC CIGARETTES: Current Trends and Evidence Long-term safety and cessation efficacy data are lacking.

13. HERMAN ® is reprinted with permission from LaughingStock Licensing Inc., Ottawa, Canada All rights reserved.

14. U.S. Department of Health and Human Services (USDHHS). (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: Report of the Surgeon General. There is no safe level of second-hand smoke. Second-hand smoke causes premature death and disease in nonsmokers (children and adults). Children: Increased risk for sudden infant death syndrome (SIDS), acute respiratory infections, ear problems, and more severe asthma 2006 REPORT of the SURGEON GENERAL: INVOLUNTARY EXPOSURE to TOBACCO SMOKE Respiratory symptoms and slowed lung growth if parents smoke Adults: Immediate adverse effects on cardiovascular system Increased risk for coronary heart disease and lung cancer Millions of Americans are exposed to smoke in their homes/workplaces. Indoor spaces: eliminating smoking fully protects nonsmokers; separating smoking areas, cleaning the air, and ventilation are ineffective.

15. EPIDEMIOLOGY of TOBACCO USE: SUMMARY Nearly one in five adults are current smokers; smoking prevalence varies by sociodemographic characteristics. Nearly half a million U.S. deaths are attributable to smoking annually, and many of these are due to diseases impacting the respiratory system. Recent trends demonstrate a shift toward increased use of e- cigarettes. These devices have not been proven to be safe and have not been established as effective aids for quitting. There is no safe level of exposure to second-hand smoke.

16. IMPACT of TOBACCO USE on RESPIRATORY HEALTH

17. SMOKING and RESPIRATORY DISEASE Acute respiratory diseases: increased risk, duration, severity Upper respiratory tract Rhinitis, laryngitis, pharyngitis, sinusitis Lower respiratory tract Bronchitis, pneumonia Chronic respiratory diseases  Asthma  Chronic obstructive pulmonary disease (COPD)  Tuberculosis  Lung cancer

18. PNEUMONIA Smokers exhibit increased risk for pneumonia Biologic mechanisms: Damages cilia Increases permeability of airway epithelium Enables infection to more easily enter lungs Reduces overall immune response Risk increases as number of cigarettes smoked increases Risk returns to baseline after ten years of not smoking

19. ASTHMA An estimated 21% of patients with asthma are current smokers Smoking increases the risk of asthma exacerbations in adults Reduced response to treatment with inhaled and systemic corticosteroids Patients with asthma should not smoke.

20. ASTHMA: IN UTERO EXPOSURE Maternal smoking results in infant/child: 1.8 times increased likelihood of developing asthma as well as lifetime history of wheezing 3.6 times increased likelihood of severe asthma Deficits in lung function up to age 6 Reduction in forced expiratory flow and suppression of child’s: ─ formation of the alveoli ─ functional residual capacity ─ tidal flow volume

21. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Characterized by airflow limitation (not fully reversible) Progressive airflow limitation associated with abnormal inflammatory lung response to noxious particles or gases Characteristic symptoms: cough, sputum production, dyspnea COPD mortality has increased dramatically in the past 50 years; currently, more women than men die due to COPD 3rd leading cause of death in the United States U.S. Department of Health and Human Services (USDHHS). (2014). The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General, p. 385. The primary risk factor for COPD is tobacco smoking.

22. COPD: BIOLOGIC MECHANISMS Tobacco smoke induces inflammation and damage to pulmonary tissue through Release of inflammatory cells and mediators Imbalance between proteases and antiproteases Oxidative stress The best treatment for COPD is to quit smoking. Medications simply manage the symptoms.

23. TUBERCULOSIS Smoking is a causal risk factor for contracting TB 2.0–2.6 increased risk compared to nonsmokers Risk increases with Number of cigarettes smoked Duration of smoking Exposure to second-hand smoke increases risk for TB in children Smoking is causally associated with recurrent TB and TB-related mortality

24. SMOKING and LUNG CANCER Lung cancer accounts for an estimated 27% of smoking-attributable deaths Smoking cessation yields meaningful improvements in all forms of cancer treatment (surgery, chemotherapy, radiation) Early-stage non-small-cell lung cancer: 5-year survival rates are up to 70% in those who quit, versus 33% in those who do not Patients who continue to smoke are nearly 2X as likely to have a recurrence and more than 4X as likely to develop a second primary tumor

25. SMOKING and LUNG CANCER (cont’d) Despite the benefits of quitting, lung cancer patients have a high prevalence of smoking and relapse to tobacco use About 50% of lung cancer patients who quit resume smoking 39% of lung cancer physicians actively provide cessation assistance to their patients

26. EFFECT of SECOND-HAND SMOKE on CYSTIC FIBROSIS PATIENTS For every 10 cigarettes/day smoked in household: FEV1 decreased by 4% FVC decreased by 3% Increase in coughing and severity of respiratory illnesses Fivefold increase in pulmonary-related hospitalizations

27. THIRD-HAND SMOKE The residual chemicals from smoking that deposit on clothing, hair, skin, and other surfaces Contains more than 250 harmful chemicals; can last for days or weeks Can cause respiratory irritation and is particularly dangerous to infants While most adults know that second-hand smoke is harmful, few know about third-hand smoke

28. SMOKING and POSTOPERATIVE COMPLICATIONS Respiratory complications Pneumonia Respiratory failure Surgical wound complications Delayed healing Wound dehiscence Infection Scarring

29. CARBON MONOXIDE (CO): PULSE OXIMETRY The CO from tobacco smoke binds to hemoglobin, taking the place of oxygen Oximeters cannot differentiate between hemoglobin molecules that are saturated in oxygen versus those carrying CO Readings will be higher Effects last for up to 4 hours after smoking a cigarette Arterial blood gas assessment is more accurate for determining oxygen saturation in patients who smoke

30. QUITTING: HEALTH BENEFITS Lung cilia regain normal function Ability to clear lungs of mucus increases Coughing, fatigue, shortness of breath decrease Excess risk of CHD decreases to half that of a continuing smoker Risk of stroke is reduced to that of people who have never smoked Lung cancer death rate drops to half that of a continuing smoker Risk of cancer of mouth, throat, esophagus, bladder, kidney, pancreas decrease Risk of CHD is similar to that of people who have never smoked 2 weeks to 3 months 1 to 9 months 1 year 5 years 10 years after 15 years Time Since Quit Date Circulation improves Walking becomes easier Lung function increases

31. BENEFICIAL EFFECTS of QUITTING: PULMONARY EFFECTS Reprinted with permission. Fletcher & Peto. (1977). BMJ 1(6077):1645–1648. Disability Death Smoked regularly and susceptible to effects of smoke Never smoked or not susceptible to smoke Stopped smoking at 45 (mild COPD) Stopped smoking at 65 (severe COPD) 25 FEV 1 (% of value at age 25) 25 50 75 100 0 5075 Age (years) COPD = chronic obstructive pulmonary disease AT ANY AGE, there are pulmonary benefits of quitting.

32. IMPACT of TOBACCO USE: SUMMARY Exposure to tobacco smoke significantly compromises pulmonary health Acute and chronic disease rates are elevated in persons of all ages who are exposed to tobacco smoke There is no safe level of exposure to second-hand smoke, and third-hand smoke can be harmful to patients with respiratory disorders Quitting smoking can improve, reverse, or halt the progression of many tobacco-related respiratory diseases and improve surgical outcomes

33. NICOTINE PHARMACOLOGY and PRINCIPLES of ADDICTION

34. WHAT IS ADDICTION? ”Compulsive drug use, without medical purpose, in the face of negative consequences” Alan I. Leshner, Ph.D. Former director, National Institute on Drug Abuse National Institutes of Health Nicotine addiction is a chronic condition with a biological basis.

35. TOBACCO DEPENDENCE: A 2-PART PROBLEM Tobacco Dependence Treatment should address the physiological and behavioral aspects of dependence. PhysiologicalBehavioral Treatment The addiction to nicotine Medications for cessation The habit of using tobacco Behavior change program

36. NICOTINE DISTRIBUTION Henningfield et al. (1993). Drug Alcohol Depend 33:23–29. Arterial Venous Nicotine reaches the brain within 1020 seconds. Nicotine reaches the brain within 10–20 seconds.

37. Nicotine enters brain Stimulation of nicotine receptors Dopamine release DOPAMINE REWARD PATHWAY Prefrontal cortex Nucleus accumbens Ventral tegmental area

38. Irritability/frustration/anger Anxiety Difficulty concentrating Restlessness/impatience Depressed mood/depression Insomnia Impaired performance Increased appetite/weight gain Cravings NICOTINE PHARMACODYNAMICS: WITHDRAWAL EFFECTS Hughes. (2007). Nicotine Tob Res 9:315–327. Most symptoms manifest within the first 1–2 days, peak within the first week, and subside within 2–4 weeks.

39. BIOLOGY of NICOTINE ADDICTION: ROLE of DOPAMINE Nicotine stimulates dopamine release Repeat administration Tolerance develops Discontinuation leads to withdrawal symptoms. Pleasurable feelings Nicotine addiction is not just a bad habit. Benowitz. (2008). Clin Pharmacol Ther 83:531–541.

40. NICOTINE ADDICTION Tobacco users maintain a minimum serum nicotine concentration in order to Prevent withdrawal symptoms Maintain pleasure/arousal Modulate mood Users self-titrate nicotine intake by Smoking/dipping more frequently Smoking more intensely Obstructing vents on low-nicotine brand cigarettes Benowitz. (2008). Clin Pharmacol Ther 83:531–541.

41. CLOSE TO HOME © 2000 John McPherson. Reprinted with permission of UNIVERSAL PRESS SYNDICATE. All rights reserved.

42. FACTORS CONTRIBUTING to TOBACCO USE Individual Sociodemographics Genetic predisposition Coexisting medical conditions Environment Tobacco advertising Conditioned stimuli Social interactions Pharmacology Alleviation of withdrawal symptoms Weight control Pleasure, mood modulation Tobacco Use

43. NICOTINE PHARMACOLOGY and ADDICTION: SUMMARY Tobacco products are effective delivery systems for the drug nicotine. Nicotine is a highly addictive drug that induces a constellation of pharmacologic effects, including activation of the dopamine reward pathway in the brain. Tobacco use is complex, involving the interplay of a wide range of factors. Treatment of tobacco use and dependence requires a multifaceted treatment approach.

44. ASSISTING PATIENTS with QUITTING

45. WHY BOTHER? Single-most effective strategy to lengthen and improve patients’ lives. Quitting tobacco has immediate and long-term benefits for all patients. It is inconsistent to provide health care and, at the same time, remain silent (or inactive) about a major health risk. TOBACCO CESSATION is an important component of PATIENT CARE.

46. Tobacco users expect to be encouraged to quit by health professionals. Screening for tobacco use and providing tobacco cessation counseling are positively associated with patient satisfaction (Barzilai et al., 2001; Conroy et al., 2005). Barzilai et al. (2001). Prev Med 33:595–599; Conroy et al. (2005). Nicotine Tob Res 7 Suppl 1:S29–S34. Failure to address tobacco use tacitly implies that quitting is not important. WHY SHOULD CLINICIANS ADDRESS TOBACCO?

47. TOBACCO DEPENDENCE: A 2-PART PROBLEM Tobacco Dependence Treatment should address the physiological and the behavioral aspects of dependence. PhysiologicalBehavioral Treatment The addiction to nicotine Medications for cessation The habit of using tobacco Behavior change program

48. EFFECTS of CLINICIAN INTERVENTIONS 1.0 1.1 1.7 2.2 n = 29 studies Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS. With help from a clinician, the odds of quitting approximately double. Compared to patients who receive no assistance from a clinician, patients who receive assistance are 1.7–2.2 times as likely to quit successfully for 5 or more months.

49. Estimated abstinence rate at 5+ months 1.0 1.8 2.5 2.4 n = 37 studies The NUMBER of CLINICIAN TYPES CAN MAKE a DIFFERENCE, TOO Compared to smokers who receive assistance from no clinicians, smokers who receive assistance from two or more clinician types are 2.4–2.5 times as likely to quit successfully for 5 or more months. Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.

50. WHY RESPIRATORY THERAPISTS? Long-term relationships with many patients Engender a sense of trust Patients listen to what you have to say Patients look to you for expert advice on issues concerning the lungs Cessation can be discussed during the course of breathing treatments, etc. You might be the ONE person who a patient listens to about smoking.

51. TOBACCO CESSATION REQUIRES BEHAVIOR CHANGE Fewer than 5% of people who quit without assistance are successful in quitting for more than a year Few patients adequately PREPARE and PLAN for their quit attempt Many patients do not understand the need to change behavior Patients think they can just “make themselves quit” Behavioral counseling is a key component of treatment for tobacco use and dependence.

52. Often, patients automatically smoke in the following situations: Behavioral counseling helps patients learn to cope with these difficult situations without having a cigarette. When drinking coffee While driving in the car When bored While stressed While at a bar with friends After meals During breaks at work While on the telephone While with specific friends or family members who use tobacco BEHAVIOR CHANGE (cont’d)

53. The 5 A’s ASK about tobacco USE ADVISE tobacco users to QUIT ASSESS READINESS to make a quit attempt ASSIST with the QUIT ATTEMPT ARRANGE FOLLOW-UP care

54. ASK about tobacco USE ADVISE tobacco users to QUIT REFER to other resources ASSIST ARRANGE BRIEF COUNSELING: ASK, ADVISE, REFER Patient receives assistance from other resources, with follow-up counseling arranged

55. about tobacco use “If it’s OK with you, it would be helpful if we could talk about your tobacco use.” “Do you, or does anyone in your household, ever smoke or use other types of tobacco or nicotine, such as e- cigarettes?” “We ask our patients about tobacco use, because it contributes to many medical conditions.” “I take time to ask all of my patients about tobacco use— because it’s important.” ASK STEP 1: ASK

56. tobacco users to quit (clear, strong, personalized) “It’s important that you quit as soon as possible, and I can help you.” “Cutting down while you are ill is not enough.” “Occasional or light smoking is still harmful.” “I realize that quitting is difficult. It is the most important thing you can do to protect your health now and in the future. I have training to help my patients quit, and when you are ready, I will work with you to design a specialized treatment plan.” ADVISE STEP 2: ADVISE

57. Consider asking: “Do you ever plan to quit?” “What might be some of the benefits of quitting now, instead of later?” “What would have to change for you to decide to quit sooner?” NOT READY TO QUIT: COUNSELING STRATEGIES If YES If NO Advise patients to quit, and offer to assist (if or when they change their mind). Most patients will agree: There is no “good” time to quit, and there are benefits to quitting sooner as opposed to later. Responses will reveal some of the barriers to quitting.

58. ADVISING PARENTS/CAREGIVERS “Smoking outside, in the doorway, or in a separate room is not enough. The smoke clings to your hair, clothes, and skin, and can irritate your child’s lungs and impair breathing.” “Quitting is the best thing you can do for the your long-term health and that of your child.”

59. COUNSELING PARENTS WHO SMOKE Explain connection between smoking and child’s illness in clear, matter-of-fact manner Refer interested parents to the quitline or other cessation programs For those not interested in quitting, offer suggestions to protect the child Discuss progress at follow-up visits

60. COUNSELING PARENTS (cont’d) Explain the connection: “Your child has impaired lung function due to___. Exposing him/her to second- or third-hand smoke causes additional problems.” “Smoking outside or by the doorway is not sufficient, because the smoke clings to clothes/hair.” “For your child, the only safe amount of exposure to smoke is none.”

61. COUNSELING PARENTS WHO ARE NOT INTERESTED IN QUITTING Do not smoke in the car or in front of your child Children who see parents smoke are more likely to smoke Wear a “smoking jacket” and remove it when entering the home Only removing exposed clothing and washing exposed skin/hair reduces risk When handling infants: Remove all clothing worn while smoking Wash hands/hair first

62. ADDITIONAL RECOMMENDATIONS Explaining the link between smoking and symptoms is important, because most parents underestimate The amount of exposure The harm of exposure Determine and modify exposure by other caregivers Refer to cessation programs Most parents are willing to modify exposure to some extent

63. FOLLOW-UP For those patients seen multiple times: Inform parents that you will be asking about their smoking behavior at each visit Offer support and encouragement Praise any change Strategize solutions to challenges, as appropriate

64. tobacco users to other resources Referral options: A doctor, a nurse, a pharmacist, or another clinician, for additional counseling A hospital-based group program Web-based programs The support program provided (at no cost) with each smoking cessation medication The toll-free telephone quitline: 1-800-QUIT-NOW REFER STEP 3: REFER

65. Brief interventions have been shown to be effective In the absence of time or expertise: Ask, advise, and refer to other resources, such as local group programs or the toll-free quitline 1-800-QUIT-NOW BRIEF COUNSELING: ASK, ADVISE, REFER (cont’d) This brief intervention can be achieved in less than 1 minute.

66. WHAT ARE “TOBACCO QUITLINES”? Tobacco cessation counseling, provided at no cost via telephone to all Americans Staffed by highly trained specialists Up to 4 – 6 personalized sessions (varies by state) Some state quitlines offer pharmacotherapy at no cost (or reduced cost) Up to 30% success rate for patients who complete sessions Most health care providers, and most patients, are not familiar with tobacco quitlines.

67. Caller is routed to language-appropriate staff Brief questionnaire Contact and demographic information Smoking behavior Choice of services Individualized telephone counseling Quitting literature mailed within 24 hr Referral to local programs, as appropriate WHEN a PATIENT CALLS the QUITLINE Quitlines have broad reach and are recommended as an effective strategy in the 2008 Clinical Practice Guideline.

68. WEB-BASED PROGRAMS www.becomeanex.org www.quitnet.com www.smokefree.gov

69. Address tobacco use with all patients. At a minimum, make a commitment to incorporate brief tobacco interventions as part of routine patient care. Ask, Advise, and Refer. MAKE a COMMITMENT…

70. HELPING PATIENTS QUIT IS a CLINICIAN’S RESPONSIBILITY THE DECISION TO QUIT LIES IN THE PATIENT’S HANDS. TOBACCO USERS DON’T PLAN TO FAIL. MOST FAIL TO PLAN. Clinicians have a professional obligation to address tobacco use and can have an important role in helping patients plan for their quit attempts.

71. IF YOU DON’T SAY ANYTHING… You inadvertently give patients… a reason to smoke, and therefore a reason not to quit. “How bad could my smoking be, if my respiratory therapist never said anything to me?” It is not necessary to conduct the entire cessation program, just get it started.

72. DR. GRO HARLEM BRUNTLAND, FORMER DIRECTOR-GENERAL of the WHO: “If we do not act decisively, a hundred years from now our grandchildren and their children will look back and seriously question how people claiming to be committed to public health and social justice allowed the tobacco epidemic to unfold unchecked.” USDHHS. (2001). Women and Smoking: A Report of the Surgeon General. Washington, DC: PHS.

73. MEDICATIONS for CESSATION

74. TOBACCO DEPENDENCE: A 2-PART PROBLEM Tobacco Dependence Treatment should address the physiological and the behavioral aspects of dependence. PhysiologicalBehavioral Treatment The addiction to nicotine Medications for cessation The habit of using tobacco Behavior change program

75. Nicotine polacrilex gum Nicorette ( OTC) Generic nicotine gum (OTC) Nicotine lozenge Nicorette Lozenge (OTC) Nicorette Mini Lozenge (OTC) Generic nicotine lozenge (OTC) Nicotine transdermal patch NicoDerm CQ (OTC) Generic nicotine patches (OTC, Rx) Nicotine nasal spray Nicotrol NS (Rx) Nicotine inhaler Nicotrol (Rx) Bupropion SR (Zyban, generic) Varenicline (Chantix) These are the only medications that are approved by the FDA for smoking cessation. FDA-APPROVED MEDICATIONS for CESSATION

76. PHARMACOTHERAPY Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS. Medications significantly improve success rates. * Includes pregnant women, smokeless tobacco users, light smokers, and adolescents. “Clinicians should encourage all patients attempting to quit to use effective medications for tobacco dependence treatment, except where contraindicated or for specific populations* for which there is insufficient evidence of effectiveness.”

77. PHARMACOTHERAPY: USE in PREGNANCY The Clinical Practice Guideline makes no recommendation regarding use of medications in pregnant smokers Insufficient evidence of effectiveness Category C: varenicline, bupropion SR Category D: prescription formulations of NRT “Because of the serious risks of smoking to the pregnant smoker and the fetus, whenever possible pregnant smokers should be offered person-to-person psychosocial interventions that exceed minimal advice to quit.” Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.

78. PHARMACOTHERAPY: OTHER SPECIAL POPULATIONS Pharmacotherapy is not recommended for: Smokeless tobacco users No FDA indication for smokeless tobacco cessation Individuals smoking fewer than 10 cigarettes per day Adolescents Nonprescription sales (patch, gum, lozenge) are restricted to adults ≥18 years of age NRT use in minors requires a prescription Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS. Recommended treatment is behavioral counseling.

79. NRT: RATIONALE for USE Reduces physical withdrawal from nicotine Eliminates the immediate, reinforcing effects of nicotine that is rapidly absorbed via tobacco smoke Allows patient to focus on behavioral and psychological aspects of tobacco cessation The use of NRT products approximately doubles quit rates.

80. PLASMA NICOTINE CONCENTRATIONS for NICOTINE-CONTAINING PRODUCTS 0 10 20 30 40 50 60 Time (minutes) Cigarette Moist snuff

81. NRT: PRECAUTIONS Patients with underlying cardiovascular disease Recent myocardial infarction (within past 2 weeks) Serious arrhythmias Serious or worsening angina NRT products may be appropriate for these patients if they are under medical supervision.

82. Resin complex Nicotine Polacrilin Sugar-free chewing gum base Contains buffering agents to enhance buccal absorption of nicotine Available: 2 mg, 4 mg; original, cinnamon, fruit, and mint (various) flavors NICOTINE GUM Nicorette; ZONNIC; generics

83. NICOTINE GUM: DOSING Dosage is based on the “time to first cigarette” (TTFC) as an indicator of nicotine dependence. Use the 2-mg gum: If you smoke your first cigarette more than 30 minutes after waking Use the 4-mg gum: If you smoke your first cigarette within 30 minutes of waking

84. NICOTINE GUM: DOSING (cont’d) Recommended Usage Schedule for Nicotine Gum Weeks 1–6Weeks 7–9Weeks 10–12 1 piece q 1–2 h1 piece q 2–4 h1 piece q 4–8 h DO NOT USE MORE THAN 24 PIECES PER DAY.

85. NICOTINE GUM: DIRECTIONS for USE Chew each piece very slowly several times Stop chewing at first sign of peppery taste or slight tingling in mouth (~15 chews, but varies) “Park” gum between cheek and gum (to allow absorption of nicotine across buccal mucosa) Resume slow chewing when taste or tingle fades When taste or tingle returns, stop and park gum in different place in mouth Repeat chew/park steps until most of the nicotine is gone (taste or tingle does not return; generally 30 minutes)

86. NICOTINE GUM: CHEWING TECHNIQUE SUMMARY Park between cheek & gum Stop chewing at first sign of peppery taste or tingling sensation Chew slowly Chew again when peppery taste or tingle fades

87. NICOTINE GUM: ADDITIONAL PATIENT EDUCATION To improve chances of quitting, use at least nine pieces of gum daily The effectiveness of nicotine gum may be reduced by some foods and beverages:  Coffee  Juices  Wine  Soft drinks Do NOT eat or drink for 15 minutes BEFORE or while using nicotine gum.

88. NICOTINE GUM: ADD’L PATIENT EDUCATION (cont’d) Chewing gum will not provide same rapid satisfaction that smoking provides Chewing gum too rapidly can cause excessive release of nicotine, resulting in Lightheadedness Nausea and vomiting Irritation of throat and mouth Hiccups Indigestion

89. NICOTINE GUM: ADD’L PATIENT EDUCATION (cont’d) Side effects of nicotine gum include Mouth soreness Hiccups Dyspepsia Jaw muscle ache Nicotine gum may stick to dental work Discontinue use if excessive sticking or damage to dental work occurs

90. NICOTINE GUM: SUMMARY DISADVANTAGES Need for frequent dosing can compromise adherence Might be problematic for patients with significant dental work Proper chewing technique is necessary for effectiveness and to minimize adverse effects Gum chewing might not be acceptable or desirable for some patients ADVANTAGES Might serve as an oral substitute for tobacco Might delay weight gain Can be titrated to manage withdrawal symptoms Can be used in combination with other agents to manage situational urges

91. NICOTINE LOZENGE Nicorette Lozenge and Nicorette Mini Lozenge; generics Nicotine polacrilex formulation Delivers ~25% more nicotine than equivalent gum dose Sugar-free mint, cherry flavors Contains buffering agents to enhance buccal absorption of nicotine Available: 2 mg, 4 mg

92. NICOTINE LOZENGE: DOSING Dosage is based on the “time to first cigarette” (TTFC) as an indicator of nicotine dependence. Use the 2-mg lozenge: If you smoke your first cigarette more than 30 minutes after waking Use the 4-mg lozenge: If you smoke your first cigarette within 30 minutes of waking

93. NICOTINE LOZENGE: DOSING (cont’d) Recommended Usage Schedule for the Nicotine Lozenge Weeks 1–6Weeks 7–9Weeks 10–12 1 lozenge q 1–2 h 1 lozenge q 2–4 h 1 lozenge q 4–8 h DO NOT USE MORE THAN 20 LOZENGES PER DAY.

94. NICOTINE LOZENGE: DIRECTIONS for USE Use according to recommended dosing schedule Place in mouth and allow to dissolve slowly (nicotine release may cause warm, tingling sensation) Do not chew or swallow lozenge Occasionally rotate to different areas of the mouth Lozenges will dissolve completely in about 20  30 minutes

95. NICOTINE LOZENGE: ADDITIONAL PATIENT EDUCATION To improve chances of quitting, use at least nine lozenges daily during the first 6 weeks The lozenge will not provide the same rapid satisfaction that smoking provides The effectiveness of the nicotine lozenge may be reduced by some foods and beverages:  Coffee  Juices  Wine  Soft drinks Do NOT eat or drink for 15 minutes BEFORE or while using the nicotine lozenge.

96. NICOTINE LOZENGE: ADD’L PATIENT EDUCATION (cont’d) Side effects of the nicotine lozenge include Nausea Hiccups Cough Heartburn Headache Flatulence Insomnia

97. NICOTINE LOZENGE: SUMMARY DISADVANTAGES Need for frequent dosing can compromise adherence Gastrointestinal side effects (nausea, hiccups, heartburn) might be bothersome ADVANTAGES Might serve as an oral substitute for tobacco Might delay weight gain Can be titrated to manage withdrawal symptoms Can be used in combination with other agents to manage situational urges

98. TRANSDERMAL NICOTINE PATCH NicoDerm CQ; generic Nicotine is well absorbed across the skin Delivery to systemic circulation avoids hepatic first- pass metabolism Plasma nicotine levels are lower and fluctuate less than with smoking

99. TRANSDERMAL NICOTINE PATCH: PREPARATION COMPARISON ProductNicoDerm CQGeneric Nicotine delivery 24 hours Availability OTCRx/OTC Patch strengths 7 mg 14 mg 21 mg 7 mg 14 mg 21 mg

100. TRANSDERMAL NICOTINE PATCH: DOSING ProductLight SmokerHeavy Smoker NicoDerm CQ  10 cigarettes/day Step 2 (14 mg x 6 weeks) Step 3 (7 mg x 2 weeks) >10 cigarettes/day Step 1 (21 mg x 6 weeks) Step 2 (14 mg x 2 weeks) Step 3 (7 mg x 2 weeks) Generic  10 cigarettes/day Step 2 (14 mg x 6 weeks) Step 3 (7 mg x 2 weeks) >10 cigarettes/day Step 1 (21 mg x 4 weeks) Step 2 (14 mg x 2 weeks) Step 3 (7 mg x 2 weeks)

101. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE Choose an area of skin on the upper body or upper outer part of the arm Make sure skin is clean, dry, hairless, and not irritated Apply patch to different area each day Do not use same area again for at least 1 week

102. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d) Remove patch from protective pouch Peel off half of the backing from patch

103. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d) Apply adhesive side of patch to skin Peel off remaining protective covering Press firmly with palm of hand for 10 seconds Make sure patch sticks well to skin, especially around edges

104. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d) Wash hands: Nicotine on hands can get into eyes or nose and cause stinging or redness Do not leave patch on skin for more than 24 hours— doing so may lead to skin irritation Adhesive remaining on skin may be removed with rubbing alcohol or acetone Dispose of used patch by folding it onto itself, completely covering adhesive area

105. TRANSDERMAL NICOTINE PATCH: ADDITIONAL PATIENT EDUCATION Water will not harm the nicotine patch if it is applied correctly; patients may bathe, swim, shower, or exercise while wearing the patch Do not cut patches to adjust dose Nicotine may evaporate from cut edges Patch may be less effective Keep new and used patches out of the reach of children and pets Remove patch before MRI procedures

106. TRANSDERMAL NICOTINE PATCH: ADD’L PATIENT EDUCATION (cont’d) Side effects to expect in first hour: Mild itching Burning Tingling Additional possible side effects: Vivid dreams or sleep disturbances Headache

107. TRANSDERMAL NICOTINE PATCH: ADD’L PATIENT EDUCATION (cont’d) After patch removal, skin may appear red for 24 hours If skin stays red more than 4 days or if it swells or a rash appears, contact health care provider—do not apply new patch Local skin reactions (redness, burning, itching) Usually caused by adhesive Up to 50% of patients experience this reaction Fewer than 5% of patients discontinue therapy Avoid use in patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis)

108. TRANSDERMAL NICOTINE PATCH: SUMMARY DISADVANTAGES When used as monotherapy, cannot be titrated to acutely manage withdrawal symptoms Not recommended for use by patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) ADVANTAGES Once-daily dosing is associated with fewer adherence problems Of all NRT products, its use is least obvious to others Can be used in combination with other agents; delivers consistent nicotine levels over 24 hours

109. NICOTINE NASAL SPRAY Nicotrol NS Aqueous solution of nicotine in a 10-ml spray bottle Each metered dose actuation delivers 50 mcL spray 0.5 mg nicotine ~100 doses/bottle Rapid absorption across nasal mucosa

110. NICOTINE NASAL SPRAY: DOSING & ADMINISTRATION One dose = 1 mg nicotine (2 sprays, one 0.5 mg spray in each nostril) Start with 1–2 doses per hour Increase prn to maximum dosage of 5 doses per hour or 40 mg (80 sprays; ~½ bottle) daily For best results, patients should use at least 8 doses daily for the first 6–8 weeks Termination: Gradual tapering over an additional 4–6 weeks

111. NICOTINE NASAL SPRAY: DIRECTIONS for USE Press in circles on sides of bottle and pull to remove cap

112. NICOTINE NASAL SPRAY: DIRECTIONS for USE (cont’d) Prime the pump (before first use) Re-prime (1-2 sprays) if spray not used for 24 hours Blow nose (if not clear) Tilt head back slightly and insert tip of bottle into nostril as far as comfortable Breathe through mouth, and spray once in each nostril Do not sniff or inhale while spraying

113. NICOTINE NASAL SPRAY: DIRECTIONS for USE (cont’d) If nose runs, gently sniff to keep nasal spray in nose Wait 2–3 minutes before blowing nose Avoid contact with skin, eyes, and mouth If contact occurs, rinse with water immediately Nicotine is absorbed through skin and mucous membranes

114. NICOTINE NASAL SPRAY: ADDITIONAL PATIENT EDUCATION What to expect (first week): Hot peppery feeling in back of throat or nose Sneezing Coughing Watery eyes Runny nose Side effects should lessen over a few days Regular use during the first week will help in development of tolerance to the irritant effects of the spray If side effects do not decrease after a week, contact health care provider

115. NICOTINE NASAL SPRAY: SUMMARY DISADVANTAGES Need for frequent dosing can compromise adherence Nasal administration might not be acceptable/desirable for some patients; nasal irritation often problematic Not recommended for use by patients with chronic nasal disorders or severe reactive airway disease ADVANTAGES Can be titrated to rapidly manage withdrawal symptoms Can be used in combination with other agents to manage situational urges

116. NICOTINE INHALER Nicotrol Inhaler Nicotine inhalation system consists of: Mouthpiece Cartridge with porous plug containing 10 mg nicotine and 1 mg menthol Delivers 4 mg nicotine vapor, absorbed across buccal mucosa

117. NICOTINE INHALER: DOSING Start with at least 6 cartridges/day during the first 3-6 weeks of treatment Increase prn to maximum of 16 cartridges/day In general, use 1 cartridge every 1-2 hours Recommended duration of therapy is 3 months Gradually reduce daily dosage over the following 6–12 weeks

118. NICOTINE INHALER: ADDITIONAL PATIENT EDUCATION Side effects associated with the nicotine inhaler include: Mild irritation of the mouth or throat Cough Headache Rhinitis Dyspepsia Severity is generally rated as mild, and frequency of symptoms declines with continued use

119. NICOTINE INHALER: ADD’L PATIENT EDUCATION (cont’d) Use inhaler at room temperature (>60  F); in cold environments, the delivery of nicotine vapor may be compromised Use the inhaler longer and more often at first to help control cravings (best results are achieved with frequent continuous puffing over 20 minutes) Effectiveness of the nicotine inhaler may be reduced by some foods and beverages Do NOT eat or drink for 15 minutes BEFORE or while using the nicotine inhaler.

120. NICOTINE INHALER: SUMMARY DISADVANTAGES Need for frequent dosing can compromise adherence Cartridges might be less effective in cold environments (≤60  F) ADVANTAGES Might serve as an oral substitute for tobacco Can be titrated to manage withdrawal symptoms Mimics the hand-to-mouth ritual of smoking Can be used in combination with other agents to manage situational urges

121. BUPROPION SR Zyban; generics Nonnicotine cessation aid Sustained-release antidepressant Oral formulation

122. BUPROPION: MECHANISM of ACTION Atypical antidepressant thought to affect levels of various brain neurotransmitters Dopamine Norepinephrine Clinical effects  craving for cigarettes  symptoms of nicotine withdrawal

123. BUPROPION: CONTRAINDICATIONS Patients with a seizure disorder Patients with a current or prior diagnosis of bulimia or anorexia nervosa Patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs Patients taking MAO inhibitors (within 14 days of initiating or discontinuing therapy)

124. Neuropsychiatric symptoms and suicide risk: Changes in mood (e.g., depression, mania) Psychosis, hallucinations, paranoia, or delusions Homicidal ideation or hostility Agitation, aggression, anxiety, or panic Suicidal ideation or attempts Completed suicide BUPROPION: WARNINGS and PRECAUTIONS Patients should be advised to stop taking bupropion SR and contact a health care provider immediately if symptoms such as agitation, hostility, depressed mood, or changes in thinking or behavior that are not typical are observed or if the patient develops suicidal ideation or suicidal behavior.

125. BUPROPION: WARNINGS and PRECAUTIONS (cont’d) Bupropion should be used with caution in the following populations: Patients with an elevated risk for seizures, including: Severe head injury Concomitant use of medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline) Severe hepatic impairment Patients with underlying neuropsychiatric conditions For a comprehensive listing of warnings and precautions, refer to the manufacturer’s prescribing information.

126. BUPROPION SR: DOSING Initial treatment 150 mg po q AM for 3 days Then… 150 mg po bid for 7–12 weeks Doses must be administered at least 8 hours apart Tapering not necessary when discontinuing therapy To ensure that therapeutic plasma levels of the drug are achieved, patients should begin therapy 1 to 2 weeks PRIOR to their quit date.

127. BUPROPION: ADVERSE EFFECTS Common side effects include the following: Insomnia (avoid bedtime dosing) Dry mouth Less common but reported effects: Tremor Skin rash

128. BUPROPION SR: SUMMARY DISADVANTAGES Seizure risk is increased Several contraindications and precautions preclude use in some patients Patients should be monitored for neuropsychiatric symptoms ADVANTAGES Oral dosing is simple and associated with fewer adherence problems Might delay weight gain Might be beneficial in patients with depression Can be used in combination with NRT agents

129. VARENICLINE Chantix Nonnicotine cessation aid Partial nicotinic receptor agonist Oral formulation

130. VARENICLINE: MECHANISM of ACTION Binds to nicotine acetylcholine receptors in the central nervous system Stimulates low-level agonist activity Competitively inhibits binding of nicotine Clinical effects  symptoms of nicotine withdrawal Blocks dopaminergic stimulation responsible for reinforcement and reward associated with smoking

131. VARENICLINE: PHARMACOKINETICS Absorption Virtually complete (~90%) after oral administration; not affected by food Metabolism Undergoes minimal metabolism Elimination Primarily renal through glomerular filtration and active tubular secretion; 92% excreted unchanged in urine Half-life ~24 hours

132. Neuropsychiatric symptoms and suicidality: Changes in mood (e.g., depression, mania) Psychosis, hallucinations, paranoia, or delusions Homicidal ideation or hostility Agitation, anxiety, or panic Suicidal ideation or attempts Completed suicide VARENICLINE: WARNINGS and PRECAUTIONS Patients should be advised to stop taking varenicline and contact a health care provider immediately if agitation, hostility, depressed mood, or changes in thinking or behavior that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior.

133. VARENICLINE: WARNINGS and PRECAUTIONS (cont’d) In some patients, use of varenicline has been associated with the following: Seizures Enhanced effects of alcohol Accidental injury Cardiovascular events Angioedema and hypersensitivity reactions Serious skin reactions These are rare events, and most have not been causally linked to varenicline use.

134. VARENICLINE: DOSING Patients should begin therapy 1 week PRIOR to their quit date. The dosage is increased gradually to minimize treatment-related nausea and insomnia. Treatment DayDosage Day 1 to day 30.5 mg qd Day 4 to day 70.5 mg bid Day 8 to end of treatment*1 mg bid Initial dose titration * Up to 12 weeks

135. VARENICLINE: ADVERSE EFFECTS Common (≥5% and 2-fold higher than placebo) Nausea Sleep disturbances (insomnia, abnormal dreams) Constipation Flatulence Vomiting

136. VARENICLINE: ADDITIONAL PATIENT EDUCATION Doses should be taken after eating, with a full glass of water Nausea and insomnia are usually temporary side effects; i f symptoms persist, notify your health care provider May experience vivid, unusual, or strange dreams during treatment Use caution driving, drinking alcohol, and operating machinery until effects of quitting smoking with varenicline are known

137. VARENICLINE: SUMMARY DISADVANTAGES Should be taken with food or a full glass of water to reduce the incidence of nausea Patients should be monitored for potential neuropsychiatric symptoms Postmarketing surveillance data indicate potential for neuropsychiatric symptoms and adverse effects not shown to be prevalent in randomized trials ADVANTAGES Oral dosing is simple and associated with fewer adherence problems Offers a different mechanism of action for persons who have failed other agents

138. LONG-TERM (  6 month) QUIT RATES for AVAILABLE CESSATION MEDICATIONS Data adapted from Cahill et al. (2012). Cochrane Database Syst Rev; Hughes et al. (2014). Cochrane Database Syst Rev; and Stead et al. (2012). Cochrane Database Sys Rev. Percent quit 16.3 15.9 10.0 9.8 18.9 8.4 23.9 11.8 17.1 9.1 19.7 11.5 12.0 28.0

139. COMBINATION PHARMACOTHERAPY Combination NRT Long-acting formulation (patch) Produces relatively constant levels of nicotine PLUS Short-acting formulation (gum, inhaler, nasal spray) Allows for acute dose titration as needed for nicotine withdrawal symptoms Bupropion SR + Nicotine Patch Regimens with enough evidence to be “recommended” first-line

140. COMBINATION THERAPIES (cont’d) These combinations have enough evidence to be “recommended” Long-term patch (>14 weeks) + ad lib 2 mg gum Long-term patch (>14 weeks) + ad lib nasal spray Standard-dose patch + oral inhaler Standard-dose patch + bupropion

141. IDENTIFY KEY ISSUES to STREAMLINE PRODUCT SELECTION* Do you prefer a prescription or nonprescription medication? Would it be a challenge for you to take a medication frequently throughout the day (e.g., a minimum of 9 times)? With the exception of the nicotine patch, all NRT formulations require frequent dosing throughout the day. If patient is unable to adhere to the recommended dosing, these products should be ruled out as monotherapy because they will be ineffective. Asking these two questions will significantly reduce the time required for product selection. * Product-specific screening—for warnings, precautions, contraindications, and personal preferences—is also essential.

142. ADHERENCE IS KEY to QUITTING Promote adherence with prescribed regimens Use according to dosing schedule, NOT as needed Consider telling the patient: “When you use a cessation product, it is important to read all the directions thoroughly before using the product. The products work best in alleviating withdrawal symptoms when used correctly, and according to the recommended dosing schedule.”

143. COMPARATIVE DAILY COSTS of PHARMACOTHERAPY $/day Average $/pack of cigarettes, $5.96

144. SUMMARY To maximize success, interventions should include counseling and one or more medications Clinicians should encourage the use of effective medications by all patients attempting to quit smoking Exceptions include medical contraindications or use in specific populations for which there is insufficient evidence of effectiveness First-line medications that reliably increase long-term smoking cessation rates include the following: Bupropion SR Nicotine replacement therapy (gum, lozenge, patch, nasal spray, inhaler) Varenicline Use of effective combinations of medications should be considered