PHP 315 Smoking Cessation 2024 PDF

Rx for Change Clinician-Assisted Tobacco Cessation Kelly Orr, PharmD, AE-C Clinical Professor The University of Rhode Island College of Pharmacy  TRAINING OVERVIEW § Epidemiology of Tobacco Use § Nicotine Pharmacology & Principles of Addiction § Drug Interact...

Rx for Change Clinician-Assisted Tobacco Cessation Kelly Orr, PharmD, AE-C Clinical Professor The University of Rhode Island College of Pharmacy  TRAINING OVERVIEW § Epidemiology of Tobacco Use § Nicotine Pharmacology & Principles of Addiction § Drug Interactions with Smoking § Forms of Tobacco § Medications for Cessation – Part 2 § Assisting Patients with Quitting (P2 Fall, PHC 415) EPIDEMIOLOGY of TOBACCO USE  “CIGARETTE SMOKING… 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 All forms of tobacco are harmful. TRENDS in ADULT CIGARETTE CONSUMPTION—U.S., 1900–2002  TRENDS in ADULT SMOKING, by SEX—United States, since 1955 60 Trends in cigarette current smoking among persons aged 18 or older In 2021, 50 Males 11.5% of adults were smoking cigarettes; 40 18.7% reported using one or more types Percent of commercial tobacco products* 30 20 Females 13.1% 10 10.1% 0 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year * cigarettes, e-cigarettes, cigars, smokeless tobacco, or pipes. 68% want to quit 55% tried to quit in the past year Graph provided by the Centers for Disease Control and Prevention. Estimates since 1992 include some-day smoking.  CURRENT* ADULT USE of ANY FORM of TOBACCO or E-CIGARETTES, U.S., 2021 14 18.7% currently used any product; 12 11.5 3.4% used 2 or more tobacco products 10 14.5% use any “combustible” product Percent 8 6 4.5 4 3.5 2.1 2 1.1 0 Cigarettes E-cigarettes Cigars, cigarillos, Smokeless tobacco Regular pipes, filtered little cigars waterpipes, hookah *Respondent reported using “every day” or “some days” at the time of survey. Cornelius ME, et al. (2023). MMWR 72:475–483.  CURRENT USE E-CIGARETTES & NICOTINE POUCHES M.S./H.S. §Most students want to quit & have tried to §67.4% past year §Most common products: Elf Bar, Breeze, & Mr. Fog Centers for Disease Control. Smoking and Tobacco Use: E-Cigarette Use Among Youth. May 15, 2024.  STATE-SPECIFIC PREVALENCE of SMOKING among ADULTS, 2014–2015 Prevalence of ` current* cigarette smoking ≥ 18.0% 15.0 – 17.9% 12.0 – 14.9% 8.0 – 11.9% Centers for Disease Control and Prevention (CDC). (2018). MMWR 67:97–102. * Has smoked ≥ 100 cigarettes during lifetime and currently smokes either every day or some days  PREVALENCE of ADULT CIGARETTE SMOKING, by RACE/ETHNICITY—U.S., 2021 White 22.6% 20.9% 12.9% Black or African American 11.7% 14.9% Hispanic 7.7% 8.8% Asian 5.4% 7.2% 0 5 10 15 Percent Cornelius ME, et al. (2023). MMWR 72:475–483.  PREVALENCE of ADULT CIGARETTE SMOKING, by EDUCATION—U.S., 2021 No high school diploma 20.1% GED diploma 30.7% High school graduate 17.1% Some college 16.1% Bachelor’s degree 5.3% Graduate degree 3.2% 0 5 10 15 20 25 30 35 Percent Cornelius ME, et al. (2023). MMWR 72:475–483.  TRENDS in TEEN SMOKING, by ETHNICITY—U.S., 1977–2021 Trends in cigarette smoking among 12th graders: 30-day prevalence of use 50 40 White 30 Hispanic 20 Black 10 0 1977 1982 1987 1992 1997 2002 2007 2012 2017 Year Institute for Social Research, University of Michigan, Monitoring the Future Project www.monitoringthefuture.org  An EFFECTIVE MARKETING STRATEGY: “LIGHT” CIGARETTES The difference between Marlboro and Marlboro Lights… an extra row of ventilation holes Image courtesy of Mayo Clinic Nicotine Dependence Center - Research Program / Dr. Richard D. Hurt The Marlboro and Marlboro Lights logos are registered trademarks of Philip Morris USA. 1936 1990  SMOKING in MOVIES n Cigarette smoking is pervasive in movies n Evident in at least ¾ of box-office hits n Average, 10.9 smoking incidents per hour Charlesworth and Glantz. (2005). Pediatrics 116:1516–1528. n There is a dose-response, causal relationship between exposure to smoking in movies and youth smoking initiation Superman II (1980) National Cancer Institute. (2008). The Role of the Media in Promoting and Reducing Tobacco Use. 70% of adults support assigning an “R” rating to movies with smoking. For more information on smoking in movies, go to http://smokefreemovies.ucsf.edu  FDA REGULATION of TOBACCO PRODUCTS The FDA Center for Tobacco Control Products is responsible for regulation of: § Cigarettes § Cigarette tobacco § Roll-your-own tobacco § Smokeless tobacco § E-cigarettes* *Not a tobacco product.  COMPOUNDS in TOBACCO SMOKE An estimated 8,700 compounds in tobacco smoke, including 72 proven or suspected human carcinogens Gases Particles n Carbon monoxide n Nicotine n Hydrogen cyanide n Nitrosamines n Ammonia n Lead n Benzene n Cadmium n Formaldehyde n Polonium-210 Nicotine is the addictive component of tobacco products, but it does NOT cause the ill health effects of tobacco use.  ANNUAL U.S. DEATHS ATTRIBUTABLE to SMOKING, 2005–2009 Percent of all smoking- attributable deaths Cardiovascular & metabolic diseases 160,600 33% Lung cancer 130,659 27% Pulmonary diseases 113,100 23% Second-hand smoke 41,280 9% Cancers other than lung 36,000 7% Other 1,633 480,000 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.  ANNUAL SMOKING-ATTRIBUTABLE ECONOMIC COSTS Health-care $132.5 billion expenditures Lost productivity costs due $156.4 billion to premature mortality Total economic burden $288.9 billion of smoking, per year Billions of US dollars Societal costs: $20.52 per pack of cigarettes smoked 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.  2014 REPORT of the SURGEON GENERAL: HEALTH CONSEQUENCES OF SMOKING MAJOR DISEASE-RELATED CONCLUSIONS: § Cigarette smoking is causally linked to diseases of nearly all organs of the body, diminished health status, and harm to the fetus. § Additionally, many adverse effects on the body such as inflammation and impaired immune function. § Exposure to secondhand 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. 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.  HEALTH CONSEQUENCES of SMOKING § Cancers § Cardiovascular diseases § Bladder/kidney/ureter § Aortic aneurysm § Blood (acute myeloid leukemia) § Coronary heart disease § Cervix § Cerebrovascular disease § Colon/rectum § Peripheral vascular disease § Esophagus/stomach § Reproductive effects § Liver § Reduced fertility in women § Lung § Poor pregnancy outcomes (e.g., congenital defects, § Oropharynx/larynx low birth weight, preterm delivery) § Pancreatic § Infant mortality § Pulmonary diseases § Other: cataract, diabetes (type 2), erectile dysfunction, § Asthma impaired immune function, osteoporosis, periodontitis, § COPD postoperative complications, rheumatoid arthritis § Pneumonia/tuberculosis § Chronic respiratory symptoms 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.  HEALTH CONSEQUENCES of SMOKELESS TOBACCO USE Periodontal effects § Gingival recession § Bone attachment loss § Dental caries Oral leukoplakia Cancer § Oral cancer § Pharyngeal cancer Oral Leukoplakia Image courtesy of Dr. Sol Silverman - University of California San Francisco  2006 REPORT of the SURGEON GENERAL: INVOLUNTARY EXPOSURE to TOBACCO SMOKE n Second-hand smoke causes premature death and disease in nonsmokers (children and adults) n Children: There is no n Increased risk for sudden infant death syndrome (SIDS), acute respiratory infections, ear problems, and more severe asthma safe level of n Respiratory symptoms and slowed lung growth if parents smoke second-hand Adults: n n Immediate adverse effects on cardiovascular system smoke. n Increased risk for coronary heart disease and lung cancer n Millions of Americans are exposed to smoke in their homes/workplaces n Indoor spaces: eliminating smoking fully protects nonsmokers n Separating smoking areas, cleaning the air, and ventilation are ineffective U.S. Department of Health and Human Services (USDHHS). (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: Report of the Surgeon General.  QUITTING: HEALTH BENEFITS Time Since Quit Date Circulation improves, walking becomes easier 2 weeks to Lung cilia regain normal function 3 months Lung function increases Ability to clear lungs of mucus 1 to 9 increases months Coughing, fatigue, shortness of Excess risk of CHD decreases to half that 1 breath decrease of those who continue to smoke year 5 Risk of stroke is reduced to that Lung cancer death rate is similar to half of people who have never years that of those who continue to smoke smoked 10 Risk of cancer of mouth, throat, years esophagus, bladder, kidney, pancreas decrease after Risk of CHD is similar to that of 15 years people who have never smoked  BENEFICIAL EFFECTS of QUITTING: PULMONARY EFFECTS AT ANY AGE, there are benefits of quitting. Never smoked 100 or not susceptible to smoke FEV1 (% of value at age 25) 75 Stopped smoking at 45 Smoked (mild COPD) 50 regularly and susceptible to Disability effects of smoke 25 Stopped smoking at Death 65 (severe COPD) 0 25 50 75 Age (years) COPD = chronic obstructive pulmonary disease Reprinted with permission. Fletcher & Peto. (1977). BMJ 1(6077):1645–1648.  Cumulative risk (%) Reduction in cumulative risk of death from lung cancer in men Age in years Reprinted with permission. Peto et al. (2000). BMJ 321(7257):323–329.  SMOKING CESSATION: REDUCED RISK of DEATH n Prospective study of 34,439 male British doctors n Mortality was monitored for 50 years (1951–2001) 15 On average, cigarette smokers die Years of life gained approximately 10 10 years younger than do nonsmokers. 5 Among those who continue smoking, at least half will die due 0 30 40 50 60 to a tobacco-related disease. Age at cessation (years) Doll et al. (2004). BMJ 328(7455):1519–1527.  FINANCIAL IMPACT of SMOKING Buying cigarettes every day for 50 years at $8.41 per pack* (does not include interest) Packs per 2.0 $306,900 Annual cost of smoking day 1.5 $230,175 1 pack per day: $3,069 1.0 $153,450 $251,725 0 100 200 300 400 Dollars lost, in thousands * Average national cost, as of January 30, 2023. Campaign for Tobacco-Free Kids. (2023).  EPIDEMIOLOGY of TOBACCO USE: SUMMARY § Fewer than 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 § Smoking costs the U.S. an estimated $288.9 billion annually § For the individual, a smoking a pack-a-day costs $3,069 annually, plus associated health-care costs § At any age, there are benefits to quitting smoking § The biggest opponent to tobacco control efforts is the tobacco industry  NICOTINE ADDICTION U.S. Surgeon General’s Report § Cigarettes and other forms of tobacco are addicting. § Nicotine is the drug in tobacco that causes addiction. § The pharmacologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine. U.S. Department of Health and Human Services. (1988). The Health Consequences of Smoking: Nicotine Addiction. A Report of the Surgeon General. CHEMISTRY of NICOTINE Pyrrolidine ring H N Pyridine ring N CH3 Nicotiana tabacum Natural liquid alkaloid Colorless, volatile base pKa = 8.0 PHARMACOLOGY Pharmacokinetics Effects of the body on the drug § Absorption § Distribution § Metabolism § Excretion Pharmacodynamics Effects of the drug on the body  NICOTINE ABSORPTION Absorption is pH-dependent n In acidic media n Ionized Ü poorly absorbed across membranes n In alkaline media n Nonionized Ü well absorbed across membranes n At physiologic pH (7.4), ~31% of nicotine is nonionized At physiologic pH, nicotine is readily absorbed. NICOTINE ABSORPTION: BUCCAL (ORAL) MUCOSA The pH inside the mouth is 7.0. Acidic media Alkaline media (limited absorption) (significant absorption) Cigarettes Pipes, cigars, spit tobacco, oral nicotine products Beverages can alter pH, affect absorption.  NICOTINE ABSORPTION: SKIN and GASTROINTESTINAL TRACT § Nicotine is readily absorbed through intact skin. § Nicotine is well absorbed in the small intestine § Low bioavailability (20-45%) due to first-pass hepatic metabolism.  NICOTINE ABSORPTION: LUNG § Nicotine is “distilled” from burning tobacco § Carried in tar droplets to the lungs § Nicotine is rapidly absorbed across respiratory epithelium § Lung pH = 7.4 § Large alveolar surface area § Extensive capillary system § Approximately 1 mg of nicotine is absorbed from each cigarette NICOTINE DISTRIBUTION 80 Arterial Plasma nicotine (ng/ml) 60 40 Venous 20 0 0 1 2 3 4 5 6 7 8 9 10 Minutes after light-up of cigarette Nicotine reaches the brain within 10–20 seconds. Henningfield et al. (1993). Drug Alcohol Depend 33:23–29. NICOTINE METABOLISM H 10–20% N excreted unchanged N CH3 in urine 70–80% ~ 10% other cotinine metabolites Metabolized and excreted in urine Adapted and reprinted with permission. Benowitz et al. (1994). J Pharmacol Exp Ther 268:296–303.  NICOTINE EXCRETION § Half-life § Nicotine t½ = 2 hr § Cotinine t½ = 16 hr § Excretion § Occurs through kidneys (pH dependent; h with acidic pH) § Through breast milk  NICOTINE PHARMACODYNAMICS Nicotine binds to receptors in the brain and other Central nervous system sites throughout the body. Cardiovascular system Exocrine glands Gastrointestinal system Adrenal medulla Other: Neuromuscular junction Sensory receptors Peripheral nervous system Other organs Nicotine has predominantly stimulatory effects.  NICOTINE PHARMACODYNAMICS (cont’d) Central nervous system Cardiovascular system n Pleasure n ­ Heart rate n Arousal, enhanced vigilance n ­ Cardiac output n Improved task performance n ­ Blood pressure n Anxiety relief n Coronary vasoconstriction n Cutaneous vasoconstriction Other n Appetite suppression n Increased metabolic rate n Skeletal muscle relaxation  NEUROCHEMICAL and RELATED EFFECTS of NICOTINE N â Dopamine â Pleasure, appetite suppression I â Norepinephrine â Arousal, appetite suppression C â Acetylcholine â Arousal, cognitive enhancement O â Glutamate â Learning, memory enhancement T â Serotonin â Mood modulation, appetite suppression I â b -Endorphin â Reduction of anxiety and tension N â GABA â Reduction of anxiety and tension E Benowitz. (2008). Clin Pharmacol Ther 83:531–541.  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.  DOPAMINE REWARD PATHWAY Prefrontal cortex Dopamine release Stimulation of Nucleus nicotine receptors accumbens Ventral tegmental Nicotine enters area brain CHRONIC ADMINISTRATION of NICOTINE: EFFECTS on the BRAIN Human smokers have increased nicotine receptors in the prefrontal cortex. High Low Nonsmoker Smoker Image courtesy of George Washington University / Dr. David C. Perry Perry et al. (1999). J Pharmacol Exp Ther 289:1545–1552.  NICOTINE WITHDRAWAL SYMPTOMS: Time Course* Irritability / Frustration / Anger Anxiety Difficulty concentrating Most symptoms manifest Restlessness / Impatience within the first 1–2 days, peak Depressed mood / Depression within the first week, and Insomnia subside within 2–4 weeks. Impaired task performance Increased appetite 6 months Weight gain Cravings Can persist for months to years after quitting 1 week 4 weeks 12 weeks Quit Former Recent quitter date tobacco user *Timeline aspect of the figure is not according to scale. Data from Hughes. (2007). Nicotine Tob Res 9:315–327. NICOTINE ADDICTION CYCLE Reprinted with permission. Benowitz. (1992). Med Clin N Am 2:415–437.  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/vaping more frequently § Smoking/vaping more intensely Benowitz. (2008). Clin Pharmacol Ther 83:531–541.  ASSESSING NICOTINE DEPENDENCE Fagerström Test for Nicotine Dependence (FTND) § Developed in 1978 (8 items); revised in 1991 (6 items) § Most common research measure of nicotine dependence; sometimes used in clinical practice § Responses coded such that higher scores suggest higher levels of dependence § Scores range from 0 to 10; score of greater than 5 suggest substantial dependence Heatherton et al. (1991). British Journal of Addiction 86:1119–1127.  NICOTINE PHARMACOLOGY and ADDICTION: SUMMARY n Tobacco products are effective delivery systems for the drug nicotine. n Nicotine is a highly addictive drug that induces a constellation of pharmacologic effects, including activation of the dopamine reward pathway in the brain. n Tobacco use is complex, involving the interplay of a wide range of factors. n Treatment of tobacco use and dependence requires a multifaceted treatment approach. DRUG INTERACTIONS with TOBACCO SMOKE  PHARMACOKINETIC DRUG INTERACTIONS with TOBACCO SMOKE Drugs that may have a decreased effect due to induction of CYP1A2: § Bendamustine § Haloperidol § Tasimelteon § Caffeine § Olanzapine § Theophylline § Clozapine § Pirfenidone § Erlotinib § Riociguat § Fluvoxamine § Ropinirole § Irinotecan (clearance increased and systemic exposure decreased, due to increased glucuronidation of its active metabolite) Smoking cessation will reverse these effects.  DRUG INTERACTION: TOBACCO SMOKE and CAFFEINE § Constituents in tobacco smoke induce CYP1A2 enzymes, which metabolize caffeine § Caffeine levels increase ~56% upon quitting § Challenges: § Nicotine withdrawal effects might be enhanced by increased caffeine levels § Insomnia can be due to ↑ caffeine levels or a side effect of a smoking cessation drug (e.g., varenicline or bupropion) § Decrease caffeine intake by about half when quitting § For individuals with a typical bedtime, suggest eliminating caffeine by early afternoon  PHARMACODYNAMIC DRUG INTERACTIONS with TOBACCO SMOKE Smokers who use combined hormonal contraceptives have an increased risk of serious cardiovascular adverse effects: § Stroke § Myocardial infarction § Thromboembolism This interaction does not decrease the efficacy of hormonal contraceptives. Women who are 35 years of age or older AND smoke at least 15 cigarettes per day are at significantly elevated risk.  The shaded rows indicate clinically significant drug interactions.  DRUG INTERACTIONS with TOBACCO SMOKE: SUMMARY Clinicians should be aware of their patients’ smoking status: § Clinically significant interactions result the combustion products of tobacco smoke, not from nicotine. § Constituents in tobacco smoke (e.g., polycyclic aromatic hydrocarbons; PAHs) may enhance the metabolism of other drugs, resulting in an altered pharmacologic response. § Changes in smoking status might alter the clinical response to the treatment of a wide variety of conditions. § Drug interactions with smoking should be considered when patients start smoking, quit smoking, or markedly alter their levels of smoking.  FACTORS CONTRIBUTING to TOBACCO USE Individual Pharmacology n Sociodemographics n Alleviation of withdrawal symptoms n Genetic predisposition Tobacco n Weight control n Coexisting medical Pleasure, mood conditions Use n modulation Environment n Tobacco advertising n Conditioned stimuli n Social interactions TOBACCO DEPENDENCE: A 2-PART PROBLEM Tobacco Dependence Physiological Behavioral The addiction to nicotine The habit of using tobacco Treatment Treatment Medications for cessation Behavior change program Treatment should address the physiological and the behavioral aspects of dependence. FORMS of TOBACCO  FORMS of TOBACCO § Cigarettes § Smokeless tobacco § Chewing tobacco § Snuff § Snus § Cigars § Pipes § Hookah (waterpipe smoking) § Electronic nicotine delivery systems (ENDS)* *e-cigarettes are devices that deliver nicotine and are not a form of tobacco. Image courtesy of the Centers for Disease Control and Prevention / Rick Ward  CIGARS § Cigar products § Traditional (premium or large) § Cigarillos § Filtered (little) cigars § Estimated 8.7 million cigar smokers in the U.S. in 2019 (3.6%) § Prevalence higher among black, non-Hispanics § Tobacco content of cigars varies greatly § One cigar can deliver enough nicotine to establish and maintain dependence § Cigar smoking is not a safe alternative to cigarette smoking  ELECTRONIC NICOTINE DELIVERY SYSTEMS: CONSIDERATIONS § Lack of product regulation and standardization can lead to variability in aerosol production and nicotine delivery1 § Nicotine yield can vary as much as 50-fold due to puff topography and device design features2 § Stated nicotine content on e-liquids often inaccurate3 § Plasma nicotine concentrations achieved with Juul devices are comparable to those achieved with cigarettes4,5 1. Walton et al., Nicotine Tob Res. 2015:17:259–269. 2. Talih et al., Nicotine Tob Res. 2015;17:150–157. 3. Davis et al., Nicotine Tob Res. 2015;17:134–14. 4. Hajek et al., Addiction. 2020;115:1141-1148. 5. Prochaska et al., Tob Control. 2022;31:e88-e93.  ELECTRONIC CIGARETTES: Potential Health Risks § Propylene glycol may cause respiratory irritation and increase the risk for asthma § Glycerin may cause lipoid pneumonia on inhalation § Nicotine is highly addictive and can be harmful § Refill cartridges with high concentrations of nicotine are a poisoning risk, especially in children § 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 are not proven to be safe.  PLASMA NICOTINE CONCENTRATIONS: Cigarettes and JUUL 25 Cigarette JUUL Nicotine concentration (ng/ml) 20 15 10 5 0 0 5 10 15 20 25 30 Time (minutes) Hajek P, et al. (2020). Addiction 115:1141–1148.  TOBACCO HARM REDUCTION “Minimizing harms and decreasing total morbidity & mortality, without completely eliminating tobacco and nicotine use.” § Acknowledges that complete abstinence is the ideal outcome, but accepts alternative ways to reduce harm among tobacco users § Continuum of health risk: ENDS IQOS (tobacco heating system; Phillip Morris International) Nicotine Combustible replacement tobacco Smokeless tobacco (chewing, snuff) Snus therapy Most risk Least risk Institute of Medicine. (2001). Committee to Assess the Science Base for Tobacco Harm Reduction. Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction. Washington (DC): National Academies Press (US).  FORMS of TOBACCO: SUMMARY § Cigarettes are, by far, the most common form of tobacco used in the U.S. § Other forms of tobacco and nicotine delivery devices exist, and some are increasing in popularity. § All forms of tobacco are harmful. § The safety/efficacy of e-cigarettes/ENDS not been not established. § Attention to all forms of tobacco is needed.