Passive Smoking and Lung Disease Medication
- Author: Timothy D Murphy, MD; Chief Editor: Girish D Sharma, MD, FCCP, FAAP more...
Medical therapies for smoking cessation have been used since the early 1900s with poor success. The use of lobeline sulfate to control cravings (later with antacids added) began in 1936 but was seriously challenged in the late 1960s through late 1970s; its use was virtually eliminated by 1980.
Meprobamate, used to minimize withdrawal, and amphetamines, used to counter excess sleepiness, are examples of drugs historically used to assist in smoking cessation. Potential for abuse and demonstration of a complete lack of efficacy led to these drugs falling out of favor. Similarly, other types of drugs have been used and tested (eg, anticholinergics, antidepressants, sedatives, tranquilizers, sympathomimetics, anticonvulsants). None of the drugs tested for smoking cessation worked well. Clonidine has demonstrated promise in helping to reduce symptoms of nicotine withdrawal but is no different than placebo in several well-controlled studies. Of all the medical therapies that have been tried, the only ones that have been shown to be effective are nicotine gum and, more recently, the nicotine patch and the antidepressant bupropion.
The problem with using medical therapy for nicotine addiction lies in nicotine's uniqueness in how it affects the CNS. Nicotine is the only drug that stimulates the CNS, leading to increased mental acuity and alertness, but with a simultaneous soothing of the peripheral nervous system. Drugs that stimulate the CNS to a similar degree, such as amphetamines, are not soothing peripherally; they are associated with tremor, nervousness, agitation, and paranoia. Drugs that are as soothing as nicotine, such as the benzodiazepines, are too depressing to the CNS and are associated with excess sleepiness and decreased mental acuity. For that reason, the best medical therapy for smoking cessation includes treatment with nicotine-replacement products.
The nicotine patch consists of a nicotine-impregnated pad within an acrylate adhesive, covered with a backing film, and attached to the skin with an adhesive layer. Nicotine, an alkaloid that binds to acetylcholine receptors, is thought to work through 2 CNS effects: (1) stimulation in the cortex through the locus ceruleus causing increased alertness and (2) cognitive performance and a reward effect via the pleasure system in the limbic system. Use of the patch is associated with increased quit rates, and the success rate doubles with the addition of some form of concomitant support.
Long-term benefits of the patch or nicotine-containing gum are not well described. In general, efficacy is greatly enhanced by concomitant therapies. Use of the antidepressant bupropion hydrochloride (Zyban, Wellbutrin) has been demonstrated to be of use in smoking cessation. A dose of bupropion of 300 mg/d correlated to nearly doubled quit rates at 2-month, 3-month, and 6-month time points compared to placebo control. Care must be taken to ensure that Wellbutrin (as an antidepressant) is not added inadvertently to Zyban (for smoking cessation) therapy.
Nicotine is the principal addictive substance in tobacco. Nicotine replacement plays an important role in smoking cessation programs. Nicotine is a pyridine alkaloid and naturally occurring autonomic drug. The drug is commercially available as the base in transdermal systems (Nicoderm CQ, Nicotrol), an oral inhaler, a nasal solution, and the polacrilex in chewing gum or lozenge. Nicotine is a ganglionic (nicotinic) cholinergic-receptor agonist. Pharmacologic actions of nicotine are complex and include various effects mediated by stereospecific binding to receptors in autonomic ganglia, adrenal medulla, neuromuscular junction, and the brain.
The pharmacokinetics of various commercially available dosage forms of nicotine and nicotine polacrilex differ principally in the rate, site, and extent of absorption of the drug; absorption is most rapid with intranasal administration of the spray (peak concentrations achieved within 4-15 min), followed by chewing gum (peaks within 25-30 min) and oral inhalation (peaks within 15-30 min). Absorption is substantially slower with the transdermal systems (peak within 2-10 h).
Buccal (chewing gum) nicotine polacrilex or a transdermal system, intranasal spray, or oral inhaler of nicotine is used for nicotine replacement therapy as a temporary adjunct in the cessation of cigarette smoking. Their use can either be unsupervised or in conjunction with a behavior modification program under medical or dental supervision.
The manufacturers currently do not recommend use of these preparations in children; however, because of the potential benefits of smoking cessation and the established efficacy of nicotine replacement therapy in adults, some clinicians recommend that such therapy be considered for adolescents who are nicotine dependent (ie, those who experience nicotine withdrawal manifestations with smoking cessation).
Nicotine polacrilex gum or lozenge (Nicorette Gum, Commit Lozenge)
Nicotine is quickly absorbed through the PO mucosa. Levels peak within 15-30 min, which closely approximates the time course of plasma nicotine levels observed after cigarette smoking. The gum or lozenge should not be swallowed.
Designed to provide systemic nicotine delivery over 16 h. Apply daily after awakening and remove before retiring; instruct patients not to use the same Nicotrol transdermal system for >16 h.
Duration of daily use for Nicoderm CQ is longer (16-24 h) than Nicotrol. Patients who crave a cigarette upon awakening should wear Nicoderm CQ system for 24 h; patients who experience vivid dreams or other sleep disturbances with application of Nicoderm CQ for 24 h should remove the transdermal system after approximately 16 h of application, before retiring. Instruct patients not to use the same Nicoderm CQ transdermal system for >24 h.
Intranasal nicotine may closely approximate time course of plasma nicotine levels observed after cigarette smoking. Peak plasma levels occur within 15 min.
Quickly absorbed and closely approximates time course of plasma nicotine levels observed after cigarette smoking (within 15 min).
Amount of nicotine released depends on method of inhalation; unlike asthma medications in metered dose inhalers, nicotine can be administered effectively with either slow deep inhalations (pulmonary administration) or rapid shallow inhalations (buccal administration).
The mechanism of how bupropion helps in smoking cessation is unclear, although noradrenergic and/or dopaminergic effects presumably are involved. The 2 primary clinical uses for bupropion are in treatment of major depression and, as extended-release tablets, as an adjunct in the cessation of smoking.
Therapy may be combined with transdermal nicotine therapy if necessary; however, labeling for both bupropion and transdermal nicotine recommends that patients who receive bupropion and transdermal nicotine concurrently be monitored for the development of hypertension related to such therapy. Patients should begin receiving bupropion while they are still smoking because steady-state plasma concentrations of the drug are not achieved until after approximately 1 wk. A cessation date should be scheduled within the first 2 weeks of therapy with bupropion and generally should be set for the second week (eg, day 8).
Used in conjunction with a support group and/or behavioral counseling. Inhibits neuronal dopamine reuptake and is a weak blocker of serotonin and norepinephrine reuptake.
Nicotinic acetylcholine receptor partial agonists
These agents bind to nicotine receptors and elicit mild nicotine central effects to ease withdrawal symptoms. They also decrease the stimulatory effect of consuming nicotine products by blocking nicotine receptors.
Partial agonist selective for alpha4, beta2 nicotinic acetylcholine receptors. Action is thought to be result of activity at a nicotinic receptor subtype, where its binding produces agonist activity while simultaneously preventing nicotine binding. Agonistic activity is significantly lower than nicotine. Also elicits moderate affinity for 5-HT3 receptors. Maximum plasma concentrations occur within 3-4 h after oral administration. Following regular dosing, steady state reached within 4 d.
Gajewska E, Malak R, Mojs E, Samborski W. [Cigarette smoking--threat from first days of life]. Przegl Lek. 2008. 65(10):709-11. [Medline].
Halterman JS, Borrelli B, Tremblay P, et al. Screening for environmental tobacco smoke exposure among inner-city children with asthma. Pediatrics. 2008 Dec. 122(6):1277-83. [Medline].
Perret JL, Walters H, Johns D, Gurrin L, Burgess J, Lowe A, et al. Mother's smoking and complex lung function of offspring in middle age: A cohort study from childhood. Respirology. 2016 Mar 11. [Medline].
Yu M, Zheng X, Peake J, Joad JP, Pinkerton KE. Perinatal environmental tobacco smoke exposure alters the immune response and airway innervation in infant primates. J Allergy Clin Immunol. 2008. 122:640-7. [Medline].
USDHHS. US Department of Health and Human Services. The health consequences of smoking: a report of the surgeon general. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2004.
Van Minh H, Giang KB, Xuan LT, Nga PT, Hai PT, Minh NT, et al. Exposure to second-hand smoke at home and its associated factors: findings from the Global Adult Tobacco Use survey in Vietnam, 2010. Cancer Causes Control. 2012 Feb 29. [Medline].
Yi O, Kwon HJ, Kim H, Ha M, Hong SJ, Hong YC, et al. Effect of environmental tobacco smoke on atopic dermatitis among children in Korea. Environ Res. 2012 Jan 20. [Medline].
Gill R, Krishnan S, Dozor AJ. Low-level environmental tobacco smoke exposure and inflammatory biomarkers in children with asthma. J Asthma. 2014 May. 51(4):355-9. [Medline].
Centers for Disease Control and Prevention. Disparities in Secondhand Smoke Exposure-United States, 1988-1994 and 1999-2004. MMWR Morb Mortal Wkly Rep. 2008. 57:744-7. [Medline].
Chen YT, Chung MC, Hsiao FH, Miao NF, Chen PL. Exploration of Parental Smokers' Experience, Perceptions, and Family's Influences on Their Smoking in the Presence of Children. ANS Adv Nurs Sci. 2012 Jan. 35(1):E1-E13. [Medline].
Johannessen A, Bakke PS, Hardie JA, Eagan TM. Association of exposure to environmental tobacco smoke in childhood with chronic obstructive pulmonary disease and respiratory symptoms in adults. Respirology. 2012 Jan 16. [Medline].
Kim CH, Lee YC, Hung RJ, McNallan SR, Cote ML, Lim WY, et al. Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO). Int J Cancer. 2014 Oct 15. 135(8):1918-30. [Medline]. [Full Text].
Schwartz JL. Review and Evaluation of Smoking Cessation Methods: The United States and Canada, 1978-1985. US DHHS, National Cancer Institute, Division of Cancer Prevention. 1987.
US DHHS. The Health Benefits of Smoking Cessation: A Report of the Surgeon General. US DHHS Public Health Service, Office of the Surgeon General, Office on Smoking. 1990.
Fathallah N, Maurel-Donnarel E, Baumstarck-Barrau K, Lehucher-Michel MP. Three-year follow-up of attitudes and smoking behaviour among hospital nurses following enactment of France's national smoke-free workplace law. Int J Nurs Stud. 2012 Feb 18. [Medline].
Fujishiro K, Stukovsky KD, Roux AD, Landsbergis P, Burchfiel C. Occupational gradients in smoking behavior and exposure to workplace environmental tobacco smoke: the multi-ethnic study of atherosclerosis. J Occup Environ Med. 2012 Feb. 54(2):136-45. [Medline]. [Full Text].
Priest N, Roseby R, Waters E, et al. Family and carer smoking control programmes for reducing children's exposure to environmental tobacco smoke. [update of Cochrane Database Syst Rev. 2003; (3): CD001746; PMID: 12917911]. Cochrane Database of Systematic Reviews. 2008. 4:CD001746. [Medline].
Gruer L, Tursan d'Espaignet E, Haw S, Fernández E, Mackay J. Smoke-free legislation: Global reach, impact and remaining challenges. Public Health. 2012 Feb 14. [Medline].
US DHHS. Preventing Tobacco Use Among Young People: A Report of the Surgeon General. Atlanta, Ga: USDHH, Public Health Service, CDC, National Center for. Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 1994. [Full Text].
Ortega Cuelva G, Cabezas Peña C, Almeda Ortega J, Saez Zafra M, Ballvé Moreno JL, Pascual Esteban JA, et al. Effectiveness of a brief primary care intervention to reduce passive smoking in babies: a cluster randomised clinical trial. J Epidemiol Community Health. 2014 Nov 11. [Medline].
Al-Delaimy WK, Crane J, Woodward A. Questionnaire and hair measurement of exposure to tobacco smoke. J Expo Anal Environ Epidemiol. 2000 Jul-Aug. 10(4):378-84. [Medline].
American Academy of Pediatrics, Committee on Environmental Hazards. American Academy of Pediatrics. Involuntary smoking--a hazard to children. Committee on Environmental Hazards. Pediatrics. 1986 May. 77(5):755-7. [Medline].
Cloutier MM, Wakefield DB, Hall CB, Bailit HL. Childhood asthma in an urban community: prevalence, care system, and treatment. Chest. 2002 Nov. 122(5):1571-9. [Medline].
Fiore MC, Novotny TE, Pierce JP, et al. Trends in cigarette smoking in the United States. The changing influence of gender and race. JAMA. 1989 Jan 6. 261(1):49-55. [Medline].
Fuji Y, Shima M, Ando M, et al. Effect of air pollution and environmental tobacco smoke on serum hyaluronate concentrations in school children. Occup Environ Med. 2002 Feb. 59(2):124-8. [Medline].
Groner J, Wadwa P, Hoshaw-Woodard S, et al. Active and passive tobacco smoke exposure: a comparison of maternal and child hair cotinine levels. Nicotine Tob Res. 2004 Oct. 6(5):789-95. [Medline].
Host A. The role of passive smoking and indoor pollution. Pediatr Pulmonol. 2004 Feb. 37 Suppl 26:218-9. [Medline].
Jaakkola MS, Piipari R, Jaakkola N, Jaakkola JJ. Environmental tobacco smoke and adult-onset asthma: a population-based incident case-control study. Am J Public Health. 2003 Dec. 93(12):2055-60. [Medline].
Lee YL, Hsiue TR, Lee CH, et al. Home exposures, parental atopy, and occurrence of asthma symptoms in adulthood in southern Taiwan. Chest. 2006 Feb. 129(2):300-8. [Medline].
National Institutes of Health, National Cancer Institute. Changes in cigarette-related disease risks and their implication for prevention and control. Smoking and Tobacco. 1997.
National Research Council. Environmental Tobacco Smoke: Measuring Exposures and Assessing Health Effects. Washington, DC: National Academy Press; 1986.
Overpeck MD, Moss AJ. Children's exposure to environmental cigarette smoke before and after birth. Health of our nation's children, United States, 1988. Adv Data. 1991 Jun 18. 1-11. [Medline].
Rushton L, Courage C, Green E. Estimation of the impact on children's health of environmental tobacco smoke in England and Wales. J R Soc Health. 2003 Sep. 123(3):175-80. [Medline].
Shiva F, Nasiri M, Sadeghi B, Padyab M. Effects of passive smoking on common respiratory symptoms in young children. Acta Paediatr. 2003 Dec. 92(12):1394-7. [Medline].
St Helen G, Jacob P 3rd, Peng M, Dempsey DA, Hammond SK, Benowitz NL. Intake of Toxic and Carcinogenic Volatile Organic Compounds from Secondhand Smoke in Motor Vehicles. Cancer Epidemiol Biomarkers Prev. 2014 Nov 14. [Medline].
US DHHS. Major Local Tobacco Control Ordinances in the United States. 1993. 1993.
US DHHS. Respiratory Health Effects of Passive smoking: Lung Cancer and Other Disorders. The Report of the U.S. Environmental Protection Agency. US DHHS, Public Health Service, National Institutes of Health;. US Environmental Protection Agency. 1993.