Year : 2017 | Volume
: 4 | Issue : 2 | Page : 69--75
Insight into nicotine addiction
Sahil Handa1, Haneet Kour2, Charu Khurana3,
1 Senior Development Editor, Wolters Kluwer Health, Gurgaon, Haryana, India
2 Senior Assistant Editor, Journal of Clinical and Diagnostic Research, New Delhi, India
3 Post Graduate Student, SGT Dental College, Gurgaon, Haryana, India
Dr. Sahil Handa
House Number - 476 A, Sector 37, Faridabad - 121 003, Haryana
The emergence of the epidemic of nicotine addiction in India and other nations is a global public health tragedy of untoward proportions. Smoking or chewing tobacco can seriously affect general, as well as oral health. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke and addiction to nicotine is the proximate cause of these diseases. This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. The pharmacologic reasons for nicotine use are an enhancement of mood, either directly or through relief of withdrawal symptoms and augmentation of mental or physical functions. Tobacco cessation is necessary to reduce morbidity and mortality related to tobacco use. Strategies for tobacco cessation involves 5A's and 5R's approach and pharmacotherapy. Dental professionals play an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. Dentists are in a unique position to educate and motivate patients concerning the hazards of tobacco to their oral and systemic health, and to provide intervention programs as a part of routine patient care.
|How to cite this article:|
Handa S, Kour H, Khurana C. Insight into nicotine addiction.CHRISMED J Health Res 2017;4:69-75
|How to cite this URL:|
Handa S, Kour H, Khurana C. Insight into nicotine addiction. CHRISMED J Health Res [serial online] 2017 [cited 2021 Jan 22 ];4:69-75
Available from: https://www.cjhr.org/text.asp?2017/4/2/69/201993
Although tobacco death rarely makes headlines, tobacco kills one person every 6 s. Tobacco kills a third to half of the people who use it, on average 15 years prematurely. Today tobacco use causes one in ten deaths among adults' worldwide, more than five million people a year. By 2030, unless urgent action is taken, tobacco's annual death toll will rise to more than eight million. If current trends continue unchecked, it is estimated that around five hundred million people alive today will be killed by tobacco. Most tobacco users will want to quit but will be unable to because of their dependence on a highly addictive substance: Nicotine. Cigarettes and other smoked tobacco products rapidly deliver the addictive drug nicotine to the brain immediately after the smokers inhale - about as efficiently as an intravenous injection with a syringe. The tobacco industry itself has referred to cigarettes as a “nicotine delivery device.” However, the effects of smoked tobacco last only a few minutes and smokers experience withdrawal symptoms unless they continue to smoke. In India, tobacco was introduced by Portuguese and British promoted cigarettes to establish tobacco industry in the country. Historically, snuff was one of the most common forms of tobacco consumed, until recently when it was overtaken by cigarettes in the early 20th century.
Forms of Tobacco,,,
Smoking tobacco products include bidis, manufactured and hand-rolled cigarettes, pipes, cigars, hookah, water pipes, sticks, and other locally produced smoking tobacco products, for example, chuttas, dhumti, chillum, and kreteks.
Smokeless tobacco products or spit tobacco include chewing tobacco products such as betel quid with tobacco, khaini, gutkha, paan masala, mainpuri tobacco, and other products such as mishri, mawa, gul, bajjar, gudakhu, and snuff.
The National Sample Survey of 1999–2000 showed that:
Bidis are smoked by at least one member of each household in:
Over one-third of households in rural areasOne-fifth of households in urban areas.
Smokeless tobacco is used by at least one member of each household in:
Almost one-third of households in rural areasAlmost one-sixth of households in urban areas.
General Health Effects of Tobacco Use
Using tobacco, primarily smoking cigarettes, has been strongly and causally linked with several adverse health consequences such as cancers (especially lung cancer), cardiovascular disease and chronic obstructive pulmonary disease. In a study done in 52 countries, smokers were found to be at 2.87 times increased risk of coronary heart disease compared to nonsmokers. Smoking is indicated as a major risk factor for tuberculosis in India. In addition to cancer risks unique to women and a greater risk for osteoporosis and tuberculosis, smoking by pregnant women and mothers may affect their offspring. Pregnancy outcomes, including lower birth weight and intrauterine growth retardation, Sudden infant death syndrome and decreased lung function are more frequent among women who smoke than among those who do not smoke.
Oral Effects of Tobacco Use
Tobacco in any form, either smoked or smokeless, can cause a wide spectrum of oral mucosal alterations or lesions. It may cause tooth stains, abrasions, smoker's melanosis, acute necrotizing ulcerative gingivitis, nicotinic stomatitis, keratotic patches, black hairy tongue, palatal erosions, and oral carcinoma. However, smokeless tobacco can induce oral keratosis and gingival recession. The type and location of the alteration/lesion varies with the type of tobacco used, the way it is used, and the frequency and duration of use.
The lesions are classified as:
Premalignant (precancerous) lesions - leukoplakia, erythroplakiaPremalignant conditions - oral submucous fibrosis, oral lichen planusOther tobacco-related lesions. Betel quid chewer's mucosa.
Cigarette smoking is a significant risk factor for periodontal disease and impaired healing after periodontal surgery. Smokers have periodontitis four times more than nonsmokers. In general, calculus deposits are also higher and gingival inflammation too  whereas highest number of decayed tooth surfaces found among chewing tobacco users than persons using other forms of tobacco. The mechanism suggested is that high levels of fermentable sugars in chewing tobacco stimulate the growth of cariogenic bacteria. The abrasive materials in tobacco products may contribute to the problem of dental attrition.
The World Health Organization describes drug dependence or addiction as “a behavioral pattern in which the use of a given psychoactive drug is given a sharply higher priority over other behaviors that once had a significantly higher value.” Among the all constituents of tobacco nicotine is the pharmacological agent that causes addiction among smokers. The addictive effect of nicotine is linked to its capacity to trigger the release of dopamine - a chemical in the brain associated with the feelings of pleasure and often perceived as aversive, producing coughing, dizziness, and/or nausea but simultaneously power of tolerance develops and withdrawal symptoms become more pronounced between successive cigarettes. The development of nicotine addiction has been characterized as a series of five stages:
PreparatoryInitial tryingExperimentationRegular useNicotine addiction.
The “preparatory” stage includes the formation of knowledge, beliefs, and expectations about smoking. “Initial trying” refers to trials with the first two or three cigarettes (events that are discussed in more detail later in this section). “Experimentation” refers to repeated, irregular use over an extended period; such smoking may be situation-specific (e.g., smoking at parties). “Regular smoking” by youths may mean smoking every weekend or in certain parts of each day (such as after school with friends). “Nicotine addiction” refers to regular smoking, usually every day, with an internally regulated need for nicotine. Thus, for individual youths, there is a progression of smoking over time from initiation to experimentation with light smoking to regular and heavy smoking.
Action of Nicotine on the Brain,,,
The nicotine molecule is shaped like the neurotransmitter acetylcholine and acts on certain cholinergic receptors in the brain and other organs of the body. By activating cholinergic receptors, nicotine enhances the release of other neurotransmitters and hormones including acetylcholine, norepinephrine, dopamine, vasopressin, serotonin, and beta-endorphin. The physiologic effects of nicotine include behavioral arousal and sympathetic neural activation. Release of specific neurotransmitters has been speculatively linked to particular reinforcing effects of nicotine. For example, enhanced release of dopamine, norepinephrine, and serotonin may be associated with pleasure as well as appetite suppression, the latter of which may contribute to lower body weight. Release of acetylcholine may be associated with improved performance on behavioral tasks and improvement of memory. Release of beta-endorphin may be associated with a reduction of anxiety and tension.
Tolerance and Withdrawal,,,
With prolonged or repetitive exposure to nicotine, the brain cells adapt in such a way as to compensate for the actions of nicotine, that is, to return brain functioning to normal. This process is called neuroadaptation. Neuroadaptation is associated with an increasing number of nicotinic receptors in the brain. Neuroadaptation results in the development of tolerance that is, a given level of nicotine comes to have less of an effect on the body, and higher levels of nicotine are needed to produce the effects that lower doses formerly produced. Substantial tolerance develops to the behavioral arousal and cardiovascular effects of nicotine when a person smokes multiple cigarettes or uses multiple doses of smokeless tobacco, even within the course of a single day. Regular tobacco users regain sensitivity to the effects of nicotine, at least in part, after overnight abstinence from tobacco.
When the brain has adapted so as to function normally in the presence of nicotine, it also becomes dependent on the presence of nicotine for normal functioning. When nicotine is not available (such as when a smoker stops smoking), the brain function becomes disturbed, resulting in a number of withdrawal symptoms.
Distribution and Elimination of Nicotine from Body,,
A cigarette delivers nicotine to the brain within 10–19 s from the start of a puff. A cigarette is typically smoked in 10 puffs and within 5 min. A typical smoker will absorb 1–2 mg of nicotine, but absorption can range from 0.5 to 3 mg. The rapid passage of nicotine from the lungs to the arterial circulation to the brain provides for rapid behavioral reinforcement for smoking and for the possibility for the smoker to control levels of nicotine in the brain and to modulate pharmacologic effects. Nicotine is also distributed extensively to other body tissues. Slow release from tissues explains in part the elimination half-life of 2–3 h.
Nicotine is eliminated primarily by liver metabolism. The rate of metabolism is quite variable from person to person, so the same level of nicotine intake may be associated with different concentrations of nicotine in the blood of different people. The main metabolite of nicotine, cotinine, has a long half-life (on average 17 h) and has been widely used by researchers as a biochemical marker of nicotine exposure.
Smokeless tobacco products vary considerably in nicotine content, pH, and levels of various carcinogens. Since nicotine is absorbed through the buccal mucosa of the smokeless tobacco user's mouth, uptake is affected by both the pH of the tobacco product and the pH of the mouth. The rate of absorption and action for nicotine from smokeless tobacco is thus slower than that from tobacco that enters the body via the lungs when smoked. The delayed effect may make smokeless products less addictive than cigarettes. However, some smokeless tobacco users report that quitting cigarettes is easier than quitting smokeless tobacco.
Intake and Accumulation of Nicotine during Smoking and Smokeless Tobacco,
The absorption of nicotine per dose is greater with use of chewing tobacco (average 4.5 mg nicotine) or snuff (average 3.6 mg nicotine) compared with that of smoking cigarettes (average 1.0 mg nicotine). The half-life of nicotine averages about 2 h. Consistent with this half-life, nicotine accumulates for 6–8 h, plateauing through the remainder of the day with regular use of smoked or smokeless tobacco, and the levels of nicotine persists overnight, even while the user sleeps. The concentration of nicotine and cotinine in the blood are similar is users of smokeless tobacco and cigarettes. The observations that levels of nicotine are similar with use of different tobacco products supports the idea that tobacco users become dependent on nicotine and seek similar levels and effects independent of the particular source of nicotine.
Clinical Aspects of Nicotine Addiction
Nicotine induces pleasure and reduces stress and anxiety. Smokers use it to modulate levels of arousal and to control mood. Smoking improves concentration, reaction time, and performance of certain tasks. Relief from withdrawal symptoms is probably the primary reason for this enhanced performance and heightened mood. Among adults the light or occasional smoker, that is, one who regularly smokes 5 or fewer cigarettes per day or who does not smoke every day, is in general less addicted than are daily smokers of more than 5 cigarettes per day. Cessation of smoking causes the emergence of withdrawal symptoms:
RestlessnessEating more than usualAnxiety/tensionImpatienceIrritability/angerDifficulty concentratingExcessive hungerDepressionDisorientationLoss of energy/fatigueDizzinessStomach or bowel problemsHeadachesInsomniaHeart palpitationsTremorsCraving cigarettes.
Diagnostic Criteria for Nicotine Withdrawal,
Daily use of nicotine for at least several weeksAbrupt cessation of nicotine use or reduction in the amount of nicotine used, followed by four (or more) of the mentioned withdrawal symptoms within 24 hClinically significant distress or impairment in social, occupational, or other important areas of functioningSymptoms not due to a general medical condition and not better accounted for by a mental disorder.
Tobacco Cesation: Effective Treatment For Nicotine Addiction
Tobacco cessation is essential to reduce the mortality and morbidity related to tobacco use. At present, India has about 18 tobacco cessation clinics across the country. This clearly is an inadequate effort taking the existing 250 million tobacco consuming population into consideration.
Overview of smoking cessation interventions:
Behavioral interventions: Includes methods such as physician advice, individual counseling by nurse or other nonphysician, group counseling, or self helpDrug interventions: Nicotine replacement therapy (transdermal patch, gum, inhaler, nasal spray), antidepressant (bupropion)Other interventions include acupuncture, hypnosis, aversive therapy, exercise, anxiolytics.
The most effective smoking cessation intervention as motivates smokers to quit by providing behavior support beyond scheduled clinical care by appropriately trained counselors.
Counseling to those who willing to quit by 5A method: Ask about tobacco use at every visit, Advise nonusers to never use tobacco, Advise users to quit, Assess the patient's readiness to quit, Assist with quitting, Arrange for follow-ups.
Counseling to those who unwilling to quit by R method: Ask/Advise the patient about the RELEVANCE of quitting, RISKS of continuing tobacco use, REWARDS of quitting, assessing ROADBLOCKS to quitting and REPEAT these at each visit.
Pharmacotherapies can be divided into nicotine replacement therapy, and nonnicotine medications that have anti-craving effects. Pharmacotherapies have an empirical record of efficacy for nicotine addiction and numerous studies have shown pharmacotherapies to significantly improve long-term-quit rates.
First-line of drugs:Nicotine replacement therapy (transdermal patch, gum, inhaler, nasal spray)Antidepressant (bupropion)Varenicline.Second-line of drugs:ClonidineNortriptyline.
Nicotine replacement therapy,,,,
A variety of products are available to relieve withdrawal symptoms in tobacco users. They are: nicotine gum, nicotine patch, nasal sprays, nasal inhaler, nicotine sublingual tablets, and lozenges and nicotine vaccine.
Nicotine gumRoute and dose: Buccal route. 2–4 mg pieces up to 10 times/dayDuration: 12–16 weeksSide effects: Sore mouthPrecautions: To be used only after target quit date.Nicotine patchRoute and dose: Transdermal route. 7–22 mg/dayDuration: 6–12 weeksSide effects: Local skin irritationPrecautions: To be used only after target quit date.Nicotine nasal sprayRoute and dose: Intranasal route. 16–32 mg/dayDuration: 12–24 weeksSide effects: Local irritationPrecautions: To be used only after target quit date.Nicotine inhalerRoute and dose: Intranasal or buccal route. 6–16 mg/dayDuration: Up to 24 weeksSide effects: Local irritationPrecautions: To be used only after target quit date.Bupropion sustained releaseRoute and dose: 150 mg once a day for 3 days increased to twice a day to begin 1–2 weeks before target quit dateDuration: 7–12 weeks maintaining up to 24 weeksSide effects: Insomnia, dry mouthContraindications: Seizures, eating disorders.
Nonnicotine agents: Anti-craving medications,,
NortryptilineNortriptyline, a tricyclic antidepressant, has also been used and found to have similar quit rates as bupropion0.15–0.75 mg/day for 3–10 weeks.ClonidineClonidine, an alpha-2 adrenoceptor antagonist used in opiate and alcohol withdrawal, also been shown to diminish some of the tobacco withdrawal symptoms75–100 mg/day for 12 weeks can be prescribed.
Role of Dental Professionals,
Dentists have an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. They can be role models by not using tobacco or by quitting successfully. Tobacco use by dentists is a significant barrier to tobacco cessation counseling. Dentists should understand that they are in an advantageous position to address the issue of tobacco control during an oral check-up, as patients would listen because they are in pain. They should:
See the harmful effects of tobacco in the mouthSee children and youth as patients and can influence them to adopt a tobacco-free lifestyleTreat women of childbearing age and can inform them of the dangers of tobacco use during pregnancyCan spend more time with patients than other clinicians and use this time to counsel tobacco users to quitCan reinforce messages given to patients by physicians and other caregivers about the dangers of tobacco use and the need to quitCan build their patients' interest in discontinuing tobacco use by showing them the actual effects in the mouthHave a duty to promote oral health and healthy lifestyles among their patients.
Prevention from Nicotine Addiction,,
Comprehensive, sustained, multicomponent programs can cut tobacco use among the population and so removal of nicotine addiction.
Strategies comprise successful comprehensive tobacco control programs include mass media campaigns, higher tobacco prices, smoke free laws and policies, evidence-based school programs and sustained community wide effortsReducing minors' access to tobacco productsIdentifying high-risk groups like young adults and pregnant women and supporting them to stop tobacco usePerforming individually or group meetings periodically about the harmful effects of tobacco use and nicotine addictionProviding smokers with a national quit line can potentially reach an additional five million quitters per year, saving three million lives within two decadesDental associations can advocate for the inclusion of tobacco cessation as an important component in national health programs such as the National Rural Health Mission, National Cancer Control Program and Reproductive and Child Health Programme.
Nicotine sustains tobacco addiction, a major cause of disability and premature death, by acting on nicotinic cholinergic receptors in the brain to trigger the release of dopamine and other neurotransmitters. Release of dopamine, glutamate, and gamma-aminobutyric acid is particularly important in the development of nicotine dependence. Having reviewed the research literature on nicotine addiction and tobacco use, the following conclusions were drawn:
Long-term tobacco use is maintained by addiction to nicotine and once addicted; a person finds it difficult to quit using tobaccoWhen youths begin using tobacco, they overestimate the proportion of tobacco use in society, underestimate the addictive nature of tobacco and the risk that they will become addicted over a long-term, and underestimate the danger that they will incur tobacco-related disease. Thus, children and youths become addicted to nicotine before they are able to fully appreciate the consequences of their behaviorAvailable evidence indicates that cigarette manufacturers control the level of nicotine in cigarettes and the nicotine delivery of their products in deliberate ways. However, “low-yield” cigarettes are not low in nicotine content and do not in general deliver less nicotine or tar to smokers than do higher-yield cigarettesAn increased understanding of the mechanisms of nicotine addiction has led to the development of behavior and pharmacotherapy intervention to withdrawal symptoms of nicotine addiction.
Research should be conducted to determine individual susceptibility to nicotine addiction. Particular areas that need research are genetic factors, affective states, and ethnic influences. Such information could facilitate the identification of high-risk children and could lead to more effective prevention strategiesFor all forms of tobacco products, research should be conducted on the characteristics of nicotine addiction in the early stages, that is, in the first few years during which the transition between experimental and addictive nicotine use occurs. Such information could contribute to more effective intervention before youth become highly addicted adult tobacco usersResearch should be conducted on the relationship between the characteristics of tobacco products and addiction. For example, as a basis in developing regulatory guidelines, it would be useful to know the minimal level of nicotine delivery from a tobacco product at which addiction will develop and/or be sustained.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||World Health Organization. WHO Report on the Global Tobacco Epidemic: Implementing Smoke-Free Environments. Geneva: World Health Organization; 2009.|
|2||Chaly PE. Tobacco control in India. Indian J Dent Res 2007;18:2-5.|
|3||Rao V, Chaturvedi P. Tobacco and health in India. Indian J Cancer 2010;47 Suppl 1:3-8.|
|4||Peter S. Essentials of Preventive and Community Dentistry. 4th ed. New Delhi: Arya Medi Publishing House; 2011. p. 141.|
|5||Global Adult Tobacco Survey GATS India 2009-2010. Ministry of Health and Family Welfare Government of India; 2009-2010.|
|6||Hiremath SS. Textbook of Preventive and Community Dentistry. 2nd ed. India: Elsevier Publications; 2011. p. 160-1.|
|7||Mishra GA, Pimple SA, Shastri SS. An overview of the tobacco problem in India. Indian J Med Paediatr Oncol 2012;33:139-45.|
|8||Ray CS, Gupta PC. Bidis and smokeless tobacco. Curr Sci 2009;96:1324-34.|
|9||Aveyard P, Raw M. Improving smoking cessation approaches at the individual level. Tob Control 2012;21:252-7.|
|10||Reddy SK, Gupta PC. Report on Tobacco Control in India. Ministry of Health and Family Welfare, Government of India; 2004.|
|11||Ray CS, The hookah – The Indian waterpipe. Curr Sci 2009;96:1319-23.|
|12||Murray JJ. The Prevention of Oral Disease. Oxford, New York: Oxford University Press; 2003. p. 170-1.|
|13||Winn DM. Tobacco use and oral disease. J Dent Educ 2001;65:306-12.|
|14||Johnson GK, Slach NA. Impact of tobacco use on periodontal status. J Dent Educ 2001;65:313-21.|
|15||Bowles WH, Kumar S, Parmar G, Saiyed HN. Nut and Tobacco Chewing. Br Dent J 2004;197:292.|
|16||Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, et al . Disease Control Priorities in Developing Countries. 2nd ed. New York: Oxford University Press; 2006. p. 869-6.|
|17||Diclemente CC. Addiction and Change: How Addictions Develop and Addicted People Recover. New York: Guilford Press; 2003.|
|18||Kenny PJ, Markou A. Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity. Neuropsychopharmacology 2006;31:1203-11.|
|19||Dajas-Bailador F, Wonnacott S. Nicotinic acetylcholine receptors and the regulation of neuronal signalling. Trends Pharmacol Sci 2004;25:317-24.|
|20||Brody AL. Functional brain imaging of tobacco use and dependence. J Psychiatr Res 2006;40:404-18.|
|21||Benowitz NL. Pharmacology of nicotine: Addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 2009;49:57-71.|
|22||Wang H, Sun X. Desensitized nicotinic receptors in brain. Brain Res Brain Res Rev 2005;48:420-37.|
|23||Govind AP, Vezina P, Green WN. Nicotine-induced upregulation of nicotinic receptors: Underlying mechanisms and relevance to nicotine addiction. Biochem Pharmacol 2009;78:756-65.|
|24||Balfour DJ. The neurobiology of tobacco dependence: A preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 2004;6:899-912. [Erratum in: Nicotine Tob Res 2005;7:307].|
|25||Le Moal M, Koob GF. Drug addiction: Pathways to the disease and pathophysiological perspectives. Eur Neuropsychopharmacol 2007;17:377-93.|
|26||Severson HH. What have we learned from 20 years of research on smokeless tobacco cessation? Am J Med Sci 2003;326:206-11.|
|27||Benowitz NL, Hukkanen J, Jacob P 3rd. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol 2009:29-60.|
|28||Karan LD, Dani JA, Benowitz NL. The pharmacology of nicotine dependence. In: Principles of Addiction Medicine. 3rd ed. Washington, DC: American Society of Addiction Medicine; 2003. p. 225-48.|
|29||Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev 2005;57:79-115.|
|30||Knott V, Heenan A, Shah D, Bolton K, Fisher D, Villeneuve C. Electrophysiological evidence of nicotine's distracter-filtering properties in non-smokers. J Psychopharmacol 2011;25:239-48.|
|31||Health consequences of smoking. Surgeon General's Report 2004. Ch. 6. 2004.|
|32||Rezvani AH, Levin ED. Cognitive effects of nicotine. Biol Psychiatry 2001;49:258-67.|
|33||World Health Organization. Tobacco Free is A Woman's Right. Available from: http://www.who.int/tobacco/wntd/2010/en/index.html. [Last accessed on 2015 Jan 18].|
|34||Baker TB, Breslau N, Covey L, Shiffman S. DSM criteria for tobacco use disorder and tobacco withdrawal: A critique and proposed revisions for DSM-5. Addiction 2012;107:263-75.|
|35||Marlow SP, Stoller JK. Smoking cessation. Respir Care 2003;48:1238-54.|
|36||Quinn VP, Hollis JF, Smith KS, Rigotti NA, Solberg LI, Hu W, et al . Effectiveness of the 5-As tobacco cessation treatments in nine HMOs. J Gen Intern Med 2009;24:149-54.|
|37||Shah M, Ray CS, Arora M. Helping your patients remain tobacco free: Quick reference guide for dentists. New Delhi: Ministry of Health and Family Welfare; 2006. Available from: http://www.whoindia.org/LinkFiles/Oral_Health_tobacco_cessation.pdf. [Last accessed on 2017 Jan 05].|
|38||Galanti LM. Tobacco smoking cessation management: Integrating varenicline in current practice. Vasc Health Risk Manag 2008;4:837-45.|
|39||Henningfield JE, Fant RV, Buchhalter AR, Stitzer ML. Pharmacotherapy for nicotine dependence. CA Cancer J Clin 2005;55:281-99.|
|40||Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2004:CD000146.|
|41||Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India Manual for Tobacco Cessation; November, 2005.|
|42||Watts SA, Noble SL, Smith PO, Disco M. First-line pharmacotherapy for tobacco use and dependence. J Am Board Fam Pract 2002;15:489-97.|
|43||Zhang B, Cohen JE, Bondy SJ, Selby P. Duration of nicotine replacement therapy use and smoking cessation: A population-based longitudinal study. Am J Epidemiol 2015;181:513-20.|
|44||Training Manual for Doctors: National Tobacco Control Programme. India: 2011.|
|45||Jiloha RC. Pharmacotherapy of smoking cessation. Indian J Psychiatry 2014;56:87-95.|
|46||Monaghan N. What is the role of dentists in smoking cessation? Br Dent J 2002;193:611-2.|
|47||Shimkhada R, Peabody JW. Tobacco control in India. Bull World Health Organ 2003;81:48-52.|
|48||Mishra GA, Kulkarni SV, Majmudar PV, Gupta SD, Shastri SS. Community-based tobacco cessation program among women in Mumbai, India. Indian J Cancer 2014;51 Suppl 1:S54-9.|
|49||Henningfield JE, Jude NR. Prevention of nicotine addiction: Neuropsychopharmacological issues. Nicotine Tob Res 1999;1 Suppl 1:S41-8.|