|Year : 2020 | Volume
| Issue : 6 | Page : 2615-2620
Nicotine replacement therapy: A friend or foe
Rajkumari E Devi1, Diplina Barman2, Shruti Sinha1, Suranjana J Hazarika2, Sreeparna Das3
1 Department of Oral Medicine and Radiology, Saraswati Dental College, Lucknow, Uttar Pradesh, India
2 Department of Public Health Dentistry, Kalinga Institute of Dental Sciences, KIIT University, Bhubaneswar, Odisha, India
3 Darshan Dental College and Hospital, Udaipur, Rajasthan, India
|Date of Submission||26-Feb-2020|
|Date of Decision||19-Mar-2020|
|Date of Acceptance||13-Apr-2020|
|Date of Web Publication||30-Jun-2020|
Dr. Shruti Sinha
Department of Oral Medicine and Radiology, Saraswati Dental College, 233, Faizabad Road, Tiwariganj, Chinhat, Lucknow 227105, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
According to the World Health Organization (WHO) Framework Convention for Tobacco Control (FCTC), tobacco cessation is a primary health-care service that should be provided not only to the people having adverse habits of consuming tobacco but also to the nonconsumer, as they can also be harmed due to its deleterious effects. Tobacco has been regarded as a potential risk factor for oral diseases such as oral potentially malignant disorders and oral cancers. Various aids of achieving cessation have been studied, including education of the ill effects of tobacco to the patient, behavioral counseling, and pharmacotherapy. Various pharmacological interventions are available nowadays but nicotine replacement therapy (NRT) is most widely used. The various types of NRT products results in general and breakthrough craving relief with immediate release of nicotine. All of these products have different levels of efficacy and variable rates of nicotine absorption. Knowledge of these will be beneficial for the patients, the budding dentist and the nation in the upcoming days ahead.
Keywords: Nicotine gum, nicotine lozenges, nicotine patch, nicotine replacement therapy, nicotine spray, tobacco
|How to cite this article:|
Devi RE, Barman D, Sinha S, Hazarika SJ, Das S. Nicotine replacement therapy: A friend or foe. J Family Med Prim Care 2020;9:2615-20
|How to cite this URL:|
Devi RE, Barman D, Sinha S, Hazarika SJ, Das S. Nicotine replacement therapy: A friend or foe. J Family Med Prim Care [serial online] 2020 [cited 2020 Jul 15];9:2615-20. Available from: http://www.jfmpc.com/text.asp?2020/9/6/2615/287867
| Introduction|| |
A wide range of ailments caused by tobacco are one of the substantial threats the general population is facing. It continues to be the substance causing maximum health damage globally. The tobacco plant refers to any of various members of the genus Nicotiana in the nightshade (Solanaceae) family. Tobacco contains nicotine as the main alkaloid, which is the principal modulator of the psychopharmacological effects associated with its addiction., The prevention and control of tobacco use is one of the rising issues globally. Tobacco cessation is one of the method which helps in improving the life expectancy and reducing the morbidity. Various aids of achieving cessation have been studied, including education of the ill effects of tobacco to the patient, behavioral counseling, and pharmacotherapy. Various pharmacological interventions are available these days but nicotine replacement therapy (NRT) is most widely used. Nicotine replacement products (NRPs) contain pure nicotine with an aim to reduce the patient's inclination towards tobacco consumption and the physiological and psychomotor withdrawal symptoms., They increase nicotine levels in the bloodstream, due to which the person will smoke fewer cigarettes, resulting in reduction in the consumption and toxicity related to it.
The dentists play a crucial role in optimizing the heavy death tolls caused by use of tobacco as dentists comes in regular close contact with the patients. The family physicians and practitioners should also be enlightened with the possible intervention aids of tobacco addiction as they can spread awareness and encourage the users in the quitting process by maneuvering the social relation of the family. Mostly, a physician's advice often works as a great motivation for the patient in quitting.
| Mechanism of Action|| |
Chemical name of nicotine is (S)-3-(1-methylpyrrolidin-2-yl) pyridine. It has a pyridine and a pyrrolidine ring, both having a tertiary amine. Nicotine acts as a full agonist resulting in stimulation of neural nicotinic acetylcholine receptors in the ventral tegmental area of the brain, which then releases the dopamine in nucleus accumbens thereby leading in reduction of nicotine withdrawal symptoms in regular smokers who tries to quit smoking. It also assists in providing coping mechanism, which makes the tobacco less active. During cigarette smoking, blood concentration of nicotine rises quickly and is at its highest level when it is about to end. Nicotine absorbed from smoke quickly reaches different parts of the body resulting in desensitization of nicotinic acetylcholine receptors when its levels in the brain are high. It again resensitizies when the level falls, resulting in its withdrawal effects.
| Types|| |
The various types of NRT products results in general and breakthrough craving relief with immediate release of nicotine. All of these products have different levels of efficacy and variable rates of nicotine absorption. They are available under these agencies: US, FDA (OTC), MHRA (OTC), and MHRA (Rx).
The first easily accessible NRT product was nicotine gum (Nicotine Polacrilex). It comes in the form of 2 and 4 mg dosages. Studies showed that 4 mg chewable gum has more success rate of withdrawal as compared to 2 mg. The dosage number is reduced gradually per day after a few weeks or months of usage. It is prescribed for 6–12 weeks, with maximum for 6 months. After 2–3 months, the chewing time is decreased, or the gum is divided into small pieces, or the nicotine gum is replaced with sugar-free gum thereby stopping it completely. Delivery is done through transmucosal route. It is chewed intermittently and retained in the mouth until the taste is strong (approximately 30 min) and then it is placed in the vestibule for allowing it to absorb into the bloodstream.
It is recommended that the patients should refrain from consuming acidic beverages such as soda, coffee, and beer for at least 15 min both before and after, as they may impede with the buccal absorption of nicotine. It should be used cautiously in patients with temporomandibular joint diseases and denture users. Nicotine gum has certain disadvantage that some people dislike its taste and have feeling of fullness in their mouth. They may even complain of mouth soreness, hiccups, dyspepsia and jaw aches. Hansson et al. performed a study to compare relief of urges to smoke, up until 5 h following treatment with a new 6 mg nicotine gum versus currently marketed 4 mg nicotine gum and concluded by saying that the 6 mg nicotine gum provided a greater reduction, faster and longer relief of urges to smoke than the 4 mg nicotine gum.
Rapid release gum provides biphasic delivery of nicotine through use of a unique gum base that allows a combination of rapid initial nicotine release. It also increases pH to facilitate rapid absorption through the oral mucosa. Increase in the dose of nicotine was done in order to provide rapid relief from craving and overdosing. Niaura et al. performed a study to assess the comparative efficacy of rapid-release nicotine gum vs. nicorette in relieving smoking cue-provoked craving and found that rapid-release nicotine gum has an advantage over conventional nicotine gum as they are rapid and results in complete relief from nicotine craving.
Nicotine lozenges can replace nicotine gum in patients who needs intermittent and controlled doses of nicotine but are unable to chew them for longer period of time. They are available as 1, 2, and 4 mg formulations. Only 20 lozenges in 24 h are recommended. It is placed sublingually for 30 min, which releases nicotine into systemic circulation. Studies showed that the amount of nicotine absorbed per lozenge appears to be somewhat higher than that delivered by gum. The advantage of nicotine lozenge is that they are easy to use and its taste is acceptable to the patient. However, they should be advised not to drink or eat 15 min before or during usage and also not to swallow and chew excessively during its consumption. Xiao et al. conducted a study to evaluate the efficacy in smoking cessation of 2 and 4 mg nicotine mint lozenges and concluded that the 4 mg nicotine lozenge provided a directionally significant improvement in smoking cessation rates.
Nicotine patch is a transdermal patch which is easy to use and results in slow release of nicotine. They are available in the ranges from 5, 10, and 15 mg doses patch, which can be worn over 16 h; however, 7, 14, and 21 mg doses patch can be worn over 24 h. Patients can place the patches over the clean and unbroken skin once in the morning, rather than using throughout the day. The 16 h patch should be removed before bedtime and 24 h patch to be removed the next morning. Plasma concentration of nicotine gets elevated during the day with the usage of nicotine patch than with any other acute NRT (nicotine gum, spray, lozenges, and inhalers) use. Patients may have side effects of insomnia and even local skin irritations are reported. DeVeaugh-Geiss et al. conducted a study to compare the single-dose pharmacokinetics of the 21-mg/24-h patch and the 25-mg/16-h patch and concluded by saying that the 21-mg patch provided a maximal nicotine concentration faster than did the 25-mg patch.
High-dose nicotine patches
Initially, the high-dose nicotine patches were available in 22-mg which were able to replace only half of baseline serum nicotine and cotinine levels in smokers. Therefore, a need for higher doses (≥42 mg) of transdermal nicotine patches was required. It can be used once daily on clean unbroken skin and removed before bedtime. Patients may suffer from local irritation and sleep disturbances. Schnoll et al. conducted a study to assess whether extended transdermal nicotine therapy increases abstinence from tobacco more than standard duration therapy in adult smokers and they concluded that extended therapy reduced the risk for a lapse and increased the chances of recovery from lapses.
Nicotine oral inhaler
Nicotine inhaler consists of a mouthpiece and a plastic cartridge containing nicotine, which mimics a cigarette/cigar. Each cartridge contains 10 mg nicotine. It can be sprayed in the mouth (not inhaled nor swallowed for few seconds); however, care should be taken that it does not touch the lips. It is mainly used in patients when they have craving for smoking. Delivery of nicotine is about 36% in the oral cavity, esophagus, stomach, and about (4%) in the lungs. Rate of absorption through the inhaler is same as that of nicotine gum which mainly occurs through oral mucosa. Its use can lead to irritation of mouth and throat. Bolliger et al. conducted a study to determine whether use of oral nicotine inhalers can result in long term reduction in smoking and concluded by saying that nicotine inhalers effectively and safely achieved sustained reduction in smoking over a period of 24 months.
Nicotine nasal spray
It is available as a multidose bottle with a pump which is fitted to a nozzle. It was designed to deliver doses of nicotine more rapidly. It delivers 0.5 mg of nicotine per 50 μL single spray. Patient is asked to take shallow puffs approximately every 2 s or alternatively 4 puffs every minute and continuing it for 30 min. It has been shown through various studies that there is more rapid delivery of nicotine in nicotine nasal sprays (NNS) when compared to other NRT products. It should not be given to patients with asthma. NNS sometimes results into nose irritation, coughing and watery eyes. Rubinstein et al. conducted a study to determine the feasibility and utility of using NNS in adolescent smokers who want to quit smoking and concluded by saying that the use of NNS as an adjunct to counseling for adolescent smokers wishing to quit was not supportive due to its unpleasant side effects, poor adherence, and consequent lack of efficacy.
Nicotine sub-lingual tablet
The recommended dose of sublingual tablet for highly nicotine dependent individuals is 16 to 24 tablets daily (i.e. 2 mg tablets maximum 30 tablets throughout the day), whereas for low dependency is 8–12 tablets daily. The tablet is placed sublingually and does not require chewing. It is recommended for at least 8–12 weeks and after that the numbers of tablets are reduced subsequently. It should be used cautiously in patients with nicotine dependence. Insomnia and mouth soreness are the major side effects associated with it. Tonnesen et al. conducted a trial study to evaluate the efficacy of nicotine sublingual tablets and two levels of support for smoking cessation in COPD patients. They showed that NRTs can be used for a longer duration in the population of COPD smokers.
| Electronic Nicotine Delivery Systems (Ends) or Electronic Cigarettes|| |
An electronic cigarette (e-cig, shisha pen, or personal vaporizer) is a device that produces vapor that resembles the look and feel of smoking. Each device contains an electronic vaporization system, rechargeable batteries, electronic controls and cartridges of the liquid that vaporizes. The vapor usually contains some nicotine and a base liquid mainly propylene glycol, glycerol, water., It comes in a variety of flavors that people can choose from. e-cig have become popular among this generation because of their realistic look, feel, and taste as compared to conventional cigarettes., However, Food and Drug Administration has reported that e-cig contains harmful components and that their usage should be stopped or as NRPs. Hajek et al. conducted a study to compare the efficacy of e-cig and NRT and found that e-cig were more effective for smoking cessation than NRT.
Jackson et al. conducted a study to assess whether dual e-cig users have lower smoking cessation rates than exclusive cigarette smokers or dual users of NRT and cigarettes. They concluded by saying that dual use of e-cig is not associated with reduced overall quit rates compared with exclusive smoking or dual use of NRT. However, dual use of e-cig is associated with a slightly higher quit attempt rate than exclusive smoking but lower than dual use of NRT.
People with intolerable withdrawal symptoms can be treated by combined therapy. A transdermal nicotine dose of 7, 14, and 21 mg along with dosage of any one acute form is the choice of combination most commonly used. To recompense the level of nicotine during abrupt craving, NRT patches can be used along with nicotine gum or a nasal spray. Nicotine patches and acute nicotine forms should be used together. These combinations help in achieving a significant though small success rate of NRT when compared to use of individual NRT separately. Combination therapy is contraindicated in nicotine dependence and insomniac patients. Mouth and airway irritation, nausea and vomiting are the most commonly reported adverse effects. Leung et al. conducted a study to compare the effectiveness of combined nicotine patch with gum versus nicotine patch alone in smoking cessation and concluded by saying that Smokers prescribed with combined NRT were more likely to quit smoking as compared to single NRT.
Nicotine vaccines are the latest innovation in NRT. A nicotine-based vaccine recognizes nicotine as foreign body and initiates an immune response against the drug. They mobilize drug specific antibodies, which results in the binding of nicotine molecules present in the blood. This prevents the drug being distributed to the brain, thus reducing its behavioral effects., They are currently under investigation.
Nicotine preloading means using a NRT prior to a quit date while smoking normally. It results in reduction of a person's drive to smoke deteriorating the level of addiction, resulting in decreased cravings after quitting smoking. It increases the rate of quitting and is assumed that nicotine preloading is reasonably effective in tobacco cessation; however, the data are limited.,
| Contraindications|| |
NRT products are contraindicated in the following conditions [Table 1].
| Precautions|| |
NRT should be given cautiously in the following conditions [Table 2].
| Advantages|| |
NRT has the following advantages , [Table 3].
Side effects of NRT
To calculate relative risk, the side effects of NRT should be compared with the side effects of smoking, thereby making NRT much safer than smoking.,,,,, [Table 4].
| Conclusion|| |
Various forms of NRT are available in different forms, doses and flavors that can help people to quit smoking. There are several advantages of NRTs but certain circumstances still hinder their recommendation. Some considerations should be given while prescribing them in these following conditions. The sugar levels should be priorly checked in diabetic patients, it should be given carefully in breast feeding females and in patients with mental health disorders. Prescribing NRTs is contraindicated in pregnant ladies, young children who are under 12 years of age, and in patients who have cardiovascular disorders. There are certain side effects associated with the use of NRTs such as nausea, vomiting, insomnia, headaches, throat soreness, and skin irritation. To calculate relative risk, the side effects of NRT should be compared with the side effects of smoking, thereby making NRT much safer than smoking.
This article reflects a way to educate and sensitize the doctors about the various choices of NRT products available in the market which can be prescribed to the tobacco users who are at the will of quitting. The doctors can further educate the society about the quitting protocols and the ease of use of these products and help in making a tobacco free society. Keeping in mind the benefits of NRT, it is essential for the professionals to become familiar with them for achieving successful tobacco cessation. Even incorporating it into an organized teaching of the undergraduate curriculum to improve confidence and knowledge will be beneficial for the patients, the budding dentist and the nation in the upcoming days ahead.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hanafin J, Clancy L. History of tobacco production and use. Prog Respir Res 2015;42:1-18.
Henningfield JE, Fant RV, Buchhalter AR, Stitze ML. Pharmacotherapy for nicotine dependence. Cancer J Clin 2005;55:281-99.
Centers for Disease Control and Prevention (US), National Center for Chronic Disease Prevention and Health Promotion (US), Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention (US); 2010. Available from: http://www.ncbi.nlm.nih.gov/books/NBK53 018/
Agarwal A, Reddy LVK, Saha S, Sinha P. Nicotine replacement therapy: An insight. Int J Oral Health Med Res 2017;4:76-9.
West R, Sohal T. “Catastrophic” pathways to smoking cessation: Findings from national survey. BMJ 2006;332:458-60.
Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2004;:CD000146. Review. Update in: Cochrane Database Syst Rev 2008;:CD000146.
Gupta R, Bharat A, Dhiman U, Sharma A. Nicotine replacement therapy: A smoking cessation aid… An overview. Int J Oral Health Dent 2019;5:69-75.
Kamala KA, Sankethguddad S, Sujith SG. An update on nicotine replacement therapy. J Oral Res Rev 2019;11:41-7. [Full text]
Benowitz NL. Nicotine addiction. N Engl J Med 2010;362:2295-303.
Flowers L. Nicotine replacement therapy. Am J Psychiatry Resid J 2016;11:4-7.
Wadgave U, Nagesh L. Nicotine replacement therapy: An overview. Int J Health Sci (Qassim) 2016;10:425-35.
Sumana CK, Nagaraj T, Nigam H, Gogula S, Saxena S. Nicotine replacement therapy: A review. J Med Radiol Pathol Surg 2018;5:6-8.
McDonough M. Update on medicines for smoking cessation. Aust Prescr 2015;38:106-11.
Chaturvedi O, Chaturvedi P. Nicotine gum in smoking cessation. Int J Contemporary Med Res 2017;4:1964-6.
Hansson A, Rasmussen T, Perfekt R, Hall E, Kraiczi H. Effect of nicotine 6 mg gum on urges to smoke, a randomized clinical trial. BMC Pharmacol Toxicol 2019;20:69.
Shiffman S, Cone EJ, Buchhalter AR, Henningfield JE, Rohay JM, Gitchell JG, et al
. Rapid absorption of nicotine from new nicotine gum formulations. Pharmacol Biochem Behav 2009;91:380-4.
Niaura R, Sayette M, Shiffman S, Glover ED, Nides M, Shelanski M, et al
. Comparative efficacy of rapid-release nicotine gum versus nicotine polacrilex gum in relieving smoking cue-provoked craving. Addiction 2005;100:1720-30.
Xiao D, Kotler M, Kang J, Wang C. A multicenter, randomized, double-blind, parallel, placebo-controlled clinical study to evaluate the efficacy and safety of a nicotine mint lozenge (2 and 4 mg) in smoking cessation. J Addict Med 2020;14:69-77.
A clinical practice guideline for treating tobacco use and dependence: A US Public Health Service report. The tobacco use and dependence clinical practice guideline panel, staff, and consortium representatives. JAMA 2000;283:3244-54. Review.
Molyneux A, Králíková E, Himmerová V. ABC of smoking cessation. Nicotine replacement therapy. Cas Lek Cesk 2004;143:781-3.
DeVeaugh-Geiss AM, Chen LH, Kotler ML, Ramsay LR, Durcan MJ. Pharmacokinetic comparison of two nicotine transdermal systems, a 21-mg/24-hour patch and a 25-mg/16-hour patch: A randomized, open-label, single-dose, two-way crossover study in adult smokers. Clin Ther 2010;32:1140-8.
Schnoll RA, Wileyto EP, Lerman C. Extended duration therapy with transdermal nicotine may attenuate weight gain following smoking cessation. Addict Behav 2012;37:565-8.
Bolliger CT, Zellweger JP, Danielsson T, van Biljon X, Robidou A, Westin A, et al
. Smoking reduction with oral nicotine inhalers: Double blind, randomised clinical trial of efficacy and safety. BMJ 2000;321:329-33.
Rubinstein ML, Benowitz NL, Auerback GM, Moscicki AB. A randomized trial of nicotine nasal spray in adolescent smokers. Pediatrics 2008;122:e595-600.
Glover ED, Glover PN, Franzon M, Sullivan CR, Cerullo CC, Howell RM, et al
. A comparison of a nicotine sublingual tablet and placebo for smoking cessation. Nicotine Tobacco Res 2002;4:441-50.
Tønnesen P, Mikkelsen K, Bremann L. Nurse conducted smoking cessation in patients with COPD using nicotine sublingual tablets and behavioral support. Chest 2006;130:334-42.
Unger M, Unger DW. E-cigarettes/electronic nicotine delivery systems: A word of caution on health and new product development. J Thorac Dis 2018;10(Suppl 22):S2588-92.
Seigel MB, Tanwar KL, Wood KS. Electronic cigarettes as a smoking cessation tool: Results from an online survey. Am J Prev Med 2011;40:472-5.
Goniewicz ML, Kuma T, Gawron M, Knysak J, Kosmider L. Nicotine levels in electronic cigarettes. Nicotine Tob Res 2013;15:158-66.
Manakil J, Miliankos A, Gray M, Itthagarun A, George R. Oral health and nicotine replacement therapy product. Eur J Gen Dent 2020;9:1-6. [Full text]
Hajek P, Phillips-Waller A, Przulj D, Pesola F, Myers Smith K, Bisal N, et al
. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med 2019;380:629-37.
Jackson SE, Shahab L, West R, Brown J. Associations between dual use of e-cigarettes and smoking cessation: A prospective study of smokers in England. Addict Behav 2020;103:106230.
Sweeney CT, Fant RV, Fagerstrom KO, McGovern JF, Henningfield JE. Combination nicotine replacement therapy for smoking cessation. CNS Drugs 2001;15:453-67.
Shah SD, Wilken LA, Winkler SR, Lin SJ. Systematic review and meta-analysis of combination therapy for smoking cessation. J Am Pharm Assoc 2008;48:659-65.
Leung MKW, Bai D, Yip BHK, Fong MY, Lai PMH, Lai P, et al
. Combined nicotine patch with gum versus nicotine patch alone in smoking cessation in Hong Kong primary care clinics: A randomized controlled trial. BMC Public Health 2019;19:1302.
Hasman A, Holm S. Nicotine conjugate vaccine: Is there a right to a smoking future? J Med Ethics 2004;30:344-5.
Aveyard P, Lindson N, Tearne S, Adams R, Ahmed K, Alekna R, et al
. Nicotine preloading for smoking cessation: The Preloading RCT. Health Technol Assess 2018;22:1-84.
Ananth CV, Smulian JC, Vintzileos AM. Incidence of placental abruption in relation to cigarette smoking and hypertensive disorders during pregnancy: A meta-analysis of observational studies. Obstet Gynecol 1999;93:622-8.
Hung TH, Hsieh CC, Hsu JJ, Chiu TH, Lo LM, Hsieh TT. Risk factors for placenta previa in an Asian population. Int J Gynaecol Obstet 2007;97:26-30.
George L, Granath F, Johansson AL, Annerén G, Cnattingius S. Environmental tobacco smoke and risk of spontaneous abortion. Epidemiol 2006;17:500-5.
Hogberg L, Cnattingius S. The influence of maternal smoking habits on the risk of subsequent stillbirth: Is there a causal relation? BJOG 2007;114:699-704.
Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: Implications for nicotine replacement therapy. J Am Coll Cardiol 1997;29:1422-31.
Dempsey DA, Benowitz NL. Risks and benefits of nicotine to aid smoking cessation in pregnancy. Drug Saf 2001;24:277-322.
Persson LG, Hjalmarson A. Smoking cessation in patients with diabetes mellitus: Results from a controlled study of an intervention programme in primary healthcare in Sweden. Scand J Prim Health Care 2006;24:75-80.
Haustein KO, Krause J, Haustein H, Rasmussen T, Cort N. Comparison of the effects of combined nicotine replacement therapy vs. Cigarette smoking in males. Nicotine Tob Res 2003;5:195-203.
Altarawneh S, Bencharit S, Mendoza L, Curran A, Barrow D, Barros S, et al
. Clinical and histological findings of denture stomatitis as related to intraoral colonization patterns of Candida albicans, salivary flow, and dry mouth. J Prosthodont 2013;22:13-22.
Mortazavi H, Safi Y, Baharvand M, Jafari S, Anbari F, Rahmani S. Oral white lesions: An updated clinical diagnostic decision tree. Dent J (Basel) 2019;7:15.
[Table 1], [Table 2], [Table 3], [Table 4]