World Journal of Pharmaceutical Research SJIF Impact Factor 6.805

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1 SJIF Impact Factor Volume 5, Issue 9, Review Article ISSN E-CIGARETTE: AN AID TO SMOKING CESSATION? Dr. Syed Kasfur Rahman 1 *, Dr. Pallavi Kawatra 2, Dr. Cuckoo Aiyappa 3, Dr. M. C. Shivamurthy 4 1,2 Post Graduate, M.S. Ramaiah Medical College, Bangalore, India. 3 Professor, M.S. Ramaiah Medical College, Bangalore, India. 4 Head of Department, M.S. Ramaiah Medical College, Bangalore, India. Article Received on 21 July 2016, Revised on 11 August 2016, Accepted on 01 Sep DOI: /wjpr *Corresponding Author Dr. Syed Kasfur Rahman Post Graduate, M.S. Ramaiah Medical College, Bangalore, India. ABSTRACT Introduction: In spite of vast awareness programs, smoking has been a rising cause of morbidity and mortality in the world today. Electronic cigarettes (E-cigarettes), also known Electronic Nicotine Delivery Systems (ENDS) are battery operated devices which vaporize a liquid, thereby mimicking the smoking process without burning tobacco. Methods: A review of the literature pertaining to Electronic cigarettes published from 2005 to 2015 was carried out in the electronic databases Pub med, Google scholar and Science direct. The search terms were: nicotine de-addiction, electronic cigarettes, smoking cessation and vaping. Results: There is limited evidence for the effectiveness of e-cigarettes in smoking cessation; however, there may be a place in therapy to help modify smoking habits or reduce the number of cigarettes smoked. The reduced exposure to toxicants of well-regulated ENDS used by established adult smokers as a complete substitution for cigarettes is likely to be less toxic than conventional cigarettes or other combusted tobacco products. But, the amount of risk reduction is presently unknown. Conclusion: Very few studies have established the efficacy and safety of E-cigarettes over a long period. Thus this review highlights the current status of E- cigarettes as a smoking cessation aid. KEYWORDS: E- Cigarette, ENDS, smoking cessation. INTRODUCTION Electronic cigarettes (E-cigarettes), also known as electronic nicotine delivery systems (ENDS) have helped in expanding the armamentarium of our battle against smoking. Vol 5, Issue 9,

2 Contrary to the name, they are not cigarettes, but battery operated devices which vapourize a liquid, thereby mimicking the smoking process without burning tobacco. Being a less harmful alternative to smoking, these have caught the attention of a large number of smokers. They are sold online, in pharmacies and supermarkets and thus have acquired a significant place in the tobacco market. Since their emergence in 2007, China remains the world s largest manufacturer of these intriguing devices. However, very few studies have established their efficacy and safety over a long period. Thus this review highlights the current status of E- cigarettes as a smoking cessation aid. Current Problem Of Smoking WHO has estimated that tobacco is currently responsible for the death of about six million people across the world each year with many of these deaths occurring prematurely. In spite of vast awareness programs, smoking has been a rising cause of morbidity and mortality in the world today. [1] Cigarette smoking harms nearly every organ of the body, causes many diseases and reduces the health of smokers in general. Smokers are more likely than nonsmokers to develop heart disease, stroke and lung cancer. Smoking can cause cancer almost anywhere in your body. [2] There are approximately 120 million smokers in India. According to WHO, India is home to 12% of the world s smokers. Approximately 900,000 people die every year in India due to smoking as of Genetic component of Smoking Tobacco dependence is a behavior contributed by both genetic and environmental factors for the variance. Heritability estimates for smoking in twin studies have ranged from 46 to 84%, indicating a substantial genetic component to smoking. Candidate gene studies have detected functional polymorphisms in genes coding for the cytochrome P450 enzymes and variations in these genes that lead to more rapid nicotine metabolism have been implicated in smoking. Similarly, smoking has been associated with polymorphisms in dopaminergic genes that may influence the dopamine receptor number and/or function. [3] Beneficial effects of smoking cessation The following Figure 1 illustrates the beneficial effects of quitting the habit of smoking [4] : Vol 5, Issue 9,

3 Figure 1: Beneficial effects of smoking cessation Why to prefer E - cigarettes? In 1976, Michael Russell s words People smoke for nicotine, but die from tar emphasized on the need of cigarettes with lesser nicotine and tar content. [5] Advantages of an E-cigarette over a conventional cigarette are as follows: 1. Lesser nicotine content [6] 2. Lesser carcinogenic substances 3. Can be used in public places 4. Mimic the act of smoking: Look like real cigarettes and glow at one end when activated by the puff: 5. Reduce craving 6. Better odour: Smoke from a traditional cigarette smells so bad because you re burning tar and chemicals in addition to the tobacco itself, E-cigarettes on the other hand do not have this ominous odor because instead of exhaling smoke, you re exhaling a vapor that evaporates almost immediately. 7. Much cheaper than traditional cigarettes While some of the entry costs of a starter kit may be a little bit higher, the month-to-month cost of electronic smoking is typically about half when compared to traditional cigarettes. Currently, E-cigarettes are not subject to any sort of taxes like traditional smokes are. Also, as the technology develops and becomes more mainstream, the cost will continue to decline. Vol 5, Issue 9,

4 8. Safer to use Traditional cigarettes by default pose serious fire hazards. Cigarettes are in fact the #1 cause of fire-related death in the United States and 7 other countries. Worldwide, fires started by lit cigarettes constitute 10% of all fire-related deaths. With e-cigarettes, you re not burning an open flame. When used as intended, there have been no reports of an e-cigarette exploding. Composition of an E-cigarette An E-cigarette has three main parts: a rechargeable lithium battery a vaporization chamber a cartridge The lithium battery powers the e-cigarette and can be charged using a charger similar to those used for cell phone batteries. The charged battery is connected to the vaporization chamber, a hollow tube that contains electronic controls and an atomizer -- the component that creates the vapor. Before the user activates the device, he or she attaches a cartridge containing nicotine liquid to the vaporization chamber. The tip of the cartridge serves as the e-cigarette's mouthpiece. Contents of the nicotine liquid: nicotine, propylene glycol &/or glycerol with flavoring agents such as menthanol, candy floss, pina colada, chocolate etc. How does an E - cigarette work? Lighting a conventional cigarette burns the tobacco, to release smoke that contains nicotine. An electronic cigarette doesn't rely on this process of combustion. Instead, it heats a nicotine liquid and converts the liquid to a vapor, or mist, that the user inhales. Figure 2: Mechanism of Action of E-Cigarettes Vol 5, Issue 9,

5 Nicotyrine Hypothesis [7] Nicotyrine forms by the gradual oxidation of nicotine in e-liquids exposed to air. E-cigs aerosolize nicotyrine along with nicotine. Nicotyrine inhibits the cytochrome P450 2A family of enzymes (CYP2A) in airways and liver. In humans, nicotine is metabolized primarily by hepatic CYP2A6. When CYP2A6 is substantially inhibited, nicotine clearance is delayed and nicotine withdrawal symptoms are attenuated. Figure 3: Nicotyrine Hypothesis Types / Generations [8] Due to their gaining popularity, numerous types of E-cigarettes have been introduced. The difference lies in their appearance, nicotine content, flavors, and the mechanism by which the liquid is being stored and farther vaporized. [9] 1. First generation/ Non rechargeable disposable: cig-a-likes: Look like cigarettes; small lithium batteries with pre filled liquid along with the atomizer in a cartridge For short time use Cheap widely available from gas stations or super markets Convenient as no refill solution or cartridge is needed Might be a starting point for many users. [10] 2. Second generation/ Rechargeable with replaceable pre filled cartridge: Ego type : Look like pens; Higher capacity lithium batteries, liquid can be refilled Various sizes from cigarette size, to compact flashlight size Various colors and styles Vol 5, Issue 9,

6 Requires battery with a charger Requires replacing or refilling nicotine cartridges. [10] 3. Third generation/ Rechargeable with a reservoir containing liquid nicotine: Tanks or Mods : very different look ; Large capacity lithium batteries, can alter the voltage of the vapour High-capacity Battery operated Lasts longer than typical rechargeable models Requires refilling the tank with nicotine solution Often recommended for heavy smokers by retailers. [10] Efficacy An online questionnaire survey conducted among 1347 respondents in 33 countries concluded that in 70% it reduced the craving to smoke. One more significant finding in the same survey was the fact that time to vape (was longer compared to time to first cigarette emphasizing on the fact that the development of dependence on these is comparatively lower. [11] A meta-analysis that pooled the results of two randomized controlled trials (RCTs), covering 662 participants, showed that smokers who used nicotine electronic cigarettes (ECs) were significantly more likely to stop smoking than smokers using placebo ECs. [12] A 2014 review found four experimental studies and six cohort studies that indicated that electronic cigarettes reduced the desire to smoke and withdrawal symptoms. This review also noted that two cohort studies found that electronic cigarettes led to a reduction in the number of cigarettes smoked per day. [13] A 2015 review found that e-cigarettes for quitting smoking were generally similar to a placebo. The same review concluded that while they may have a benefit for decreasing cigarette use in smokers, they have a limited benefit in quitting smoking. [14] There is limited evidence for the effectiveness of e-cigarettes in smoking cessation; however, there may be a place in therapy to help modify smoking habits or reduce the number of cigarettes smoked. [15] Vol 5, Issue 9,

7 Safety concerns Most ENDS products have not been tested by independent scientists but the limited testing has revealed wide variations in the nature of the toxicity of contents and emissions. Associated with eye and airway irritation caused by exposure to propylene glycol Increase in diastolic BP. [16] Inconsistency in nicotine content Long term evaluation of the toxicological content of the vapor not available hence no conclusive evidence about the asscociation of ENDS use with chronic diseases like cancers. One of the studies done on E-cig exposed mice, suggests that they can result in decrease bacterial clearance from the airway by interfering with the phagocytosis capacity of the alveolar macrophages. [17] Addictive potential Cytotoxicity of the e-liquid that has raised concerns about pregnant women who use ENDS or are exposed to second-hand ENDS aerosol. [18] Bystanders are exposed to the aerosol exhaled by ENDS users, which increases the background level of some toxicants, [19] nicotine [20] as well as fine and ultrafine particles in the air. Nevertheless the level of toxicants, nicotine and particles emitted from one ENDS is lower than that of conventional cigarette emissions. Aerosol usually contains some carcinogens and other toxicants at average levels of 1 2 orders of magnitude lower than in tobacco smoke, but higher than in a nicotine inhaler. For some brands, the level of some of these cancer causing agents, such as formaldehyde and other toxicants like acrolein have been found to be as high as in the smoke produced by some cigarettes. [21] ENDS are not yet regulated under the FDA tobacco regulatory authority, unlike traditional cigarettes. Hence, there is lack of mandatory manufacturing standards for ENDS and few quality controls are in place. [22] The risks of nicotyrine exposure include impaired clearance of all CYP2A substrates and any effects of the metabolic products of nicotyrine. [7] CONCLUSION In summary, the existing evidence shows that ENDS aerosol is not merely water vapour as is often claimed in the marketing for these product. However, the reduced exposure to Vol 5, Issue 9,

8 toxicants of well-regulated ENDS used by established adult smokers as a complete substitution for cigarettes is likely to be less toxic for the smoker than conventional cigarettes or other combusted tobacco products. But, the amount of risk reduction is presently unknown. The 2014 Surgeon General s Report concluded that noncombustible products such as ENDS are much more likely to provide public health benefits only in an environment where the appeal, accessibility, promotion and use of cigarettes and other combusted tobacco products are being rapidly reduced. [2] REFERENCES 1. Zhang J, Ou J-X, Bai C-X. Tobacco smoking in China: prevalence, disease burden, challenges and future strategies. Respirology Nov; 16(8): Health CO on S and. Smoking and Tobacco Use; 50 th Anniversary Surgeon General s Report. [cited 2015 Aug 13]. 3. Franck C, Budlovsky T, Windle SB, Filion KB, Eisenberg MJ. Electronic cigarettes in North America: history, use, and implications for smoking cessation. Circulation, 2014 May 13; 129(19): Health CO on S and. Smoking and Tobacco Use; 2010 Surgeon General s Report: How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking- Attributable Disease. [cited 2015 Nov 23]. 5. Russell MA. Low-tar medium-nicotine cigarettes: a new approach to safer smoking. BMJ Jun; 1(6023): Cooke A, Fergeson J, Bulkhi A, Casale TB. The Electronic Cigarette: The Good, the Bad, and the Ugly. J allergy Clin Immunol Pract. Jan; 3(4): Abramovitz A, McQueen A, Martinez RE, Williams BJ, Sumner W. Electronic cigarettes: The nicotyrine hypothesis. Med Hypotheses Jun. 8. Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv drug Saf. SAGE Publications, 2014 Apr; 5(2): Lopez AA, Eissenberg T. Science and the Evolving Electronic Cigarette. Prev Med (Baltim) Jul. 10. Brandon TH, Goniewicz ML, Hanna NH, Hatsukami DK, Herbst RS, Hobin JA, et al. Electronic nicotine delivery systems: a policy statement from the American Association for Cancer Research and the American Society of Clinical Oncology. Clin Cancer Res. American Association for Cancer Research, 2015 Feb 1; 21(3): Vol 5, Issue 9,

9 11. Dawkins L, Turner J, Roberts A, Soar K. Vaping profiles and preferences: an online survey of electronic cigarette users. Addiction Jun; 108(6): McRobbie H, Bullen C, Hartmann-Boyce J, Hajek P. Electronic cigarettes for smoking cessation and reduction. Cochrane database Syst Rev Dec 17; 12: CD Gualano MR, Passi S, Bert F, La Torre G, Scaioli G, Siliquini R. Electronic cigarettes: assessing the efficacy and the adverse effects through a systematic review of published studies. J Public Health (Oxf) Aug 9; fdu Schraufnagel DE. Electronic Cigarettes: Vulnerability of Youth. Pediatr Allergy Immunol Pulmonol, 2015 Mar 1; 28(1): Orr KK, Asal NJ. Efficacy of electronic cigarettes for smoking cessation. Ann Pharmacother Nov; 48(11): Schuurmans MM. [Electronic Cigarettes: Lifestyle Gadget or Smoking Cessation Aid?]. Praxis (Bern 1994) Jul; 104(14): Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim J-H, Sudini K, et al. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One. Public Library of Science, 2015 Jan; 10(2): e Farsalinos KE, Romagna G, Allifranchini E, Ripamonti E, Bocchietto E, Todeschi S, et al. Comparison of the cytotoxic potential of cigarette smoke and electronic cigarette vapour extract on cultured myocardial cells. Int J Environ Res Public Health Oct; 10(10): Schober W, Szendrei K, Matzen W, Osiander-Fuchs H, Heitmann D, Schettgen T, et al. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health Jul; 217(6): Czogala J, Goniewicz ML, Fidelus B, Zielinska-Danch W, Travers MJ, Sobczak A. Secondhand exposure to vapors from electronic cigarettes. Nicotine Tob Res Jun; 16(6): Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control Mar 6; 23(2): Benowitz NL, Goniewicz ML. The regulatory challenge of electronic cigarettes. JAMA. American Medical Association, 2013 Aug 21; 310(7): Vol 5, Issue 9,