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Last updated March 2011 Safety of smoking cessation medications Slide 2 Last updated March 2011 Safety section ChairNeal BenowitzUniversity of California San Francisco, USA Carolyn DreslerArkansas Department of Health, USA Steve S HechtUniversity of Minnesota, USA John HughesUniversity of Vermont, USA Anne M JosephMinneapolis VA Medical Center, USA Jacques Le HouezecFreelance consultant (France), and University of Nottingham, UK Cheryl OnckenUniversity of Conneticut, USA Maxine StitzerJohns Hopkins University, USA Slide 3 Last updated March 2011 1 USDHHS. The Health Consequences of Smoking: Nicotine Addition. 1988. 2 Royal College of Physicians. London: 2008. 3 Benowitrz. In Nicotine Safety and Toxicity; pp 185195 NY: OUP. 4 Hoffman and Hoffman. J Toxicol Environ Health 1997; 50: 30764. 5 Smith et al. Food Chem Toxicol 2003; 41: 807817. Nicotine vs. tobacco smoke The main adverse effect of nicotine from tobacco is addiction, which sustains tobacco use 1-2 Other toxicants in tobacco smoke, not nicotine, are responsible for majority of adverse health effects 3,4 > 4000 different chemicals tar, carbon monoxide, irritant and oxidant gases > 80 carcinogens (11 are group 1 carcinogens) 5 Nicotine dependence leads to continued exposure to toxicants in tobacco smoke Slide 4 Last updated March 2011 1 US Department of Health and Human Services, Bethesda, MD, 2001. 2 Surgeon General's report 2010 3 Hoffman and Hecht. IN Handbook of Experimental Pharmacolgy, pp 63102; 1990 Heidelberg: Springer-Verlag 4 Hecht. J Natl Cancer Inst. 1999; 91: 11941210. Nicotine and cancer Nicotine per se is not a substantial cause of cancer 1-2 Any cancer-related risks from short-term NRT are insignificant compared to the risks of smoking Other tobacco smoke constituents are believed to be responsible for cancers 3,4 Slide 5 Last updated March 2011 1 US Department of Health and Human Services, Bethesda, MD, 2001. 2 Benowitz et al. J Pharmacol Exp Ther 1994; 268: 296303. 3 Hecht et al. Proc Natl Acad Sci USA. 2000; 97: 12493-12497. 4 Carmella et al. Carcinogenesis 1997; 18: 101106. Nicotine and cancer Studies carried out in rodents demonstrate that under normal conditions nicotine is not carcinogenic 1 Carcinogenic, nicotine-derived nitrosamines may be formed in the body under certain conditions 24 levels would be low and represent minimal risk during short term NRT further research required to establish any risk associated with long term use of NRT Nicotine can inhibit apoptosis (cell death) and enhance angiogenesis in cell and experimental animal test systems 5-9 This could in theory promote the spread of cancers. However this risk has not been documented in people 5 Porubin et al. J Agric Food Chem, 2007; 55: 7199-7204. 6 Stepanov et al. Cancer Res. 2009; 69: 8236-8240. 7 Cooke. Life Sci, 2007; 80: 2347-2351. 8 West et al. J Clin Invest, 2003; 111: 81-90. 9 Dasgupta et al. Proc Natl Acad Sci USA, 2006; 103: 6332-6337. Slide 6 Last updated March 2011 Smoking and cardiovascular disease Smoking increases risk of CVD Smoking-related factors contributing to CV risk: increased thrombogenesis carbon monoxide oxidative damage hyperlipidaemia Smoking cessation significantly reduces risk within 13 years 1-2 Smoking cessation using NRT has a favourable effect on these contributing factors 3 1 Rosenberg et al. N Engl J Med. 1990; 322: 213217. 2 Rosenberg et al. N Engl J Med. 1985; 313: 15111514. 3 Ludviksdottir et al. J Intern Med. 1999; 246: 6166. Slide 7 Last updated March 2011 1 Joseph et al. N Engl J Med. 1996; 335:17921798. 2 Tzivoni et al. Cardiovasc Drugs Ther. 1998; 12:239244. 3 Working Group. Arch Intern Med. 1994; 154:989995. 4 Greenland et al. Drug Saf. 1998; 18: 297308. NRT and cardiovascular disease NRT can be used safely by majority of people with cardiovascular disease, even with concomitant smoking 1 3 Meta-analyses show no difference in rate of acute MI between NRT patch and placebo 4-6 N.B. majority of studies excluded patients with CVD at baseline The benefits of NRT outweigh the risks, even in smokers with cardiovascular disease 79 5 Mills et al. Tob Induc Dis. 2010; 8: 8. 6 Hays & Ebbert. Drugs. 2010; 70: 2357-2372. 7 Benowitz. Prog Cardiovasc Dis. 2003; 46: 91-111. 8 Joseph & Fu. Prog Cardiovasc Dis. 2003; 45: 429-441. 9 Hubbard et al. Tob Control. 2005; 14: 41621. Slide 8 Last updated March 2011 1 USDHHS. Surgeon General's Report. 2001. 2 Steyn et al. Paediatr Perinat Epidemiol. 2006; 20: 90-99. 3 Fried et al. Neurotoxicol Teratol. 1998; 20: 293-306. 4 Jacobsen et al. Neuropsychopharmacology. 2007; 32: 2453-2464. 5 Romano et al. Pediatrics, 2006; 117: 2101-2110. 6 Slotkin et al.. Brain Res Bull. 1995; 38: 69-75. 7 Slotkin et al. Neuropsychopharmacology. 2006; 31: 2462-2475. 8 Benowitz & Dempsey. Nicotine Tob Res. 2004; 6 Suppl 2: S189-202. Smoking, NRT and pregnancy Maternal smoking is associated with poor pregnancy and childhood outcomes 15 Many toxicants in tobacco smoke could be responsible Nicotine is a potential foetal teratogen Nicotine may contribute to obstetrical complications in pregnant women and to sudden infant death syndrome 6,7 Benefits of NRT outweigh the risks of smoking during pregnancy 8 reduce or eliminate the exposure of fetus to other toxicants in tobacco smoke reduce overall dose and duration of exposure to nicotine Slide 9 Last updated March 2011 Nicotine replacement therapy NRT delivers nicotine without the toxicants from tobacco 1 NRT helps combat the symptoms of withdrawal 2 Nicotine dose from NRT is lower and administered more gradually than with smoking and this reduces the addictive potential 1,3 1 Benowitz & Gourlay. J Am Coll Cardiol. 1997; 29: 1422-1431. 2 Silagy et al. Cochrane Database Syst Rev. 2004; (3): CD000146. 3 Le Houezec. Int J Tuberc Lung Dis. 2003; 7: 811-819. Slide 10 Last updated March 2011 Minutes Increase in nicotine concentration ( ng/ml ) Cigarette Gum 4 mg Gum 2 mg Inhaler Nasal spray Patch 510 15 20 25 30 0 2 4 6 8 10 12 14 Plasma nicotine levels (smoking and NRT) Source: Balfour DJ & Fagerstrm KO. Pharmacol Ther. 1996; 72: 51-81. Slide 11 Last updated March 2011 1 West et al. Psychopharmacology. 2000; 149: 198-202. 2 Stitzer & de Wit. In: Benowitz, NL. Nicotine Safety and Toxicity. pp. 1998 119-131 New York, Oxford University Press. 3 Henningfield & Keenan. J Consult Clin Psychol. 1993; 61: 743-750. 4 Hughes. In Nicotine Safety and Toxicity, 1998; pp. 147-157. New York: OUP Abuse liability of NRT Prevalence of abuse and dependence with current NRT products is nil (patch) or very low (