Nicotine gum

Oncken CA, Hatsukami DK, Lupo VR, et al Effects of short-term use of nicotine gum in pregnant smokers. Clin Pharmacol Ther 59 654-61, 1996 Pomerleau OF, Pomerleau CS Neuroregulators and the reinforcement of smoking towards a biobehavioral explanation. Neurosci Biobehav Rev 8 503—513, 1984 Prochazka AV, Weaver MJ, Keller RT, et al A randomized trial of nortriptyline for smoking cessation. Arch Intern Med 158 2035-2039, 1998 Puska P, Korhonen HJ, Vartiainen E, et al Combined use of nicotine patch and gum compared with gum alone in smoking cessation a clinical trial in North Karelia. Tob Control 4 231-235, 1995... 

Nicotine patch Transdermal Nicotine gum Buccal Nicotine lozenge Buccal Nicotine nasal spray Intranasal 7-22 mg/day (started at 21 mg per day x 2 weeks then 14 mg per day x 2 weeks then 7 mg/day) 20-40 mg/day 2 or 4 mg/piece one piece every 2 hours up to 10 times/day 20-40 mg/day 2-4 mg/lozenge one lozenge every 2 hours, up to 10 times/day 16-32 mg/day 1-2 mg/spray, one in each nostril up to 16 times/day... 

Sublingual (SL) In the mouth under the tongue this allows the tablet or gum to slowly dissolve, so that the released drug can be gradually absorbed across the buccal mucosal membrane. Nicotine gum is administered by this route. 

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

First-line pharmacotherapies for smoking cessation are bupropion sustained release, nicotine gum, nicotine inhaler, nicotine nasal spray, and... 

Nicotine gum simiiariy increases aipha and beta activity on the EEG and decreases theta activity (Pickworth et ai. 1986). In contrast, denicotinized cigarettes do not have any EEG effects (Pritchard et ai. 1999). 

Hindmarch I, Kerr JS, Sherwood N. (1990). Effects of nicotine gum on psychomotor performance in smokers and non-smokers. Psychopharmacology (Berlin). 100(4) 535-41. 

Fig. 2 Blood nicotine concentrations during and after cigarette smoking for 9 min, oral snuff (2.5 g), chewing tobacco (average 7.9 g), and nicotine gum (two 2-mg pieces). Average values for 10 subjects ( SEM). Reprinted from Benowitz et al. (1988) with permission from American Society for Clinical Pharmacology and Therapeutics...

McKennis H, Jr., Turnbull LB, Bowman ER, Tamaki E (1963) The synthesis of hydroxycotinine and studies on its structure. J Org Chem 28 383-387 McNabb ME (1984) Chewing nicotine gum for 3 months what happens to plasma nicotine levels Can Med Assoc J 131(6) 589-592... 

McNabb ME, Ebert RV, McCusker K (1982) Plasma nicotine levels produced by chewing nicotine gum. JAMA 248(7) 865-868... 

Shiffman S, Shadel WG, Niaura R, Khayrallah MA, Jorenby DE, Ryan CF, Ferguson CF (2003) Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Psychopharmacology 166 343-350... 

Watkins SS, Koob GF, Markou A (2000) Neural mechanisms underlying nicotine addiction acute positive reinforcement and withdrawal. Nicotine Tob Res 2 19-37 West RJ, Russell MA (1985) Effects of withdrawal from long-term nicotine gum use. Psychol Med 15 891-893... 

F%.1 Venous blood concentrations in nanograms of nicotine per miUimeter of blood as a function of time for various nicotine delivery systems. Data on the cigarette delivering about 1 mg nicotine (filled square), oral snuff delivering 3.6 mg (filled circle), and 4 mg nicotine gum (star) are from those published by Benowitz et al. (1988). Data on 1 mg nicotine nasal spray (filled triangle) are from Schneider et al. (1996). Data on 21 mg transdermal nicotine patch (open square) are from Benowitz (1993). Data on the 4 mg nicotine lozenge (open circle) are from Choi et al. (2003)... 

Currently approved NRT products include the transdermal nicotine patch and several acute NRT products, including nicotine gum, lozenge, sublingual tablet, vapor inhaler, and nasal spray. The single-dose nicotine plasma curves for transdermal patch, gum, nasal spray, lozenge, as well oral snuff and a cigarette, are illustrated in Fig. 1 (note for the sake of simphcity, the curve for sublingual tablet is not illustrated, but because of the route of nicotine delivery, the plasma curve is qualitatively similar to nicotine gum). 

A small sublingual nicotine tablet has been developed and is currently being marketed in many European countries, but is not yet available in the USA. The product is designed to be held under the tongue, where the nicotine is absorbed sublingually over about 30 min. The product that is currently available contains 2 mg nicotine, of which 1 mg is absorbed via the buccal mucosa. Compared to the gum and lozenge, the sublingual tablet demands even less activity from the user. The levels of nicotine obtained by use of the 2-mg tablet and 2-mg nicotine gum are similar (Molander and Lunell 2001). 

As shown in Fig. 1, the speed of nicotine uptake in venous blood following several forms of nicotine delivery varies widely, from that of the very slow pattern of nicotine appearance in the blood (several hours to peak level) produced by current transdermal nicotine medications to the explosive rise produced by tobacco smoke inhalation. Nicotine gum, lozenge, tablet, and vapor inhaler can provide more rapid delivery of nicotine than the patch, but the speed and amount obtained are constrained by use patterns. Smokeless tobacco products deliver their nicotine more rapidly than nicotine gum and with less physical effort, but are still slower than cigarettes in their nicotine dehvery. 

Eagerstrom KO, Schneider NG, Lunell E (1993) Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology 111 271-277... 

Tiffany ST, Cox LS, Elash CA (2000) Effects of transdermal nicotine patches on abstinence-induced and cue- elicited craving in cigarette smokers, J Consult Clin Psychol 68 233-240 Tonnesen P (1988) Dose and nicotine dependence as determinants of nicotine gum efficacy. Prog Clin Biol Res 261 129-144... 

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