Tobacco and Public Health - TCSC Indonesia

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PHARMACOLOGY OF NICOTINE ADDICTION
characteristics by means such as pH manipulation of tobacco and tobacco smoke (FDA
1995, 1996; Slade et al. 1995; Kessler et al. 1996; Hurt and Robertson 1998). For example,
buffering compounds in smokeless tobacco products (FDA 1995, 1996; Tomar and
Henningfield 1997) can alter the speed and amount of nicotine delivery of the products.
Similarly, menthol, and perhaps compounds such as levulinic acid (Bates et al.
1999), may alter the effects of nicotine delivered by smoke by enabling smokers to
inhale larger quantities of smoke by making the smoke feel less harsh and by reducing
concerns about the smoke toxicity because of the perceived smoothness (Henningfield
et al. 2002). Product design and ingredients can also be employed to control the mean
particle size to optimize the efficient inhalation of nicotine deep into the lungs where
absorption is rapid and virtually complete (Royal College of Physicians 2000).
Characteristics that contribute to larger amounts of smoke being more deeply
absorbed into the lung could also contribute to more rapid absorption of nicotine as
well as increasing the probability ofdiseases such as deep lung adenocarcinomas
(Hoffman and Hoffman 1997; Thun and Burns 2001).
The idea that cigarette smoke is a chemical cocktail that produces effects beyond
those produced by nicotine and/or which may modulate nicotine’s effects has received
increasing support since the 1990s. This has led to the conclusion that tobaccodelivered
nicotine is not only more toxic, but more addictive than pure nicotine forms
(Henningfield et al. 2000; Royal College of Physicians 2000). Additionally, it appears
that non-nicotine components of cigarette smoke inhibit monoamine oxidase which
could contribute to an antidepressant effect of smoking (Volkow et al. 1999).
Acetaldehyde, a metabolite of alcohol, which contributes to its subjective effects, is
present in cigarette smoke and can act synergistically with nicotine to produce stronger
reinforcing effects than either nicotine or acetaldehyde alone (FDA 1995, 1996; Bates
et al. 1999). Research on this topic was conducted by the tobacco industry and modern
cigarettes can be engineered to increase their delivery of acetaldehyde either by adding
the substance or by including certain sugars, which yield acetaldehyde upon pyrolysis
(FDA 1995, 1996; Bates et al. 1999).
Nicotine toxicology
Although nicotine can be a lethal poison at very high dosages, relative to those typically
delivered by use of tobacco or nicotine replacement medications, its toxicological
effects in tobacco use are modest compared to the many carcinogens and other toxins
present in tobacco products and the many more produced when tobacco products
are burned (Hoffman and Hoffman 1997; Benowitz 1998). Nonetheless, nicotine
delivered by tobacco products and medications is not entirely benign. Nicotine can
produce a variety of potential adverse effects depending upon the dose and pattern of
administration. ‘For example, nicotine is a fetal neuroteratogen in rats and there is
concern that nicotine from cigarette smoking during pregnancy might contribute
to developmental and behavioral problems in children of mothers who smoke.’