Tobacco and Public Health - TCSC Indonesia

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PHARMACOLOGY OF NICOTINE ADDICTION
percentage of unionized nicotine molecules in tobacco material can be influenced by
the pH of the product or its aqueous medium, with the concentration of free base
nicotine increasing logarithmically as a function of increasing pH (Henningfield et al.
1995b). The pKa of nicotine is 8, and thus 50% of the nicotine is unionized and free to
be rapidly absorbed at an aqueous pH of 8. The alkaline smoke typical of cigars
(typically 7.0–8.5) enables efficient absorption of nicotine through the mouth without
inhalation (Henningfield et al. 1999; Baker et al. 2000). The mildly acidic smoke of
cigarettes (pH 5.5–6.5) produces less throat irritation and is easier to inhale than
higher pH cigar smoke, but no nicotine is absorbed in the mouth and smoke must be
inhaled to absorb nicotine (Hoffman and Hoffman 1997). Since addictive drug effects
are intensified by faster delivery (O’Brien 1996), the dual consequence of a potentially
more addictive form of nicotine delivery and the well-documented greater lung toxicity
due to the repetitive exposure of the lung to the smoke results (Hoffman and Hoffman
1997). Therefore, even though a cigar potentially delivers more nicotine and toxins, the
risk of lung disease is less than that associated with cigarette smoking (National Cancer
Institute 1998; Baker et al. 2000).
Smokeless tobacco products such as snuff, include ‘starter’ products (tobacco industry
term) that are generally at pH levels of approximately 7.0, whereas products that
experienced users tend to ‘graduate’ to (tobacco industry term) generally show an
aqueous pH of 7.5–8.5) (Henningfield et al. 1995b). Snuff products with higher pH
levels than products with similar nicotine content produce more rapidly rising and
higher plasma nicotine levels as well as higher heart rates and stronger subjective
effects (Fant et al. 1999).
An additional consequence of smoke inhalation is the generation of arterial plasma
nicotine spikes that can be up to ten times greater than simultaneously measured
venous levels within the first minute following the smoking of a cigarette (Henningfield
et al. 1993). Similar effects occur with smoked cocaine and appear to contribute to its
powerful reinforcing effects (Evans et al. 1996). Consistent with these observations,
tobacco products that deliver nicotine more rapidly are demonstrated to be of higher
abuse liability in standard testing than pharmaceutical products, which deliver nicotine
more slowly (Henningfield and Keenan 1993; Stitzer and De Witt 1998). These observations
are consistent with product design and ingredients: Whereas, tobacco products
are designed to maximize addictive potential, pharmaceutical products are designed
and labeled to minimize the risk of addiction and abuse (Henningfield and Slade 1998;
Slade and Henningfield 1998).
Cross population variation in nicotine metabolism. There is much individual variability
in the CYP2A6 activity of human liver samples, and much variability in the rate of
nicotine metabolism among individuals and populations. Studies of racial/ethnic
differences have shown slower metabolism of nicotine and cotinine in Chinese
Americans, and slower metabolism of cotinine African Americans compared to