Tobacco and Public Health - TCSC Indonesia

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PHARMACOLOGY OF NICOTINE ADDICTION
could produce dependence and withdrawal. By 1987, the APA concluded that the role
of nicotine was sufficiently well established to merit the classification of nicotine
dependence and nicotine withdrawal disorders. In contrast, WHO (1992) continues to
refer to the substance ‘tobacco’ as opposed to its drug, ‘nicotine’ just as it refers to the
substance ‘cannabinoids’ as opposed to their drug, tetrahydrocannabinol. This is
based on the reasoning that even though nicotine is the critical drug that defines the
disorders, in practice, withdrawal signs from pure nicotine systems (e.g. nicotine gum
and patches) are generally weak and the establishment of dependence on pure nicotine
preparations is not a known public health problem.
Both the APA and WHO approaches have merit and scientific rationale. The WHO
approach to emphasize the importance of the tobacco vehicle is highly relevant to
recent advances in the understanding of tobacco use that have begun to unravel the
contributions of tobacco product ingredients and designs, which may be determinants
of the risk, severity, and prevalence of nicotine addiction. These issues will be addressed
in the present analysis. Despite the many research questions that need to be explored to
fully understand the mechanisms underlying dependence on tobacco and nicotine,
there is a strong science foundation upon which to guide policy aimed at reducing the
prevalence of tobacco use and eradicating tobacco-caused diseases.
Pharmacology of nicotine
Nicotine is an alkaloid that is present in concentrations of about 1–3% in tobacco
cultivated for commercial tobacco products (Browne 1990). The concept that the
pharmacologic effects of tobacco primarily reflect the actions of nicotine has been
widely accepted, at least since Lewin’s analysis from the 1920s (translated into English
in 1931 and reprinted in 1964) in which he concluded. ‘The decisive factor in the effect
of tobacco, desired or undesired, is nicotine…’ For example, prominent effects of
tobacco on muscle tone, heart rate, and blood pressure, as well as behavioral and mood
altering effects, can be mimicked by administration of nicotine (Benowitz 1990;
Henningfield et al. 1996; Taylor 1996).
Nicotine is a potent and powerful agonist of several subpopulations of nicotinic
receptors of the cholinergic nervous system (Henningfield et al. 1996; Vidal
1996; Paterson and Nordberg 2000). Acute doses of 1 mg per 70 kg accelerate
heart rate and alter mood, although daily users are substantially less sensitive to
such effects than non-users (US DHHS 1988; Soria et al. 1996; Taylor 1996; Foulds
et al. 1997). The half-life of nicotine averages approximately 2 h but is longer
in persons in the presence of a genetic polymorphism of the liver enzyme
CYP2A6, which is the primary metabolic pathway of nicotine (Tyndale and Sellers
2001; Benowitz et al. 2002). The prevalence of CYP2A6 alleles that are associated
with reduced enzymatic activity is higher in Asians than in Caucasians or
African Americans, and this difference may contribute to lower daily cigarette
consumption and a lower risk of lung cancer in Asians compared to Caucasians