Tobacco and Public Health - TCSC Indonesia

Pickworth et al. 1995; Shiffman et al. 1998). Humans report generally similar subjective
effects from intravenous nicotine as from smoked tobacco (Henningfield et al.
1985; Jones et al. 1999). Tobacco craving is only partially relieved by pharmaceutical
forms of nicotine, reflecting the facts that (1) cravings can be elicited by factors that
are not mitigated by nicotine (e.g. the smell of smoke, the sight of other people smoking,
and tobacco advertisements), and (2) tobacco smoke constituents other than nicotine
(e.g. ‘tar’ and other smoke constituents) can reduce craving independently of
nicotine (Butchsky et al. 1995) and may have synergistic effects with nicotine in cigarettes
to provide more effective nicotine relief than cigarette smoke-delivered nicotine
(Rose et al. 1993).
Rodent models of nicotine withdrawal have been developed and serve in the
evaluation of medications for treating withdrawal (e.g. Malin et al. 1992, 1998a, b). The
most useful is one in which the frequency of signs are observed and coded from a
checklist which includes writhes and gasps, wet shakes and tremors, ptosis, bouts of
teeth chattering and chewing, and miscellaneous less frequent signs such as foot licks,
scratches, and yawns (Malin et al. 1992). Episodes of locomotor immobility lasting
longer than a minute are also recorded. Another rodent model that might be of
particular relevance to disruption of behavioral performance in humans is one in
which acute nicotine abstinence disrupted food-maintained learned behaviors (Carroll
et al. 1989).
Dose-related effects
JACK E. HENNINGFIELD AND NEAL L. BENOWITZ 133
As with many drugs, understanding the mechanisms of the effects of nicotine is
complicated by the fact total dose, rate of delivery, and amount of prior exposure are
important determinants (Ernst et al. 2001). For example, 1 mg nicotine delivered by
smoke inhalation may produce cardiac acceleration and mood alteration, whereas the
approximately 1 mg nicotine delivered per hour by transdermal nicotine patch
produces no reliable change in mood or cardiovascular measure (Benowitz 1990;
Pickworth et al. 1994). Furthermore, observed effects involve a diverse array of
mechanisms, which operate differentially at different dosages. For example, stimulation
of nicotinic cholinergic receptors in the spinal cord may directly alter muscle tone,
whereas heart rate acceleration and mood alteration appear to be primarily mediated
by catecholamines release that is modulated by nicotine (e.g. release of norepinephrine
and increased brain dopamine, respectively) (Benowitz 1990; Balfour and Fagerstrom
1996; Henningfield et al. 1996).
Nicotine is rapidly and efficiently absorbed when inhaled into the lung (Benowitz
1990). It is also well absorbed through the skin, nasal passages, and the oral mucosa,
although the speed of its absorption through the mucosa is directly related to the
fraction of nicotine that is in a ‘free-base’ or unionized state, as opposed to that which
is in the ‘bound’ or in the ionized state. The alkaloid nature of nicotine implies that the