| Drug
Class: CNS Stimulant |
|
| Chemical
Structure: The empirical formula is C10H14N2 |
 |
|
Nicotine |
Drug
Combinations:
Street drug users sometimes mix tobacco with other drugs such as cannabis
or phencyclidine (PCP) and smoke the combination. A majority of alcoholics
and alcohol abusers smoke as well. It has been shown that smoking
enhances the metabolism of some other drugs, including antidepressants.
This effect is from tar in the cigarette and not the nicotine.
Pharmacokinetics:
Nicotine is readily absorbed from the respiratory tract, buccal membranes
and skin. 80-90% of nicotine is metabolized in the body mainly by
the liver, but also by the kidney and lung. The major metabolites
of nicotine are cotinine and 1-N-nicotine oxide. In the body, the
half-life of nicotine is about 2 hours while the half-life of its
major metabolite is about 18 hours. Both nicotine and its metabolites
are eliminated by the kidney. Nicotine is also excreted in the milk
of lactating women who smoke.
Pharmacologic
actions:
Nicotine activates cholinergic receptors directly, and it produces
a wide cascade of physiologic actions. Among these is the release
of neurotransmitter and hormones but especially catecholamines. The
release of epinephrine by nicotine especially from adrenal medulla,
causes an increase in free fatty acids, glycerol, and lactate concentrations
in the blood. Nicotine stimulates the release of a varieity of pituitary
hormones, including adrenocorticotropic hormone (ACTH), prolactin,
growth hormone, and vasopressin. All nicotinic effects appear to be
blocked by drugs such as mecamylamine, a non-competitive blocker that
occupies the ion channel and not the nicotinic binding site.
Lethality:
There is a long latency to disease ( several decades for cancer and
atherosclerotic disease). However, approximately 390,000 deaths/year
in the US are attributed to smoking. A lethal dose in adults is estimated
to be approximately 60 mg. A few drops of pure nicotine on the tongue
would quickly kill a healthy adult.
Tolerance
and dependence:
Tolerance is seen in both experimental animals and humans after a
single dose of nicotine. Tolerance is regarded as a clinical manifestation
of neuronal adaptation to nicotine. Nicotine receptors are upregulated
in the brains of smokers.
Withdrawal
syndromes:
Withdrawal syndromes occur upon stopping regular tobacco consumption.
In humans, the syndrome may begin within a few hours after the last
dose and may continue for several weeks. Tobacco withdrawal, although
distressing, is not life-threatening. Signs include craving for nicotine,
irritability, frustration, anxiety, depression and increase in appetite.
Reinforcing
Effects:
Nicotine fosters its own administration by both positive and negative
reinforcement. The potential for nicotine to induce pleasurable subjective
states or "euphoria" is considered positive reinforcement.
Relief of withdrawal is the most recognized negative reinforcement.
Its reinforcing actions are thought to be related to the central stimulation
of nicotinic cholinergic receptors which eventually leads to dopamine
release. Both the dopaminergic and endorphinergic systems have been
implicated in the reinforcing properties of nicotine.
Medical
use:
Gum and patches containing nicotine are used as substitutes for smoking
or chewing tobacco by addicts attempting to quit.