STIMULANTS
A variety of drugs in
distinct pharmacological and chemical classes can be considered under the broad
classification as stimulants. Xanthines and methylxan-thines constitute a weak
class of stimulants that includes caffeine, theophylline (aminophylline), and
theobromine. Caffeine is freely available in coffee, colas, and certain
over-the-counter pills. A low degree of tolerance devel-ops to some of their
effects and a mild withdrawal syn-drome is observed following immediate
cessation of their repeated use.
The primary class of
stimulants for which there is a tremendous addiction problem is the
sympathomimetic stimulants, which include cocaine, amphetamine,
metham-phetamine (Desoxyn), methylphenidate
(Ritalin), and phenmetrazine.
Sympathomimetic stimulant
drugs have very high abuse potential. They are typically used repeatedly for a
short period during which time the user escalates the dose to greater and
greater levels to attain the desired degree of euphoria. Extended uninterrupted
use of stimulants for 24 to 72 hours is often referred to as a run and usually ends in a crash (24–36 hours of sleep) once the
individ-ual is exhausted physically. Besides illicit sources of stimulants,
approximately 5 billion doses of these drugs are prescribed per year, and there
appears to be a sig-nificant degree of abuse via prescription diversion.
While some stimulants, such
as amphetamine and methylphenidate, are taken orally, others are either
volatilized for inhalation or snorted as the solid (nasal insufflation). It is necessary to convert cocaine and methamphetamine to their free base so that
they can be volatilized. Methamphetamine and cocaine are also abused via the intravenous route.
Most of the sympathomimetic
stimulants exhibit similar pharmacological properties, differing primarily in
the magnitude of their effects. Acute drug administration produces feelings of
euphoria, elation, and alertness. Intravenous injections of cocaine and
amphetamine can produce a very intense rush
of sensations that resemble sexual orgasm. At small doses cognition increases
and mood is elevated. As the dose of drug escalates during a run, the overall
activity of the individual changes from task performance to one generally
characterized by stereotypical movements. The person starts performing certain
behaviors repeatedly. Some grind or gnash their teeth. Many continuously touch
or pick at their face or extremities. At this stage the individual becomes
suspi-cious and may develop anxiety or paranoia. Acute toxic paranoid psychosis
can develop, but it usually requires a longer period of abuse than a single
acute session.
Besides stimulating the CNS,
these drugs activate the autonomic nervous system. Individuals have
tachy-cardia, hypertension, and possibly arrhythmias. Auto-nomic hyperactivity
is also expressed as hyperthermia and mydriasis. More serious effects include
the possibil-ity of myocardial infarction, cerebrovascular hemor-rhage,
seizure, and death.
In brief, the most commonly
abused of these drugs, such as cocaine, work primarily as indirect agonists of
the catecholamine neurotransmitter systems via in-hibitory actions upon the
transmitter reuptake system. Considerable evidence supports a role for dopamine
in mediating the rewarding effects of cocaine. There is also evidence that
blockade of serotonin uptake may con-tribute to cocaine’s actions.
Tolerance to stimulants develops
fairly rapidly, even in the therapeutic dose range. It is the rapid development
of tolerance that leads to the escalation of dose during drug abuse runs.
Chronic stimulant abuse
alters the personality of the abuser. These and related changes are the result
of neu-rotoxicity and are not characterized as either acute drug effects or
withdrawal signs. Individuals have delusions of being pursued or persecuted and
therefore become suspicious and paranoid. They become self-occupied and hostile
toward others. Long-term abuse can pro-duce toxic psychosis that closely
resembles schizophre-nia and must be treated with neuroleptic drugs
(haloperidol, chlorpromazine). This psychosis can de-velop even within 1 to 2
weeks if the person is on a run of very high doses of stimulants.
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