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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