DRUG ABUSE Psychostimulants: The Anphetamines and Cocaine

The psychostimulants is a group of drugs with differing structures and common actions such as increased motor activity and lessening of sleep necessity. These drugs decrease fatigue, induce euphoria and have sympathomimetic effects (they increase sympathetic nervous system actions). The psychostimulants includes drugs of the amphetamine group and cocaine.

Amphetamines

The most common group of psychostimulant drugs, it includes dextroamphetamine (or, symply, amphetamine) methamphetamine, and phenmetrazine. Methylenodioxyamphetamine (MDA) and methylenodioxymethamphetamine (MDMA – "ecstasy") have been introduced more recently. The effect of these last mentioned drugs are more amphetamine-like than hallucinogenic.

Amphetamine derivates can act in different ways, but they probably exert their actions by increasing neurotransmitters release.

Amphetamine-like drugs are classified as indirect action agonists of noradrenergic, dopaminergic, and serotonergic synapses. These actions result from the inhibition both of neurotransmitters reuptake and of the enzyme monoamine oxidase (MAO).

Amphetamine is an indirect action agonist of amines, specially of noradrenaline and dopamine:

• It is a competitive inhibitor of noradrenaline and dopamine transport; in high doses it inhibits also serotonine reuptake.
• It causes dopamine and noradrenaline release that does not depend on calcium (it induces neurotransmitter release, independently of nerve terminals depolarization).
• It competitively inhibits MAO.

Amphetamine-like drugs display a typical abstinence pattern, characterized by signs and symptoms that are just the opposite of those drug induced-phenomena. Deprived of the drug, pushers become sleepy, voraciously hungry, exhaust, and sometimes, psychically depressed. Tolerance quickly sets in, and drug abusers can take doses bigger than those used to induce anorexia.

Cocaine

Cocaine is an alkaloid extracted from a shrub belonging to the Erythroxylon genus, grown in Andean and Amazonian regions.

Cocaine dependence stem from its psychostimulating properties and its local anesthetic action. Dopamine is thought to be important in the brain reward system and its increase can answer for the great dependence potential of cocaine.

Cocaine chloride can be administered in many different ways. It can be inhaled and thus absorbed by nasal mucosa. Cocaine causes constriction of nasal arterioles leading to a vascular reduction that limits its absorption, Chronic use frequently brings about nasal septum necrosis and perforation, due to sustained vasoconstriction.

Intravenously injected cocaine induces an extremely quick, intense, and short-lived effect. More recently, its use via lungs became increasingly popular. The drug is then smoked in cigars or pipe-like devices. The drug form then used is crack,  a free-base prepaired by alkalinizing cocaine chloride and employing non-polar solvents to extract it. Although part of the alkaloid is destroyed by heat, cocaine is quickly taken up by the lungs, reaching peak blood levels in just a few minutes, comparable to venous administration although for a reduced time. Intravenous injection is seldom used because of the possible intoxication caused by the excessive dose. Most of the cardiovascular alterations and arrhytmias are caused by intravenously injected cocaine.

Ample varations can be found on the potence and purity of illegally supplied cocaine.

Cocaine plasmatic half-life is short. Thus the effects of an isolated dose lasts only one hour or even a little less than that. Consequently the euphoria experiencing can be repeated several times during the course of one day or one night.

In normal doses cocaine increases dopamine and noradrenaline but only in higher doses does it increase serotonin. This increase happens because cocaine blocks the reuptake of these 3 neurotransmitters. Although this mechanism of action is generally agreed upon, discordances still exist about the competititive or non-competitive action.

Cocaine capability to induce mood alterations are dependent on the amount of dopamine and noradrenaline that are released in the brain.

The psychostimulant effect varies in intensity, from moderate to toxic, according to dose-increasing.

Tolerance sets for many of the described effects and the appetite suppressant effect comes up in a few weeks.

When cocaine is ingested together with alcohol, a conjugated cocetylene metabolite is formed. It has psychoactive properties and a half-life longer than that of both cocaine and alcohol, separately ingested. The accumulation of this metabolite quickly leads to intoxication.

Cardiovascular effects of cocaine are complex and dose-dependent. Noradrenaline increase makes total peripheral resistance greater, elevating arterial blood presure. This vasoconstriction decreases skin heat loss, thus contributing to hyperthermia. Local anesthetic effects interfere with myocardial conduction, leading to cardiac arrhytmias and convulsions.

Paranoid psychoses and bacterial endocarditis, due to contaminated syringes, are complications of the chronic use of cocaine.

Intoxications due to excessive doses of cocaine are commonly fatal, with arrhytmias, respiratory depression, and convulsions.

(Click here to see animations on cocaine effects)