Cocaine is a stimulant and local anesthetic with potent vasoconstrictor properties. The leaves of the coca plant (Erythroxylon coca ) contain 0.5 to 1% cocaine. The drug produces physiologic and behavioral effects when administered orally, intranasally, intravenously, or via inhalation following pyrolysis (smoking). Cocaine increases synaptic concentrations of the monamine neurotransmitters dopamine, norepinephrine, and serotonin by binding to transporter proteins in presynaptic neurons and blocking reuptake. The reinforcing effects of cocaine appear to be related to effects on dopaminergic neurons in the mesolimbic system.

Prevalence of Use
Cocaine is widely available throughout the United States, and cocaine abuse occurs in virtually all social and economic strata of society. The prevalence of cocaine abuse in the general population has been accompanied by an increase in cocaine abuse by heroin-dependent persons, including those in methadone maintenance programs. Intravenous cocaine is often used concurrently with intravenous heroin. This combination purportedly attenuates the postcocaine “crash” and substitutes a cocaine “high” for the heroin “high” blocked by methadone.

Acute and Chronic Intoxication
There has been an increase in both intravenous administration and inhalation of pyrolyzed cocaine via smoking. Following intranasal administration, changes in mood and sensation are perceived within 3 to 5 min, and peak effects occur at l0 to 20 min. The effects rarely last more than 1 h. Inhalation of pyrolyzed materials includes inhaling crack/cocaine or smoking coca paste, a product made by extracting cocaine preparations with flammable solvents, and cocaine free-base smoking. Free-base cocaine, including the free base prepared with sodium bicarbonate (crack), has become increasingly popular because of the relative high potency of the compound and its rapid onset of action (8 to 10 s following smoking).

Cocaine produces a brief, dose-related stimulation and enhancement of mood and an increase in cardiac rate and blood pressure. Body temperature usually increases following cocaine administration, and high doses of cocaine may induce lethal pyrexia or hypertension. Because cocaine inhibits reuptake of catecholamines at adrenergic nerve endings, the drug potentiates sympathetic nervous system activity. Cocaine has a short plasma half-life of 45 to 60 min. Cocaine is metabolized by plasma esterases, and cocaine metabolites are excreted in urine. The very short duration of the euphorigenic effects of cocaine observed in chronic abusers is probably due to both acute and chronic tolerance. Frequent self-administration of the drug (two to three times per hour) is often reported by chronic cocaine abusers. Alcohol is used to modulate both the cocaine high and the dysphoria associated with the abrupt disappearance of cocaine’s effects. A metabolite of cocaine, cocaethylene, has been detected in blood and urine of persons who concurrently abuse alcohol and cocaine. Cocaethylene induces changes in cardiovascular function similar to those of cocaine alone, and the pathophysiologic consequences of alcohol abuse plus cocaine abuse may be additive when both are used together.

Cocaine and Other Commonly Abused Drugs

The prevalent assumption that cocaine inhalation or intravenous administration is relatively safe is contradicted by reports of death from respiratory depression, cardiac arrhythmias, and convulsions associated with cocaine use. In addition to generalized seizures, neurologic complications may include headache, ischemic or Hemorrhagic stroke, or subarachnoid hemorrhage. Disorders of cerebral blood flow and perfusion in cocaine-dependent persons have been detected with magnetic resonance spectroscopy (MRS) studies. Severe pulmonary disease may develop in individuals who inhale crack cocaine; this effect is attributed both to the direct effects of cocaine and to residual contaminants in the smoked material. Hepatic necrosis has been reported to occur following crack cocaine use.

Although men and women who abuse cocaine may report that the drug enhances libidinal drive, chronic cocaine use causes significant loss of libido and adversely affects reproductive function. Impotence and gynecomastia have been observed in male cocaine abusers, and these abnormalities often persist for long periods following cessation of drug use. Women who abuse cocaine have reported major derangements in menstrual cycle function including galactorrhea, amenorrhea, and infertility. Chronic cocaine abuse may cause persistent hyperprolactinemia as a consequence of disordered dopaminergic inhibition of prolactin secretion by the anterior pituitary. Cocaine abuse by pregnant women, particularly the smoking of crack, has been associated with both an increased risk of congenital malformations in the fetus and perinatal cardiovascular and cerebrovascular disease in the mother. However, cocaine abuse per se is probably not the sole cause of these perinatal disorders, since many problems associated with maternal cocaine abuse, including poor nutrition and health care status as well as polydrug abuse, also contribute to risk for perinatal disease.

Protracted cocaine abuse may cause paranoid ideation and visual and auditory hallucinations, a state that resembles alcoholic hallucinosis. Psychological dependence on cocaine, indicated by inability to abstain from frequent compulsive use, has also been reported. Although the occurrence of withdrawal syndromes involving psychomotor agitation and autonomic hyperactivity remains controversial, severe depression (“crashing”) following cocaine intoxication may accompany drug withdrawal.

Treatment of cocaine overdose is a medical emergency that is usually best managed in an intensive care unit. Cocaine toxicity produces a hyperadrenergic state characterized by hypertension, tachycardia, tonic-clonic seizures, dyspnea, and ventricular arrhythmias. Intravenous diazepam in doses up to 0.5 mg/kg administered over an 8-h period has been shown to be effective for control of seizures. Ventricular arrhythmias have been managed successfully by administration of 0.5 to 1.0 mg of propranolol intravenously. Since many instances of cocaine-related mortality have been associated with concurrent use of other illicit drugs (particularly heroin), the physician must be prepared to institute effective emergency treatment for multiple drug toxicities.

Treatment of chronic cocaine abuse requires combined efforts of primary care physicians, psychiatrists, and psychosocial care providers. Early abstinence from cocaine use is often complicated by symptoms of depression and guilt, insomnia, and anorexia, which may be as severe as those observed in major affective disorders. Individual and group psychotherapy, family therapy, and peer group assistance programs are often useful for inducing prolonged remission from drug use. A number of medications used for the treatment of various medical and psychiatric disorders have been administered to reduce the duration and severity of cocaine abuse and dependence. However, no available medication is both safe and highly effective for either cocaine detoxification or maintenance of abstinence. Some psychotherapeutic interventions may be effective; however, no specific form of psychotherapy or behavioral modification is uniquely beneficial.

Provided by ArmMed Media
Revision date: July 5, 2011
Last revised: by Sebastian Scheller, MD, ScD