Discussion: Cocaine has been used for thousands of years. Knowledge of its mind-altering function dates to at least 2000 BC. For centuries, indigenous mineworkers in Andean countries have used cocaine derived from the chewing of coca leaves as an endurance-enhancement agent. Spanish physicians reported the first European use of coca for medicinal purposes in 1596. Cocaine was not isolated from coca leaves until 1859.
Crack, which is generally sold in the form of "rocks," may also be sold in large pieces called slabs. These are approximately the size and shape of a stick of chewing gum and are sometimes scored to form smaller pieces.
The chemical name for cocaine is benzoylmethylecgonine. It is derived from the leaves of Erythroxylon coca, a shrub indigenous to Peru, Bolivia, Mexico, the West Indies, and Indonesia. Cocaine is a bitter crystalline alkaloid with the molecular formula of C17H21NO4. Ecgonine, an important part of the cocaine molecule, is an ester-type local anesthetic that belongs to the tropane family, which also includes atropine and scopolamine.
The primary effect of cocaine is blockade of norepinephrine reuptake; its secondary effect is marked release of norepinephrine. Cocaine also causes moderate release and reuptake blockade of serotonin and dopamine. Its marked local anesthetic effects are caused by blocking the sodium channels, which inhibits the conduction of nerve impulses, decreasing the resting membrane potential and the amplitude of the action potential while simultaneously prolonging the duration of the action potential.
Cocaine also blocks potassium channels. In some cellular membranes, it may block sodium-calcium exchange. The drug is fat soluble and freely crosses the blood-brain barrier. Cocaine appears to stimulate the CNS, with particular activity in the limbic system. There, it potentiates dopaminergic transmission in the ventral basal nuclei, producing the pleasurable behavioral effects that result in its widespread use.
Cocaine enters the United States in the form of a hydrochloride salt, having undergone numerous steps in refinement from the original coca leaf. In its hydrochloride form, cocaine may be absorbed topically across all mucosal membranes, including the oral, nasal (insufflation or snorting), GI, rectal, urethral, and vaginal membranes. It may also be injected intravenously (IV) or ingested. Ingested cocaine is poorly absorbed from the stomach (because it is a weak base with a pKa of 8.6), but it is readily absorbed from the duodenum.
Crack is produced when the hydrochloride molecule is commonly removed by ether extraction, which frees the basic cocaine molecule, the so-called freebase. Heating does not destroy freebase, rather it melts at 98°C and vaporizes at higher temperatures; these are physical properties that allow it to be smoked. Crack is lipid soluble and therefore rapidly absorbed in the pulmonary capillaries.
All of the cocaine injected IV is delivered to the circulatory system versus 20-30% of cocaine that is ingested or inhaled. Crack cocaine has a lower absorption rate compared to the hydrochloride salt form.
Approximately 30-50% of cocaine is metabolized by hepatic esterases and plasma pseudocholinesterase, resulting in the formation of ecgonine methyl ester. Spontaneous nonenzymatic hydrolysis of another 30-40% results in benzoylecgonine. Both products are water-soluble, metabolically active, and capable of increasing BP. Benzoylecgonine, which has a half-life of 7.5 hours, can induce seizures, perhaps even hours to days after the last use. Most of the remaining amount of cocaine is metabolized by hepatic N-demethylation into norcocaine, which is metabolically active.
The literature reflects tremendous variability in the reported lethal dose of cocaine in adults. The range is as little as 20 mg IV to a mean of 500 mg ingested orally to 1.4 g.
Most acute cocaine-related nontraumatic deaths are the result of tachydysrhythmias. Other causes of sudden death associated with cocaine use include stroke, subarachnoid hemorrhage, hyperthermia, and the consequences of agitated delirium. MI can result from acute vasospasm, dysrhythmias, or chronic accelerated atherogenic disease.
Cocaine acts as a CNS stimulant by inhibiting presynaptic reuptake of norepinephrine, dopamine, and serotonin. It also causes release of epinephrine by the adrenal glands. The intensity and duration of the stimulant effects of cocaine are mediated by the rate at which blood levels of cocaine rise (a function of the route of administration, see Table 1) and the peak of blood levels. Cocaine-induced seizure is a severe manifestation of toxicity. The frequency of seizures ranges from 1-29%.
Agitated delirium, also known as excited delirium, is a common presentation in patients dying from cocaine toxicity. Patients with excited delirium have an immediate onset of bizarre and violent behavior, which included aggression, combativeness, hyperactivity, hyperthermia, extreme paranoia, unexpected strength, and/or incoherent shouting. This is usually followed by cardiorespiratory arrest.
Other signs and symptoms include hyperthermia. |
14 MONTH OLD WITH SUSPECTED COCAINE INGESTION
