Historical records of indigenous cultures in South America describe early stimulant use by chewing leaves of the Erythroxylum coca plant, a practice that continues today. Cocaine was first used therapeutically in 1884 for ophthalmologic procedures. Amphetamines were first synthesized in 1887, and in 1932 they were first marketed medicinally in an inhaler form as a bronchodilator. Use of methamphetamine to enhance physical and intellectual performance began in the 1930s. These drugs have limited therapeutic roles but are widely used as drugs of abuse. Clinical effects and toxicity are due to sympathetic nervous system stimulation.
Cocaine is the naturally occurring alkaloid found in E. coca, a plant indigenous to South America. The water-soluble hydrochloride salt is absorbed across all mucosal surfaces, including oral, nasal, GI, and vaginal epithelium; thus, cocaine can be topically applied, swallowed, or injected IV. The hydrochloride (salt) form is most often insufflated (snorted) or injected IV. The freebase form of cocaine can be prepared in several ways. A common method uses an alkali, such as sodium bicarbonate, to produce "crack cocaine," a freebase form that is stable to pyrolysis that, when smoked, produces the popping sound that characterizes its name. The onset and duration of action vary with the route of administration (Table 187-1).
TABLE 187-1Pharmacokinetics of Cocaine ||Download (.pdf) TABLE 187-1 Pharmacokinetics of Cocaine
|Route of Exposure ||Onset of Action ||Peak Action ||Duration of Action |
|IV ||<1 min ||3–5 min ||30–60 min |
|Nasal insufflation (snorting) ||1–5 min ||20–30 min ||60–120 min |
|Inhalation (smoking) ||<1 min ||3–5 min ||30–60 min |
|GI ||30–60 min ||60–90 min ||Unknown |
When cocaine is insufflated nasally, the delayed and prolonged effect is a result of vasoconstrictive properties that limit mucosal absorption as well as the swallowing of a portion of the insufflated cocaine, which is then absorbed from the stomach. GI absorption is also delayed by vasoconstriction, producing delayed peak effect.
Cocaine is primarily metabolized to ecgonine methyl ester by plasma cholinesterase. Relative deficiency of this enzyme may predispose affected patients to life-threatening toxicity.1 Benzoylecgonine is the other major metabolite excreted in the urine and is the target compound detected in routine urine toxicology screens. Cocaethylene is a long-acting metabolite formed when cocaine is used in combination with ethanol. Cocaethylene has vasoconstrictive properties similar to those of cocaine.
Cocaine is both a CNS stimulant and a local anesthetic.2,3 Central effects are mediated by enhancement of excitatory amino acids and blockade of presynaptic reuptake of norepinephrine, dopamine, and serotonin. The excess of neurotransmitters at postsynaptic receptor sites leads to sympathetic activation, producing the characteristic ...