Historical records document stimulant use since ancient times
by indigenous cultures in the region of South America, whose members
chewed Erythroxylum coca leaves. 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 for the treatment of congestion.
Therapeutic use of methamphetamine to enhance physical and intellectual
performance began in the 1930s. Currently these drugs have limited
therapeutic roles, but are widely used as drugs of abuse. All of
these substances cause their effects and toxicity by stimulation
of the sympathetic nervous system.
Cocaine and methamphetamine abuse is a major problem in the U.S.,
although accurate assessment of prevalence is limited.
The 2008 National Household Survey on Drug Abuse reported that
an estimated 5.3 million Americans had used cocaine within the past
year and 1.9 million had used cocaine within the past month.1 This
report estimates that during 2008 there are over 700,000 new cocaine
users in the U.S., averaging about 2000 new initiates per day.1 One
third of drug-related ED visits in the U.S. are related to cocaine
use.2 Fatal injuries (homicides, suicides, falls,
and overdoses) after cocaine use are a leading cause of death among
young adults in New York City, and probably in many other urban
locations as well.3 Statistics from the United
Nations show that methamphetamine is the second most commonly abused
drug worldwide, following cannabis, and is used by 0.6% of
the global population.4 In both Australia and the
U.S., methamphetamine was involved in a significant percentage of
drug-related ED visits.5–7 The incidence
of methamphetamine use is highest in the western U.S., but is increasing
in other regions.
During 2008, the American Association of Poison Control Centers
received reports of 32,476 exposures to cocaine, methamphetamine,
and related amphetamines, with 30 deaths identified.8
Cocaine is the naturally occurring alkaloidal extract of E.
coca, a plant indigenous to South America. The water-soluble
hydrochloride salt is absorbed across all mucosal surfaces, including
the 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 and
can be smoked, producing the popping sound that characterizes its
name. The onset and duration of action vary with the route of administration
181-1 Pharmacokinetics of Cocaine
| Save Table
181-1 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 peak effect occurs within
30 minutes, and the duration of effect is 1 to 2 hours. The delayed
and prolonged effect is a result of vasoconstrictive properties
that limit mucosal absorption as well as swallowing of a portion
of the insufflated cocaine, which is then absorbed from the stomach.
GI absorption is also delayed by vasoconstriction, producing a peak
effect at 90 minutes. Both the IV and the inhalational routes produce
a rapid onset of action (less than 1 min) with a duration of 30
to 60 min.
Cocaine is primarily metabolized to ecgonine methyl ester by
plasma cholinesterase. Relative deficiency of this enzyme may predispose
affected patients to life-threatening toxicity.9 Benzoylecgonine is
the other major metabolite excreted in the urine and is the compound
for which most urine toxicology screens routinely test. Cocaethylene is
a long-acting metabolite formed when cocaine is used in combination
with ethanol. Cocaethylene has been found to have vasoconstrictive
properties similar to those of cocaine and a longer half-life.
Cocaine is both a central nervous system stimulant and a local
anesthetic.10 Central effects are mediated through
activation of the sympathetic nervous system via enhanced effects
of excitatory amino acids and blockade of presynaptic reuptake of
norepinephrine, dopamine, and serotonin. The resultant excess of
neurotransmitters at postsynaptic receptor sites leads to sympathetic
activation, producing the characteristic physical findings of mydriasis,
tachycardia, hypertension, and diaphoresis, and predisposing the
user to dysrhythmias, seizures, and hyperthermia. Cocaine use produces
a euphoria associated with enhanced alertness and a general sense
of well-being. It is thought that the psychological addiction, drug
craving, and withdrawal effects are mediated by interference with
dopamine and serotonin balance in the central nervous system. Subsequent
dopamine depletion at the nerve terminals may account for the dysphoria
and depression associated with long-term abuse.
Like other local anesthetics, cocaine inhibits conduction of
nerve impulses by blocking fast sodium channels in the cell membrane.
Cocaine also has quinidine-like effects on conduction, causing QRS-complex widening
and QT-interval prolongation. Thus, in large doses, cocaine may
exert a direct toxic effect on the myocardium, resulting in negative inotropy,
wide-complex dysrhythmia, bradycardia, and hypotension.
Amphetamines comprise a broad class of structurally similar derivatives of
phenylethylamine.11 The derivative methamphetamine,
also known as “ice,” is abused by ingestion, IV
injection, inhalation, or nasal insufflation. As with cocaine, the
absorption and peak effects following methamphetamine use occur
rapidly with inhalation, nasal insufflation, and IV injection (Table 181-2). Modification of the basic amphetamine structure
produces substances with additional psychoactive properties.11 Over
50 such “designer” amphetamines have been created
(Table 181-3), ...