Cocaine produces a sense of intense euphoria and mental alertness, making it one of the most addictive of all drugs. Experimental animals will press a lever more than 1000 times and will forgo food and drink to obtain the drug. In cocaine users, although physical dependence seems not to occur, the psychologic dependence is profound. Intense cravings are particularly severe in the first several months after abstinence and can recur for years.
Acute overdose produces seizures, cardiac arrhythmias, and respiratory arrest. The following are the important manifestations of cocaine toxicity:
Cardiovascular effects. The most serious physical effects of cocaine relate to its acute action on the cardiovascular system. Cocaine is a sympathomimetic agent (
Fig. 8.12 ), both in the CNS, where it blocks the reuptake of dopamine, and at adrenergic nerve endings, where it blocks the reuptake of both epinephrine and norepinephrine while stimulating the presynaptic release of norepinephrine. The net effect is the accumulation of these neurotransmitters in synapses and excessive stimulation, manifested by tachycardia, hypertension, and peripheral vasoconstriction. Cocaine also induces myocardial ischemia, the basis for which is multifactorial. It causes coronary artery vasoconstriction and promotes thrombus formation by facilitating platelet aggregation. Cigarette smoking potentiates cocaine-induced coronary vasospasm. Thus, by increasing myocardial oxygen demand by its sympathomimetic action and, at the same time, reducing coronary blood flow, cocaine often triggers myocardial ischemia, which may lead to myocardial infarction. Cocaine also can precipitate lethal arrhythmias by enhanced sympathetic activity as well as by disrupting normal ion (K+, Ca2+, Na+) transport in the myocardium. These toxic effects are not necessarily dose related, and a fatal event may occur in a first-time user with what is a typical mood-altering dose.
CNS effects. The most common CNS findings are hyperpyrexia (thought to be caused by aberrations of the dopaminergic pathways that control body temperature) and seizures.
Effects on the fetus. In pregnant women, cocaine may cause decreased blood flow to the placenta, resulting in fetal hypoxia and spontaneous abortion. Neurologic development may be impaired in the fetuses of pregnant women who are chronic drug users.
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Euphoria, paranoia, hyperthermia DopaminePresynaptic axon Postsynaptic dendrite
Fig. 8.12 Theeffectofcocaineonneurotransmission.Thedruginhibitsreuptakeoftheneurotransmittersdopamineandnorepinephrineinthecentralandperipheralnervoussystems.Hypertension, cardiac arrhythmia, myocardial infarct, cerebral hemorrhage, and infarct Norepinephrine • Chronic cocaine use. Chronic use may cause (1) perforation of the nasal septum in snorters, (2) decrease in lung diffusing capacity in users who inhale the smoke, and (3) the development of dilated cardiomyopathy.