Cocaine intoxication

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Cocaine intoxication
Kokain - Cocaine.svg
Cocaine
Classification and external resources
Specialty psychiatry
ICD-10 F14.0
ICD-9-CM 305.6
MedlinePlus 000946
eMedicine article/813959
MeSH D019970

Cocaine intoxication refers to the immediate and deleterious effects of cocaine on the body. Although cocaine intoxication and cocaine dependence can be present in the same individual, these syndromes present with different symptoms.

Signs and symptoms[edit]

Cocaine increases alertness, feelings of well-being, euphoria, energy, competence, sociability, and sexuality. Common side effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding. With prolonged use, the drug can cause insomnia, anorexia, tachycardia, hallucinations, and paranoid delusions.[1] Possible lethal side effects include rapid heartbeat, abnormal heart rhythms, tremors, convulsions, markedly increased core temperature, renal failure, heart attack, stroke and heart failure.[2]

Depression with suicidal ideation may develop in heavy users.[3] Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons.[4] Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), which can eventually lead to its complete disappearance.[5]

Studies have shown that cocaine usage during pregnancy triggers premature labor[6] and may lead to abruptio placentae.[7]

Overdose[edit]

Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes tachyarrhythmias and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, respiratory failure, stroke, cerebral hemorrhage, or heart failure. Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction. Cocaine and/or associated hyperthermia may cause muscle cell destruction (rhabdomyolysis) and myoglobinuria resulting in renal failure. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the National Institute on Drug Abuse, approximately 5000 deaths occur annually in the US due to cocaine overdose.[8]

Withdrawal[edit]

Physical withdrawal is not dangerous; however, physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia or hypersomnia, anger, increased appetite and psychomotor retardation or agitation. Cocaine and its metabolites are completely eliminated from the body by 3 days.[9]

Pathophysiology[edit]

Cocaine pharmacodynamics involve multiple complex mechanisms, although its half-life is short (~ 1 hour).[9] This drug binds and blocks monoamine (dopamine, epinephrine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. Cocaine's acute effect in the central nervous system is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain). When this effect ceases due to metabolism of cocaine, depletion of associated neurotransmitters, and receptor down-regulation (tachyphylaxis), the cocaine user may experience dysphoria, or a "crash" after the initial high. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use. Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation is another deleterious effect, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation.[10] Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Similar to local anesthetics such as lidocaine, cocaine blocks sodium channels and interferes with action potential propagation.[11] This Vaughn-Williams class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.[12][13][14][15]

Management[edit]

Emergency treatment of cocaine-associated hyperthermia consists of administering a benzodiazepine sedation agent, such as diazepam (Valium) or lorazepam (Ativan) to enhance muscle relaxation and decrease sympathetic outflow from the central nervous system. Physical cooling is best accomplished with tepid water misting and cooling with a fan (convection and evaporation), which can be carried out easily in the field or hospital.[16][17] There is no specific pharmacological antidote for cocaine overdose. The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with a benzodiazepine.[18] Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A comprehensive systematic review of all pharmacological treatments of cocaine cardiovascular toxicity revealed benzodiazepines may not always reliably lower heart rate and blood pressure.[19]

Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate.[19] Nitroglycerin is useful for cocaine-induced chest pain, but the possibility of reflex tachycardia must be considered.[20] Alpha-blockers such as phentolamine have been recommended[18] and may be used to treat cocaine-induced hypertension and coronary arterial vasoconstriction, but these agents do not reduce heart rate.[19][21] Furthermore, phentolamine is rarely used, not readily available in many emergency departments, and many present-day clinicians are unfamiliar with its use and titratability. Calcium channel blockers may also be used to treat hypertension and coronary arterial vasoconstriction,[22] but fail to lower tachycardia based on all cocaine-related studies.[19] Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil are preferable, as dihydropyridine agents such as nifedipine have much higher risk of reflex tachycardia.

Agitated patients are best treated with benzodiazepines, but antipsychotics such as haloperidol and olanzapine may also be useful.[19] The alpha-2 agonist dexmedetomidine may also be useful for treatment of agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports.[19] Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachyarrhythmias in several case reports.

The use of beta-blockers for cocaine cardiovascular toxicity has been subject to a relative contraindication by many clinicians for several years despite extremely limited evidence. The phenomenon of “unopposed alpha-stimulation,” in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in cocaine-abusing patients, is controversial.[23][24] This rarely-encountered and unpredictable adverse effect has resulted in some clinicians advocating for an absolute contraindication of the use of all beta-blockers, including specific, non-specific, and mixed.[25] Many clinicians have disregarded this dogma and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia.[26][27][28][29][30] Of the 1,744 total patients identified in the aforementioned systematic review,[19] only 7 adverse events were from putative cases of “unopposed alpha-stimulation” due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1).[31][32][33][34][35] Some detractors of beta-blockers for cocaine-induced chest pain have cited minimal acute mortality and the short half-life of the drug, making it unnecessary to aggressively treat any associated tachycardia and hypertension.[25][36] However, the long-term effect of cocaine use and development of heart failure, with early mortality, high morbidity, and tremendous demand on hospital utilization should be taken under consideration.[37][38][39]

The mixed beta/alpha blocker labetalol has been shown to be safe and effective for treating concomitant cocaine-induced hypertension and tachycardia, without any “unopposed alpha-stimulation” adverse events recorded.[19][40][41] The use of labetalol is approved by a recent AHA/ACC guideline for cocaine and methamphetamine patients with unstable angina/non-STEMI.[42]

References[edit]

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