++
The clinical features of cocaine and amphetamine toxicity are the result of their sympathomimetic, vasoconstrictive, psychoactive, and local anesthetic properties affecting a variety of organ systems.2,3,4,9
++
Cocaine induces dysrhythmias, myocarditis, cardiomyopathy, and acute coronary syndromes.16 Other vascular complications include aortic rupture and aortic and coronary artery dissection. Even at relatively low doses, cocaine induces vasoconstriction in coronary arteries, contributing to cocaine-induced chest pain.17 Coronary vasoconstriction is exacerbated by β-adrenergic blockade and antagonized by phentolamine, which suggests mediation through stimulation of α-adrenergic receptors.18 This effect is further potentiated by cigarette smoking. In addition to promoting vasospasm, cocaine potentiates acute coronary syndrome by increasing atherogenesis through increased platelet aggregation, thrombogenesis, and accelerated atherosclerosis.
++
The patient most at risk for cocaine-associated acute coronary syndrome is a male between 20 and 40 years old, who is a cigarette smoker and who regularly uses cocaine.19,20 All routes of cocaine administration are associated with chest pain, acute coronary syndrome, ST-elevation myocardial infarction, and non–ST-elevation myocardial infarction. Atypical chest pain is common.
++
Acute coronary syndromes and aortic dissection are also reported in association with ephedrine, phenylpropanolamine, and amphetamine use.21 Mitral and aortic valve abnormalities associated with use of the amphetamine combination phentermine-fenfluramine prompted a voluntary recall of these drugs. Cardiopulmonary toxicity from other amphetamine diet aids has also been reported.
++
Dysrhythmias induced by cocaine can result from sympathomimetic stimulation, blockade of the sodium channel during depolarization, inhibition of the potassium channel during repolarization, and effects on calcium channel current.16,22 Sympathomimetic-induced dysrhythmias are tachycardias, such as sinus tachycardia, reentrant supraventricular tachycardia, and atrial fibrillation and flutter. Sodium channel blockade produces a rightward shift of the terminal portion of the QRS complex as seen on the frontal plane ECG leads, a pattern similar to that of cyclic antidepressants.23 Progressive toxicity may induce a complete right bundle-branch block or a prolonged QRS >120 ms that, when combined with sinus tachycardia, produces a wide-complex tachycardia. Cocaine can induce the ECG appearance of the Brugada pattern, although it is not clear whether this is strictly a toxic effect or if the sodium channel–blocking effect of cocaine unmasked an underlying genetic predisposition to the Brugada syndrome.24
++
Potassium channel blockade impairs repolarization, prolonging the QT interval on the ECG.23 The effects of cocaine on calcium channel current are dose dependent and complex, but at concentrations associated with clinical toxicity, prolongation of both depolarization and repolarization is seen, as well as enhanced dispersion in repolarization.22 Delayed repolarization and enhanced dispersion promote early afterpotentials that can trigger reentrant dysrhythmias, such as ventricular tachycardia and a variant, torsades de pointes.
++
Takotsubo syndrome, transient apical ballooning of the left ventricle, has been associated with cocaine use. The physiology is not clearly understood but has been attributed to the effects of a sympathomimetic surge on the myocardium after cocaine use.25
++
Neurologic syndromes associated with cocaine abuse include seizures, intracranial infarctions, and hemorrhages. Hyperadrenergic tone induces severe transient hypertension, hemorrhage, or focal vasospasm, and, sometimes, exacerbation of underlying abnormalities of cerebral blood vessels. Cerebral vasoconstriction following cocaine administration has been observed using magnetic resonance angiography.26
++
Other CNS manifestations reported after cocaine use include spinal cord infarctions, cerebral vasculitis, and intracranial abscesses. Choreoathetosis and repetitive movements (termed "crack dancing") are associated with cocaine and amphetamine intoxication and appear related to dopamine dysregulation. Acute dystonic reactions following cocaine use and withdrawal are also observed. Unilateral blindness has been reported secondary to central retinal artery occlusion, and bilateral blindness can be caused by diffuse vasospasm. A syndrome of corneal abrasions and ulcerations secondary to smoke and irritation is known as "crack eye." Keratitis caused by methamphetamine use has been described as well.
++
"Cocaine washout" is a syndrome that may occur in patients after a prolonged crack binge and results from depletion of neurotransmitters. Patients have a depressed level of consciousness but can be aroused to normal with stimulation. Resolution of lethargy can take up to 24 hours.
++
Amphetamine, phenylpropanolamine, and ephedrine use are associated with intracranial hemorrhage, infarction, encephalopathy, and seizures.4,9 Amphetamines can also cause a CNS vasculitis resulting in focal neurologic deficits. A profound paranoid psychosis can be seen with long-term amphetamine abuse and withdrawal.
++
Respiratory effects of cocaine use are more common in patients who smoke crack cocaine. Pulmonary hemorrhage, barotrauma, pneumonitis, asthma, and pulmonary edema have been observed.27 Pneumomediastinum, pneumothorax, and pneumopericardium result from barotrauma secondary to performance of the Valsalva maneuver after inhalation or nasal insufflation in an attempt to enhance drug effect. Pneumonitis, asthma, and bronchiolitis may be an immunologic phenomenon or may result from numerous adulterants in illicit preparations.
++
Inhalation of crack cocaine is associated with new-onset bronchospasm, likely the result of local airway irritation.28,29 Acute lung injury associated with cocaine use is multifactorial and may be catecholamine-mediated because a similar syndrome has been described in patients with adrenergic excess from pheochromocytoma and intracranial hemorrhage. Upper airway irritation and a "thermal" uvulitis can occur in patients smoking crack cocaine.
++
Cocaine-induced mesenteric vasospasm may produce intestinal ischemia, bowel necrosis, ischemic colitis, and splenic infarctions. In addition, GI ulceration, bleeding, and perforation occur in association with cocaine use. Advanced tooth decay (termed "meth mouth") is common in habitual methamphetamine users. The reasons are presumably multifactorial and are related to poor oral hygiene, persistent dry mouth, consumption of high-carbohydrate carbonated beverages, jaw clenching, and tooth grinding. The belief that contamination with acidic or corrosive substances from the manufacturing process is responsible for this condition is not supported by analysis of illicitly produced methamphetamine.
++
MDMA users may develop hyponatremia due to drug-induced secretion of vasopressin in the setting of overhydration with water. There is limited evidence suggesting that synthetic cathinones may cause similar effects, and they have been associated with several deaths.
++
Cocaine or amphetamine use may cause traumatic and nontraumatic rhabdomyolysis.30,31 In cocaine-induced rhabdomyolysis, up to one-third of patients develop acute kidney failure.31 Risk factors for rhabdomyolysis include altered mental status, seizures, dysrhythmias, and hemodynamic instability. Stimulants may further exacerbate renal injury by producing hyperthermia, vasoconstriction, hypotension, and hypovolemia. Renal infarction has been described following IV cocaine use.
++
Cocaine is a potent vasoconstrictor that affects uteroplacental blood flow. Cocaine abuse during pregnancy is associated with an increased incidence of spontaneous abortions, abruptio placentae, fetal prematurity, and intrauterine growth retardation.32,33 Both spontaneous abortions and abruptio placentae appear to occur from placental vasoconstriction and increased uterine contractility, with concomitant maternal hypertension. A breastfed infant can become intoxicated secondary to maternal cocaine use. Methamphetamine abuse during pregnancy has detrimental effects on fetal growth.