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Amphetamines and cocaine are widely abused for their euphorigenic and stimulant properties. Both drugs may be smoked, snorted, ingested, or injected. Amphetamines and cocaine produce central nervous system stimulation and a generalized increase in central and peripheral sympathetic activity. The toxic dose of each drug is highly variable and depends on the route of administration and individual tolerance. The onset of effects is most rapid after intravenous injection or smoking. Amphetamine derivatives and related drugs include methamphetamine (“crystal meth,” “crank”), MDMA (“Ecstasy”), ephedrine (“herbal ecstasy”), and methcathinone (“cat” or “khat”). Methcathinone derivatives and related synthetic chemicals such as methylenedioxypyrovalerone (MDPV) have become popular drugs of abuse and are often sold as purported “bath salts.” Amphetamine-like reactions have also been reported after use of synthetic cannabinoids (eg, “Spice” and “K2”). Nonprescription medications and nutritional supplements may contain stimulant or sympathomimetic drugs such as ephedrine, yohimbine, or caffeine (see also Theophylline & Caffeine section).


Presenting symptoms may include anxiety, tremulousness, tachycardia, hypertension, diaphoresis, dilated pupils, agitation, muscular hyperactivity, and psychosis. Muscle hyperactivity may lead to metabolic acidosis and rhabdomyolysis. In severe intoxication, seizures and hyperthermia may occur. Sustained or severe hypertension may result in intracranial hemorrhage, aortic dissection, or myocardial infarction; chronic use may cause cardiomyopathy. Ischemic colitis has been reported. Hyponatremia has been reported after MDMA use; the mechanism is not known but may involve excessive water intake, syndrome of inappropriate antidiuretic hormone (SIADH), or both.

The diagnosis is supported by finding amphetamines or the cocaine metabolite benzoylecgonine in the urine. Note that many drugs can give false-positive results on the immunoassay for amphetamines, and most synthetic stimulants do not react with the immunoassay, giving false-negative results.


A. Emergency and Supportive Measures

Maintain a patent airway and assist ventilation, if necessary. Treat seizures as described at the beginning of this chapter. Rapidly lower the body temperature in patients who are hyperthermic (temperature higher than 39–40°C). Give intravenous fluids to prevent myoglobinuric kidney injury in patients who have rhabdomyolysis.

B. Specific Treatment

Treat agitation, psychosis, or seizures with a benzodiazepine such as diazepam, 5–10 mg, or lorazepam, 2–3 mg intravenously. Add phenobarbital 15 mg/kg intravenously for persistent seizures. Treat hypertension with a vasodilator drug such as phentolamine (1–5 mg intravenously) or nitroprusside, or a combined alpha- and beta-adrenergic blocker such as labetalol (10–20 mg intravenously). Do not administer a pure beta-blocker such as propranolol alone, as this may result in paradoxical worsening of the hypertension as a result of unopposed alpha-adrenergic effects.

Treat tachycardia or tachyarrhythmias with a short-acting beta-blocker such as esmolol (25–100 mcg/kg/min by intravenous infusion). Treat hyperthermia as described above. Treat hyponatremia as outlined in Chapter 21.

Luethi  D  et al. Designer drugs: mechanism of action and adverse effects. Arch Toxicol. 2020;94:1085.
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