Toxicology & Substance Use · Topic 11 of 17

Cocaine & Sympathomimetic Toxicity

Toxicology · stimulants

Cocaine & Sympathomimetic Toxicity

Catecholamine excess: sedate with IV benzodiazepines, cool the hyperthermia aggressively, and avoid beta-blockers while cocaine intoxication persists.

Key numbers

IV benzodiazepines first, titratedlorazepam 2–3 mg IV

Cool aggressively: ice-water immersionT > 40 °C

01 · GiveIV benzodiazepines first, titrated

IV benzodiazepines are first-line for agitation, seizures, hypertension and tachycardia: lorazepam 2–3 mg IV (diazepam or midazolam 5 mg) every 10–20 minutes, doubling if no response; doses far above usual may be needed.

02 · AvoidNo beta-blocker in acute cocaine intoxication

Avoid beta-blockers during acute cocaine intoxication (traditional concern: unopposed alpha stimulation and coronary vasospasm); meta-analyses show no clear harm, so labetalol or carvedilol may be used selectively after stabilization.

03 · DoCool aggressively: ice-water immersion

Hyperthermia (often > 40 °C) kills: sedate and cool aggressively — ice-water immersion lowers 45 °C to < 40 °C within 30 minutes; otherwise evaporative cooling — plus IV normal saline to maintain urine flow.

Presentation

What you'll see

Agitation, tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis must knowThe sympathomimetic toxidrome (cocaine, amphetamines, methamphetamine, MDMA, cathinones) is agitation or delirium, tachycardia, hypertension, hyperthermia, mydriasis and diaphoresis, with seizures in severe cases.

Do right now

In this order

First moves

IV benzodiazepines first, titratedlorazepam 2–3 mg IV

→

Cool aggressively: ice-water immersionT > 40 °C

→

Cocaine chest pain: benzodiazepine plus nitroglycerin

Why each step

IV benzodiazepines first, titratedIV benzodiazepines are first-line for agitation, seizures, hypertension and tachycardia: lorazepam 2–3 mg IV (diazepam or midazolam 5 mg) every 10–20 minutes, doubling if no response; doses far above usual may be needed.

Cool aggressively: ice-water immersionHyperthermia (often > 40 °C) kills: sedate and cool aggressively — ice-water immersion lowers 45 °C to < 40 °C within 30 minutes; otherwise evaporative cooling — plus IV normal saline to maintain urine flow.

Cocaine chest pain: benzodiazepine plus nitroglycerinTreat cocaine-associated chest pain with benzodiazepines plus nitroglycerin and standard ACS therapy including aspirin; add phentolamine 1–5 mg IV slowly or a calcium channel blocker for persistent vasospasm or hypertension.

Management

Orders

Refractory hypertension: nitrates, nicardipine or phentolamineHypertension that persists after adequate benzodiazepines is treated with IV nitrates (nitroprusside or nitroglycerin), nicardipine, or the alpha-blocker phentolamine.

Refractory agitation: phenobarbital or propofol, intubateIf benzodiazepines fail, give phenobarbital or propofol and intubate; paralyze with a nondepolarizing agent (avoid worsening hyperkalemia) and monitor with continuous EEG, because paralysis hides seizures.

Work up chest pain as ACS or dissectionEvaluate cocaine chest pain like any possible ACS (serial ECGs, troponin, chest radiograph) and image for aortic dissection when suspected; urine benzoylecgonine confirms cocaine exposure but levels do not guide care.

Cocaine STEMI: primary PCI preferred over fibrinolysisStimulant-associated STEMI is treated by standard ACS pathways with primary PCI preferred; use fibrinolysis cautiously, because severe hypertension, seizures, trauma or aortic dissection raise bleeding risk.

Red flags & don'ts

Avoid harm

Avoid phenothiazines for sedation avoidDo not sedate stimulant toxicity with phenothiazines: they lower the seizure threshold and their anticholinergic effects impair heat loss. Avoid ketamine in amphetamine toxicity — its stimulant effects add to the toxicity.

Wide QRS from cocaine: give sodium bicarbonate complicationCocaine blocks cardiac sodium channels, widening the QRS and risking ventricular tachycardia; treat wide-complex tachycardia with IV sodium bicarbonate (lidocaine is an alternative) and avoid class Ia and Ic antiarrhythmics.

Vasoconstriction injures heart, aorta, brain and gut complicationCocaine-induced vasoconstriction causes myocardial infarction and coronary vasospasm, aortic dissection, ischemic and hemorrhagic stroke, intestinal and renal ischemia; rhabdomyolysis, kidney failure and pneumothorax or pneumomediastinum also occur.

MDMA: check sodium for hyponatremia complicationMDMA (ecstasy) raises vasopressin; with heavy water intake and sweating it causes hypo-osmolar hyponatremia with cerebral edema and seizures — check sodium; treat with fluid restriction or hypertonic saline.

More detail

Reference

Show 6 reference facts

Cocaine blocks reuptake of norepinephrine, dopamine and serotonin; amphetamines increase their release. Smoked or IV cocaine peaks in 3–5 minutes and lasts 15–20 minutes, so mild cocaine toxicity often needs no treatment.

Cocaine taken with alcohol forms cocaethylene in the liver, a stimulant metabolite with a longer duration of effect than cocaine.

When the history does not fit (persistent tachycardia and hyperthermia after a 'downer', or no clear stimulant use), broaden the work-up — head CT, lumbar puncture, infectious and metabolic tests; adulteration (eg, fentanyl) is common.

Body packers and stuffers may need gastrointestinal decontamination or surgical removal; irrigate the nares after intranasal cocaine to remove residual powder.

Chronic cocaine use causes myocardial fibrosis, left ventricular hypertrophy and cardiomyopathy, nasal septal perforation, and cognitive impairment; use in pregnancy raises the risk of spontaneous abortion and placental abruption.

For amphetamine toxicity, IM midazolam is preferred when there is no IV access (most reliable IM absorption); IV diazepam or lorazepam last longer. Clonidine or dexmedetomidine are third-line for arrhythmias.

Pearl

Benzodiazepines first: one drug class calms the agitation, the blood pressure and the heart rate before any antihypertensive is needed.

Sources · Merck Manual Professional — Cocaine (Jun 2026) · Merck Manual Professional — Amphetamines · Iliakis P, Ntalekou K, et al. Acute Coronary Syndrome and Recreational Drug Use: A Comprehensive Review. Medicina (Kaunas) 2026;62(8):1477 · Merck Manual Professional — Methylenedioxymethamphetamine (MDMA) · Lavonas EJ et al. 2023 AHA Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning. Circulation 2023;148:e149–e184 · US Pharmacist (Nov 2023) — Managing poisoning-induced cardiac arrest or life-threatening toxicity (summary of the 2023 AHA update) · Bruccoleri RE, Burns MM. A literature review of the use of sodium bicarbonate for the treatment of QRS widening. J Med Toxicol 2016;12:121–129 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).