What cardiac toxicities are associated with stimulant drugs of abuse such as cocaine, methamphetamine, amphetamine‑type drugs, and MDMA, and how should acute management be approached?

Cardiac Effects of Stimulant Drugs of Abuse

Overview of Cardiovascular Toxicity

Stimulant drugs of abuse—including cocaine, methamphetamine, amphetamines, and MDMA—cause significant cardiac toxicity through sympathomimetic effects, direct myocardial damage, and ion channel blockade, requiring specific management strategies that differ from standard cardiac care. 1, 2

Acute Cardiovascular Effects

Cocaine and Methamphetamine:

• Tachycardia and hypertension result from catecholamine reuptake inhibition causing β-adrenergic and α-adrenergic receptor stimulation 1, 2
• Coronary vasospasm occurs through direct vasoconstrictor effects, precipitating myocardial ischemia even in patients without obstructive coronary artery disease 1
• Acute coronary syndrome (ACS) develops from increased myocardial oxygen demand, decreased supply via vasoconstriction, enhanced platelet aggregation, and endothelial dysfunction 1
• Arrhythmias including wide-complex tachycardia, QRS prolongation, QT prolongation, ventricular tachycardia, and asystolic cardiac arrest occur due to sodium and potassium channel blockade 1, 2, 3

Amphetamines:

• Cardiovascular manifestations include arrhythmias, hypertension or hypotension, and circulatory collapse 4, 5
• Up to 70% of methamphetamine users demonstrate ECG abnormalities, most commonly tachycardia 1

MDMA (Ecstasy):

• Associated with myocardial hypertrophy similar to other stimulants, increasing risk for sudden death and heart failure 6

Chronic Cardiovascular Complications

Long-term stimulant use causes:

• Dilated cardiomyopathy and progressive myocyte damage 1, 7, 8
• Accelerated atherosclerosis 1
• Myocarditis and necrotizing vasculitis (particularly methamphetamine) 1, 7
• Pulmonary hypertension 1, 7
• Myocardial hypertrophy with increased risk of sudden cardiac death 6

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Acute Management Approach

Initial Stabilization for Acute Intoxication

For patients with acute cocaine or methamphetamine intoxication presenting with hypertension, tachycardia, or chest pain:

1. Benzodiazepines are the first-line treatment for acute cocaine intoxication, addressing both central and peripheral manifestations of sympathomimetic toxicity 1, 9

   • Lorazepam or diazepam effectively manage hypertension, tachycardia, and agitation 1
   • Enhance GABA(A) receptor function inhibited by cocaine 9

2. Nitroglycerin (alone or combined with benzodiazepines) for hypertension and chest pain 1

3. Additional vasodilators for severe hypertension or coronary vasospasm:

   • Calcium channel blockers 1
   • Phentolamine (α1-adrenergic antagonist) 1
   • Morphine for chest discomfort 1

Critical Management Pitfall: Beta-Blocker Avoidance

Intravenous beta-blockers MUST be avoided in patients with signs of acute cocaine intoxication (euphoria, tachycardia, hypertension) because cocaine stimulates both α- and β-adrenergic receptors; beta-blockade results in unopposed α-stimulation causing worsening coronary vasospasm 1

• Beta-blockers may be safe in patients with recent cocaine use but WITHOUT acute intoxication signs 1

Management of Life-Threatening Complications

Wide-Complex Tachycardia or Cardiac Arrest:

• Sodium bicarbonate (1 mEq/kg IV bolus, 8.4% solution) is reasonable for wide-complex tachycardia or cardiac arrest from cocaine poisoning, repeated until hemodynamic stability and QRS <120 ms 1
• Lidocaine is reasonable for wide-complex tachycardia through competitive sodium channel binding 1
• Standard ACLS protocols should be followed for cardiac arrest 1

Hyperthermia:

• Rapid external cooling is recommended for life-threatening hyperthermia using evaporative or immersive cooling (superior to cooling blankets or cold packs) 1
• Hyperthermia is rapidly life-threatening and associated with increased mortality 1, 2

Coronary Vasospasm/ACS:

• Vasodilators (nitrates, phentolamine, calcium channel blockers) are reasonable for cocaine-induced coronary vasospasm or hypertensive emergencies 1
• Otherwise, treat ACS in cocaine users the same as non-users, except avoid beta-blockers during acute intoxication 1

Amphetamine/Methamphetamine-Specific Considerations

Treatment parallels cocaine management due to similar pathophysiological effects 1:

• Benzodiazepines for sympathomimetic symptoms
• Vasodilators for hypertension and chest pain
• Avoid beta-blockers during acute intoxication

Severe overdose management (per FDA labeling):

• Gastric lavage and activated charcoal if recent ingestion 4
• Sedation for central stimulation 4, 5
• Intravenous phentolamine for severe hypertension 4
• Chlorpromazine antagonizes central stimulant effects 4
• Avoid urinary acidification if rhabdomyolysis/myoglobinuria present due to acute renal failure risk 4

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Diagnostic Considerations

Consider stimulant use in:

• Young patients presenting with chest pain or ACS without traditional risk factors 1, 8
• Patients with unexplained tachycardia, hypertension, or arrhythmias 1, 2
• Frequency of ACS is <10% among cocaine/methamphetamine users, and death is rare 1

Urine drug screening:

• Typically positive 1-4 hours after use, remaining positive 2-4 days 1

ECG findings:

• QRS prolongation, QT prolongation, wide-complex tachycardia, Brugada pattern 1, 2
• ST-elevation may indicate vasospastic angina 1

Cardiac MRI should be considered in symptomatic cocaine users to assess extent and evolution of myocardial injury, with repeat imaging at 4-8 months to evaluate response to abstinence and therapy 8

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Long-Term Management Considerations

For chronic users with cardiomyopathy:

• Standard heart failure management applies 7, 8
• Cardiac MRI provides prognostic information and identifies silent myocardial damage 8
• Use of implantable cardioverter-defibrillators in drug abusers with chronic systolic heart failure is sensitive and controversial 3
• Multidisciplinary approach including substance abuse treatment is essential 10

Risk factor modification:

• Smoking cessation (cocaine use with tobacco intensifies cardiovascular effects) 2
• Abstinence from stimulants 8
• Treatment of hypertension and other cardiovascular risk factors 10