What is the most appropriate medication to treat hypertension in a patient with a cocaine overdose, presenting with tachycardia, anxiety, diaphoresis, headache, confusion, and severe hypertension?

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Phentolamine is the Most Appropriate Medication

For cocaine-induced hypertensive emergency with severe hypertension (230/120), phentolamine is the most appropriate choice among the options provided, as it is an alpha-blocker specifically indicated for hypertensive emergencies caused by catecholamine excess. 1

Why Phentolamine (Option D)

  • Phentolamine directly reverses cocaine-induced coronary artery vasospasm and hypertension through alpha-adrenergic blockade, addressing the underlying mechanism of cocaine toxicity 2, 1

  • The American Heart Association guidelines specifically identify phentolamine as a reasonable agent for severe cocaine-associated cardiovascular toxicity 2

  • Initial dosing is 5 mg IV bolus, with additional boluses every 10 minutes as needed to achieve blood pressure control 1

  • Phentolamine demonstrated reversal of cocaine-induced coronary artery vasospasm in the cardiac catheterization laboratory 2

Why NOT the Other Options

Esmolol (Option B) - Contraindicated

  • Pure beta-blockers like esmolol are contraindicated in cocaine toxicity due to the risk of unopposed alpha-adrenergic stimulation, which can paradoxically worsen hypertension and coronary vasospasm 2, 1, 3

  • A retrospective case series of 7 patients with cocaine toxicity treated with esmolol showed no consistent improvement in hypertension or tachycardia, and 3 of 7 patients developed adverse effects including worsening hypertension 2

  • Historical case reports document propranolol-induced hypertensive crisis in cocaine intoxication, with blood pressure increases requiring nitroprusside rescue 3

  • The American College of Cardiology explicitly recommends avoiding pure beta-blockers in cocaine toxicity 1

Isoproterenol (Option A) - Worsens Toxicity

  • Isoproterenol is a beta-agonist that would exacerbate cocaine's sympathomimetic effects, worsening tachycardia and hypertension 4

  • This represents the opposite of appropriate treatment for cocaine overdose

N-Acetylcysteine (Option C) - No Role

  • N-acetylcysteine has no established role in treating cocaine-induced hypertension or cardiovascular toxicity 2, 1, 5

  • This medication is used for acetaminophen overdose and as a mucolytic, not for sympathomimetic toxicity

Optimal Treatment Algorithm

First-Line: Benzodiazepines

  • Before or concurrent with phentolamine, administer benzodiazepines (lorazepam 2-4 mg IV or diazepam 5-10 mg IV) to reduce central nervous system stimulation and sympathetic drive 1

  • Benzodiazepines address agitation, anxiety, and the underlying catecholamine surge, and may partially control hypertension 2, 1

Second-Line: Add Vasodilator

  • If severe hypertension persists after benzodiazepines, add phentolamine as described above 1

  • Alternative vasodilators include calcium channel blockers (nicardipine, clevidipine) or nitroglycerin, though these are not among the answer choices 1, 5

Additional Considerations

  • Monitor for wide-complex tachycardia, which may require sodium bicarbonate due to cocaine's sodium channel blocking effects 1

  • Assess for hyperthermia, which requires rapid cooling as it can be life-threatening 1

  • Establish continuous cardiac monitoring and IV access for all cocaine overdose patients 1

Critical Pitfall to Avoid

The most dangerous error would be selecting esmolol (Option B), as pure beta-blockade in cocaine toxicity can precipitate severe hypertensive crisis through unopposed alpha-adrenergic vasoconstriction. 2, 1, 3, 6 This phenomenon has been documented in multiple case reports and is consistently cited as a contraindication in current guidelines. Even mixed beta/alpha blockers like labetalol should only be used after alpha blockade is established, as labetalol's beta-blocking effects are more potent than its alpha-blocking properties 2, 7

References

Guideline

Initial Treatment for Cocaine-Induced Hypertensive Emergency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treatment of cocaine cardiovascular toxicity: a systematic review.

Clinical toxicology (Philadelphia, Pa.), 2016

Research

β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon.

Journal of cardiovascular pharmacology and therapeutics, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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