Why is phentolamine given in stimulant overdose?

Phentolamine in Stimulant Overdose

Phentolamine is given in stimulant overdose because it is a nonselective alpha-adrenergic receptor antagonist that effectively reverses the severe hypertension and coronary artery vasoconstriction caused by excessive catecholamine stimulation from drugs like cocaine and amphetamines. 1

Mechanism of Action

• Phentolamine blocks alpha-adrenergic receptors, directly counteracting the alpha-adrenergic overstimulation that occurs with stimulant toxicity 2
• It produces immediate decreases in blood pressure through vasodilation, helping to reverse the dangerous hypertension seen in stimulant overdose 3
• Phentolamine specifically reverses cocaine-associated coronary artery vasoconstriction, as demonstrated in cardiac catheterization studies 1

Clinical Indications

• Recommended for hypertensive emergencies induced by catecholamine excess, including cocaine toxicity, amphetamine overdose, and clonidine withdrawal 1, 2
• Particularly useful in hyperadrenergic syndromes where alpha-adrenergic blockade is needed to control severe hypertension 1
• Effective for treating the alpha-adrenergic toxicity seen with phenylpropanolamine and other sympathomimetic agents 4, 5

Dosing in Stimulant Overdose

• For adults: 5 mg IV bolus, which can be repeated every 10 minutes as needed to lower blood pressure to target 1, 2
• For pediatric patients: 0.1-0.2 mg/kg up to a maximum of 10 mg 2
• Continuous hemodynamic monitoring is essential during administration due to risk of hypotension 2

Evidence of Efficacy

• Cardiac catheterization studies show that phentolamine returns coronary arterial diameter to baseline after cocaine-induced narrowing 1
• In a rat model of phenylpropanolamine poisoning (a sympathomimetic stimulant), phentolamine pretreatment significantly reduced mortality (14% vs 71% in controls) and prevented myocardial injury 5
• Case reports demonstrate successful treatment of amphetamine toxicity with phentolamine, including in cases presenting with posterior reversible encephalopathy syndrome 6

Treatment Algorithm for Stimulant Overdose

1. First-line: Begin with benzodiazepines to reduce central nervous system stimulation and agitation 1
2. If hypertension persists despite benzodiazepines:
   • Add phentolamine 5 mg IV bolus, repeating every 10 minutes as needed 1, 2
   • Alternative agents include nicardipine or nitroprusside 1
3. For coronary ischemia: Add nitroglycerin and aspirin in addition to benzodiazepines 1
4. Avoid beta-blockers (including labetalol) as they may worsen coronary vasoconstriction by leaving alpha effects unopposed 1

Cautions and Contraindications

• Monitor for hypotension, which can occur rapidly after administration 2, 3
• Use with caution in patients with coronary artery disease as rapid blood pressure reduction may precipitate myocardial ischemia 2
• Reflex tachycardia may occur due to the vasodilatory effects 2, 7

Comparison with Other Agents

• Unlike beta-blockers, phentolamine does not worsen coronary vasoconstriction in cocaine toxicity 1
• Nitroglycerin and benzodiazepines are also effective for cocaine-induced hypertension and chest pain, but phentolamine specifically addresses the alpha-adrenergic component 1
• Calcium channel blockers have shown variable results in cocaine toxicity and should not be used as first-line treatment 1