What is the best antihypertensive medication for a patient with hypertension and cocaine abuse?

Best Antihypertensive for Cocaine-Induced Hypertension

Benzodiazepines (diazepam or lorazepam) are the first-line treatment for cocaine-induced hypertension, followed by nitroglycerin if blood pressure remains elevated, with calcium channel blockers as third-line agents; beta-blockers should be avoided due to risk of unopposed alpha-stimulation and paradoxical worsening of hypertension. 1, 2

First-Line: Benzodiazepines

• Start with benzodiazepines (lorazepam 2-4 mg IV or diazepam 5-10 mg IV) as initial therapy for all patients with cocaine-induced hypertension, as they reduce both central sympathetic outflow and peripheral manifestations of cocaine intoxication 1, 2
• Benzodiazepines address the underlying pathophysiology by reducing catecholamine reuptake inhibition and psychomotor agitation that drives the hypertensive response 2
• The 2023 American Heart Association guidelines explicitly recommend benzodiazepines as the mainstay of initial blood pressure management in acute cocaine poisoning 2

Second-Line: Nitroglycerin

• Add nitroglycerin (sublingual or IV infusion starting at 5-10 mcg/min) if hypertension persists after benzodiazepines 1, 2
• Nitroglycerin reverses cocaine-associated coronary vasoconstriction and has been shown to effectively reduce both hypertension and tachycardia when combined with benzodiazepines 1, 2
• This combination is particularly effective because it addresses both the sympathetic overdrive (benzodiazepines) and direct vasoconstrictive effects (nitroglycerin) of cocaine 1

Third-Line: Calcium Channel Blockers

• Consider calcium channel blockers (verapamil, diltiazem 20 mg IV, or nicardipine/clevidipine infusion) if hypertension remains uncontrolled after benzodiazepines and nitroglycerin 1, 2
• Both verapamil and diltiazem have been shown to reverse cocaine-induced hypertension, coronary arterial vasoconstriction, and tachycardia 2
• The 2023 AHA guidelines give a Class 2a recommendation (reasonable to administer) for vasodilators including calcium channel blockers in cocaine-induced hypertensive emergencies 2

Alternative Agent: Phentolamine

• Phentolamine (alpha-1 blocker, 5-10 mg IV bolus) may be used for persistent hypertension by reversing cocaine-induced coronary artery vasoconstriction through alpha-adrenergic antagonism 1, 2
• Limited evidence exists, but phentolamine addresses the alpha-mediated vasoconstriction that cocaine produces 3

Critical Contraindication: Beta-Blockers

• Never use selective beta-blockers (propranolol, metoprolol, esmolol) in acute cocaine intoxication due to risk of unopposed alpha-adrenergic stimulation, which can cause paradoxical hypertension and worsened coronary vasospasm 1, 4, 5
• A classic case report demonstrated propranolol causing a paroxysmal increase in blood pressure requiring nitroprusside rescue in a cocaine-toxic patient 5
• The mechanism involves beta-2 receptor blockade eliminating peripheral vasodilation while leaving alpha-1 mediated vasoconstriction unopposed 5, 6
• The American Heart Association explicitly recommends against beta-blockers in patients with signs of acute cocaine intoxication 4

Special Consideration: Combined Alpha-Beta Blockers

• Labetalol and carvedilol have mixed evidence and should generally be avoided in acute cocaine toxicity 2
• The 2012 ACC/AHA guidelines give only a Class IIb recommendation (may be reasonable) for combined alpha-beta blockers like labetalol, noting this is the weakest level of recommendation 2
• A systematic review found no adverse events with labetalol/carvedilol in 1744 subjects, but the theoretical concern of unopposed alpha-stimulation persists since their beta-blocking effects are more potent than alpha-blocking effects 3, 7
• If considering labetalol, ensure a vasodilator has been given within the previous hour 4

Monitoring Targets

• Aim for gradual blood pressure reduction of 20-25% in mean arterial pressure within the first hour to avoid precipitous drops 1
• Maintain continuous cardiac monitoring to detect arrhythmias, QRS widening, or QT prolongation from cocaine's sodium and potassium channel blockade 2
• Assess for end-organ damage including myocardial ischemia, as cocaine causes both coronary vasospasm and accelerated atherosclerosis 1

Common Pitfall to Avoid

• The most dangerous error is reaching for beta-blockers to treat tachycardia and hypertension in cocaine toxicity, as this can precipitate severe hypertensive crisis and coronary vasospasm 1, 4, 5
• Always start with benzodiazepines first, even if the patient appears severely hypertensive, as this addresses the root cause of sympathetic hyperactivity 1, 2