Appropriate Agents for Cocaine-Induced Hypertensive Emergencies

In their article, "Hypertensive Emergencies and Urgencies: Update on Management"(CONSULTANT, March 2004, page 341), Drs Iris Reyes and Rex Mathewwrite that labetalol is specifically indicated for most hypertensive emergencies,"especially stroke and acute cocaine intoxication." In fact, labetalol is potentiallydeadly and is contraindicated in acute hypertension and/or concomitant chestpain related to cocaine intoxication. Labetalol and other β-blockers should beavoided in this setting.Cocaine is a powerful sympathomimetic agent that stimulates both α_1- andβ₁- and β₂-receptors. α₁-Stimulation causes marked vasoconstriction of peripheralarteries, which results in hypertension; more importantly, it causes vasoconstrictionof the epicardial coronary arteries, which can lead to ischemic myocardial injury.Fortunately, the potent α₁-mediated vasoconstriction associated with cocaineis limited by the coexisting vasodilatory effect mediated by the β₂-receptors. If a patientwith hypertension caused by acute cocaine intoxication were given labetalol(or any other β-blocker), the result would be complete β-blockade, which wouldlead to relatively unopposed vasoconstriction mediated solely by α₁-receptors. Labetalol,which has both α- and β-adrenergic blocking activity, reverses the cocaine-induced increase insystemic arterial pressure but exerts no demonstrable effect on cocaine-induced vasoconstriction of thecoronary arteries.It is prudent to assume that there may likely be coronary vasoconstriction along with hypertensioneven in young, otherwise healthy patients with no comorbid evidence of other atherosclerotic risk factors.Cocaine-related hypertension can be reversed safely and effectively with nitroglycerin and calcium channelblockers, such as verapamil. Cocaine-induced vasoconstriction of the coronary arteries can be reversedwith phentolamine, an α₁-receptor antagonist. The revised guidelines of the American Heart Association(AHA) for emergency cardiovascular care recommend nitroglycerin, calcium channel blockers,and benzodiazepines as first-line agents for patients with cocaine-related myocardial ischemia andhypertension. Phentolamine is a second-line agent, and β-blockers are contraindicated in this setting.---- Matthew Zaccheo, DO
St Luke's Hospital
Bethlehem, Pa
Much debate surrounds the treatment ofhypertension associated with cocainetoxicity. The advantage of labetalol overpure β-blockers is the additional α-adrenergicblockade that labetalol provides.Treatment with pure β-adrenergic blockers, such as propranolol,has been shown to enhance some of the cardiovasculareffects of cocaine. A controlled study by Sofuogluand colleagues¹ demonstrated that labetalol reduces theincreases in systolic blood pressure and heart rate inducedby repeated doses of smoked cocaine. In another study,labetalol failed to reverse the coronary vasoconstrictioninduced by intranasal cocaine in subjects who underwentcardiac catheterization, but it exerted no demonstrableadverse effect on cocaine-induced vasoconstriction of thecoronary arteries.² Numerous authors therefore recommendthe selective use of labetalol in patients with cocainetoxicity--first intravenously in the acute setting and thenorally for long-term therapy. Intravenous nitroglycerin orverapamil can also be used because they reverse both thevasoconstriction and hypertension caused by acute cocaineexposure.Still, the use of β-blockers as a class in the setting ofcocaine toxicity remains controversial. The AmericanCollege of Cardiology/AHA guidelines recommend β-blockers for select conditions caused by cocaine toxicity.³However, it should be noted that this recommendation isbased only on expert consensus. The Advanced CardiovascularLife Support guideline revision of 2000 recommendsthat nitrates be used as first-line therapy in patientswith a history of cocaine abuse and ventricular arrhythmiasor acute coronary syndromes.⁴ It also suggests that separate review of the literature surrounding this issue, Knuepfer⁵ justifiablyconcludes that there are insufficient experimental and clinical data at this timeto determine whether labetalol may be beneficial in treating cocaine toxicity.---- Rex Mathew, MD
Hospital of the University of Pennsylvania
Philadelphia

References:

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