In their article, "Hypertensive Emergencies and Urgencies: Update on Management"
(CONSULTANT, March 2004, page 341), Drs Iris Reyes and Rex Mathew
write that labetalol is specifically indicated for most hypertensive emergencies,
"especially stroke and acute cocaine intoxication." In fact, labetalol is potentially
deadly and is contraindicated in acute hypertension and/or concomitant chest
pain related to cocaine intoxication. Labetalol and other β-blockers should be
avoided in this setting.
Cocaine is a powerful sympathomimetic agent that stimulates both α1- and
β1- and β2-receptors. α1-Stimulation causes marked vasoconstriction of peripheral
arteries, which results in hypertension; more importantly, it causes vasoconstriction
of the epicardial coronary arteries, which can lead to ischemic myocardial injury.
Fortunately, the potent α1-mediated vasoconstriction associated with cocaine
is limited by the coexisting vasodilatory effect mediated by the β2-receptors. If a patient
with hypertension caused by acute cocaine intoxication were given labetalol
(or any other β-blocker), the result would be complete β-blockade, which would
lead to relatively unopposed vasoconstriction mediated solely by α1-receptors. Labetalol,
which has both α- and β-adrenergic blocking activity, reverses the cocaine-induced increase in
systemic arterial pressure but exerts no demonstrable effect on cocaine-induced vasoconstriction of the
It is prudent to assume that there may likely be coronary vasoconstriction along with hypertension
even 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 channel
blockers, such as verapamil. Cocaine-induced vasoconstriction of the coronary arteries can be reversed
with 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 and
hypertension. Phentolamine is a second-line agent, and β-blockers are contraindicated in this setting.
---- Matthew Zaccheo, DO
St Luke's Hospital
Much debate surrounds the treatment of
hypertension associated with cocaine
toxicity. The advantage of labetalol over
pure β-blockers is the additional α-adrenergic
blockade that labetalol provides.
Treatment with pure β-adrenergic blockers, such as propranolol,
has been shown to enhance some of the cardiovascular
effects of cocaine. A controlled study by Sofuoglu
and colleagues1 demonstrated that labetalol reduces the
increases in systolic blood pressure and heart rate induced
by repeated doses of smoked cocaine. In another study,
labetalol failed to reverse the coronary vasoconstriction
induced by intranasal cocaine in subjects who underwent
cardiac catheterization, but it exerted no demonstrable
adverse effect on cocaine-induced vasoconstriction of the
coronary arteries.2 Numerous authors therefore recommend
the selective use of labetalol in patients with cocaine
toxicity--first intravenously in the acute setting and then
orally for long-term therapy. Intravenous nitroglycerin or
verapamil can also be used because they reverse both the
vasoconstriction and hypertension caused by acute cocaine
Still, the use of β-blockers as a class in the setting of
cocaine toxicity remains controversial. The American
College of Cardiology/AHA guidelines recommend β-
blockers for select conditions caused by cocaine toxicity.3
However, it should be noted that this recommendation is
based only on expert consensus. The Advanced Cardiovascular
Life Support guideline revision of 2000 recommends
that nitrates be used as first-line therapy in patients
with a history of cocaine abuse and ventricular arrhythmias
or acute coronary syndromes.4 It also suggests that separate review of the literature surrounding this issue, Knuepfer5 justifiably
concludes that there are insufficient experimental and clinical data at this time
to determine whether labetalol may be beneficial in treating cocaine toxicity.
---- Rex Mathew, MD
Hospital of the University of Pennsylvania
1. Sofuoglu M, Brown S, Babb DA, et al. Effects of labetalol treatment on the physiological and subjective
response to smoked cocaine. Pharmacol Biochem Behav. 2000;65:255-259.
2. Boehrer JD, Moliterno DJ, Willard JE, et al. Influence of labetalol on cocaine-induced coronary vasoconstriction
in humans. Am J Med. 1993;94:608-610.
3. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of patients
with unstable angina and non-ST–segment elevation myocardial infarction—summary article: a report
of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee
on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002;40:1366-1374.
4. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: advanced
cardiovascular life support: section 1: Introduction to ACLS 2000: overview of recommended changes
in ACLS from the guidelines 2000 conference. The American Heart Association in collaboration with the International
Liaison Committee on Resuscitation. Circulation. 2000;102(8 suppl):I86-I89.
5. Knuepfer MM. Cardiovascular disorders associated with cocaine use: myths and truths. Pharmacol Ther.
FOR MORE INFORMATION:
- Eagle KA, Isselbacher EM, DeSanctis RW, and the International Registry for Aortic Dissection (IRAD)
Investigators. Cocaine-related aortic dissection in perspective. Circulation. 2002;105:1529-1530.
- Lange RA, Hillis LD. Cardiovascular complications of cocaine use. N Engl J Med. 2001;345:351-358.