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J Cardiovasc Pharmacol Ther. 2017 May;22(3):239-249. doi: 10.1177/1074248416681644. Epub 2016 Dec 14.

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

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1 Department of Emergency Medicine, University of California Davis Medical Center, Sacramento, CA, USA.
2 Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3 Department of Emergency Medicine, Drexel University, Philadelphia, PA, USA.
4 Emergency Medical Associates, EmCare Partners Group, Parsippany, NJ, USA.
5 Emergency Medical Associates, Tampa Bay, FL, USA.
6 Department of Cardiology, Hospital Universitario de Canarias, Tenerife, Spain.
7 Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.


Cocaine abuse remains a significant worldwide health problem. Patients with cardiovascular toxicity from cocaine abuse frequently present to the emergency department for treatment. These patients may be tachycardic, hypertensive, agitated, and have chest pain. Several pharmacological options exist for treatment of cocaine-induced cardiovascular toxicity. For the past 3 decades, the phenomenon of unopposed α-stimulation after β-blocker use in cocaine-positive patients has been cited as an absolute contraindication, despite limited and inconsistent clinical evidence. In this review, the authors of the original studies, case reports, and systematic review in which unopposed α-stimulation was believed to be a factor investigate the pathophysiology, pharmacology, and published evidence behind the unopposed α-stimulation phenomenon. We also investigate other potential explanations for unopposed α-stimulation, including the unique and deleterious pharmacologic properties of cocaine in the absence of β-blockers. The safety and efficacy of the mixed β-/α-blockers labetalol and carvedilol are also discussed in relation to unopposed α-stimulation.


cardiovascular; cocaine; toxicity; unopposed; vasoconstriction; α; β-blocker

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