title: β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon.
abstract: 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.
authors.affiliation: 1 Department of Emergency Medicine, University of California Davis Medical Center, Sacramento, CA, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Richards
authors.affiliation: 2 Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Judd E
authors.initials: JE
authors.lastname: Hollander
authors.affiliation: 3 Department of Emergency Medicine, Drexel University, Philadelphia, PA, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ramoska
authors.affiliation: 4 Emergency Medical Associates, EmCare Partners Group, Parsippany, NJ, USA.
authors.forename: Fareed N
authors.initials: FN
authors.lastname: Fareed
authors.affiliation: 5 Emergency Medical Associates, Tampa Bay, FL, USA.
authors.forename: I Charles
authors.initials: IC
authors.lastname: Sand
authors.affiliation: 6 Department of Cardiology, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: María Manuela
authors.initials: MM
authors.lastname: Izquierdo Gómez
authors.affiliation: 7 Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lange
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000697:Central Nervous System Stimulants; D011942:Receptors, Adrenergic, alpha; D003042:Cocaine
keywords: cardiovascular; cocaine; toxicity; unopposed; vasoconstriction; α; β-blocker