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Several pharmacological options exist for treatment of cocaine-induced cardiovascular toxicity. For the past 3 decades, the phenomenon of unopposed \u03b1-stimulation after \u03b2-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 \u03b1-stimulation was believed to be a factor investigate the pathophysiology, pharmacology, and published evidence behind the unopposed \u03b1-stimulation phenomenon. We also investigate other potential explanations for unopposed \u03b1-stimulation, including the unique and deleterious pharmacologic properties of cocaine in the absence of \u03b2-blockers. The safety and efficacy of the mixed \u03b2-\/\u03b1-blockers labetalol and carvedilol are also discussed in relation to unopposed \u03b1-stimulation.<\/jats:p>","DOI":"10.1177\/1074248416681644","type":"journal-article","created":{"date-parts":[[2017,1,14]],"date-time":"2017-01-14T01:10:17Z","timestamp":1484356217000},"page":"239-249","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":59,"title":["\u03b2-Blockers, Cocaine, and the Unopposed \u03b1-Stimulation Phenomenon"],"prefix":"10.1177","volume":"22","author":[{"given":"John R.","family":"Richards","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of California Davis Medical Center, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judd E.","family":"Hollander","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Ramoska","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Drexel University, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fareed N.","family":"Fareed","sequence":"additional","affiliation":[{"name":"Emergency Medical Associates, EmCare Partners Group, Parsippany, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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