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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.

Background: Topical cocaine is sometimes used for the treatment of epistaxis, as it has both potent anesthetic and vasoconstrictive properties. Cocaine has unpredictable cardiovascular effects, such as sudden hypertension, tachycardia, coronary arterial vasoconstriction, and dysrhythmia., Case Report: We report a case of acute iatrogenic cardiovascular toxicity from the use of topical cocaine in a 56-year-old man presenting to the Emergency Department with profound epistaxis. To prepare for cauterization and nasal packing, the patient received 4% topical cocaine-soaked nasal pledgets. He became hypertensive, tachypneic, tachycardic, and dysphoric immediately after administration. To directly counter these adverse hyperadrenergic effects, the patient was given 10 mg intravenous labetalol, a mixed β- and α-blocker. This instantly normalized his vital signs and adverse subjective effects. His epistaxis was successfully treated, and he was discharged 1 h later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We believe that emergency physicians should be aware of the unpredictable acute cardiovascular toxicity of topical cocaine. Labetalol represents an effective first-line treatment, which, unlike benzodiazepines, directly counters the pharmacologic effects of cocaine and has no respiratory or sedative side effects. Labetalol, with its mixed β/α-blocking properties, also mitigates the potential for "unopposed α-stimulation.", (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Cocaine abuse is a major worldwide health problem. Patients with acute cocaine toxicity presenting to the emergency department may require urgent treatment for tachycardia, dysrhythmia, hypertension, and coronary vasospasm, leading to pathological sequelae such as acute coronary syndrome, stroke, and death., Objective: The objective of this study is to review the current evidence for pharmacological treatment of cardiovascular toxicity resulting from cocaine abuse., Methods: MEDLINE, PsycINFO, Database of Abstracts of Reviews of Effects (DARE), OpenGrey, Google Scholar, and the Cochrane Library were searched from inception to November 2015. Articles on pharmacological treatment involving human subjects and cocaine were selected and reviewed. Evidence was graded using Oxford Centre for Evidence-Based Medicine guidelines. Treatment recommendations were compared to current American College of Cardiology/American Heart Association guidelines. Special attention was given to adverse drug events or treatment failure. The search resulted in 2376 articles with 120 eligible involving 2358 human subjects. Benzodiazepines and other GABA-active agents: There were five high-quality (CEBM Level I/II) studies, three retrospective (Level III), and 25 case series/reports (Level IV/V) supporting the use of benzodiazepines and other GABA-active agents in 234 subjects with eight treatment failures. Benzodiazepines may not always effectively mitigate tachycardia, hypertension, and vasospasm from cocaine toxicity. Calcium channel blockers: There were seven Level I/II, one Level III, and seven Level IV/V studies involving 107 subjects and one treatment failure. Calcium channel blockers may decrease hypertension and coronary vasospasm, but not necessarily tachycardia. Nitric oxide-mediated vasodilators: There were six Level I/II, one Level III, and 25 Level IV/V studies conducted in 246 subjects with 11 treatment failures and two adverse drug events. Nitroglycerin may lead to severe hypotension and reflex tachycardia. Alpha-adrenoceptor blocking drugs: There were two Level I studies and three case reports. Alpha-1 blockers may improve hypertension and vasospasm, but not tachycardia, although evidence is limited. Alpha-2-adrenoceptor agonists: There were two high-quality studies and one case report detailing the successful use of dexmedetomidine. Beta-blockers and β/α-blockers: There were nine Level I/II, seven Level III, and 34 Level IV/V studies of β-blockers, with 1744 subjects, seven adverse drug events, and three treatment failures. No adverse events were reported for use of combined β/α-blockers such as labetalol and carvedilol, which were effective in attenuating both hypertension and tachycardia. Antipsychotics: Seven Level I/II studies, three Level III studies, and seven Level IV/V case series and reports involving 168 subjects have been published. Antipsychotics may improve agitation and psychosis, but with inconsistent reduction in tachycardia and hypertension and risk of extrapyramidal adverse effects. Other agents: There was only one high level study of morphine, which reversed cocaine-induced coronary vasoconstriction but increased heart rate. Other agents reviewed included lidocaine, sodium bicarbonate, amiodarone, procainamide, propofol, intravenous lipid emulsion, propofol, and ketamine., Conclusions: High-quality evidence for pharmacological treatment of cocaine cardiovascular toxicity is limited but can guide acute management of associated tachycardia, dysrhythmia, hypertension, and coronary vasospasm. Future randomized prospective trials are needed to evaluate new agents and further define optimal treatment of cocaine-toxic patients.

Assesses the influence of cocaine on the plasma constituents involved in endogenous thrombosis and thrombolysis. Procurement of blood samples in 22 patients undergoing cardiac catheterization after the administration of intranasal saline or cocaine; Measurement of the plasma concentrations of fibrinogen, plasminogen and lipoprotein(a).

Discusses the effects of large concentrations of cocaine infusion on the coronary circulation in humans. Demographic and medical profile of respondents; Factors influencing cocaine plasma levels; Hemodynamic and arteriographic variables to intracoronary cocaine.

Objective: To define the temporal characteristics of cocaine-induced coronary vasoconstriction in humans and to assess the relation between cocaine-induced coronary vasoconstriction and the blood concentration of cocaine and its main metabolites.Design: Randomized, double-blind, controlled clinical trial.Setting: Cardiac catheterization laboratory of a large teaching hospital.Patients: Eighteen patients (16 men and 2 women, 37 to 65 years of age) having catheterization for evaluation of chest pain.Measurements: At catheterization, patients received intranasal saline (8 patients) or cocaine, 2 mg/kg body weight (10 patients). Cineangiographic examination of the left coronary artery and quantitation of the blood concentration of cocaine and its metabolites were done before (baseline) and 30, 60, and 90 minutes after administration of intranasal saline or cocaine.Results: In response to cocaine, proximal coronary arterial diameter decreased from 2.4 +/- 1.6 mm (mean +/- SD) at baseline to 2.0 +/- 1.4 mm at 30 minutes (P less than 0.05). This change corresponded temporally to the peak blood concentration of cocaine. At 60 minutes, the cocaine concentration decreased and coronary artery diameter returned to baseline (2.3 +/- 1.6 mm) (P greater than 0.05 compared with baseline). At 90 minutes, all patients had recurrent vasoconstriction (1.9 +/- 1.4 mm, P less than 0.05) despite a further decrease in the blood cocaine concentration. This vasoconstriction corresponded temporally with an increasing blood concentration of cocaine's main metabolites, benzoylecgonine and ethyl methyl ecgonine. No changes were observed in the control group.Conclusion: Intranasal cocaine causes recurrent coronary vasoconstriction, which may be due to its metabolites. [ABSTRACT FROM AUTHOR]

Study Objective: To determine whether beta-adrenergic blockade augments cocaine-induced coronary artery vasoconstriction.Design: Randomized, double-blind, placebo-controlled trial.Setting: A cardiac catheterization laboratory in an urban teaching hospital.Patients: Thirty clinically stable patient volunteers referred for catheterization for evaluation of chest pain.Interventions: Heart rate, arterial pressure, coronary sinus blood flow (by thermodilution), and epicardial left coronary arterial dimensions were measured before and 15 minutes after intranasal saline or cocaine administration (2 mg/kg body weight) and again after intracoronary propranolol administration (2 mg in 5 minutes).Measurements and Main Results: No variables changed after saline administration. After cocaine administration, arterial pressure and rate-pressure product increased; coronary sinus blood flow fell (139 +/- 28 [mean +/- SE] to 120 +/- 20 mL/min); coronary vascular resistance (mean arterial pressure divided by coronary sinus blood flow) rose (0.87 +/- 0.10 to 1.05 +/- 0.10 mm Hg/mL.min); and coronary arterial diameters decreased by between 6% and 9% (P less than 0.05 for all variables). Subsequently, intracoronary propranolol administration caused no change in arterial pressure or rate-pressure product but further decreased coronary sinus blood flow (to 100 +/- 14 mL/min) and increased coronary vascular resistance (to 1.20 +/- 0.12 mm Hg/mL.min) (P less than 0.05 for both).Conclusions: Cocaine-induced coronary vasoconstriction is potentiated by beta-adrenergic blockade. Beta-adrenergic blocking agents probably should be avoided in patients with cocaine-associated myocardial ischemia or infarction. [ABSTRACT FROM AUTHOR]

Presents a study of the cardiovascular complications of cocaine use. Pharmacology and mechanisms of action; Cocaine-related myocardial ischemia and infarction; Cocaine, cigarette-smoking and alcohol use; Cocaine-induced myocardial dysfunction and dysrythmias; Endocarditis; Aortic dissection; Conclusion that as a result of the increased use of cocaine, related visits to emergency departments, hospitalizations, cardiovascular complications, and deaths has risen dramatically.

Background: In humans, the use of cocaine and cigarette smoking each increases the heart's metabolic need for oxygen but may also decrease the supply of oxygen. As cocaine abuse has proliferated, cocaine-associated chest pain, myocardial infarction, and sudden death have occurred, especially among smokers. We assessed the influence of intranasal cocaine and cigarette smoking, alone and together, on myocardial oxygen demand and coronary arterial dimensions in subjects with and subjects without coronary atherosclerosis. Methods: In 42 smokers (28 men and 14 women; age, 34 to 79 years; 36 with angiographically demonstrable coronary artery disease), we measured the product of the heart rate and systolic arterial pressure (rate-pressure product) and coronary arterial diameters before and after intranasal cocaine at a dose of 2 mg per kilogram of body weight (n = 6), one cigarette (n = 12), or intranasal cocaine at a dose of 2 mg per kilogram followed by one cigarette (n = 24). Results: No patient had chest pain or ischemic electrocardiographic changes after cocaine use or smoking. The mean (±SE) rate-pressure product increased by 11 ±2 percent after cocaine use (n = 30, P<0.001), by 12 ±4 percent after one cigarette (n = 12, P = 0.021), and by 45 ±5 percent after both cocaine use and smoking (n = 24, P<0.001). As compared with base-line measurements, the diameters of nondiseased coronary arterial segments decreased on average by 7 ±1 percent after cocaine use (P<0.001), by 7 ±1 percent after smoking (P<0.001), and by 6 ±2 percent after cocaine use and smoking (P<0.001). The diameters of diseased segments decreased by 9 ±2 percent after cocaine use (n = 18, P<0.001), by 5 ±5 percent after smoking (n = 12, P = 0.322), and by 19 ±4 percent after cocaine use and smoking (n = 12, P<0.001). The increase in the rate-pressure product and the decrease in the diameters of diseased segments caused by cocaine use and smoking together were greater (P<0.001 and P = 0.037, respectively) than the changes caused by either alone. Conclusions: The deleterious effects of cocaine on myocardial oxygen supply and demand are exacerbated by concomitant cigarette smoking. This combination substantially increases the metabolic requirement of the heart for oxygen but simultaneously decreases the diameter of diseased coronary arterial segments. (N Engl J Med 1994;330:454-9.) [ABSTRACT FROM AUTHOR]