WBR0367

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Author [[PageAuthor::Serge Korjian, M.D.,Gonzalo A. Romero, M.D. [1](Reviewed by Serge Korjian)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology
Sub Category SubCategory::Cardiology, SubCategory::General Principles
Prompt [[Prompt::A 25-year-old man is brought to the emergency department by ambulance for altered mental status. His mother contacted emergency medical services after finding him unconscious on his bedroom floor. She reports that her son is a very healthy person with no significant past medical history. He was only recently diagnosed with performance anxiety that was interfering with his daily functioning at his new job as a financial advisor. The mother also notes that her son has been very anxious for the past week because of an upcoming project presentation. On admission, the patient's blood pressure is 80/55 mm Hg, heart rate is 42/min, and temperature is 36.7 ᵒC (98 ᵒF). The patient is not responsive, but opens his eyes to painful stimuli. An ECG tracing is obtained and shown below. Which of the following medications is the most appropriate choice for the acute treatment of this patient?

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Answer A AnswerA::Cyproheptadine
Answer A Explanation [[AnswerAExp::Cyproheptadine is used to treat moderate to severe cases of serotonin syndrome. The syndrome can be caused by SSRIs excess, or combination with MAO inhibitors, buspirone, meperidine, linezolid, and dextromethorphan.]]
Answer B AnswerB::Glucagon
Answer B Explanation [[AnswerBExp::Glucagon is the medication of choice to treat beta-blocker intoxication. It is hypothesized that glucagon works at a non-beta-adrenergic site to increase inotropy, and atrioventricular conduction.]]
Answer C AnswerC::Flumazenil
Answer C Explanation [[AnswerCExp::Flumazenil is the antidote for benzodiazepine intoxication. It is both diagnostic and therapeutic.]]
Answer D AnswerD::Atropine
Answer D Explanation [[AnswerDExp::Although atropine can be used to increase heart rate in sinus bradycardia and certain forms of atrioventricular block, it is not very effective in the treatment of patients with beta-blocker toxicity. In addition, patients with third degree block do not benefit from atropine.]]
Answer E AnswerE::Sodium bicarbonate
Answer E Explanation [[AnswerEExp::Sodium bicarbonate is the treatment of choice for TCA intoxication. Despite popular belief, the use of sodium bicarbonate in TCA toxicity is not aimed at alkalinizing the urine to increase its urinary excretion. It is used to provide a sodium load that corrects the QRS prolongation, and an alkaline blood pH to increase the protein bound fraction of the TCA.]]
Right Answer RightAnswer::B
Explanation [[Explanation::The classical treatment for patients with performance anxiety is a non-selective beta-blocker, most commonly propranolol. A key consideration in this question, other than the consistent clinical presentation, is the possibility of self-medication with a higher dose of propranolol given an upcoming stressful event. Beta-blocker toxicity manifests as bradycardia, hypotension, atrioventricular block, arrhythmias, and seizures. Given the non-selective nature of propranolol, bronchospasm is also a possible complication particularly in patients with pre-existing bronchospastic pulmonary disease. The ECG tracing may vary, showing anything from simple sinus bradycardia to third degree block (seen in this patient's tracing). The initial management for patients with propranolol toxicity includes activated charcoal; however, given the altered mental status of the patient, charcoal should be withheld. Along with initial fluid administration, glucagon is the treatment of choice for patients with beta-blocker toxicity. Glucagon increases heart rate and myocardial contractility, and improves atrioventricular conduction. These properties are unaffected by the presence of beta-blockers suggesting that glucagon's mechanism of action may bypass the beta-adrenergic receptor site. This may also explain why atropine and isoproterenol are not very effective in reversing the bradycardia and hypotension of beta-blocker overdose.

Educational Objective: Glucagon is the treatment of choice for patients with suspected or confirmed beta-blocker toxicity.
References: Peterson CD, Leeder JS, Sterner S. Glucagon therapy for beta-blocker overdose. Drug Intell Clin Pharm. 1984;18(5):394-8.
Kerr GW, Mcguffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001;18(4):236-41.]]

Approved Approved::Yes
Keyword WBRKeyword::propranolol, WBRKeyword::antidotes, WBRKeyword::beta-blocker, WBRKeyword::toxicity, WBRKeyword::glucagon
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