Glucagon for B-Blocker Overdose - DrofRx

1 USE OF Glucagon AS AN ANTIDOTE FOR THE MANAGEMENT OF SEVERE. -BLOCKER OR CALCIUM CHANNEL BLOCKER Overdose . TOXICOLOGY dependent upon the pharmacodynamic and kinetic characteristics of the specific There are 3 types of -adrenergic receptors agent ingested. Pharmacologic found in the human body. 1-receptors properties such as lipophilicty, primarily reside in heart muscle, 2- membrane-stabilizing activity, and receptors are primarily found in bronchial intrinsic sympathomimetic activity and peripheral vascular smooth muscle, and contribute to the degree of toxicity and 3-receptors, which are found in adipose are dependent upon which -blocker is tissue and the heart. Activation of each of ingested. Symptoms of -blocker these receptors results in a variety of intoxication can present as early as one physiological responses. Stimulation of 1- to two hours following ingestion, and are receptors results in an increase in usually present by the sixth hour intracellular cyclic AMP leading to increased following heart rate, contractility, and AV node conduction.

2 Stimulation of 2-receptors Glucagon MECHANISM OF ACTION. results in relaxation (dilation) of the bronchial and peripheral smooth muscles. Glucagon is a polypeptide hormone that Stimulation of 3-receptors results in is most often used therapeutically to catecholamine-induced thermogenesis and treat severe hypoglycemia. It interacts may reduce cardiac contractility. with the Guanine Nucleotide-Binding Protein-Coupled Receptor (GPCR) on the - blockers are competitive antagonists of plasma membrane of target cells. The these -adrenergic receptors. The most primary effects of Glucagon are mediated commonly used - blockers are specific to by cyclic AMP stimulated the 1-receptor, resulting in an indirect phosphorylation. Usually, the effects of decrease of intracellular levels of cyclic AMP Glucagon are primarily reserved to the with a resultant decrease in heart rate and liver. At higher concentrations, however, contractility.

3 Additional mechanisms Glucagon exerts effects on other tissues, explaining their physiological effects have including the myocardium, resulting in an been hypothesized, but antagonism of the increase in cyclic AMP and thus, -adrenergic receptor is their primary increased inotropic and chronotropic mechanism of action. , 3. As expected, the manifestations of - RECONSTITUTION AND STABILITY. blocker intoxication are merely an extension of their pharmacology. The most common 1mg Glucagon vials are stocked with an effects of toxicity include bradycardia and accompanying diluent (Sterile Water for hypotension, with myocardial depression Injection). When compounding the initial and cardiogenic shock being noted in the bolus, the reconstituted product should most severe cases. Other symptoms can be placed in the appropriate size syringe include heart block, mental status changes for the volume being administered.

4 Including coma and seizures, respiratory When compounding a bag for depression and bronchospasm and infusion, the product should be These effects are reconstituted with the provided diluent and added to 5% dextrose calcium provides inotropic and (D5W).. It is important to note that the hemodynamic support in this setting6. hospital supply of Glucagon can be consumed quickly when managing - MONITORING. blocker intoxication, necessitating the acquisition of Glucagon from nearby Administration of Glucagon can cause hospitals. The LHS standard infusion on hypokalemia and hyperglycemia. When the Med Drips button is 10mg/100mL administering large doses for the D5W. treatment of B-Blocker intoxication, adequate monitoring of serum glucose Unfortunately, data concerning the stability and potassium should be performed to of the product are not available. A maintain these concentrations at normal compounded bag of Glucagon would levels (BG between 80-120 mg/dL and therefore be given a 24-hour expiration serum potassium at mMol/L.)

5 Date by the central pharmacy sterile Monitoring of heart rate should be products area in compliance with performed in order to assess response to departmental policy. therapy, with normal heart rates being desired (60-80 beats per minute). DOSAGE AND ADMINISTRATION. CONTRAINDICATIONS. Glucagon should be given as a bolus dose of 5-10 mg (50-150 mcg/kg) over 1-2 The use of Glucagon is contraindicated in minutes. Repeat boluses may be given patients with a history of insulinoma or every 5-10 minutes. Glucagon has a pheochromocytoma, as well as in relatively short duration of action patients with known hypersensitivity to (approximately 10-15 minutes). Therefore, the product. 5. a continuous infusion of Glucagon at a rate of 2-5 mg/hour (50-100 ADVERSE REACTIONS. mcg/kg/hour) with a max of 10mg/hr should follow bolus administration in order The most commonly encountered to decrease repeated boluses as well as the adverse reactions that occur with rate of adverse reactions associated with Glucagon administration are nausea and high concentrations, such as nausea and vomiting, with a high incidence being , 4 associated with more rapid infusions (1mg/min as an IV push or infusion rates Consider also using a calcium gluconate of ~10mg/hr).

6 Because of this, airway bolus and infusion (1-2gram bolus followed control should be considered before by a 1gram per hour infusion) if the administration of Glucagon . More rare patient has peripheral access, or calcium adverse reactions include chloride for central line access to augment hypersensitivity reactions including or take place of Glucagon . Intravenous hypotension, respiratory distress, and urticaria. 1. DeWitt CR, Waksman JC. Pharmacology, Pathophysiology and Management of Calcium Channel Blocker and B-Blocker toxicity. Toxicol Rev 2004; 23(4): 223- 238. 2. Up-To-Date, Version [online database]. Waltham, MA: Up-To-Date, Inc;. Updated November 18th, 2004. 3. Michel T: Treatment of Myocardial Infarction In Brunton LL, Lazo JS, Parker KL: Goodman The Pharmacological Basis of Therapeutics. 11th Edition. New York, NY: McGraw-Hill; 2006. 4. Bailey, B. Glucagon in -blocker and calcium channel blocker overdoses: a systematic review.

7 J Toxicol Clin Toxicol 2003; 41:595. 5. Glucagen [package insert]. Bedford, OH: Bedford Laboratories; 2003. 6. Safir E, Fermin B. Beta blocker toxicity. UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2007. Updated November 18th, 2004. 2/2007. Jonathan Ward, PharmD.