1. Glucagon
ALLYSON CORD

3. MOA
 Polypeptide counterregulatory hormone
 Secreted by alpha cells of the pancreas and stomach
 Increases cAMP
 GPCR: coupled to Gs proteins that stimulate adenyl cyclase
activity to produce increased cAMP
 Inhibits PDE activity to prevent cAMP breakdown

4. Clinical Effects
 Liver tissue
 Promotes hepatic glycogenolysis and gluconeogenesis to raise BG
levels
 Requires hepatic glycogen stores
 Delayed effect
 Increased BG levels promote insulin release
 GI tract
 Decreases motility
 Relaxes smooth muscle of the stomach, duodenum, small bowel, and
colon

5. Clinical Effects
 Heart
 Increased cAMP  increases HR, contractility, and BP
 Max chronotropic effect dependent on circulating ionized calcium
 Hypo and hypercalcemia blunts max response
 Mini-glucagon  arachidonic acid release  increased cardiac
contractility
 Cardiac tissue metabolizes glucagon to mini-glucagon
 Arachidonic acid effects calcium to increase contractility
 Effects decreased with severity and chronicity of CHF
 Not dysrhythmogenic

6. Indications
 Hypoglycemia
 IV, IM, SQ = 1mg. May repeat in 15 minutes PRN.
 Give IV dextrose ASAP
 Delayed effect
 Diagnostic aid: relaxation of GI tract
 IM = 1-2mg
 IV = 0.2-0.75mg

7. Indications: Off-label
 BB or CCB induced myocardial depression (w/ or w/o
hypotension) unresponsive to standard measures
 IV = 3-10mg (or 0.05-0.15mg/kg) bolus infused over 1-2 mins
followed by infusion of 3-5 mg/hr (or 0.05-0.1 mg/kg/hr)
 Only follow with infusion is response to bolus
 Titrate infusion to response
 Glucagon vs HDI
 Animal studies: more sustained effect and better survival rate with
HDI

8. BB Overdose MOA

9. Precautions
 Nausea/vomiting
 Dose dependent
 Anticipate and manage
 Place in lateral recumbent
position
 Antiemetics
 Tachyphylaxis or
desensitization
 Possibly worse with
continuous administration
 Decreased GI motility
 May impede decontamination
attempts
 Hypokalemia
 Hyperglycemia  insulin
secretion  hypokalemia
 Stimulation of Na/K/ATPase in
skeletal muscle 
hypokalemia
 Insulinoma
 Feedback increase in insulin
 Worse hypoglycemia
 Pheochromocytoma
 Catecholamine release
 Hypertensive crisis

10. Drug-drug Interactions
 Epinephrine
 Potentiates and prolongs hyperglycemia and CV effects
 PDE inhibitors (milrinone, amrinone)
 Decrease metabolism of cAMP
 Synergistic effect
 HDI
 Inhibits glycogenolysis and gluconeogenesis
 Anticholinergic agents
 Increase GI ADRs
 Indomethacin
 May diminish the therapeutic effect of glucagon
 Vitamin K Antagonist
 Glucagon may enhance the anticoagulant effect of VKA

11. Monitoring
 BP
 BG
 ECG
 HR
 Mentation

12. Quiz!
 T/F: Glucagon can increase HR, contractility, and BP
 True
 T/F: Both hypocalcemia and hypercalcemia can blunt
glucagon’s max response
 True
 T/F: Anticholinergics can be helpful in reducing
glucagon’s GI ADRs
 False
 T/F: Glucagon therapy can raise serum potassium
levels.
 False

13. References
 Howland M. Antidotes in Depth. In: Hoffman RS,
Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds.
Goldfrank's Toxicologic Emergencies, 10e. New York,
NY: McGraw-Hill; 2015.
 Glucagon. Lexi-Drugs. Lexicomp Online. Wolters
Kluwer Health, Inc. Hudson, OH. Available
at: http://online.lexi.com. Accessed December 29,
2015.
 Engebretsen K, Kaczmarek K, Morgan J, Holger J. High-
dose insulin therapy in beta-blocker and calcium
channel-blocker poisoning. Clin Toxicol (Phila) [serial
online]. April 2011;49(4):277-283. Available from:
MEDLINE Complete, Ipswich, MA. Accessed December
29, 2015.

14. Questions?