Glucagon Therapy

Reviewed and revised 21 November 2016

CLASS

  • polypeptide hormone (29 amino acids, MWt 3485 g/mol) secreted by alpha cells of the pancreas

PRESENTATION

  • glucagon HCl 1mg lyophilsied powder/ 1 mL solvent in vials or pre-filled syringes

MECHANISM OF ACTION

  • Agonist at glucagon-specific Gs-protein coupled receptor, activates adenylyl cyclase resulting in increased [cAMP]i
  • Physiological effects
    • CVS: positive inotropy and chronotropy similar to beta-agonists (but bypassing the adrenergic receptor)
    • Liver and adipose tissue: glycogenolysis, gluconeogenesis, and ketogenesis resulting in increased blood glucose and ketones
    • Smooth muscle (e.g. LES): GI relaxation (may be caused by mechanisms independent of adenylyl cyclase)
    • No effect on skeletal muscle (no glucagon receptors)
  • Pharmacological doses of glucagon also causes secretion of:
    • insulin by normal islet beta cells
    • catecholamines from phaeochromocytoma
    • calcitonin by medullary carcinoma cells

DOSE

Beta-blocker or Calcium channel blocker toxicity

  • 5mg IV bolus then repeat after 5min if no effect
  • If clinical response then start infusion of 2-5mg/h in 5% dextrose
  • abandon use if no response to 10mg

Hypoglycemia

  • 1-2 mg IM stat in adults

INDICATIONS

  • Hypogylcemia rescue (especially prehospital)
  • Anaphylaxis in patients on beta-blockers that fail to respond to adrenaline
  • Traditionally used for beta-blocker and calcium channel blocker overdose, now largely abandoned by Australian toxicologists

ADVERSE EFFECTS

  • dose-dependent nausea and vomiting (especially after large boluses)
  • hyperglycemia
  • hypokalemia
  • tachyphylaxis with continued use in laboratory studies

PHARMACOKINETICS

  • Absorption
    • degraded by proteolysis in the GI tract
    • IV: effects begin within 1–3 minutes, are maximal at 5–7 minutes, and last 10–15 minutes
    • Peak plasma levels at 13 minutes for IM injection and 20 minutes for SC injection
  • Distribution
    • VD = 0.25 L/kg
  • Metabolism
    • rapidly metabolised in plasma, liver and kidney (each accounts for about a third of metabolic clearance)
  • Elimination
    • t1/2 = 8-18 min (up to 45 min following IM injection due to slower systemic absorption)

EVIDENCE

OTHER INFORMATION

  • A glucagon nasal spray has recently been approved by the FDA for hypoglycaemia rescue
  • Glucagon is not recommended for treatment of impacted esophageal food boluses due to significant side effects and poor effectiveness

CCC Pharmacology Series

LITFL

Journal articles

  • Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol. 2003;41(5):595-602. PMID: 14514004.
  • Use of glucagon for oesophageal food bolus impaction. Emergency Medicine Journal. 32(1):85-8. 2015. [pubmed]

FOAM and web resources

  • GlucaGen Hypokit Prescribing Information, Denmark: Novo Nordisk; 2005; [cited 22 November 2010]. URL: http://www.novonordiskcare.com.
  • GlucaGen Hypokit Medicines Data Sheet, New Zealand: Novo Nordisk Pharmaceuticals Ltd.; 25 August 2009; [cited 22 November 2010]. URL: http://www.medsafe.govt.nz.

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the  Clinician Educator Incubator programme, and a CICM First Part Examiner.

He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.

His one great achievement is being the father of three amazing children.

On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.