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

References and Links

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.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

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

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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