Hormone · Antidote
Glucagon
Indications
- Severe hypoglycemia without IV access (IM, SC or nasal)
- β-blocker poisoning with bradycardia or hypotension (off-label; AHA 2023 class 2a)
- Calcium channel blocker poisoning, as an adjunct (off-label; AHA 2023 class 2b)
- Anaphylaxis refractory to epinephrine in a patient taking β-blockers (off-label)
- Diagnostic aid: briefly stops GI motility for radiologic studies
Dosing
| Where | Dose |
|---|---|
| Reversal and antidotes | Glucagon: 3–10 mg IV for beta-blocker or calcium channel blocker overdose, then infusion |
On the quick cards
Mechanism of action
Glucagon acts on its own Gs-coupled receptor, separate from β-adrenoceptors, on hepatocytes, myocardium and GI smooth muscle. Gs activates adenylyl cyclase and raises cAMP: in the liver, protein kinase A drives glycogenolysis and gluconeogenesis; in the heart, cAMP increases calcium entry, contractility, rate and AV conduction even when β receptors are blocked; in the gut it relaxes smooth muscle. It therefore bypasses the occupied β receptor in β-blocker poisoning, though its cardiac effect is modest and fades with continued use.
Pharmacology
- Metabolic: glucose rises within 10 min of an IM or SC dose if liver glycogen is present; it also stimulates insulin release, lipolysis and ketogenesis
- Cardiovascular: raises heart rate and contractility without β receptors; the response to an IV bolus fades within about 20 min; it can also lower SVR
- GI: relaxes the stomach, bowel and lower esophageal sphincter within about 1 min IV (label); nausea and vomiting are common at high doses
Pharmacokinetics
| Onset | IV: about 1 min; IM or SC: glucose rises within 10 min |
|---|---|
| Peak | Glucose peaks 26–30 min after IM or SC (label) |
| Duration | IV bolus: about 10–25 min (label GI data), so poisoning needs an infusion |
| Half-life | IV 8–18 min; apparent 26 min after IM and 42 min after SC |
| Distribution | Vd 0.25 L/kg (label) |
| Metabolism | Proteolysis in the liver, kidney and plasma; no CYP role |
| Clearance | 13.5 mL/kg/min (label) |
| Routes | IV, IM or SC at 1 mg/mL after mixing; 3 mg nasal powder; poisoning doses need several 1 mg vials |
Chemistry
- A 29-amino-acid peptide (MW 3,483) identical to human glucagon, cut from proglucagon in pancreatic α cells; related to GLP-1, secretin and VIP
- Synthetic or recombinant; supplied as 1 mg of freeze-dried powder with lactose
- Poorly soluble near neutral pH, so it is dissolved with an acidic glycerin diluent or sterile water to 1 mg/mL at pH 2.5–3.5
- Unstable once dissolved, as the peptide aggregates into fibrils: use right after mixing and discard the rest (label)
Adverse effects and cautions
In the one-pagers
- Vasopressors and InotropesChoosing the agent by shock type and patient: β-blocker or CCB toxicity: Epinephrine or norepinephrine: Glucagon, high-dose insulin, milrinone, calcium
- Toxidromes and AntidotesCardiotoxic drugs: Beta-blockers: Glucagon 2–10 mg IV, then infusion: Bypasses beta receptors; vomiting
- Toxins, Stings and Anaphylaxis in the FieldAnaphylaxis drugs (NASEMSO): Glucagon (Merck): 1-5 mg IV over 5 min: Beta-blocked, poor epinephrine response
- Abdominal, GI Bleeding, GU and Dialysis EmergenciesSwallowed objects: Glucagon does not seem particularly effective; effervescent agents and meat tenderizer are not recommended (Merck). Dyspnea, stridor or wheeze point to the airway instead.
- BurnsBurn shock and the systemic response: From about day 3 the flow phase takes over: catecholamines rise up to 50-fold, with cortisol and glucagon (Williams 2009), driving tachycardia, fever, high cardiac output, low SVR, insulin resistance and muscle wasting, so fever and tachycardia no longer prove infection. In children with burns over 30% TBSA the response was still measurable 3 years later (Jesc
- Common EMS MedicationsGlucose, overdose and electrolytes: Glucagon, hormone: Low glucose, no IV; beta-blocker OD (CCB unclear): 1 mg IM (3 mg nasal); OD 2–10 mg IV: Pheochromocytoma; weak if glycogen depleted
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Sources
- FDA label: Glucagon for Injection, Amphastar (2025)
- FDA label: Glucagon for Injection, Fresenius Kabi (2019)
- AHA 2023 focused update: poisoning
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.