Toxicology – Antidote: Glucagon for Beta-Blocker Poisoning

Indication

Glucagon may be used in beta-blocker overdose, particularly when significant bradycardia, hypotension, or reduced cardiac contractility is present.

Mechanism of Action

Normally, stimulation of cardiac beta receptors activates a G protein, which stimulates adenylyl cyclase. This increases cAMP, activates protein kinase A, increases calcium entry into cardiac cells, and improves heart rate and contractility.

In beta-blocker poisoning, this pathway is blocked at the beta receptor. Glucagon can bypass the blocked receptor by activating its own receptor and stimulating adenylyl cyclase through a separate pathway.

This leads to:

• Increased cAMP
• Increased intracellular calcium
• Improved cardiac contractility
• Increased heart rate

A useful way to remember this is that glucagon activates adenylyl cyclase through a “backdoor” pathway that does not depend on beta receptors.

Administration

Glucagon is given intravenously, often as an initial bolus followed by a continuous infusion if the patient responds.

Because relatively large doses may be required in toxicologic emergencies, treatment should be directed by a poison center or medical toxicologist.

Adverse Effects

The most common adverse effect is:

• Nausea and vomiting

Antiemetic therapy may therefore be useful. Hyperglycemia can also occur.

Key Points

• Glucagon can bypass beta-receptor blockade and increase intracellular cAMP.
• It may improve bradycardia and myocardial contractility in beta-blocker poisoning.
• Vomiting is common after administration.
• In severe beta-blocker toxicity, glucagon is usually one part of a broader resuscitation strategy that may also include vasopressors and hyperinsulinemic euglycemia therapy.