What is the recommended antidote for beta-blocker overdose?

• A. Epinephrine
• B. Atropine
• C. Glucagon
• D. Calcium gluconate

Answer: (C)

When beta-blocker overdose depresses the heart by blocking β-adrenergic signaling, you need something that can stimulate the heart without relying on those blocked receptors. Glucagon provides that, acting on its own receptor on cardiac cells to raise cAMP via Gs protein and activate adenylate cyclase. This increases intracellular calcium and enhances heart rate and contractility even though the β receptors are blocked, effectively reversing the core problem.

Epinephrine depends on adrenergic receptors to raise heart rate and contractility, which are blunted during β-blockade, limiting its effectiveness. Atropine addresses vagal slowing but doesn’t improve the depressed cardiac output from β-blockade. Calcium gluconate can help in some overdose scenarios but doesn’t bypass the blocked β-receptors like glucagon does, making it a less direct antidote for this situation.