Glucagon

Mechanism

Pharmacological Group and Molecular Target

Synthetic pancreatic hormonal polypeptide, allosteric activator of myocardial adenylate cyclase.

Detailed Mechanism of Action

Beta-blocking drugs and calcium channel antagonists block beta-1 adrenergic receptors or myocardial L-type calcium channels, preventing normal cellular calcium entry and the generation of cyclic adenosine monophosphate (cAMP), resulting in extreme bradycardia, refractory hypotension, and cardiogenic shock. Glucagon has a specific membrane hormone receptor in myocardial cells independent of beta-adrenergic receptors. The binding of glucagon to its receptor directly activates the stimulatory subunit of the Gs protein, which allosterically stimulates the enzyme adenylate cyclase to synthesize cellular cAMP, increasing cytosolic calcium indirectly, which significantly improves the inotropism and chronotropism of the compromised myocardium:

Indicators and dose

Specific Clinical Indications

• Severe refractory hypotension and bradyarrhythmias associated with overdose by beta-blockers or calcium antagonists (choice as second-line therapy if classic vasopressor and inotrope support fails).
• Severe hypoglycemia induced by insulin or oral antidiabetics when intravenous route with hyperatonic dextrose is not available.

Dosage Scheme and Infusion Protocols

• Initial Bolus Dose (Adult): 5 mg to 10 mg slowly intravenously infused over 2-3 minutes. If no increase in blood pressure or heart rate is observed after 10 minutes, a second identical bolus can be repeated.
• Maintenance Infusion: Once the initial positive clinical response is established, start a continuous intravenous infusion at a rate of 2 mg to 5 mg/hour diluted in 5% glucose serum to prevent rapid exhaustion of the inotropic effect.
• Frequent Side Effect: Glucagon at therapeutic doses intensely stimulates the emetic center, inducing massive vomiting in almost 90% of conscious patients. It is mandatory to prophylactically secure the airway (intubation or safety position) to avoid pneumonia due to chemical aspiration.