How does glucagon work in beta (beta blockers) overdose?

Mechanism of Glucagon in Beta Blocker Overdose

Glucagon works in beta blocker overdose by bypassing the blocked beta-adrenergic receptors, activating hepatic adenyl cyclase directly to increase cardiac contractility, heart rate, and improve hemodynamics. 1

Physiological Mechanism

• Glucagon is a vasoactive polypeptide that counteracts beta blocker effects by activating adenylate cyclase in the liver, promoting glycogenolysis and increasing cardiac function independently of beta-adrenergic receptors 2, 1
• This bypass mechanism allows glucagon to increase heart rate and myocardial contractility even when beta receptors are blocked by overdosed beta blockers 3, 4
• Glucagon works through a separate G-protein coupled receptor system that increases intracellular cAMP levels, similar to beta-receptor stimulation but through a different pathway 5
• Recent clinical research confirms that high-dose glucagon produces significant hemodynamic effects regardless of beta-adrenergic blockade 6

Clinical Effects in Beta Blocker Overdose

• Glucagon administration increases heart rate, systolic blood pressure, diastolic blood pressure, and cardiac output even in the presence of beta blockade 6
• The American Heart Association recommends glucagon as a reasonable treatment (Class IIa recommendation) for bradycardia or hypotension due to beta blocker poisoning 2
• Hemodynamic improvements typically include:
  • Increased heart rate (chronotropic effect)
  • Improved cardiac contractility (inotropic effect)
  • Reversal of atrioventricular conduction blocks 3, 5

Administration Protocol

• The recommended dosing regimen is a bolus of 3-10 mg IV administered over 3-5 minutes 1
• This should be followed by a continuous infusion of 3-5 mg/hour due to the transient effects of glucagon 1, 4
• Continuous infusion may be preferable to repeated boluses as it provides more stable and potentially longer-lasting hemodynamic effects 6
• The American College of Cardiology recommends glucagon as first-line therapy for symptomatic beta blocker-induced bradycardia 7

Limitations and Side Effects

• Common side effects include nausea and vomiting, which occur in up to 80% of patients despite antiemetic pretreatment 6
• Glucagon may temporarily increase blood pressure and heart rate in patients taking beta blockers, which requires monitoring in patients with coronary artery disease 8
• Glucagon may lose its effectiveness in patients with depleted glycogen stores 7
• When used with indomethacin, glucagon may lose its ability to raise blood glucose or even produce hypoglycemia 8

Place in Treatment Algorithm

1. Initiate standard supportive measures (airway, breathing, circulation) 2
2. For symptomatic bradycardia or hypotension due to beta blocker overdose:
   • Administer glucagon bolus (3-10 mg IV) followed by infusion (3-5 mg/h) 1, 7
   • Consider vasopressors for persistent hypotension 2
   • For refractory cases, high-dose insulin therapy is recommended (Class I recommendation) 2
   • Consider extracorporeal life support for shock refractory to pharmacological interventions 2

Evidence Quality and Limitations

• Evidence supporting glucagon use in beta blocker overdose is primarily based on animal studies and case reports 5
• The 2023 AHA guidelines give glucagon a Class IIa recommendation with level of evidence C-LD (limited data) 2
• Recent randomized clinical trials confirm glucagon's hemodynamic effects regardless of beta blockade, supporting its use in overdose situations 6

Glucagon remains an important component in the management of beta blocker overdose, particularly for addressing bradycardia and hypotension, though high-dose insulin therapy has emerged as a first-line treatment for hypotension refractory to or used in conjunction with vasopressor therapy 2.