DESCRIPTION

Glucagon is a naturally occurring hormone that is secreted in response to hypoglycemia.

FORMS AND USES

• Lyophilized powder is available in 1- or 10-mg vials, but it is most commonly supplied in 1-mg vials. The diluent may contain phenol 2 mg/ml as a preservative.
• A glucagon emergency kit contains 1 mg in an autoinjector syringe.

MECHANISM OF ACTION

• Glucagon increases blood sugar by stimulating hepatic gluconeogenesis and glycogenolysis. It also stimulates cyclic adenosine monophosphate (cAMP) production, which increases intracellular calcium and leads to increased heart rate and contractility.
• Because a beta-receptor agonist also increases cAMP concentration, it is thought that glucagon may bypass the receptor blockade caused by beta-receptor blocking drugs.

DRUG AND DISEASE INTERACTIONS

• Glucagon may increase anticoagulation of patients treated with warfarin.
• The hypoglycemic effects of both insulin and oral hypoglycemic agents are antagonized.

PREGNANCY AND LACTATION

US FDA Pregnancy Category B. Animal studies indicate no fetal risk and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in pregnant women do not.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Treatment is indicated for cardiac toxicity from beta-blockers or calcium channel blockers.
• Specific indications:
  • Bradycardia, which is refractory to standard interventions including administration of atropine (see SECTION IV, beta-Receptor Blocking Drugs and Calcium Channel Blocking Drugs chapters for standard interventions).
  • Hypotension, which is refractory to standard interventions including administration of isotonic saline, atropine, calcium (in the case of calcium channel blockers), and vasopressor (dopamine, norepinephrine or epinephrine).
  • Glucagon is typically used after atropine has been administered and an infusion of vasopressor (e.g., dopamine, norepinephrine) has been initiated.
• Nontoxicologic indications include hypoglycemia, esoophageal food impaction, premedication for gastrointestinal endoscopy or radiographic procedures, asthma, acute biliary colic, colonic spasm secondary to acute diverticulitis, refractory congestive heart failure, and refractory anaphylaxis.

CONTRAINDICATIONS

• Hypersensitivity to glucagon.
• Hypoglycemia caused by severe insulin or oral hypoglycemic should be treated with infusion of dextrose instead of glucagon.

ADVERSE EFFECTS

• Nausea and vomiting are common
• Anaphylactoid or anaphylactic reactions
• Hyperglycemia
• Hypoglycemia, produced by paradoxical insulin release in a patient with an insulinoma
• Catecholamine release and hypertension may occur in a patient with pheochromocytoma
• Hypokalemia, due to hyperglycemia and intracellular shift of both glucose and potassium
• Toxicity from phenol diluent (contains 2 mg/ml)
  • Thrombophlebitis and metabolic acidosis occur, due to effects of the phenol diluent.
  • If the dose of glucagon to be administered is greater than 2 mg, it should be reconstituted with normal saline or D5W to avoid phenol toxicity.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

BOLUS DOSE

• The adult dose is an initial bolus of 5 to 10 mg intravenously over 1 minute; if there is no effect within 5 minutes, a repeat dose, up to 10 to 20 mg, can be administered.
• The pediatric dose is 50 µg/kg bolus over 1 minute; if there is no effect within 5 minutes, a repeat dose, up to 10 mg, can be administered.

MAINTENANCE INFUSION

• The phenol diluent should not be used when reconstituting glucagon for continuous infusions; instead, it should be reconstituted with normal saline or D5W.
• The adult dose is 2 to 10 mg/h, titrated to the desired effect on heart rate and blood pressure.
• The pediatric dose is 0.07 mg/kg/h, titrated to the desired effect on heart rate and blood pressure.

Section Outline:

• BOLUS DOSE
• MAINTENANCE INFUSION

• When toxicity to a beta-receptor or calcium channel blocker develops, the pharmacy should be immediately alerted.
  • Many pharmacies do not stock enough glucagon to manage even one severely poisoned patient, and it is not uncommon that an initial bolus infusion of glucagon would consume the glucagon supply for an entire health-care facility.
  • More glucagon can often be found in the radiology and gastrointestinal departments or can be obtained from another institution.
• If metabolic acidosis develops, the phenol-containing diluent should not be used to reconstitute glucagon.
• Vomiting is very common with use of high-dose glucagon.

Poisoning by hormones and synthetic substitutes: insulins and antidiabetic agents.

RECOMMENDED READING

Howland MA. Glucagon. In: Goldfrank LR, Flomenbaum NE, Lewin NS, et al. eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Edwin K. Kuffner

Reviewer: Richard C. Dart