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Hypoglycemia: Glucagon

Background: Glucagon was originally thought to be a “contaminant” that caused hyperglycemia found in pancreatic extracts in studies from 1923. Looking for the hyperglycemic mechanism of this “contaminant” led to the nobel prize-winning discovery of cyclic adenosine monophosphate (c-AMP) in the 1960s. Full understanding of this hormone did not come until the 1970s, when somatostatin was discovered and found to inhibit the action of Glucagon.

Glucagon is a peptide hormone, synthesized and secreted by Alpha cells of the pancreas. Its main action is to stimulate glycogenolysis, i.e. release of stored glucose (glycogen) from the liver. It also inhibits glycogen synthesis thus averting further storage of glucose in the liver, and increases gluconeogenesis in the liver from protein and fat. Other actions include transiently paralyzing the smooth muscles of the intestines. After a 12-16 hour fast, arterial and venous concentrations range between 25 and 150 pg/ mL and, the normal human pancreas contains approximately 700- 1000 micrograms of glucagons.

Manufacturing: Synthetic Glucagon is manufactured by genetically engineering E. coli. It is prepared as a powder and freeze-dried.

Route: IV, IM, SQ

Preparation: It is administered by mixing with 1mL of glycerin.

Dosage: [Children < 44 pounds] 0.03-0.1 mg/kg/dose IV/IM q20min prn; not to exceed 0.5 mg/dose; not to be administered at concentrations >1 mg/mL. [Adults & Children >44 pounds] 1mg (1unit). After mixing, the solution should appear clear and without floating particles and should not be discolored. Metabolism: Kidney (23-39%) > Liver. ↓ catabolism of Glucagon seen in renal failure and starvation. No changes seen in diabetics or liver disease.

Major Stimulation of Glucagon Secretion: Hypoglycemia, exercise, trauma, infection, and other stress. Hypoglycemia both directly (stimulates Alpha cells) and indirectly (↓ insulin secretion which otherwise tonically inhibits Glucagon) increases Glucagon release. Other contributions come from: NorEpi (autonomic adrenergic), acetylcholine (cholinergic), and peptidergic neural & epinephrine (adrenomedullary signals). ***In Diabetics (type 1&2), alpha cells can become dysfunctional and not secrete Glucagon in response to hypoglycemia, predisposing diabetics to severe hypoglycemia. Similar problems occur in chronic pancreatitis and in pts s/p pancreatectomy.

Interactions: Effects of anticoagulants may be enhanced by glucagon (although onset may be delayed); monitor prothrombin activity and for signs of bleeding in patients receiving anticoagulants; adjust dose accordingly.

Pregnancy: B- no studies in pregnant women, some risk seen in animals.

Side effect: N/V

Contraindications: Not to be administered to patients with little to no glycogen stores: starvation (including chronic alcoholics), adrenal insufficiency, pheochromocytomas or chronic hypoglycemia.

Mechanisms of Action: [figure needed]

Effects: Glucagon dose, in appropriate patients, will produce maximal glucose effects 5-20min (IV) and approximately 30 min for IM/ SQ.