Glucagon
Glucagon
Glucagon, a hyperglycemic drug that raises blood glucose levels, is a hormone normally produced by the alpha cells of the islets of Langerhans in the pancreas.
Pharmacokinetics
After subQ, I.M., or I.V. injection, glucagon is absorbed rapidly. Glucagon is distributed throughout the body, although its effect occurs primarily in the liver.
Metabolism and excretion
Glucagon is degraded extensively by the liver, kidneys, and plasma, and at its tissue receptor sites in plasma membranes. It’s removed from the body by the liver and the kidneys.
Pharmacodynamics
Glucagon regulates the rate of glucose production through:
- glycogenolysis, the conversion of glycogen back into glucose by the liver
- gluconeogenesis, the formation of glucose from free fatty acids and proteins
- lipolysis, the release of fatty acids from adipose tissue for conversion to glucose.
Pharmacotherapeutics
Glucagon is used for emergency treatment of severe hypoglycemia. It’s also used during radiologic examination of the GI tract to reduce GI motility.
Drug interactions
Glucagon interacts adversely only with oral anticoagulants, increasing the tendency to bleed. Adverse reactions to glucagon are rare.
Adverse reactions to oral antidiabetic drugs
Hypoglycemia is a major adverse reaction to oral antidiabetic drugs, especially when combination therapy is used. Here are some common adverse reactions to individual oral antidiabetic drugs.
Sulfonylureas
- nausea
- epigastric fullness
- blood abnormalities
- water retention
- rash
- hyponatremia
- photosensitivity
Metformin
- metallic taste
- nausea and vomiting
- abdominal discomfort
Acarbose
- abdominal pain
- diarrhea
- Flatulence
Thiazolidinediones
- Weight gain
- Swelling
How glucagon raises glucose levels
When adequate stores of glycogen are present, glucagon can raise glucose levels in patients with severe hypoglycemia. What happens is easy to follow:
- Initially, glucagon stimulates the formation of adenylate cyclase in the liver cell.
- Adenylate cyclase then converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP).
- This product initiates a series of reactions that result in an active phosphorylated glucose molecule.
- In this phosphorylated form, the large glucose molecule can’t pass through the cell membrane.
- Through glycogenolysis (the breakdown of glycogen, the stored form of glucose), the liver removes the phosphate group and allows the glucose to enter the bloodstream, raising blood glucose levels for short-term energy needs.
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