VPT 311: General and Systemic Veterinary Pharmacology (2+1)

Oral hypoglycaemic drugs

ORAL HYPOGLYCEMIC AGENTS

Sulphonyl ureas

• These are agents that were first introduced as oral hypoglycemic agents.
• There are two groups of sulphonamides namely first and second generation sulphonyl ureas.
• First generation includes tolbutamide, chlorpropamide, acetohexamide and tolazanide.
• Second generation includes glibenclamide, glipizide and gliclazide.
• In the pancreatic beta cells, sulphonyl ureas decrease ATP dependent potassium channels in the plasma membrane.
• This results in depolarization and release of insulin.
• Presence of atleast 30% functional beta cells is essential for the action of sulphonylureas.
• This group of drugs is often used in combination with metformin.
• They are bound to plasma proteins, metabolised by the liver and excreted by the kidney.
• They can cross the placenta (hence not used in pregnancy) and are to be taken before a meal.
• Side effects include hypoglycemia, GIT effects, rash and increased weight.
• There is interaction with NSAIDs and sulphonamides (making hypoglycemia more likely).
• If used with alcohol they will cause severe hypoglycemia.

Biguanides

• This group includes phenformin and metformin.
• They cause little or no hypoglycemia in non-diabetic subjects and do not stimulate pancreatic beta cells.
• Presence of insulin is essential for their action.
• They suppress hepatic gluconeogenesis and glucose output from the liver, enhance binding of insulin to its receptors and stimulate insulin mediated glucose disposal.
• They increase glucose uptake into skeletal muscle and may decrease the absorption of glucose.
• This group of drugs have a short half life and are excreted by the kidney.
• Side effects include hypoglycemia, nausea, vomiting and diarrhea.

Meglitidine analogs

• Repaglinide lowers blood glucose by stimulating the release of insulin from the pancreas. It achieves this by closing ATP-dependent potassium channels in the membrane of the beta cells. This depolarizes the beta cells, opening the cells' calcium channels, and the resulting calcium influx induces insulin secretion. Eg: repaglinide

Thiazolidinediones

• It works as an insulin sensitizer, by binding to the proxisome proliferator-activated receptors (PPARs) in fat cells and making the cells more responsive to insulin. Eg: rosglitazone

α glucosidase inhibitor

• It is a starch blocker, and inhibits alpha glucosidase, an intestinal enzyme that releases glucose from larger carbohydrates. Eg: acarbose