ORAL HYPOGLYCEMICS

These are drugs administered orally to lower blood glucose level used in mild diabetes. They are grouped as Sulphonylureas and Biguinides.

Sulphonyl ureas

These compounds are chemically related to sulphonamides.

First generation: Tolbutamide, Chlorpropamide

Second generation: Glibenclamide, Glipizide

Mechanism: hypoglycemic action is due to Stimulation of insulin release from b cell, Depression of glucagon secretion, Increase number of insulin receptor, Reduce insulin output from liver (Decrease hepatic gluconeogenesis and glycogenolysis)

Pharmacokinetics: They are rapidly absorbed from the gastrointestinal tract. They are also extensively plasma protein bound and are mainly metabolized in the liver.

Use: Mild diabetes mellitus in old patients (type II)

Adverse reaction: The toxicity of these compounds is remarkably low. The important toxic effects include: hypoglycemia, allergic skin rash and bone marrow depression, cholestatic jaundice (esp. chlorpropamide)

Side effects: Gastric irritation, prolonged hypoglycemia (esp. chlorpropamide), large doses confusion, vertigo, ataxia, leucopenia, aggranulocytosis, thrombocytopenia, and teratogenecity

Drug interaction:

1. Hypoglycemia is enhanced by sulphonamides, phenylbutazone
2. Alcohol produces “Disulfirum” like action (flushing of the face, severe headache, vomiting etc.)
3. Sulphonyl ureas increase anticoagulant effect of oral anticoagulant
4. Thiazides oppose the action of sulphonylureas.