Friday, August 6, 2010

sulphonylureas - interesting facts

Sulphonylureas are widely used all over the world to manage diabetes. There are 3 generations
First generation - Acetohexamide, Chlorpropamide, Tolbutamide, Tolazamide
Second generation - Glipizide, Gliclazide, Glibenclamide (glyburide), Glyclopyramide
Third generation - Glimepiride

1.They were accidentally discovered by a French researcher working on dogs with typhoid fever!

2.The first sulfonylurea became available in 1955. ( metformin was also discovered in a French laboratory and became available in France in 1959, but it was not available in the United States until 1995 !)

3.The main difference between the generations is how well they bind to the sulfonylurea receptor, with each progressive generation binding more tightly and thus requiring a lower dose to bring about the same amount of insulin secretion.

4. They all act by increasing insulin release by beta cells. Since 50% of beta cell mass is lost by the time diabetes is diagnosed, and it continues to drop as beta cells are lost in the disease process, the sulphonylureas loose their antiglycemic effects as the disease progresses. This is nicely shown in ADOPT trial (2006).check it out! (especially the graph on page 2433)

5.Of all the sulphonylureas, glimepiride preserves ischemic preconditioning of the myocardium (ability to tolerate ischemia - so less anginal pain,minimize irreversible injury & protect myocardial function ). This is because glimepiride binds less avidly to K+ channels in myocardium,than other sulphonylureas. check these 2 interesting articles on this topic (European Heart Journal 1998, Circulation 2002 ).

So, this has been my preferred sulphonylurea for all my patients.
Annnnd ..everyone have a wonderful weekend!!