Sulfonylureas

Summary

The sulfonylureas are a class of drugs used to treat diabetes mellitus, especially type 2 diabetes mellitus. The sulfonylureas can be split into two generations: the older first generation drugs, and the newer second generation drugs. First generation sulfonylureas include tolbutamide and chlorpropamide. Second generation sulfonylureas include glimepiride, glyburide, and glipizide.

All sulfonylureas share a common mechanism of action. These drugs act on the beta cell membrane in the pancreas. The sulfonylureas directly close potassium channels, which causes depolarization of the beta cell. This then causes calcium influx into the cell, which leads to the release of both insulin and C-peptide.

Regarding side effects, all sulfonylureas should be used with caution in renal insufficiency, since decreased kidney function can increase the risk of experiencing side effects. The sulfonylureas are sulfa drugs and can cause sulfa allergies. These drugs are also notable for causing weight gain and hypoglycemia in patients.The first generation sulfonylurea drugs are specifically known to cause a disulfiram-like reaction to alcohol. This is one of the reasons why the first-generation sulfonylureas are not as preferred compared to the newer second-generation drugs.

Key Points

• Sulfonylureas
  • First Generation Drug Names
    • Chlorpropamide
    • Tolbutamide
    • Note: This is not unique but -mide is a common suffix
  • Second Generation Drug Names
    • Glipizide
    • Glyburide
    • Glimepiride
    • Note: This is not unique but -ride and -zide are common suffixes
  • Mechanism
    • Close ATP-dependent potassium channels in pancreatic beta cell membrane
      • → cell depolarization
        • Via decreased outflow of potassium from the cell
      • → increased calcium influx
        • Via opening of voltage-gated calcium channels
      • → insulin release and C-peptide release
        • Intracellular calcium causes fusion of vesicles and release of insulin
        • Since increased insulin is endogenous in origin, it is released along with the byproduct C-peptide inside the pancreas
  • Clinical Use
    • Treats diabetes mellitus
      • Often used to treat type 2 diabetes mellitus, especially in patients with high blood sugar unresponsive to initial treatment with metformin
  • Side Effects
    • Disulfiram-like reaction (1st generation only)
      • Causes adverse reaction to alcohol
      • These drugs are rarely used due to this side effect
    • Hypoglycemia
      • Increased risk in renal insufficiency
      • Insulin drives sugar into cells, which removes glucose from the bloodstream. If too much insulin is given, too much glucose can be driven into cells and blood glucose levels can get too low.
    • Weight gain
      • Think: Released insulin drives sugar into cells and fattens them up (increased anabolism)
    • Sulfa allergies
      • As evidenced by the sulfo- in their name