Some science behind the scenes

Sulfonylureas

 

Sulphonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2.

They act by increasing insulin release from the beta cells in the pancreas. They first inhibit ATP-sensitive potassium channels in pancreatic beta cells. This inhibition then causes cell membrane depolarization opening voltage-dependent calcium channels. This results in an increase in intracellular calcium in the beta cell and subsequent stimulation of insulin release. There is some evidence that sulfonylureas also sensitize beta-cells to glucose, that they limit glucose production in the liver, that they decrease lipolysis (breakdown and release of fatty acids by adipose tissue) and decrease clearance of insulin by the liver.

It is very difficult to control the doses of these drugs – particularly when the people have not been told to change their dietary habits. Sulfonylureas, may induce hypoglycemia [a lower than normal level of blood sugar/glucose] as a result of excesses in insulin production and release. This typically occurs if the dose is too high.

Sulfonylureas can induce weight gain. Other side-effects are: abdominal upset, headache and hypersensitivity reactions. Some of the first generation drugs cause nausea, vomiting, diarrhea, and constipation, facial flushing after the ingestion of alcohol and increased secretion of antidiuretic hormone (ADH), which can lead to hyponatremia.

Sulfonylureas are potentially teratogenic and cannot be used in pregnancy or in patients who may become pregnant. Impairment of liver or kidney function increase the risk of hypoglycemia, and are contraindications. All sulfonylureas carry an FDA-required warning about increased risk of cardiovascular death.

There are two generations of this class of drug. Second-generation sulfonylureas have increased potency by weight, compared to first-generation sulfonylureas.

Not all secondary sufonylureas have the same risks of hypoglycemia. According to Wikipedia, Glibenclamide (glyburide) is associated with an incidence of hypoglycemia of up to 20–30%, compared to 2% to 4% with glimepiride.

On the other hand there are a number of drug interactions that can greatly affect the potency of these drugs. For example, the hypoglycemic action may be potentiated by phenylbutazone, alcohol, fluconazole, beta-blockers, and possibly ACE inhibitors, which given the link between heart disease and diabetes is significant. Interactions with NSAIDs like Salicylates, Sulphonamides, Chloramphenicol, coumadin and probenecid may also potentiate the hypoglycemic action of glimepiride. On the other hand, Thiazides, other diuretics, phothiazides, thyroid products, oral contraceptives, phenytoin tend to produce hyperglycemia 

First generation

  • Carbutamide

  • Acetohexamide

  • Chlorpropamide

  • Tolbutamide

  • Tolazamide

Second generation

  • Glipizide

  • Gliclazide

  • Glibenclamide (glyburide)

  • Gliquidone

  • Glyclopyramide

  • Glimepiride