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Diabeta

Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2 ("adult-onset"). They act by increasing insulin release from the beta cells in the pancreas. more...

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Drugs in this class

First generation:

  • Chlorpropamide
  • Tolbutamide
  • Tolazamide

Second generation:

  • Glipizide
  • Gliclazide
  • Glibenclamide
  • Glimepiride
  • Gliquidone

Chemistry

Please see individual members of the class for their chemical structure

All sulfonylureas have a central phenyl ring with two branching chains

Pharmacology

Method of action

Sulfonylureas bind to an ATP-dependent K+ channel on the cell membrane of pancreatic beta cells. This inhibits a tonic, hyperpolarizing outflux of potassium, which causes the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.

There is some evidence that sulfonylureas also sensitize β-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.

Pharmacokinetics

Various sulfonylureas have different pharmacokinetics. The choice depends on the propensity of the patient to develop hypoglycemia - long-acting sulfonylureas with active metabolites can induce hypoglycemia. They can, however, help achieve glycemic control when tolerated by the patient. The shorter-acting agents may not control blood sugar levels adequately.

Due to varying half-life, some drugs have to be taken twice (tolbutamide) or three times a day rather than once (glimepiride). The short-acting agents may have to be taken about 30 minutes before the meal, to ascertain maximum efficacy when the food leads to increased blood glucose levels.

Some sulfonylureas are metabolised by liver metabolic enzymes (cytochrome P450) and inducers of this enzyme system (such as the antibiotic rifampicin) can therefore increase the clearance of sulfonylureas. In addition, because some sulfonylureas are bound to plasma proteins, use of drugs that also bind to plasma proteins can release the sulfonylureas from their binding places, leading to increased clearance.

Uses

Sulfonylureas are used almost exclusively in diabetes mellitus type 2. Other types of diabetes generally do not respond to sulfonylurea therapy, or (in diabetes of pregnancy) there are other contraindications.

Although for many years sulfonylureas were the first drugs to be used in new cases of diabetes, in the 1990s it was discovered that obese patients might benefit more from metformin.

Read more at Wikipedia.org


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