Sulfonylurea drugs

Cvetkovic RS, Plosker GL. (2007) Exenatide A review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs 67 935-954. 

NIDDM is strongly associated with obesity,dd and dieting and exercise often provide adequate control of blood glucose. Sulfonylurea drugs such as the following induce an increase in the number of insulin receptors formed and are also widely used in treatment of the condition.66 These drugs bind to and inhibit ATP-sensitive K+ channels in the P cell membranes. A defect in this sulfonylurea receptor has been associated with excessive insulin secretion... 

Hypoglycemia appears to be less of a problem with glimepiride than with other sulfonylurea drugs. In nine patients who had severe hypoglycemia associated with glimepiride the hydroxylated metabolite was detectable 4—8 hours longer than glimepiride itself. 

Sulfonylurea drugs basic and clinical considerations. Sydney, Australia, 20 November 1988Proceedings. Diabetes Care 1990 13(Suppl 3) l-58. 

Moses AM, Howanitz J, Miller M. Diuretic action of three sulfonylurea drugs. Ann Intern Med 1973 78(4) 541-4. 

Bussing R, Gende A. Severe hypoglycemia from clarithromycin-sulfonylurea drug interaction. Diabetes Care 2002 25(9) 1659-61. 

Intrauterine fetal death and prolonged symptomatic neonatal hypoglycemia have been reported after treatment of the mother with sulfonylurea drugs (13,14). 

Q10 Sulfonylurea drugs enhance insulin secretion. They bind to the receptors on the /1-cells of the islets of Langerhans, causing a partial depolarization of the cell membrane, influx of calcium ions and a reduction in potassium efflux. The ultimate result is increased insulin secretion. These drugs also increase the sensitivity of the /1-cells to stimuli that cause insulin secretion, possibly by increasing the intracellular levels of a cyclic nucleotide second... 

Sulfonylurea derivatives such as tolbutamide (Figure 5.14) bind to the sulfonylurea receptor and thereby promote the closing of the Kj, channel. This amplifies the secretion of insulin - a desirable effect in type II diabetics, who suffer not from an absolute lack of insulin (as type I diabetics do) but from an inadequate response to it. Sulfonylurea drugs can be used orally, which is more convenient than insulin therapy. It is also less prone to result in excessive insulin action (hypoglycemia), since the physiological signal is amplified but not substituted. However, commonly the (3-cells wear out eventually, and insulin therapy has to be instituted anyway. 

A multiple compartment system would probably be necessary to obtain a rate constant for metabolism, distribution rate constant, rate constant for absorption, etc. Sulfonylurea drugs may lower blood sugar by stimulating the beta cells of the pancreatic islets to release endogenous insulin. Also, it has been reported that the sulfonylureas block the degradation of insulin by the enzyme insulinase13. 

G. Muller, The molecular mechanism of the insulin-mimetic/sensitizing activity of the antidiabetic sulfonylurea drug amaryl. Mol. Med., 2000, 6, 907-933. 

G. Muller and S. Wied, The sulfonylurea drug, ghmepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro. Diabetes,... 

Wdhlin-Boll, E. Melander, A. High-performance liquid chromatographic determination of glipizide and some other sulfonylurea drugs in serum. J.Chromatogr., 1979, 164, 541-546... 

Tolbutamide, a sulfonylurea drug that increases insulin secretion, also increases the secretion of pancreatic somatostatin. 

Garratt KN, Brady PA, Hassinger NL, GriU DE, Terzic A, Holmes DR Jr. Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction. J Am Coll Cardiol 1999 33(1) 119-124. 

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