Sulfonylureas agents

Type 2 diabetes mellitus For type 2 diabetes, as an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy, with or without a concurrent sulfonylurea agent and/or metformin. 

Repaglinide en nateglinide are not sulfonylurea agents but their mechanism of action is very alike. Repaglinide is the first carbamoylmethyl-benzoic acid derivative that has been registred for the treatment of diabetes mellitus. It closes ATP-dependent potassium channels in the beta cell membrane with consequent depolarization, opening of calcium channels and increased insulin release. It is rapidly absorbed with peak plasma levels after 1 hour. It has a protein binding of over 98%. 

Three classes of oral therapeutic agent are available for treating patients with diabetes mellitiis (NIDDM) the arylsulfonylureas (known simply as sulfonylureas), biguanides, and a-glycosidase inhibitors. Since 1977, only the sulfonylureas have been approved for use in the United States, although the other classes are used elsewhere. 

Table 2. Sulfonylureas Used as Oral Hypoglycemic Agents...

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

Relative potency alone does not determine dmg selection because maximal effectiveness is similar for all agents. A single daily dose of any sulfonylurea, except tolbutamide, is sometimes adequate to control blood glucose in NIDDM patients. 

Yet another example of a so-called pharmacophoric group is the biguanide functionality, a grouping associated with oral antidiabetic activity (see the section on sulfonylureas for a fuller discussion of this activity). Condensation of 2-phenethylamine with dicyanamide affords directly the orally active hypoglycemic agent phenformin (88). ... 

Sulfonylureas represent the first class of oral antidiabetes agents approved for use in the United States. These drugs are classified as being either first- or second-generation agents. Both classes of sulfonylureas are equally effective when given at... 

Metformin also has been shown to produce beneficial effects on serum lipid levels and thus has become a first-line agent for type 2 DM patients with metabolic syndrome. Triglyceride and low-density lipoprotein (LDL) cholesterol levels often are reduced by 8% to 15%, whereas high-density lipoprotein (HDL) cholesterol improves by approximately 2%. A modest weight loss of 2 to 3 kg (4.4—6.6 lb) also has been reported with metformin therapy. Metformin often is used in combination with a sulfonylurea or a thiazolidinedione for synergistic effects. 

Sulfonamides Sulfonylureas, phenytoin, warfarin Decreased metabolism of other agent Monitor blood glucose, SDC, PT... 

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