First Generation Sulfonylureas

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Information about First Generation Sulfonylureas

The first generation sulfonylureas include acetohexamide, chlorpropamide, tolazamide and tolbutamide, oral hypoglycemic agents that are used in therapy of type 2 diabetes.

Liver safety of First Generation Sulfonylureas

They are well known, but rare causes of clinically apparent liver injury.

Mechanism of action of First Generation Sulfonylureas

The sulfonylureas are substituted arylsulfonylureas, their differences being in the types of substitutions at the two ends of the molecule. The sulfonylureas lower blood glucose through an increase in secretion of insulin from the pancreatic beta cells. They may also have other extra-pancreatic hypoglycemic actions that are important during prolonged therapy. The first generation sulfonylureas have been largely replaced in routine use by the second generation agents, which are more potent and administered in lower doses largely on a once daily basis. Nevertheless, some patients are still maintained on first generation agents.

Dosage and administration for First Generation Sulfonylureas

Chlorpropamide (klor proe' pa mide) is available in generic forms and previously under the brand name of Diabinese in tablets of 100 and 250 mg, the recommended dose initially being 100 to 250 mg daily with increases every 5 to 7 days to a maximum of 750 mg daily. Tolazamide (tol az' a mide) is available in generic forms and under the brand name of Tolinase in tablets of 100, 250 and 500 mg, the recommended dose initially being 100 to 250 mg once daily, with increases thereafter to a maximum of 1000 mg daily. Tolbutamide (tol bue' ta mide) is available in generic forms and previously under the brand name of Orinase in tablets of 500 mg, the recommended dose initially being 1000 to 2000 mg daily in two divided doses, with increases thereafter to a maximum of 3000 mg daily. Acetohexamide (a seet" oh hex' a mide) was previously available in generic forms and under the brand name of Dymelor in tablets of 250 and 500 mg, the recommended dose initially being 250 to 500 mg daily with increases thereafter to a maximum of 1500 mg daily. Acetahexamide has been withdrawn from use and is no longer available.

Side effects of First Generation Sulfonylureas

Common side effects of the first generation sulfonylureas include headache, dizziness, paresthesias, abdominal discomfort, and nausea. These agents are also associated with an “antabuse” like response to alcohol (flushing, nausea, palpitations, hypotension and dizziness) and patients should be advised not to drink alcoholic beverages while on these agents. All sulfonylureas can cause hypoglycemia.

Antidiabetics

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