tolazamide

Tolazamide is an oral hypoglycemic agent in the sulfonylurea class, a first-generation drug used to improve glycemic control in adults with type 2 diabetes. It is sold under various brand names, including Tolinase. It is typically used as an adjunct to diet and exercise when glycemic control is not achieved with lifestyle measures alone.

Mechanism of action: Tolazamide binds to sulfonylurea receptors on pancreatic beta cells, closing ATP-sensitive potassium channels (KATP). This depolarizes the cell membrane and opens voltage-gated calcium channels, triggering Ca2+-dependent insulin release. The drug thereby increases endogenous insulin secretion in the presence of glucose. It may also provide modest improvements in peripheral insulin sensitivity.

Pharmacokinetics: Tolazamide is taken orally and undergoes hepatic metabolism with renal excretion of metabolites and some unchanged drug. The onset of action occurs within 1–2 hours, with the peak effect occurring in the ensuing hours. Its duration is relatively long among sulfonylureas, necessitating monitoring for potential hypoglycemia, especially in at-risk individuals.

Indications: It is indicated for the treatment of type 2 diabetes mellitus to improve glycemic control in conjunction with diet and exercise, particularly when monotherapy is insufficient. It is not indicated for type 1 diabetes or diabetic ketoacidosis.

Contraindications and cautions: Contraindicated in patients with hypersensitivity to sulfonylureas, in diabetic ketoacidosis, and in those with significant hepatic or renal impairment where hypoglycemia risk is heightened. Caution is advised in the elderly, during pregnancy and lactation, and in patients with conditions that predispose to hypoglycemia.

Adverse effects and interactions: The major adverse effect is hypoglycemia, which can be serious. Weight gain and gastrointestinal upset are also reported. Interactions include increased hypoglycemia risk with alcohol, and potential masking of hypoglycemia symptoms by beta-blockers; other drug interactions may alter tolazamide’s effect.