Indications
Tolbutamide is indicated for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes. This medication is used in conjunction with a proper diet and exercise regimen to help manage blood glucose levels in affected patients.
Pharmacodynamics
Tolbutamide belongs to the class of first-generation sulfonylurea antidiabetic agents. It functions by lowering blood glucose levels in individuals with type II diabetes. The drug is notably twice as potent compared to its second-generation counterpart, glipizide. Tolbutamide exerts its therapeutic effects by stimulating the pancreas to secrete insulin and enhancing the body's efficient use of insulin. It is crucial for this mechanism that the pancreas retains its ability to produce insulin.
Absorption
Upon oral administration, tolbutamide is rapidly absorbed and detectable in plasma within 30 to 60 minutes. The peak plasma concentrations are typically reached within 3 to 5 hours. The rate of absorption remains consistent when the drug is taken with food but increases under conditions of higher pH levels.
Metabolism
Tolbutamide is metabolized primarily in the liver, mainly through the oxidation of its p-methyl group, resulting in the formation of the carboxyl metabolite, 1-butyl-3-p-carboxyphenylsulfonylurea. It may also be converted to hydroxytolbutamide. Unlike antibacterial sulfonamides, tolbutamide does not undergo acetylation as it lacks a p-amino group.
Mechanism of Action
Tolbutamide functions by decreasing blood glucose levels in individuals with non-insulin-dependent diabetes mellitus (NIDDM) through the direct stimulation of insulin release from functional beta cells within the pancreatic islets. This process involves interaction with the sulfonylurea receptor on the beta cell. Tolbutamide exerts its effect by inhibiting ATP-sensitive potassium channels on the beta cell membrane, which prevents potassium efflux, leading to cell membrane depolarization. This depolarization facilitates calcium influx, which then binds with calmodulin, activating kinases and triggering the exocytosis of insulin-containing granules, paralleling the natural glucose response.
