Hypoglycemic drugs tolbutamide

Sulfonamides may inhibit the (hepatic) metabolism of the oral hypoglycemic drugs tolbutamide (Orinase) and chloq ropamide (Diabinese). This would increase the possibility of a hypoglycemic reaction. 

These compounds structurally related to sulfonamides are oral hypoglycemic drugs and used for treatment of non-insulin-dependent diabetes. The best known derivatives are tolbutamide [(l-n-butyl-3-p-tolylsulfonyl)urea, 51] and the more potent glyburide IV- 4-[j9-(2-methoxy-5-chlorobenzamido)ethyl]benzosulfonyl -N -cyclohexylurea, 52188 189. 

It is employed for the treatment of Type 2 diabetes mellitus which is found to be 100 folds more potent than tolbutamide in evoking the pancreatie seeretion of insulin. It essentially differs from other oral hypoglycemic drugs wherein the ensuing toleranee to this specific action evidently does not take place. 

The mechanism of action of the hypoglycemic drugs is not clear, but tolbutamide and chlorpropamide have been found to inhibit cyclic AMP phosphodiesterase and thereby increase the intracellular concentrations of cyclic AMP. 

Tolbutamide, N-[(butylamino)carbonyl]-4-methylbenzenesulphona-mide N-(butylamino) carbonyl-p-toluene sulphonamide is a sulphonlylurea that is orally active as a hypoglycemic agent. The drug stimulates the poncreatic islet beta cells to release extra insulin. It also inhibits phosphodiesterase, which preserves cyclic AMP and thus favor glycogenolysis in a number of tissues. 

The drug with the higher affinity constant will successfully displace the drug with the lower. The result is an increase in the free drug concentration of the latter. For example, tolbutamide (an oral hypoglycemic agent used in maturity-onset diabetes mellitus) is approximately 95 percent bound and 5 percent free (see Table 4.1). In the presence of the anti-inflammatory drug phenylbutazone (which is nearly 100 percent... 

Drug potentiation Transient potentiation of the hypoglycemic effect of tolbutamide (see p. 260) or the anticoagulant effect of warfarin or of bishydroxycoumarin (see p. 199) results from their displacement from binding sites on serum albumin. Free methotrexate (see p. 378) levels may also rise through displacement. 

The oral administration of tolbutamide sodium resulted in a rapid and pronounced reduction in blood glucose, whereas the free acid was found to produce a more gradual hypoglycemic effect. This was attributed to the dissolution rate of the sodium salt being about 275 times greater than that of the free acid. Therefore it was concluded that the more slowly dissolving free acid was, the more useful the form of the drug for the treatment of diabetes. 

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