Hypoglycemic drugs chlorpropamide

In 70 non-insulin-dependent patients with diabetes, taking one of five different oral hypoglycemic drugs, 21% of prescriptions were associated with a low plasma sodium concentration, but it was lower than 129 mmol/1 in only 8% (75). Every oral hypoglycemic agent was associated with a low plasma sodium concentration, which normalized on withdrawal. Extreme hyponatremia was only seen with chlorpropamide and, in one case, with glibenclamide. 

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. 

Chlorpropamide Diabinese) has a relatively slow onset of action, with its maximal hypoglycemic potential often not reached for 1 or 2 weeks. Similarly, several weeks may be required to eliminate the drug after discontinuation of therapy. This drug can cause flushing, particularly when taken with alcohol, and can also cause hyponatremia. This effect has been employed to treat some patients who have partial central diabetes insipidus, an unrelated condition due to a pituitary ADH deficiency. 

Acetohexamide is a blood-glucose-lowering drug of the sulfonylurea class. The first-generation oral hypoglycemic agents include tolbutamide (Orinase), acetohexamide (Dymelor), tolazamide (Tolinase), and chlorpropamide... 

Tolbutamide and chlorpropamide are oral hypoglycemic agents with low solubilities and dissolution rates in water. Both drugs have several polymorphic forms (Forms I-IV etc. for tolbutamide and Forms A-C etc. for chlorpropamide). The dissolution rates of the metastable forms of both drugs are higher than those of the stable forms (Form I and Form A for tolbutamide and chlorpropamide, respectively). The metastable Form IV and Form C are obtained by the spray-drying... 

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