Hormonal Sulphonylureas

SULPHONYLUREAS THYROID HORMONES 1 hypoglycaemic effect of sulphonylureas Due to these drugs causing hyperglycaemia, the mechanism being uncertain at present T doses of sulphonylureas are often required for adequate glycaemic control... 

Chlorpropamide (but not other sulphonylureas) and carbamazepine are effective in partial pituitary diabetes insipidus, i.e. some natural hormone production remains, because they act on the kidney potentiating the effect of vasopressin on the renal tubule. H5q oglycaemia may occur with chlorpropamide. 

The sulphonylureas, particularly chlorpropamide, may infrequently induce a syndrome of inappropriate secretion of antidiuretic hormone (augmenting hypothalamic-pituitary release of this hormone) characterized by water retention, hyponatraemia, low serum osmolality and high urine osmolality, and central nervous system signs. Water retention and dilutional hyponatraemia have occurred after administration of chlorpropamide and tolbutamide to NIDDM patients, especially those with congestive heart failure or hepatic cirrhosis. Glipizide, acetohexamide (Moses et al., 1973), tolazamide, glibenclamide are mildly diuretic. 

D. Wiggins and G. F. Gibbons, The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas, Biochem. J., 1992, 284, 457-462. 

Metaraminol is almost devoid of lipolytic activity and it acts therefore as a powerful inhibitor of FFA mobilization The well-known observation that insulin can decrease the release of FFA and glycerol from adipose tissue in vitro, even in the absence of glucose and lipolytic hormones, has prompted investigators to see whether drugs known to lower blood glucose such as sulphonylureas have a similar activity. In isolated adipose tissue cells, sulphonylmeas (tolbutamide, tolazamide) decrease the rate of FFA release in a way similar to that of insulin. This effect is not mediated by insulin because it is still present when anti-insulin is added and it seems to be a direct effect, possibly at the level of adenyl cyclase activation. Accordingly, the intravenous injection of tolbutamide in man reduces plasma FFA levels. 

Apart from mediating the action of catecholamines, cAMP and its congener cGMP are common secondary-transmitters of hormone action. For example, they play the main part in liberating insulin from the pancreas in vivo. Tolbutamide, and similar sulphonylureas, which are used to alleviate the diabetes of elderly people, somewhat selectively inhibit pancreatic phosphodiesterase and thus preserve cAMP from destruction (Goldfine et al. 1971). Activity within a series of sulphonylureas is positively correlated with lipophilicity and also with binding by serum albumin (Seydel, Ahrens, and Losert, 1975). These cyclic phosphates also mediate the diuretic effect of vasopressin, and the action of ACTH and many other hormones (Sutherland, 0ye, and Butcher, 1965). 

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