Different Cardiac Effects of Hypoglycaemic Sulphonylurea Compounds

The result of the UGDP study (1) suggested that the increased cardiovascular mortality among diabetics could be related to tolbutamide treatment. The mortality of diabetics in coronary care units is known to be significantly higher than that of metabolically healthy patients (2). The hypoglycaemic sulphonylureas alter the electrical and mechanical functions of the heart directly under “in vitro” (3,4) and “in vivo” conditions (5,6,7). Lasseter et al. (8) and Crass et al. (9) suggested that the increase in Purkinje fibers automaticity, myocardial contractile force, and the elevation of arterial blood pressure induced by hypoglycaemic sulphonylureas might be responsible for the development of increased cardiovascular mortality in diabetics. It was also demonstrated that a second generation sulphonylurea compound, glibenclamide, decreases the automaticity and the conduction time in the Purkinje fibers (3) and did not elevate the arterial blood pressure (5) in contrast to the first generation sulphonylureas (Figure 1). Furthermore, it was demonstrated that in diabetic patients tolbutamide and carbutamide enhanced while glibenclamide did not influence the incidence of digitalis intoxication, or that of multifocal ventricular ectopic beats during digitalis therapy (10). Koltai et al. (11) documented further that the incidence of lethal and nonlethal myocardial infarction is increased in tolutamide, chlorpropamide and carbutamide treated diabetics.