According to Balant, hypoglycemic sulphonylurea compounds differ in their chemical structure and can be divided into two groups. Carbutamide, tolbutamide, chlorpropamide and gliclazide are first-generation compounds, while glibenclamide, glipizide and glimepiride are second-generation agents. First-generation agents exert their hypoglycemic effect at high concentrations, while second-generation agents act at low concentrations. Our experimental in vivo studies demonstrated that the first-generation sulphonylureas potentiate the provoked arrhythmias, while the second-generation agents depress them. Clinical observations seem to support this finding.
To analyze these divergencies, the sulphonylurea cheap drugs were investigated in isolated rabbit heart preparations. The compounds did not exert any effect on the nomotopic and junctional automaticities. Glibenclamide proved to depress the automaticity of Purkinje fibres, while the other agents enhanced it. In further in vitro tests involving isolated left atria and strips from the anterior free wall of right ventricles, only glibenclamide enhanced conduction time, effective refractory period and electrical threshold dose-dependently. These data led to the conclusion that glibenclamide has a definite antiarrhythmic effect in vitro, while the other second-generation compounds show only in vivo evidence for antiarrhythmic action, and that the first-generation agents are not proarrhythmogenic in vitro, although they are capable of stimulating provoked arrhythmias in vivo. However, these in vitro electrophysiological studies were not able to explain completely the divergent cardiac effects of these hypoglycemic sulphonylureas. Your shopping for best quality medications is going to be pleasant and very affordable every time: make sure of it yourself when you visit the best pharmacy to buy as this is the kind of experience every patient is looking forward to.