Insulin Disopyramide

INSULIN ANTIARRHYTHMICS -DISOPYRAMIDE t risk of hypoglycaemic episodes -particularly in patients with impaired renal function. Hypoglycaemic attacks may occur even when plasma levels of disopyramide are within the normal range (attacks occurring with plasma disopyramide levels of 1-4ng/mL)... 

Additional investigations in the second case suggested enhanced insulin secretion induced by toxic disopyramide concentrations as the probable mechanism. 

Disopyramide and its metabolite mono-isopropyl disopyramide T secretion of insulin (considered to be due to inhibition of potassium-ATP channels). Suggestion that disopyramide causes an impairment of the counterregulatory (homeostatic) mechanisms that follow hypoglycaemia... 

Not fully established. An in vitro study using human liver microsomes indicated that erythromycin inhibits the metabolism (mono-A-dealkylation) of disopyramide which, in vivo, would be expected to reduce its loss from the body and increase its serum levels. Clarithromycin and azithromycin probably do the same. The increased serum levels of disopyramide can result in adverse effects such as QT prolongation and torsade de pointes, and may result in enhanced insulin secretion and hypoglycaemia. - Both intravenous erythromycin and clarithromycin" alone have been associated with prolongation of the QT interval and torsade de pointes. Therefore, disopyramide and macrolides may have additive effects on the QT interval in addition to the pharmacokinetic interaction. 

Disopyramide occasionally causes hypoglycaemia, which may be severe. Isolated reports describe severe hypoglycaemia when dis-opyramide was given to diabetic patients taking gliclazide, or metformin and/or insulin. 

Disopyramide occasionally and unpredictably causes hypoglycaemia, which may be severe. " The reasons are not fully understood, but in vitro studies suggest that disopyramide and its main metabolite may enhance insulin release from the pancreas. There is a report of severe hypoglycaemia in an 82-year-old woman with diabetes who was taking gliclazide. 

Horie M, Mizuno N, Tsuji K, Haruna T, Ninomiya T, Ishida H, Seino Y, Sasayama S. Disopyramide and its metabolite enhance insulin release from clonal pancreatic p-cells by blocking K tp channels. Cardiovasc Drugs Ther (2001) 15, 31-9. 

OnodaN, Kawagoe M, Shimizu M, Komori T, Takahashi C, Oomori Y, Hirata Y. A case of non-insulin dependent diabetes mellitus whose insulin requirement was m kedly reduced after disopyramide treatment for arrhythmia. Nippon Naika Gakkai Zas i (1989) 78, 820-5. 

---