Diazoxide is a non-diuretic drug closely related chemically to the thiazide diuretics. In injectable form it serves as an antihypertensive agent, but it is also used orally for the management of symptomatic hypoglycaemia. The antihypertensive action will not be discussed here.
Diazoxide produces a prompt increase in blood glucose by a direct inhibitory action on the secretion of insulin by the beta-cells of the islets of Langerhans in the pancreas. The same potassium channel of central importance for regulating glucose-mediated insulin release is the target for hypoglycaemic sulphonylureas and the hyperglycaemic action of diazoxide.
The hyperglycaemia produced by diazoxide in pancreatectomised dogs suggests an additional extrapancreatic mechanism, probably involving release of catecholamines (adrenaline and noradrenaline) from storage sites in the adrenal medulla and sympathetic nerve endings.
Diazoxide is not always effective in controlling hypoglycaemia from sulphonylureas overdose or insulinoma. The effect of diazoxide in hypoglycaemia is dependent of the intensity of insulin release and whether that release is intrinsically responsive to diazoxide at all. If the release mechanism is unresponsive to the sulphonylureas receptor, which could happen in abnormal tissue such as an insulinoma, then there may be little or no response to diazoxide. If the amount of insulin release is very great, whether due to insulinoma or sulphonylureas then diazoxide may reduce but not eliminate the insulin release and may therefore have no effect on plasma glucose. Essentially the process is a competitive one so that the more insulin release there is the less will be the effect of diazoxide.
Bolus doses (300mg slow IVI, PRN) and infusions (50 to 100 mg/hr IV) have both been used.