Chlorpropamide-Induced Water Retention in Patients with Diabetes Mellitus

Abstract

Two patients with diabetes mellitus who were treated with chlorpropamide developed a symptomatic clinical state of hyponatremia and water intoxication. Chemical abnormalities and symptoms were reversed when the drug was withdrawn. On water-loading tests both patients were shown to have an impaired water excretion when pretreated with chlorpropamide. Six patients with diabetes mellitus were given oral water loads, and all showed an impaired water diuresis with chlorpropamide. Similarly, 23 water-loaded normal subjects demonstrated impaired water excretion with chlorpropamide. In thirteen water-loaded normal subjects pretreated with tolazamide, however, no antidiuresis was demonstrated, and, in fact, this drug caused a significant diuresis. The studies indicate that chlorpropamide can cause impaired water diuresis in both normal subjects and patients with diabetes mellitus. Since patients with diabetes mellitus may have an underlying inability to excrete water normally, chlorpropamide treatment may produce sufficient water retention to cause clinically severe hyponatremia and water intoxication. The drug may act by stimulating antidiuretic hormone (ADH) release, as well as by augmenting the effects of ADH on the renal tubule.