The effect of diazoxide, potassium chloride, and ammonium chloride on serum and urinary uric acid.

I would like to tell you about two studies in which we have recently been involved, at the University of Michigan. The first concerns the effects of diazoxide on uric acid excretion. Diazoxide is chemically similar to chlorothiazide (Fig. l O l ) , differing by the absence of a free sulfamyl group. However, its pharmacologic effects are quite different. Studies following the oral administration of diazoxide have shown that it lowers blood pressure, as does chlorothiazide, but has antidiuretic properties, decreasing sodium, potassium and chloride e~cretion.l-~ It has also been found to produce hyperglycemia, to an extent prohibiting its usefulness for chronic However, intravenously it produces a prompt fall in blood pressure and has thus been recommended for the treatment of hypertensive crisis.? The effect of intravenous diazoxide upon blood pressure, electrolyte, and uric acid excretion was studied, but only the last will be recorded here in any detail. The effects of 300 mg. of diazoxide (the usual recommended dose) was studied in nine subjects; one subject received 600 mg. and another 300 mg. of intravenous diazoxide plus 1.5 Gm. of oral probenecid. The effect of 300 mg. of chlorothiazide given intravenously was also studied in four of these subjects. Figure 102 depicts the changes in urinary uric acid. Both 30 mg. and 600 mg. doses of diazoxide produced a decrease in urate excretion. This effect was completely blocked by probenecid. Chlorothiazide, given intravenously, produced a urate diuresis, as has been previously demonstrated by Dr. Demartini.8 The urate clearance: creatinine clearance ratio was similarly affected (Fig. 103), demonstrating that these changes in uric acid excretion were not solely due to changes in the glomerular filtration rate. The effects of these two drugs are compared and summarized in Fig. 104. We postulate that diazoxide in 300 mg. and 600 mg. doses decreases urate excretion by blocking renal tubular secretion of uric acid. Intravenous chloro-