The Acute Hemodynamic Effects of Diazoxide in Man

IN THE past 10 years many new drugs that lower blood pressure have been introduced for the treatment of hypertension. Several of them have not withstood the rigors of controlled clinical trials; others have faded away because side effects precluded their successful application. The useful hypotensive drugs developed have provided the physician one means to prolong the life of the individual with malignant hypertension, hypertensive heart failure, or encephalopathy and reverse many of the signs and symptoms of the disease. The purpose of this paper is to present our observations of the acute hemodynamic effects of a new hypotensive drug, diazoxide, in man. Diazoxide is a nondiuretic benzothiadiazine synthesized by Dr. J. G. Topliss, M. H. Sherlock, and Dr. N. Sperber of the Chemical Research Division, Schering Corporation, and subsequently evaluated for hypotensive and diuretic activities.2 3 It lacks the free sulfamyl group that chlorothiazide possesses. It also has a methyl group in the 3 position and chloride in the 7 instead of the 6 position. When given intravenously to dogs, diazoxide decreases arterial pressure and total peripheral resistance, but increases heart rate, stroke volume, cardiac output, transmural right atrial pressure, and isometric myocardial contractile strength.4 In man arterial pressure is lowered within 30 seconds. Supine as well as standing pressures are reduced. The depres-