Use of Spironolactone and Hydrochlorothiazide in Treatment of Oedema

Over the last few years it has become increasingly apparent that excessive aldosterone secretion plays some part in the genesis and maintenance of oedema, whether this be due to congestive cardiac failure, the nephrotic syndrome, or hepatic cirrhosis (Luetscher and Johnson, 1954 ; Axelrad et al., 1955 ; Duncan et al., 1956 ; Dyrenfurth et al, 1957). Considerable interest therefore is attached to the diuretic action of the 17 spirolactone steroids developed by Kagawa et al. (1957). Most investigators are agreed that these compounds act as specific aldosterone antagonists (Wolff et al., 1957 ; Liddle, 1957, 1958 ; Salassa et al, 1958 ; Ross and Bethune, 1959). Two early spirolactone derivatives, SC.5233 and SC.8109, showed promise in the treatment of oedematous patients (Liddle, 1957, 1958 ; Boit? et al, 1958) and of cases of hepatic cirrhosis with ascites (Kerr et al, 1958). The former compound, however, was not active by mouth ; the second was, but only in large doses. A new derivative, spironolactone (SC.9420), which is more potent, has recently been developed (Gantt and Dyniewicz, 1959), and the purpose of this study was to investigate its clinical value.