Five Years' Experience with the Evaluation of Diuretic Agents.

PRIOR TO the advent of potent oral diuretics, pareliteral mercurial drugs were the mainstays of diuretic therapy. In the search for orally effective diuretic agents, several events stand out. In 1949, Schwartz1 reported the diuretic effect of sulfanilamide in patients with congestive heart failure. In 1953, acetazolamide, a sulfonamide derivative and a potent carbonic anhydrase inhibitor, became available for clinical use.2' 3 Then, in 1957, Novello and Sprague4 synthesized chlorothiazide, a benzothiadiazine compound. The availability of the thiazide drugs represented a major breakthrough in the search for potent oral diuretics. Subsequently, in the continuing search for the ideal diuretic agent, the pharmaceutical industry has made available a large number of additional drugs. There are at least nine analogues of the basic benzothiadiazine molecule now available or soon to be released for clinical use. Also introduced during recent years were chlorthalidone (a phthalimidine diuretic), quinethazone (a quinazolinone), and spironolactone (an antialdosterone agent). With such a plethora of agents it is obviously important for the practicing physician to know which drugs are superior. During the past o years, we have investigated the clinical pharmacology of the newer diuretic agents by a standardized methodology. The analysis of the data obtained in the evaluation of 12 different diuretic agents plus 2 combinations of drugs comprise the body of this report. The sensitivity of the