Ethacrynic Acid

Ethacrynic acid is one of the most used loop diuretics, acting by inhibiting NKCC2 which is specifically found in the thick ascending loop of Henle in the kidneys. Inhibition of NKCC2 significantly increases the concentrations of Na⁺, K⁺, and Cl⁻ in the tubule, and reduces hypertonicity in the surrounding interstitium, causing less water to be reabsorbed into the blood. Eventually, more urine will be produced and excreted, and a decrease in blood volume can be achieved. Loop diuretics have been used for the treatment of fluid overload/edema in congestive heart failure, acute pulmonary edema, nephrotic syndrome, hepatic ascites, renal failure, as well as other edematous disorders.

References:

1. Vardanyan R, Hruby V. Synthesis of Best-Seller Drugs. Chapter 21 - Diuretics, 2016, 317-327.

2. Zins GR, Walk RA, Gussin RZ, et al. The diuretic activity of ethacrynic acid in rats. Journal of Pharmacology and Experimental Therapeutics, 1968, 163(1): 210-215.