The clinical pharmacology of ethacrynic acid.

Ethacrynic acid (Edecrin) is a loop diuretic that produces a prompt and profound diuresis. The primary action of ethacrynic acid is the inhibition of the activity of the Na⁺-K⁺-2Cl⁻ symporter in the thick ascending limb of the loop of Henle. The onset of action is usually within 30 minutes after an oral dose and within 5 minutes after an intravenous injection. After oral administration, peak diuretic effect occurs in about 2 hours and the effect lasts about 6-8 hours. After intravenous administration, peak diuretic effect occurs within 30 minutes and the diuretic effect is virtually completed in 2-4 hours. The bioavailability of ethacrynic acid approximates 100%, with maximal blood level between 40 and 92 minutes. The elimination half-life has been reported to be less than 1 hour, but highly variable (average 30 minutes with a range of 12-160 minutes). Intravenous ethacrynic acid has a prompt venous dilatory effect and immediately relieves symptoms of pulmonary congestion, before a diuresis can occur. Ethacrynic acid is effective in all types of edema whether there is clinical acidosis, alkalosis, or electrolyte imbalance. Most side effects of ethacrynic acid can be attributed to its effectiveness (volume depletion); however, it may cause metabolic alkalosis that is preventable by KCl replacement. Ethacrynic acid has ototoxic effect that occasionally results in temporally or permanent deafness. Despite limitations, ethacrynic acid has been employed in the treatment of congestive heart failure and other edematous states, especially in patients allergic to sulfa-containing drugs because all the other loop diuretics have a sulfa moiety.