Etacrynic acid

Etacrynic acid acts on the ascending limb of the loop of Henle and on the proximal and distal tubules. Urinary output is usually dose dependent and related to the magnitude of fluid accumulation. Water and electrolyte excretion may be increased several times over that observed with thiazide diuretics, since etacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, etacrynic acid is effective in many patients who have significant degrees of renal insufficiency. Etacrynic acid has little or no effect on glomerular filtration or on renal blood flow, except following pronounced reductions in plasma volume when associated with rapid diuresis.

The electrolyte excretion pattern of ethacrynic acid varies from that of the thiazides and mercurial diuretics. Initial sodium and chloride excretion is usually substantial and chloride loss exceeds that of sodium. With prolonged administration, chloride excretion declines, and potassium and hydrogen ion excretion may increase. Etacrynic acid is effective whether or not there is clinical acidosis or alkalosis.

Although etacrynic acid, in carefully controlled studies in animals and experimental subjects, produces a more favorable sodium/potassium excretion ratio than the thiazides, in patients with increased diuresis excessive amounts of potassium may be excreted.

Onset of action is rapid, usually within 30 minutes after an oral dose of etacrynic acid or within 5 minutes after an intravenous injection of etacrynic acid. After oral use, diuresis peaks in about 2 hours and lasts about 6 to 8 hours.

The sulfhydryl binding propensity of ethacrynic acid differs somewhat from that of the organomercurials. Its mode of action is not by carbonic anhydrase inhibition.

Ethacrynic acid does not cross the blood-brain barrier.