indication

For the treatment of high blood pressure and edema caused by diseases like congestive heart failure, liver failure, and kidney failure.

pharmacology

Ethacrynic acid is a monosulfonamyl loop or high ceiling diuretic. Ethacrynic 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 ethacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, ethacrynic acid is effective in many patients who have significant degrees of renal insufficiency. Ethacrynic 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.

mechanism of action

Ethacrynic acid inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. Diuretics also lower blood pressure initially by reducing plasma and extracellular fluid volume; cardiac output also decreases, explaining its antihypertensive action. Eventually, cardiac output returns to normal with an accompanying decrease in peripheral resistance. Its mode of action does not involve carbonic anhydrase inhibition.

toxicity

Overdosage may lead to excessive diuresis with electrolyte depletion.

biotransformation

Hepatic.

absorption

Onset of action is rapid, usually within 30 minutes after an oral dose of ethacrynic acid or within 5 minutes after an intravenous injection of ethacrynic acid.

drug interactions

Amikacin: Increased ototoxicity

Cisplatin: Increased ototoxicity

Colesevelam: Bile acid sequestrants such as colesevelam may decrease the absorption of loop diuretics such as ethacrynic acid. Monitor for decreased serum concentrations/therapeutic effects of loop diuretics if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.

Deslanoside: Possible electrolyte variations and arrhythmias

Digitoxin: Possible electrolyte variations and arrhythmias

Digoxin: Possible electrolyte variations and arrhythmias

Gentamicin: Increased ototoxicity

Ginseng: Ginseng may decrease the therapeutic effect of diuretic, ethacrynic acid.

Ibuprofen: The NSAID, ibuprofen, may antagonize the diuretic and antihypertensive effects of the loop diuretic, ethacrynic acid.

Indomethacin: The NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, ethacrynic acid.

Kanamycin: Increased ototoxicity

Netilmicin: Increased ototoxicity

Streptomycin: Increased ototoxicity

Sulindac: The NSAID, sulindac, may decrease the diuretic and antihypertensive effects of the loop diuretic, ethacryninc acid.

Tobramycin: Increased ototoxicity

Trandolapril: The loop diuretic, Ethacrynic acid, may increase the hypotensive effect of Trandolapril. Ethacrynic acid may also increase the nephrotoxicity of Trandolapril.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.