Ethacrynic acid ototoxicity

Ototoxicity, as evidenced by transient or permanent hearing loss, is a serious side effect of ethacrynic acid, and occurs less frequently with furosemide. Bumetanide is claimed to have only 20% of the ototoxic potential of furosemide (43). It has been reported that patients treated with torasemide at high doses for four weeks did not suffer hearing loss (36). 

Loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid) are all equally effective when given in equivalent doses. Therefore, selection is based on the side-effect profile, cost, and pharmacokinetics of the agents. The incidence of ototoxicity is significantly higher with ethacrynic acid compared to the other loop diuretics therefore, its use is limited to patients who are allergic to the sulfa component in the other loop diuretics.15 While ototoxicity is a well-established side effect of furosemide, its incidence is greater when administered by the intravenous route at a rate exceeding 4 mg per minute.16 Torsemide has not been reported to cause ototoxicity. 

The ototoxic effects of streptomycin are potentiated by the coadministration of ethacrynic acid, furosemide, mannitol, and possibly other diuretics. 

Ototoxicity has been reported during therapy with all loop diuretics. This effect seems to be dose related and is most common in patients with renal insufficiency. Deafness is usually reversed when these drugs are discontinued, but irreversible hearing loss has been reported after administration of ethacrynic acid, and this has led to a marked decrease in its use. 

Aminoglycosides e.g. Ethacrynic acid, furosemide, skeletal Increased ototoxicity, increased... 

Ototoxicity Ototoxicity (vestibular and cochlear) is directly related to high peak plasma levels and duration of treatment. Deafness may be irreversible and has been known to affect fetuses in utero. Patients simultaneously receiving another ototoxic drug such as the loop diuretics furosemide, bumetanide, ethacrynic acid (see p. 227) or cisplatin (see p. 396), are particulary at risk. Vertigo and loss of balance may also occur because these drugs affect the vestibular apparatus. 

Orsulakova A, Schacht J. A biochemical mechanism of the ototoxic interaction between neomycin and ethacrynic acid. Acta Otolaryngol 1982 93(l-2) 43-8. 

Of the loop diuretics currently available, furosemide (Lasix), bumetanide (Bumex), and torsemide (Demadex) are widely used in the treatment of heart failure. Due to the increased risk of ototoxicity, ethacrynic acid (Edecrin) should be reserved for patients who are allergic to sulfonamides or who have developed interstitial nephritis on alternative drugs. 

Ethacrynic Acid (Ethacrynate) (1 If Orally for edema, IV for pulmonary edema. Most ototoxic, more Gl distress, less likely to cause alkalosis. Otherwise like furosemide. 

Similar to the other high-ceiling diuretics, ethacrynic acid inhibits the NaVKV2CI symporter in the ascending limb of the loop of Henie to promote a marked diuresis. Sodium, chloride, potassium, and calcium excretion are increased following oral or intravenous administration of ethacrynic acid. Oral administration of ethacrynic acid results in diuresis within 1 hour and a duration of action of 6 to 8 hours. Toxicity induced by ethacrynic acid is similar to that induced by furosemide and bumetanide. Ethacrynic acid is not widely used, however, because it induces a greater incidence of ototoxicity and more serious gastrointestinal effects than those of furosemide or bumetanide. 

Mathc RH, Klein WJ. Ototoxicity of ethacrynic acid and aminoglycoside antibiotics in uremia. (1969) 280, 1223-4. 

Ivfeitz GJ, Beal DD, Krames L. Ototoxicity of ethacrynic acid. Demonstrated in a human temporal bone. Arch Otolaryngol (1969) 90, 152-5. 

TranBaHity P, Meulemans A, Manuel C, Stericers O, Wassef M. Critical appraisal of the experimental studies on the ototoxic interacticm between ethacrynic acid and am inc lycoside antibiotics. A pharmacddnedcal standpoint ScandAu[Pg.288]

Komune S, Snow JB. Potentiating effects ofcisplatin and ethacrynic acid in ototoxicity. Otolaryngol ( 9S ) 107,594-7. 

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