Ethacrynate

Diuretics are needed to return to normal the expanded extracellular volume that other antihypertensive agents produce, such as fluid retention and blood volume expansion, via compensatory mechanisms of the body. The loss of efficacy of antihypertensive agents can be restored if a diuretic is used concomitandy. In the treatment of hypertension, high ceiling or loop diuretics, such as furosemide, ethacrynic acid, and bumetanide, are no more efficacious than the thiazide-type of diuretics. In fact, these agents cause more side effects, such as dehydration, metaboHc alkalosis, etc, and therefore, should not be used except in situations where rapid elimination of duid volume is cleady indicated. 

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). 

Methohexital sodium Butyramidophenol Acebutolol Butyric anhydride lopanoic acid Tyropanoate sodium n-Butyryl chloride Ethacrynic acid... 

The loop diuretics, furosemide (Lasix) and ethacrynic acid (Edecrin), increase the excretion of sodium and chloride by inhibiting reabsorption of these ions in the... 

Loop diuretics are used in the treatment of edema associated with CHF, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. These drug s are particularly useful when a greater diuretic effect is desired. Furosemide is the drug of choice when a rapid diuresis is needed or if the patient has renal insufficiency. Furosemide and torsemide are also used to treat hypertension. Ethacrynic acid is also used for the short-term management of ascites caused by a malignancy, idiopathic edema, or lymphedema. 

Loop diuretics are contraindicated in patients with known hypersensitivity to the loop diuretics or to the sulfonamides, severe electrolyte imbalances, hepatic coma, or anuria, and in infants (ethacrynic acid). 

Loop diuretics are used cautiously in patients with renal dysfunction. The loop diuretics are Pregnancy Category B (ethacrynic acid and torsemide) and C drugp (furosemide and bumetanide) and must be used cautiously during pregnancy and lactation. Furosemide is used in children but should be used cautiously. The loop diuretics are used cautiously in patients with liver disease, diabetes, lupus erythematosus (may exacerbate or activate the disease), or diarrhea. Patients with... 

These discoveries generated a lot of effort over the successive 25 years in the preparation of especially designed drug delivery systems for the controlled release of radioactive progesterone [654], colchicine [656], naproxen [657,673, 674], mitomycin C [675-677], inulin [678], trimethoprin [657], succinylsul-fathiazole [657], ethacrynic acid [653], and steroids [633], regardless of whether these drugs are physically trapped in polyphosphazene matrices, or chemically bonded to the polymer skeleton. 

Oakley AJ, Lo Bello M, Mazzetti AP, Federici G, Parker MW. The glutathione conjugate of ethacrynic acid can bind to human pi class glutathione transferase Pl-1 in two different modes. FEES Lett 1997 419 32-6. 

Fig. 2. Agents controlling the opening of Cl -channels. The structural formula, the name, the respeetive Cl -channel, and an appropriate reference are provided. (A) Note the similarity of GABA, taurine, and P-alanine. Note also that DPC and its analogues such as NPPB contain a -alanine backbone. (B) The structure of torasemide comes close to both DPC and furosemide or buraetanide. It blocks the Na ZCPK" -cotransporter with very high affinity and with lesser affinity also the TAL-Cl -channel. Note that IAA-94 is related to phenoxyaeetic acids (e.g., ethacrynic acid). Amidine is related to IAA-94 but it has a positive net charge. Amidine as well as IAA-94 block the ICOR channel at around lO mol/1 [63].

Table 5 Effect of Anion-Channel Antagonists (Anthracene-9-carboxylic acid, ethacrynic acid each 100 fiM) and of Brefeldin A (Exocytosis Inhibitor 45 fiM) on Release of Phytosiderophores from Roots of Fe-Deficient Barley and Mai/.e...

Control (H,0) Anthracene-9- carboxylie acid Ethacrynic acid Brefeldin-A... 

Acetazolamide, captopril, ethacrynic acid, furosemide, hydralazine, methazolamide, methyldopa, procainamide, thiazide diuretics, and ticlopidine... 

Identify the implicated agent and the severity of reaction ° Ethacrynic acid may be a safe alternative to furosemide... 

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 diuretic properties of ethacrynic acid (95) were at one time attributed to its role as a Michael... 

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