Etacrynic acid

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Etacrynic acid
Etacrynic acid.svg
Systematic (IUPAC) name
[2,3-dichloro-4-(2-methylenebutanoyl)phenoxy]acetic acid
Clinical data
AHFS/Drugs.com International Drug Names
MedlinePlus a682857
Legal status ?
Routes Oral
Pharmacokinetic data
Protein binding > 98%
Identifiers
CAS number 58-54-8 YesY
ATC code C03CC01
PubChem CID 3278
DrugBank DB00903
ChemSpider 3163 YesY
UNII M5DP350VZV YesY
KEGG D00313 YesY
ChEBI CHEBI:4876 YesY
ChEMBL CHEMBL456 YesY
Chemical data
Formula C13H12Cl2O4 
Mol. mass 303.138 g/mol
 YesY (what is this?)  (verify)

Etacrynic acid (INN) or ethacrynic acid (USAN), trade name Edecrin, is a loop diuretic used to treat high blood pressure and the swelling caused by diseases like congestive heart failure, liver failure, and kidney failure.

Unlike the other loop diuretics, etacrynic acid is not a sulfonamide[1] and thus, its use is not contraindicated in those with sulfa allergies.

Ethacrynic acid is a phenoxyacetic acid derivative containing a ketone group and a methylene group. A cysteine adduct is formed with the methylene group and this is the active form.

Administration[edit]

Ethacrynic acid is sold in 25 mg and 50 mg tablets for oral use. The sodium salt (ethacrynate sodium) can also be given intravenously. The IV solution must be prepared and maintained with a pH above 5.

Adverse effects[edit]

As a diuretic, ethacrynic acid can cause frequent urination, but this usually resolves after taking the drug for a few weeks.

Ethacrynic acid can also cause low potassium levels, which may manifest as muscle cramps or weakness. It has also been known to cause reversible or permanent hearing loss(ototoxicity)[2] and liver damage[3] when administered in extremely high dosages. On oral administration, it produces diarrhea; intestinal bleeding may occur at higher doses.

Mechanism of action[edit]

Ethacrynic acid acts by inhibiting sodium-potassium-chloride cotransport in the ascending loop of Henle. Loss of potassium ions is less marked but chances of hypochloremic alkalosis are greater. The dose response curve of ethacrynic acid is steeper than that of furosemide and, in general, it is less manageable; dose range is 50-150mg.

Ethacrynic acid and its glutathione-adduct are potent inhibitors of glutathione S-transferase family members, which are enzymes involved in xenobiotic metabolism. This family of enzymes has recently been shown to have a high rate of genetic variability.

References[edit]

  1. ^ Somberg JC, Molnar J (January 2009). "The Pleiotropic Effects of Ethacrynic Acid". Am J Ther 16: 102. doi:10.1097/MJT.0b013e3181961264. PMID 19142157. 
  2. ^ Bosher SK (1980). "The nature of the ototoxic actions of ethacrynic acid upon the mammalian endolymph system. I. Functional aspects". Acta Otolaryngol. 89 (5–6): 407–18. doi:10.3109/00016488009127156. PMID 7446061. 
  3. ^ Datey et al.; Deshmukh, SN; Dalvi, CP; Purandare, NM (1967). "Hepatocellular damage with ethacrynic acid". Br. Med. J. 3 (5558): 152–153. doi:10.1136/bmj.3.5558.152. PMC 1842848. PMID 6028103.