Etacrynic acid

Etacrynic acid
Systematic (IUPAC) name
[2,3-dichloro-4-(2-methylenebutanoyl)phenoxy]acetic acid
Clinical data
Trade names Edecrin
AHFS/Drugs.com International Drug Names
MedlinePlus a682857
Legal status
  • (Prescription only)
Routes of
administration
Oral, IV
Pharmacokinetic data
Protein binding > 98%
Identifiers
CAS Number 58-54-8 YesY
ATC code C03CC01
PubChem CID 3278
IUPHAR/BPS 7179
DrugBank DB00903 YesY
ChemSpider 3163 YesY
UNII M5DP350VZV YesY
KEGG D00313 YesY
ChEBI CHEBI:4876 YesY
ChEMBL CHEMBL456 YesY
Chemical data
Formula C13H12Cl2O4
Molar mass 303.138 g/mol
  (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.

Medical use

Ethacrynic acid is a diuretic that is used to treat edema when a stronger agent is required. It is available as a pill or injected form. The pill is used to treat edema associated with congestive heart failure, cirrhosis and renal disease, accumulation of liquid in the belly associated with cancer or edema, and management of hospitalized children with congenital heart disease or nephrotic syndrome. The injected form is used to rapidly remove water from the body when needed - for example in acute pulmonary edema - or when a person cannot take the medicine in pill form.[2]

Adverse effects

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)[3] and liver damage[4] when administered in extremely high dosages. On oral administration, it produces diarrhea; intestinal bleeding may occur at higher doses.

Mechanism of action

Ethacrynic acid acts by inhibiting NKCC2 in the thick ascending loop of Henle and the Macula Densa. 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

  1. Somberg JC, Molnar J; Molnar (January 2009). "The Pleiotropic Effects of Ethacrynic Acid". Am J Ther 16 (1): 102–4. doi:10.1097/MJT.0b013e3181961264. PMID 19142157.
  2. Merck and FDA Etacrynic acid Label. Last updated February 2005 per FDA site for NDA 016093 injected form and FDA site for NDA 016092 oral form per index here, each accessed January 16, 2016
  3. 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.
  4. Datey, KK; 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.
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