Etacrynic acid

Etacrynic acid

Systematic (IUPAC) name
[2,3-dichloro-4-(2-methylenebutanoyl)phenoxy]acetic acid
Clinical data
AHFS/Drugs.com	International Drug Names
MedlinePlus	a682857
Pregnancy cat.	?
Legal status	?
Routes	Oral
Pharmacokinetic data
Protein binding	> 98%
Identifiers
CAS number	58-54-8
ATC code	C03CC01
PubChem	CID 3278
DrugBank	APRD00251
ChemSpider	3163 Y
UNII	M5DP350VZV Y
KEGG	D00313 Y
ChEBI	CHEBI:4876 Y
ChEMBL	CHEMBL456 Y
Chemical data
Formula	C13H12Cl2O4
Mol. mass	303.138 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C13H12Cl2O4/c1-3-7(2)13(18)8-4-5-9(12(15)11(8)14)19-6-10(16)17/h4-5H,2-3,6H2,1H3,(H,16,17) Y Key:AVOLMBLBETYQHX-UHFFFAOYSA-N Y
Y(what is this?)  acid (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.

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

Administration

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

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

Etacrynic 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] On oral administration, it produces diarrhea; intestinal bleeding may occur at higher doses.

Mechanism of action

Etacrynic 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

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1842848.