Etacrynic acid
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| 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 |
| Routes of administration | Oral, IV |
| Legal status |
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| Pharmacokinetic data | |
| Protein binding | > 98% |
| Identifiers | |
| CAS Number |
58-54-8  |
| ATC code | C03CC01 (WHO) |
| PubChem | CID 3278 |
| IUPHAR/BPS | 7179 |
| DrugBank |
DB00903 |
| ChemSpider |
3163 |
| UNII |
M5DP350VZV |
| KEGG |
D00313 |
| ChEBI |
CHEBI:4876 |
| ChEMBL |
CHEMBL456 |
| Chemical data | |
| Formula | C13H12Cl2O4 |
| Molar mass | 303.138 g/mol |
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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
- ↑ 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.
- ↑ 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
- ↑ 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.
- ↑ 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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