Ethacrynic acid
Encyclopedia
Etacrynic acid or ethacrynic acid (USAN
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

), trade name Edecrin, is a loop diuretic
Loop diuretic
Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency...

 used to treat high blood pressure
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

 and the swelling
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

 caused by diseases like congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

, liver failure
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...

, and kidney failure.

Unlike the other loop diuretics, etacrynic acid is not a sulfonamide
Sulfonamide (medicine)
Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...

 and thus, its use is not contraindicated in those with sulfa allergies.

Etacrynic acid is a phenoxyacetic acid derivative containing a ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...

 and a methylene
Methylene
Methylene is a chemical species in which a carbon atom is bonded to two hydrogen atoms. Three different possibilities present themselves:* the -CH2- substituent group: e.g., dichloromethane ....

 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 intravenous
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...

ly. The IV solution must be prepared and maintained with a pH above 5.

Adverse effects

As a diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...

, 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
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...

, which may manifest as muscle cramps or weakness. It has also been known to cause reversible or permanent hearing loss (ototoxicity
Ototoxicity
Ototoxicity is damage to the ear , specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based...

) and liver damage. 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
Thick ascending limb of loop of Henle
The thick ascending limb of loop of Henle also known as distal straight tubule, is a segment of the nephron in the kidney. It can be divided into two parts: that in the renal medulla, and that in the renal cortex.-Medullary thick ascending limb:...

. 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
Glutathione S-transferase
Enzymes of the glutathione S-transferase family are composed of many cytosolic, mitochondrial, and microsomal proteins. GSTs are present in eukaryotes and in prokaryotes, where they catalyze a variety of reactions and accept endogenous and xenobiotic substrates.GSTs can constitute up to 10% of...

 family members, which are enzymes involved in xenobiotic metabolism
Xenobiotic metabolism
Xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as drugs and poisons...

. This family of enzymes has recently been shown to have a high rate of genetic variability.
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