Ethacrynic Acid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Store at or below 24 °C (75 °F). Protect from freezing. /Ethacrynic acid oral soln/

Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container. /Ethacrynic acid tablets/

Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. /Ethacrynate sodium for injection/

Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water soln. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

The high-ceiling diuretics may interact adversely with other drugs. Ethacrynic acid and furosemide are significantly bound to plasma albumin and may compete for sites on the protein with drugs such as warfarin and clofibrate. ...One should be judicious in the use of any cephalosporin in conjunction with...ethacrynic acid.

The ototoxic interaction between aminoglycoside antibiotics (Streptomycin, Kanamycin, etc.) and loop-inhibiting diuretics, such as ethacrynic acid, has been well documented. This interaction causes extensive destruction of the hair cells of the cochlea. Viomycin, Capreomycin, and Polymyxin B, when given with ethacrynic acid , were found to produce cochlear hair cell damage that was similar to that produced by aminoglycoside antibiotics admin with ethacrynic acid.

Treatment of mice with Neomycin (100 mg/kg bw, IM) 60 min prior to ethacrynic acid led to a 3-5 fold higher accumulation of ethacrynic acid in cochlear structures. It is suggested that Neomycin breaks down hemolabyrinthine or tissue permeability barriers and allows increased penetration of the other drug into the inner ear.

The temporal bones of a patient who suffered sudden deafness and ataxia after admin of both furosemide and ethacrynic acid, were examined by light and electron microscopy. There was no loss of hair or supporting cells. Some hair cells, in both the vestibular neuroepithelium and the organ of corti, particularly in the basal turn, were more densely staining and more granular than normal. Membrane whorls also were common within mitochondria of such cells. The endoplasmic reticulum of some spiral ganglion cells was dilated. The major cytologic changes were found in the stria vascularis of the cochlea and dark cell areas of the vestibular system. There was marked dilatation of the intercellular fluid spaces, consistent with the biochemical observation that loop diuretics interfere first with enzyme systems responsible for fluid transport within the inner ear.

For more Interactions (Complete) data for ETHACRYNIC ACID (11 total), please visit the HSDB record page.

Since diuresis and natriuresis occur so rapidly using ethacrynic acid, reductions in blood volume lead to a decrease in mean arterial pressure. Reduced cardiac index and reflex tachycardia can also occur due to the sudden decrease in preload. Within one use, intravenous ethacrynic acid can precipitate immediate volume depletion that can potentially be life-threatening. Because of this, close monitoring of blood pressure is advisable during use.

Currently, there is no antidote described in the literature for the toxicity of ethacrynic acid. Toxicity usually occurs in elderly patients with diminished renal function leading to volume depletion and, in some cases, toxicity. When adverse side effects occur, rapid discontinuation of ethacrynic acid and supportive care can lead to the resolution of symptoms.

The following may be especially important in patient monitoring... : Blood pressure measurements (recommended at periodic intervals in patients being treated for hypertension; selected patients may be taught to monitor their blood pressure at home and report the results at regular physician visits); Blood urea nitrogen and Carbon dioxide (determinations recommeded at periodic intervals during therapy); Electrolyte concns (determinations recommended at periodic intervals, especially if patients are also taking cardiac glycosides or systemic steroids, or when severe hepatic cirrhosis is present); Glucose, serum and Hepatic function and Renal function and Uric acid, serum (determinations recommended at periodic intervals); Hearing exams (recommended at periodic intervals in patients receiving prolonged high-dose iv therapy); Weight measurements (recommended prior to initiation of therapy and at periodic intervals during therapy to monitor water loss). /Loop diuretics/

/HUMAN EXPOSURE STUDIES/ Vertigo, tinnitus with a sense of fullness in the ears, and temporary (lasting 1-24 hr) or permanent deafness have occurred following use of ethacrynic acid. These effects are most likely to occur after iv admin of ethacrynate sodium in patients with severe impairment of renal function or in patients receiving other ototoxic drugs. Headache, fatigue, apprehension, and mental confusion have also occurred in patients receiving ethacrynic acid.

/HUMAN EXPOSURE STUDIES/ Ototoxicity in mother and newborn treated with diuretic and kanamycin in 3rd trimester.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Ethacrynic acid

Ambiguous-DILI-concern

5

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ The following early changes occurred in pinna reflex and in inner ear morphology of guinea pigs treated iv with ethacrynic acid (80 mg/kg): Transient loss of pinna reflex occurred in wide frequency range (20 K-500 HZ) immediately after the treatment. Narrowing of deeper capillary network of the stria vascularis occurred soon after the treatment. The change was reversible. Outer hair cells underwent cytoplasmic swelling and marked depression of supravital reduction of nitro-BT. These changes were reversible.

/LABORATORY ANIMALS: Acute Exposure/ In 2.5 hr after iv admin of ethacrynic acid (60 mg/kg) to guinea pigs, potential of ductus cochlearis fell, cochlear marginal cells showed morpholgical changes, involving stria vascularis and Reissner's membrane.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Ethacrynic acid given orally to mice @ dose of 100 mg/kg/day for 21 days decr blood sugar levels and liver phosphorylase levels and incr liver glycogen levels.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A 79 wk study in rats at doses up to 45 times the human dose revealed no evidence of a tumorigenic effect.

For more Non-Human Toxicity Excerpts (Complete) data for ETHACRYNIC ACID (8 total), please visit the HSDB record page.

The kinetics of degradation of ethacrynic acid solutions at concentrations of 22.1-149.2 mmol/l and at 20-60 °C, followed a 2nd order reaction and were fitted to the arrhenius equation using the least squares regression analysis. Degradation of ethacrynic acid produced a dimer through a Diels-Alder type condensation.

Thiazide diuretic overdose should be treated by immidiate evacuation of the stomach followed by supportive symptomatic treatment and monitoring of serum electrolyte concn and renal function. /Thiazide diuretics/

SKIN CONTACT: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. ...

EYE CONTACT: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline soln for 20-30 min while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hopital even if no symptoms (such as redness or irritation) develop.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hopital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital.

LD50 Mouse iv 175 mg/kg /Ethacrynate sodium/

LD50 Mouse oral 627 mg/kg

LD50 Rat oral 1 g/kg

LD50 Rat ip 43 mg/kg

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl ethacrynic acid, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

MEDICATION (VET)

MEDICATION

Preparation: ... E. M. Schultz, J. M. Sprague, BE 612755 ... eidem, US 3255241 (1962, 1966 both to Merck & Co.).

2,3-Dichlorophenoxyacetic acid is subjected to a Friedel-Crafts reaction with butyryl chloride to form the 4-butyryl derivative. This undergoes a Mannich reaction with formaldehyde and dimethylamine, the product decomposing thermally to introduce the methyl group

Ethacrynic acid /Edecrin/ is available for oral use as 25 and 50 mg tablets. The sodium salt of ethacrynic acid is available for intravenous use.

ethacrynic acid oral solution; ethacrynic acid tablets USP: 25 mg, 50 mg; ethacrynate sodium for injection USP: 50 mg