Loop Diuretics: Ethacrynic Acid
Indication
Ethacrynic acid is commonly used in the management of edema secondary to CHF and hepatic or renal disease. It may also be used in the treatment of hypertensive patients.
Mechanism of Action
Ethacrynic acid is a loop diuretic that functions through inhibition of reabsorption of sodium and chloride from the ascending loop of Henle.
It interferes with the chloride-binding cotransport system (Na+-K+-2C1~ symporter) and halts salt transport in these segments. This action causes increased excretion of water, sodium, potassium, and chloride. The drug also inhibits calcium and magnesium reabsorption in the ascending limb by eliminating the transepithelial potential difference.
Dosing
Children:
Oral: l mg/kg/dose every 24 to 48 hours; adjust dose as needed at 2- to 3-day intervals to a maximum of 3 mg/kg/day
I.V.: 0.5 to 1 mg/kg/dose (maximum, 50mg/dose); repeated doses not routinely recommended but may be administered every 8 to 12 hours
Adults:
Oral: 25 to 400mg/day in one to two divided doses
I.V.: 0.5 to lmg/kg/dose (maximum, lOOmg/dose); repeat doses not routinely recommended but maybe administered every 8 to 12 hours
Note Avoid use in patients with a Cr clearance (ClCr) less than 10 mL/min
Pharmacokinetics
Ethacrynic acid has an onset of action within 30 minutes of administration of oral doses and within 5 minutes of I.V. injection. The duration of diuresis is approximately 6 to 8 hours after oral and 2 hours after I.V. administration. The drug is rapidly absorbed and hepatically metabolized to an active cysteine conjugate. The half-life ranges from 30 to 70 minutes, and the drug and metabolites are eliminated in the bile and urine.
Monitoring parameters: serum electrolytes, renal function,blood pressure, hearing
Contraindications: anuria, hypotension, metabolic alkalosis with hypokalemia, hyponatremic dehydration
Precautions/Adverse Effects
Warning: loop diuretics are potent agents. Excess amounts may lead to profound diuresis with fluid and electrolyte loss. Close medical supervision and dose evaluation is required. Use with corticosteroids may increase risk of GI hemorrhage. Avoid use in patients with severe renal impairment (ClCr< 10 mL/min).
Adverse effects of ethacrynicacidincludehypotension,fluidandelectrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia), hyperglycemia, thrombocytopenia, neutropenia, agranulocytosis, abnormal liver function test results, GI irritation or bleeding, ototoxicity (higher risk than other loop diuretics), hyperuricemia, phlebitis, headache, rash, and hematuria.
Drug-Drug Interactions
Ethacrynic acid administration causes increased potassium losses with amphotericin and steroids. Use of ethacrynic acid with aminoglycosides increases the risk of ototoxicity; increases the anticoagulant affects of warfarin; and decreases lithium excretion. Decreased glucose tolerance with ethacrynic acid may increase requirements of oral antidiabetic agents.
Poisoning Information
Symptoms of ethacrynic acid overdose may include acute and profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume, and circulatory collapse. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting, and cramps. Treatment is supportive and symptomatic, and replacement of fluid and electrolyte losses maybe necessary.
Compatible Diluents/Administration
Ethacrynic acid is stable for 24 hours at room temperature when mixed at 1 mg/mL in D5W or NS; inject slowly over 20 to 30 minutes. Ethacrynic acid is a tissue irritant and is not to be administered I.M. or subcutaneously.
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