Fusix Mechanism of Action

Pharmacology: Pharmacodynamics: Mode or Mechanisms of Action: Frusemide inhibits the reabsorption of electrolytes in the ascending limb of the loop of Henle. The drug also decreases reabsorption of sodium and chloride and increases potassium excretion in the distal renal tubule and exerts a direct effect on electrolyte transport at the proximal tubule.
Frusemide diuresis results in enhanced excretion of sodium, chloride, potassium, hydrogen, calcium, magnesium, ammonium, bicarbonate, and possibly phosphate.
Frusemide has some renal vasodilator effect. Renal vascular resistance decreases and renal blood flow increases following administration of the drug. When large doses of frusemide are administered to patients with chronic renal insufficiency, glomerular filtration rate may be increased temporarily. A fall in renal blood flow and glomerular filtration rate may occur if excessive drug-induced diuresis results in a reduction in plasma volume.
Pharmacokinetics: Absorption: Tablet: About 60% of single 80-mg oral dose of frusemide was absorbed from GI tract. When administered to fasting adults in this dosage, the drug appeared in the serum within 10 minutes, reached a peak concentration of 2.3 μg/ml in 60-70 minutes, and was almost completely cleared from the serum in 4 hours. When the same dose was given after a meal, the serum concentration of frusemide increased slowly to a peak of about 1 μg/ml after 2 hours and similar concentrations were present 4 hours after ingestion. The diuretic effect of orally administered frusemide is apparent within 30 minutes to 1 hour and is maximal in the first or second hour. The duration of action is usually 6-8 hours. The maximum hypotension effect may not be apparent until several days after frusemide therapy is begun. In patients with severely impaired renal function , the diuretic response may be prolonged.
Injection: After IV administration of frusemide, diuresis occurs within 5 minutes, reaches a maximum within 20-60 minutes, and persists for approximately 2 hours. After IM administration, peak plasma concentrations are attained within 30 minutes. Onset of diuresis occurs somewhat later than after IV administration. In patients with severely impaired renal function, the diuretic response may be prolonged.
Distribution: The drug crosses the placenta and is distributed into milk. Frusemide is approximately 95% bound to plasma proteins in both normal and azotemic patients.
Elimination: Plasma concentrations of frusemide decline in a biphasic manner.
In patients with normal renal function, a small amount of frusemide is metabolized in the liver to the defurfurylated derivative, 4-chloro-5-sulfamoylanthranilic acid. Frusemide and its metabolite are rapidly excreted in urine by glomerular filtration and by secretion from the proximal tubule. In patients with normal renal function, approximately 50% of an oral dose is excreted in the urine within 24 hours. 69-97% of these amounts is excreted in the first 4 hours. The remainder of the drug is eliminated by nonrenal mechanisms including degradation in the liver and excretion of unchanged drug in the feces. In patients with marked renal impairment without liver disease, nonrenal clearance of frusemide is increased so that up to 98% of the drug is removed from the plasma within 24 hours. Frusemide is not removed by hemodialysis.
Tablet: The elimination half-life was more prolonged in 1 patient with concomitant liver disease.