Frusemide

It is a loop diuretic.

Mechanism of action

secreted into the renal tubule by the organic anion transporter in the proximal tubule
inhibits the Na+ K+ 2Cl- co-transporter in the thick ascending limb of loop of Henle by binding to Cl- binding site
increases local prostaglandin synthesis
weak carbonic anhydrase inhibitor

Actions in renal tubule:

abolish corticomedullary osmotic gradient
block positive and negative free water clearance (urine becomes isosmotic with plasma)
increases bicarbonate excretion and urine pH by inhibiting carbonic anhydrase
increases excretion of K+ (by increasing Na+ reaching the distal tubule)
increases excretion of Ca2+, Mg2+
decreases excretion of uric acid by competing with uric acid secretion in proximal tubule via organic anion transporter and by increasing proximal tubule absorption by decrease in ecf volume

Changes in renal hemodynamics (by local prostaglandin synthesis)

increases renal blood flow transiently
diverts blood flow from outer to mid cortical zone
gfr is not changed inspite of increased blood flow due to compensatory mechanisms

Changes in systemic hemodynamics (by prostaglandin synthesis)

Pharmacokinetics

rapid absorption when given orally
60% oral bioavailability
low lipid solubility
highly plasma protein bound
partly conjugated with glucuronic acid
mainly excreted unchanged in urine by glomerular filtration, proximal tubular secretion
some part excreted in bile
plasma t1/2 – 1-2hours (prolonged in pulmonary edema, hepatic and renal insufficiency)

Dose

20-80mg OD in morning

Adverse effects: