Mechanism of action:
They inhibit Na+/K+/2Cl- symport on luminal membrane of thick ascending limb of Henle’s loop causes
a. Decreased reabsorption of NaCl
b. Lessen the normal lumen positive potential that derives from K+ recycling resulting in increased excretion of Mg2+ and Ca2+
They also promote prostaglandin synthesis. Prostaglandins also have some role as diuretic.
They produce large amount of urine.
1. Acute pulmonary edema of heart failure
2. Acute pulmonary edema (When given IV)
3. Impaired renal function
They causes an increased tub ular Ca2+ excretion.
6. Increased intracranial pressure
7. Diabetic nephropathy
8. Hypertensive situations
They have short duration of action of approximately 2-4.5 hours. They are eliminated by glomerular filtration and tubular secretion. Their half life depends on the renal function. They are excreted through urine.
They have almost similar adverse effects as those of thiazide diuretics. But they may cause severe electrolytic imbalances and water depletion.
• Hypersensitivity reactions:
Skin rash, interstitial nephritis
• Water, electrolytes and acid-base balance:
Voiding of extra water, Hypercalcemia, hyponatremia, Hypomagnesemia,
Hypokalemic metabolic alkalosis:
More Na+ at the collecting tubule results in more K+ exchange with Na+ in the tubule. This results in hypokalemia.
More K+ loss results in more H+, resulting in hypokalemic alkalosis.
This can be reduced by the use of potassium sparing diuretics or potassium rich foods.
Transient granulocytopenia and thrombocytopenia
Severe pain and tenderness in patients with renal failure
Affect on hearing.
Blocks secretion of uric acid by competitively working at renal and biliary secretary systems. This results in gouty attacks.
They cause a reduction in blood volume. This results in hypotension, shock and cardiac arrhythmias.
It is contraindicated in patients with hepatic coma, hypokalemia, hypotension and hypersensitivity to sulfonamides.
Indomethacin interferes with the production of prostaglandin synthesis, so that is why causes some inhibitory effects on diuretic action of loop diuretics.