diuretics 2

• Loop diuretics


  • High potency: They are the most powerful of all diuretics causing 15-25% of sodium in the filtrate to be excreted
  • Short duration of action 2-4 hrs
  • Prompt onset of action 0.5-1 hr after oral administration and 5-10 min, following IV injection
  • Effective at low GFR even below 10 ml/min
• loop diuretics

  • Furosemide
  • Bumetanide
  • Ethacrynic acid
• They are sulfonamide derivatives except ethacrynic acid
• Mechanism of action


  1. They inhibit NaCl reabsorption in the thick ascending loop of Henle. They act on the apical cell membrane where they inhibit the cotransport of Na+/K+/2Cl

  2. They may also inhibit NaCl reabsorption in the proximal tubules
• Thiazides are relatively ineffective in the setting of renal failure because of the decreased delivery of the drug into the tubular fluid and the limited distal tubule sodium reabsorption
• Mechanism of action


  They have a venodilator action directly and/or indirectly through stimulating cyclooxygenase activity resulting in increased synthesis of vasodilator prostaglandins PGE2 and PGI2. These prostaglandins may contribute in the renal haemodynamic changes produced by these drugs, increase glomerular filtration and also increase water and sodium excretion
• Pharmacological actions of loop diuretics

  • They are potent diuretics increasing Na+ and Cl- excretion in urine along with an equiosmotic amount of water
  • They enhance the excretion of both Ca2+ and Mg2+
  • They enhance k+ secretion at distal tubules due to increase Na+ load at this segment which stimulate Na+ reabsorption in exchange with K+ at this segment
  • They increase renal blood flow and cause redistribution of blood flow within renal cortex
  • They are weak inhibitors of carbonic anhydrase enzyme
  • They have immediate venodilator action after IV administration
  • They decrease urinary excretion of uric acid
  • Hyperglycemia due to decrease release of insulin [ less than thiazide]
• Potassium sparing diuretics


  They fall into two groups: Spironolactone which inhibits the action of aldosterone, and Amiloride and triamterene which block luminal sodium channels. All of these agents exert a weak diuretic effect and decrease the excretion of potassium and hydrogen ion
• Mechanism of action of potassium-sparing diuretics

  They reduce Na+ reabsorption and K+ secretion by antagonizing the effects of aldosterone in the late part of the distal convoluted tubule (DCT) and collecting tubule
• Spironolactone


  Inhibits the action of aldosterone by competitively binding to the mineralocorticoid receptors and preventing subsequent cellular events that regulate K+ and H+ secretion and Na+ reabsorption
• Amiloride and triamterene


  • Bind to and block the epithelial sodium channels (ENaC) and thereby decrease absorption of Na+ and excretion of K+ in the cortical collecting tubule, independent of the presence of mineralocorticoids
  • They inhibit Na+/H+ exchange at DCT and collecting tubules by a direct action on tubular transport, and thus inhibit H+ excretion, resulting in some degree of alkalinization of the urine which is less marked with amiloride
  • They promote the excretion of uric acid i.e. mild uricosuric
• Osmotic diuretics


  They are a class of diuretics that work by increasing the osmotic pressure in the renal tubules, thereby reducing the reabsorption of water and electrolytes
• Therapeutic uses of furosemide

  • Acute pulmonary edema
  • Edematous conditions due to chronic heart failure, hepatic cirrhosis complicated by ascites and nephrotic syndrome
  • Hypertension, especially in individuals with diminished renal function
  • Hypertensive emergencies and cerebral edema
  • Acute renal failure, to increase the rate of urine flow and enhance K+ excretion to convert oliguric renal failure to non-oliguric failure
  • Treatment of hypercalcemia, to block calcium reabsorption and increase calcium excretion
• Acute pulmonary edema treatment with furosemide or bumetanide

  1. Decreases intravascular volume and preload

  2. Improves pulmonary congestion
• Adverse effects of furosemide

  1. Hypovolemia and hypotension

  2. Hypokalemia and metabolic alkalosis due to hydrogen ion excretion

  3. Hypomagnesemia and hypocalcemia

  4. Hyperuricemia

  5. Hyperglycemia (hypokalemia leads to decreased insulin secretion resulting in hyperglycemia)

  6. Dose-related ototoxicity in the form of deafness, may or may not be reversible

  7. Allergy and cross allergy between furosemide and sulfonamide