Types of diuretics

• Diuretics


  Used to remove inappropriate water volume (Edema, Volume overload), Correct specific ion imbalances
• Diuretic classes by mechanism of action

  • Loop diuretics
  • Thiazide diuretics
  • Potassium-sparing diuretics
  • Carbonic anhydrase inhibitors
  • Osmotic diuretics
• Loop diuretics


  • Inhibit the reabsorption of sodium and chloride in the thick, ascending loop of Henle, resulting in loss of sodium, chloride and water into the urine
  • Furosemide is a sulfonamide derivative; most commonly administered diuretic in veterinary medicine
  • Furosemide induces beneficial hemodynamic effects before the onset of diuresis (Vasodilation increases renal blood flow, thereby increasing renal perfusion and lessening fluid retention; renal vasodilation depends on the local synthesis of prostaglandins)

  
• Thiazide diuretics


  • Act on the proximal portion of the distal convoluted tubule to inhibit sodium resorption and promote potassium excretion
  • Hydrochlorothiazide and chlorothiazide
  • Not as potent as furosemide; infrequently used in veterinary medicine
  • Because the thiazides act on a different site of the renal tubule than other diuretics, they may be combined with a loop diuretic or potassium-sparing diuretic
• Potassium-sparing diuretics


  • Act to prevent sodium reabsorption in the collecting tubule by either binding epithelial sodium channels (amiloride, triamterene) or by inhibiting aldosterone receptors (spironolactone, eplerenone); prevents excessive excretion of K+ in urine and decreased retention of water
  • Spironolactone - most frequently used in vet med
  • Can be added to furosemide or thiazide therapy
• Carbonic anhydrase inhibitors


  • Act on the proximal tubule to non-competitively and reversibly inhibit carbonic anhydrase, which decreases the formation of carbonic acid from carbon dioxide and water
  • Reduced formation of carbonic acid results in fewer hydrogen ions within proximal tubule cells
  • Because hydrogen ions are normally exchanged with sodium ions from the tubule lumen, more sodium is available to combine with urinary bicarbonate
  • Diuresis occurs when water is excreted with sodium bicarbonate
  • As bicarbonate is eliminated, systemic acidosis results
  • Because intracellular potassium can substitute for hydrogen ions in the sodium resorption step, carbonic anhydrase inhibitors also enhance potassium excretion

  
• Osmotic diuretics


  • Increase osmotic pressure; inhibit water reabsorption in the proximal convoluted tubule and the thin descending loop of Henle and collecting duct
  • Mannitol, dimethyl sulfoxide (DMSO), urea, glycerol and isosorbide
  • Mannitol is commonly used in small animals but is expensive for use in adult large animals, so DMSO is often used in its place
  • Mannitol acts as a protectant against further renal tubular damage and initiates an osmotic diuresis
  • DMSO is an oxygen-derived free radical scavenger and an osmotic diuretic

  
• Where does loop diuretics inhibit the reabsorption of sodium, and chloride

  Thick ascending loop of henle
• What does the use of loop diuretics result in 


  It results in the loss of sodium chloride and water in the urine
• Give an example of a commonly used loop diuretic

  Furosemide
• What do thiazide diuretics act on 


  They act on the proximal portion of the distal convoluted tubule
• What do thiazide diuretics inhibit and promote 


  They inhibit sodium reabsorption

  And promote potassium excretion
• Give two examples of thiazide diuretics

  Hydrochlorothiazide and chlorothiazide
• What is the MOA of potassium sparing diuretics

  Prevent sodium reabsorption in the collecting tubule by:

  1. Binding epithelial sodium channels
  2. Inhibiting aldosterone receptors