Diuretics: 

A diuretic is a substance that promotes diuresis, the increased production of urine. This can be a drug, or any other substance. Diuretics are often referred to as “water pills” and are used to increase the amount of water and salt excrete out from the body as urine. 

They are commonly used to treat conditions like high blood pressure and congestive heart failure.

CLASSIFICATION in TERMS of Site of Action:

  1. Carbonic Anhydrase inhibitor: (Post convoluted tubule)--- Acetazolamide
  2. Osmotic Diuretics: (Descending limb of Henlie's Loop)--- Mannitol
  3. Loop Diuretics (Na+-K+-2Cl- Symporter inhibitors)/ High ceiling: (Ascending Limb of Loop of Henle) --- Furosemide
  4. Inhibitors of Na+ Cl- symport (Thiazide and thiazide-like Diuretics): (DCT) ---Chlorothiazide
  5. K+ Sparing Diuretics (Inhibitors of renal epithelial Na+ channels): (Collecting Tubule)--- Spironolactone

How do loop diuretics, thiazide diuretics, and potassium-sparing diuretics differ in their mechanisms of action at the molecular level?

 

Loop Diuretic

Thiazide Diuretic

K+ sparing Diuretic

Site of Action

Ascending Limb of Loop of Henlie

Distal Convoluted Tubule

Collecting Duct

Specific Binding

Na+K+2Cl- Cotransporter  

Na+Cl- Symporter

Renal Epithelial Na+ channel & Na/ K ATPase pump

MOA

Blocks the Na+K+2Cl- Cotransporter (Competitive inhibition of Cl- binding site)

¯

Inhibits Na, Cl and K reabsorption

¯

­ Urine

¯

¯ Blood volume

Blocks the Na+Cl- Symporter

¯

¯ Reabsorption of Na, Cl

¯

­ Excretion of Na, Cl

¯

­ Urine

Aldosterone Receptor Blocker

¯

¯ Expression of Lumen Na channel → ¯ Transport of Na to the Collecting tubule cell

&

¯ Expression Na/ K ATPase pump → ¯ Transport of Na to Blood (¯ K to the urine)

¯

­ Na and Water in the urine

 

 


 


 


 

Side effects 

  1. Hypokalemic Metabolic Alkalosis 
  2. Risk of Acidosis (K+ sparing)
  3. Electrolyte imbalance 
  4. Dehydration 
  5. Diarrhea 
  6. Muscle Weakness (Decreased Calcium) 
  7. Renal Stone (chronic use) 
  8. Hyperuricemia 

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