Loop Diuretics (-"mide" & -"nide")

Question 1

MoA

Answer 1

1. Inhibits Na+/K+/2Cl- cotransporter in Loop of Henle
   
   • –> abolishes corticomedullary gradient, preventing concentration of urine at the CCT
2. Stimulates PGE release –> afferent arteriole dilation
3. **SULFONAMIDE-type diuretic

Question 2

Clinical Uses

Answer 2

1. **first line treatment for fluid overload states
   
   • acute decompensated HF –> pulmonary edema
   • cirrhosis –> ascites
   • edema in nephrotic syndrome
2. HTN
3. hypercalcemia

Question 3

Adverse Effects

Answer 3

1. **allergy (sulfa-based diuretic)/acute interstitial nephritis
2. hypocalcemia & hypomagnesemia
3. ototoxicity- tinnitus, vertigo, hearing impairment, deafness
   
   • there is an Na+/K+/2Cl- cotransporter in the inner ear as well and loop diuretics are able to bind to these too
   • increased risk with high dose, IV infusion, patients with CKD (decreased GFR –> increased levels remain in blood), and patients taking aminoglycosides
4. dehydration & hypotension
5. hyperuricemia –> gout
   
   • ​​result from volume contraction:
     
     • loss of blood volume increases PCT reabsorption of Na+ to try to compensate –> many macromolecules follow Na+ absorption in the PCT (uric acid, calcium, etc.)
6. alkalosis & hypokalemia

Question 4

Contraindications

Answer 4

1. patients with sulfa allergy
2. chronic kidney disease-SOMETIMES
   
   • the large volume of filtrate may induce more kidney damage
   • decreased GFR also increases chance of overdose, which increases risk of ototoxicity
3. patients on drugs that increase ototoxicity (ex: aminoglycosides)
4. patients with gout
5. patients with history of renal calculi