K+ sparing diuretics (spironolactone, eplerenone, amiloride, triamterene)

Question 1

MoA

Answer 1

1. Prevent reabsorption of Na+ at CCT –> prevents K+ and H+ secretion into the renal tubule lumen exchange for this
   
   • **typically u_sed with loop diuretics or thiazides_ in order to prevent absorption of the Na+ they are trying to eliminate
2. spironolactone has anti-adrenergic activity + anti-progesterone activity

Question 2

Clinical Uses

Answer 2

1. used in combination with thiazide or loop diuretics to prevent Na+ reabsorption back into the blood to prevent increasing BP
2. amiloride for Liddle syndrome
   
   • caused by mutation that causes constitutive ENaC channel activation in CCT
3. amiloride for nephrogenic DI, particularly caused by lithium
   
   • lithium prevents ADH from binding to V2 receptors –> no stimulation of ENaC channels –> causes nephrogenic DI
4. spironolactone for hirsutism & PCOS
   
   • due to anti-androgen properties
5. spironolactone for HF
6. spironolactone for ascites
7. hyperaldosteronism
8. prevention of hypokalemia
   
   • –> decreased risk of deadly cardiac arrhythmias

Question 3

Adverse Effects

Answer 3

1. hyperkalemia
   
   • –> risk of deadly arrhythmias
2. endocrine effects –> unpredictive menstrual cycle in females
   
   • results from cross-reactivity with progesterone receptors
     
     • difficulty planning for pregancy as a result
3. endocrine effects –> hyper-estrogenism in males
   
   • gynecomastia
   • decreased libido
   • infertility
   • shrinkage of testes
   • loss of body hair
   • loss of muscle mass