Spironolactone

Chemical

Aldosterone antagonist

Use

  1. Heart failure
  2. Cirrhosis with ascites
  3. Hypertension
  4. Nephrotic syndrome
  5. Hyperaldosteronism (Conn’s disease)

Presentation

  • 25/50/100mg tablets
  • Combined with thiazide/frusemide

Dose

100 – 400mg OD

MoA (mechanism)

  • Synthetic steroid
  • Competitive antagonist of Aldosterone
  • Binds aldosterone receptor → inactivates
  • Prevents translocation of receptor & binding to DNA
  1. Failure to synthesise proteins which stimulate Na/K/ATPase pump
  2. Upregulate Na+ apical channel
  • ↓Na+ reabsorption & stops K/H+ secretion

* PRINCIPLE CELLS *

PD

Renal: diuresis with retention of K+

Metabolic: anti-androgenic effect

PK

A

OBA 70%

Extensive hepatic 1st pass metabolism

D

90% PPB

M

Hepatic to multiple metabolites, including CANRENONE, which is active

E

Metabolites in urine, t ½ B 2hrs

Adverse Effects

  • Hyperkalaemia
  • Vomiting & GI disturbances
  • Menstrual irregularities
  • Gynaecomastia