Pharm

Spironolactone

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Spironolactone, Aldactone

  • Definition
  1. Potassium-Sparing Diuretic via aldosterone blockade
  • Indications
  1. Left-sided Congestive Heart Failure
    1. First line agent for NYHA Class III or IV Heart Failure, in conjunction with ACE Inhibitor and Beta Blocker
    2. Monitor for Hyperkalemia (esp. with ACE Inhibitor) and renal dysfunction
    3. May use Eplerenone as an alternative (but more expensive)
  2. Edematous states
    1. Cirrhosis
    2. Primary Hyperaldosteronism
    3. Nephrotic Syndrome
  3. Hyperandrogenism in women
    1. Hirsutism
    2. Polycystic Ovary Disease
  4. Refractory Hypertension
    1. See Hypertension Combination Therapy
  • Contraindications
  1. Anuria
  2. Renal Insufficiency with Serum Creatinine over 2.4 mg/dl (GFR <30 ml/minute/1.73m2)
  3. Hyperkalemia (Serum Potassium >5 meq/L)
  • Drug Interactions
  1. Increased Serum Potassium (Hyperkalemia risk)
    1. Potassium Supplementation
    2. NSAIDs
    3. ACE Inhibitor
    4. Trimethoprim-Sulfamethoxazole
  2. Increases Digoxin half-life
  3. Salicylates decreases Spironolactone effect
  • Dosing
  1. Congestive Heart Failure
    1. Start 12.5 mg orally daily
    2. May increase to 25 mg orally daily after 4 weeks (up to 50 mg, but increased risk of Hyperkalemia)
    3. Monitor Serum Potassium at 3 days, 7 days and then monthly for the first 3 months
  2. Diuretic: 50-100 mg PO per day divided qd to bid
  3. Hyperandrogenism: 50 mg PO bid
  4. Hypertension: 12.5 to 50 mg PO qd
  • Pharmacokinetics
  1. Primarily renal excretion
  2. Half-life: 14 to 16 hours
  • Adverse Effects
  1. Gynecomastia (in men)
  2. Hyperkalemia
    1. Avoid excessive Dietary Potassium
  • Mechanism
  1. General
    1. Spironolactone is a aldosterone competitive inhibitor
    2. Acts at distal convoluted renal tubule
  2. Congestive Heart Failure
    1. Works synergistically with ACE Inhibitors in CHF
    2. ACE Inhibitors block Angiotensin II production
      1. Renal response is to increase Aldosterone
      2. Spironolactone blocks aldosterone escape