USMLE Step 1




Cardiovascular Pharm



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Key Points

  • Digoxin and Digitoxin
    • Also known as the cardiac glycosides
      • Derived from the foxglove plant, digitalis purpurea
      • Digitoxin is a more stable form of digoxin with a longer half-life
    • Mechanism
      • Inhibition of Na+/K+ ATPase
        • Reversible block of Na+/K+ ATPase leads to increased intracellular Na+
          • Increased Na+ stimulates increased Na+/Ca2+ exchange → increased Ca2+ influx → ↑ cardiac contractility
      • Increased vagal tone (CN X)
        • Slows conduction at SA and AV node
        • Decreases heart rate
    • Clinical Use
      • Heart Failure
        • Due to increased calcium influx leading to positive inotropic effect (increased contractility)
      • Atrial fibrillation
        • Due to slowed conduction at AV node (reduces ventricular rate) and depression of SA node
        • 2nd line after metoprolol/diltiazem (due to side effect profile)
    • Adverse Effects
      • Narrow therapeutic window (toxicity is common)
        • Especially in hypokalemia (increased drug binding since potassium competes with digoxin), hypovolemia, and renal failure (decreased clearance)
      • Visual disturbances
        • May see yellow halos around objects
      • AV block
        • Due to conduction blockade at AV node
      • Hyperkalemia
      • Nonspecific GI (nausea, vomiting, diarrhea) and nervous (fatigue, confusion, weakness) side effects
    • Reversal
      • Anti-digoxin Fab fragments
        • Can reverse both digoxin and digitoxin