Cardiac glycosides including digoxin, digitalis, and digitoxin are drugs that work in two ways.

First, they can inhibit the sodium/potassium pump in the heart, causing sodium levels to rise. The increased sodium levels inside the cell indirectly activate a sodium/calcium exchanger to bring more calcium into the cell. More calcium causes more contractility in cardiac muscle. This increased contractility is useful in the treatment of heart failure.

Second, digoxin can increase vagal tone, which acts mainly on the pacemaker SA and AV nodes to slow conduction. By slowing conduction down the AV node, digoxin is a useful drug in rate control for atrial fibrillation.

Note that these drugs are rarely administered first-line, mainly due to their narrow therapeutic windows. Patients taking these drugs often experience toxicity, which includes symptoms like disturbed color vision, AV heart block, as well as non-specific GI and neurological symptoms.

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