Digoxin

Summary

Digoxin is a type of cardiac glycoside. Clinically, digoxin is used to treat A-Fib (Atrial Fibrillation) and heart failure.

Moving to mechanisms, digoxin stimulates the vagus nerve, which slows pacemaker activity in the SA node, slows conduction in the AV node, and leads to an overall slowing of the heart rate. Digoxin also directly inhibits the sodium potassium pump, which stimulates sodium-calcium exchange in order to increase calcium levels inside heart cells. This increase in calcium leads to positive inotropy, referring to increased contractility of the heart.

Moving onto side effects, taking digoxin can lead to hyperkalemia. In fact, the amount of elevation in blood potassium is correlated with mortality due to digoxin toxicity. Digoxin should also be used with caution in patients with hypokalemia or kidney damage, since either of these conditions can increase the likelihood of developing digoxin toxicity. Other side effects of digoxin include symptoms of cholinergic overload, arrhythmias, blurry yellow vision, and heart block.

Finally, digoxin toxicity can be treated by providing anti-digoxin antibody fragments, which bind digoxin and neutralize it in the bloodstream. While waiting for these antibody fragments to work, supportive measures can also be performed, such as installing a cardiac pacer, administering magnesium, or slowly normalizing potassium levels in the bloodstream.

Key Points

• Digoxin (Cardiac Glycosides)
  • Mechanism
    • Directly inhibits Na+/K+ Pump (ATPase)
      • Leads to increased intracellular Na+
      • Causes calcium influx via Na+/Ca2+ exchanger
        • Increased intracellular sodium concentrations caused by blocking the sodium-potassium pump causes this exchanger to bring calcium into the cell
      • Increased Ca2+ current into cell
        • ↑ cardiac contractility (positive inotropy)
    • Stimulates vagus nerve (increased vagal tone)
      • Slows pacemaker action at SA node
        • Decreases heart rate
      • Slows conduction at AV node
  • Clinical Use
    • Treats Heart Failure
      • Due to increased calcium influx leading to positive inotropic effect (increased contractility)
    • Treats 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)
  • Side Effects
    • Use with caution in:
      • Renal failure
        • Reduces excretion of drug from body
        • Drugs that decrease renal function can also affect clearance (e.g. verapamil, amiodarone, quinidine)
      • Hypokalemia
        • increases permissiveness for drug binding at Na+/K+ pump
      • Drugs that displace digoxin from tissue binding sites
    • Symptoms of Cholinergic Overload (nausea, vomiting, diarrhea)
      • Due to increase in vagal tone
    • Blurry yellow vision
      • May see yellow halos around objects
    • Arrhythmias (Pro-arrhythmic)
    • Heart (AV) block
      • Due to conduction blockade at AV node
    • Can lead to hyperkalemia
      • Sign of poor prognosis (mortality)
        • Hyperkalemia has been associated with toxicity and eventual death in patients taking digoxin
  • Antidote/Reversal
    • Anti-digoxin Fab fragments
      • De-facto treatment for digoxin toxicity
    • Slowly normalize K+
    • Cardiac pacer
    • Magnesium