Physiology · Year 1 · from Physiology

Case 3: Digoxin Toxicity - Na+/K+-ATPase Inhibition

Clinical Image

Source: Clinical case illustration - Na+/K+-ATPase inhibition mechanism

Patient Presentation

A 78-year-old female with a history of atrial fibrillation and heart failure with reduced ejection fraction (HFrEF) presents with nausea, vomiting, visual disturbances (seeing yellow-green halos around lights), and confusion over the past two days. She recently started taking a new medication for her arthritis (ibuprofen) prescribed by another physician.

Demographics

  • Age: 78 years
  • Sex: Female
  • Past Medical History: Atrial fibrillation, HFrEF (EF 35%), CKD stage 3

Chief Complaint

Nausea, vomiting, visual disturbances, and confusion

Physical Examination

  • Blood pressure: 110/68 mmHg
  • Heart rate: 44 bpm (bradycardic)
  • Temperature: 36.5C
  • General: Confused, oriented to person only
  • Cardiovascular: Irregularly irregular rhythm, now with long pauses
  • Neurological: Mild disorientation, visual complaints of yellow-green halos

Workup

  • Serum digoxin level: 3.8 ng/mL (toxic; therapeutic 0.8-2.0 ng/mL)
  • Serum potassium: 5.8 mEq/L (elevated)
  • Serum creatinine: 2.1 mg/dL (increased from baseline 1.4)
  • ECG: Atrial fibrillation with complete heart block and slow ventricular escape rhythm, ST segment "scooping" (digoxin effect)

Diagnosis

Digoxin toxicity precipitated by NSAID-induced acute kidney injury and drug interaction

Treatment

  1. Discontinue digoxin immediately
  2. Discontinue ibuprofen
  3. Digoxin immune Fab (Digibind) for life-threatening arrhythmias
  4. Correct electrolyte abnormalities (avoid giving calcium)
  5. Temporary pacing if symptomatic bradycardia persists
  6. IV fluids for AKI management
  7. Supportive care for GI and neurological symptoms
  8. Drug interaction education upon discharge

Physiological Principles Demonstrated

  • Na+/K+-ATPase function: The Na+/K+-ATPase maintains electrochemical gradients by pumping 3 Na+ out and 2 K+ in per ATP hydrolyzed. This pump consumes ~30% of cellular ATP at rest.
  • Digoxin mechanism: Cardiac glycosides like digoxin inhibit the Na+/K+-ATPase, increasing intracellular Na+. This reduces the gradient driving the Na+/Ca2+ exchanger (NCX), leading to less calcium extrusion and higher intracellular calcium, enhancing contractility.
  • Toxicity mechanism: Excessive Na+/K+-ATPase inhibition causes dangerous intracellular calcium overload, leading to delayed afterdepolarizations, triggered activity, and arrhythmias. Hyperkalemia worsens toxicity by further impairing the pump.
  • Drug interactions: NSAIDs reduce renal blood flow and GFR, decreasing digoxin clearance (digoxin is renally eliminated) and precipitating toxicity.
  • Antidote mechanism: Digoxin immune Fab (Digibind) binds free digoxin in the bloodstream, preventing it from binding to the Na+/K+-ATPase and allowing redistribution from tissues.

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