Pharmacodynamics

Direct inhibition of the Na⁺/K⁺ ATPase in cardiac myocytes.
This leads to ↑ intracellular Na⁺, which reduces the activity of the Na⁺/Ca²⁺ exchanger.
The result is ↑ intracellular Ca²⁺, leading to increased contractility (positive inotropy).
Also increases vagal tone, which slows conduction through the AV node and decreases heart rate.

Digoxin poisoning

Electrolyte imbalances
- Hypokalemia: digoxin competes with K⁺ for binding to Na⁺/K⁺-ATPase
Medical conditions
- Renal failure (reduced digoxin excretion)
- Volume depletion (e.g., treatment with diuretics)
Drug interactions
- Treatment with verapamil, diltiazem, amiodarone, and/or quinidine: These drugs may displace digoxin from tissue binding sites and decrease renal elimination.
  - Both mechanisms of action lead to increased digoxin serum levels.

Acute and chronic poisoning: Symptoms are less obvious in chronic poisoning.
- Vagal symptoms: nausea, vomiting, diarrhea, abdominal pain, anorexia
- Arrhythmia symptoms: palpitations, syncope, and presyncope
Chronic poisoning
- Confusion, fatigue, lethargy, weakness, and disorientation
- Visual disturbances
  - Blurred vision, halos, scotomas, diplopia
  - Photophobia
  - Xanthopsia (yellow-tinted vision)

Digoxin Effect (Therapeutic level, not toxicity):
- Scooped ST segment depressions (“Salvador Dalí moustache” or “reverse tick” sign).
- T-wave flattening or inversion.
- Shortened QT interval.
Toxic ECG Changes:
- Most common: Frequent premature ventricular contractions (PVCs).
- Most classic/pathognomonic: Atrial tachycardia with AV block or bidirectional ventricular tachycardia.
- Increased automaticity combined with AV nodal blockade is the hallmark. This can lead to various arrhythmias, including sinus bradycardia, any degree of AV block, and slow atrial fibrillation.

The diagnosis is primarily clinical, based on symptoms and ECG findings.
Serum digoxin levels can be helpful but do not always correlate with toxicity, especially in chronic cases where electrolyte disturbances can cause toxicity even within the “therapeutic” range (0.5-2.0 ng/mL).
Hyperkalemia is the most significant prognostic indicator in acute poisoning.

Supportive Care: Stop digoxin, correct electrolyte abnormalities (especially K⁺ and Mg²⁺), and provide continuous cardiac monitoring.
Atropine: For severe bradycardia.
Activated Charcoal: May be used for acute ingestion if within 1-2 hours.
Antidote: Digoxin-specific antibody fragments (DigiFab/Digibind).
- Indications: Life-threatening arrhythmias (e.g., ventricular tachycardia, severe bradycardia), K⁺ >5.5 mEq/L in an acute setting, or end-organ dysfunction from hypoperfusion.
- After Fab fragments are given, serum digoxin levels are unreliable as they measure both bound and free drug.