14 - Digoxin

Question 1

Indications for digoxin

Answer 1

• CHF
• Atrial fibrillation, atrial flutter
• PAT (paroxysmal atrial tachycardia)

Question 2

Digoxin PK

Answer 2

• BA = 60-80%
• Vd = 5-10 L/kg
• Protein binding = 25%
• Elimination
• • 60-80% renal
• • t1/2 = 30-50 h

Question 3

Describe digoxin metabolism

Answer 3

• Enteric inactivation of digoxin by Eubacterium lentum (inactivated in the gut)
• • Up to 40% inactivation in 10-15% of the population (we don’t know if someone is in this population)
• • Antibiotic interaction (2-fold serum cardiac glycoside concentration increases => potential toxicity)

Question 4

Digoxin PD

Answer 4

• Onset of action (po) = 1.5-6 h

- Maximal effect (po) = 4-6 h

Question 5

Digoxin toxic dose

Answer 5

• 1 mg in child (few leaves of oleander or foxglove)
• 3 mg in adult
• Dose > 10 mg in healthy subjects (> 3 mg in healthy children) = cardiac arrest

Question 6

Toxic digoxin serum levels?

Answer 6

> 2 ng/mL

Question 7

Risk factors for digoxin toxicity

Answer 7

• Drug interactions
• • Amiodarone (inhibits renal tubular secretion of digoxin)
• • Antibiotics (decrease population of chronic bacteria)
• • Quinidine
• • Verapamil
• Disease -> renal failure, MI, electrolyte imbalances
• • Mortality = 3-25% higher in elderly

Question 8

Signs & sx of acute digoxin overdose

Answer 8

• Vomiting
• Hyperkalemia
• Sinus bradycardia
• Sinoatrial arrest
• 2nd or 3rd degree AV block
• Ventricular tachycardia/fibrillation
• *Note – digoxin toxicity causes intracellular myocardial hypercalcemia

Question 9

Signs & sx of chronic digoxin intoxication

Answer 9

• Visual disturbances (dyschromatopsia)
• Weakness
• Sinus bradycardia
• Atrial fibrillation
• Ventricular arrhythmias (tachycardia, fibrillation)
• Accelerated junctional tachycardia
• Paroxysmal atrial tachycardia
• Hypokalemia and hypomagnesemia (from use of diuretics)

Question 10

Digoxin overdose management

Answer 10

• Emergency and supportive measures
• • Protect airways, assist ventilation
• • Treat hyperkalemia
• • Treat bradycardia or heart block
• • Treat ventricular tachyarrhythmias
• Decontamination (gastric emptying, activated charcoal)
• Enhanced elimination (MDAC)
• Antidotes = digoxin-specific antibody fragments (DigiFab)
• Monitor digoxin levels

Question 11

Indications of DigiFab

Answer 11

• Life-threatening cardiac glycosides toxicity
• Px w/ progressive bradydysrhythmias (severe sinus bradycardia or 2nd or 3rd-degree heart block unresponsive to atropine)
• Px w/ severe ventricular dysrhythmias (VT or VF)
• Px w/ potassium > 5.5 mEq/mL
• Acute ingestions:
• • > 4 mg in healthy child (> 0.1 mg/kg)
• • > 10 mg in healthy adult
• Serum concentrations > 10 ng/mL (lower in elderly)
• Rapid progression of clinical signs and sx (cardiac and GI effects) and rising potassium levels

Question 12

Describe DigiFab

Answer 12

• High specificity (no cross-reactivity w/ endogenous steroids)
• Sufficient cross-reactivity for other cardiac glycosides
• Pure, safe, and effective
• DigiFab antibodies bind to intravascular free digoxin
• Binding affinity of DigiFab for digoxin much greater than affinity of digoxin for ATPase

Question 13

Dose and administration of DigiFab

Answer 13

• Administered as infusion over 15 minutes to 2 hours (usually at least 30 minutes)
• Time to onset of response = 19 min (0-60 minutes)
• Time to complete response = 90 mins (30-360 minutes)
• Dose:
• • Each vial binds 0.5 mg of digoxin
• • # of vials = digoxin serum concentration (ng/mL) * weight

Question 14

Empiric dosing of DigiFab

Answer 14

• Acute ingestion = 10-20 vials for adult and child

- Chronic toxicity = 3-6 vials for adult; 1-2 vials for child

Question 15

Are digoxin serum levels measured after administration of DigiFab?

Answer 15

No, serum levels become irrelevant