Digoxin

Aka: Digoxin, Lanoxin, Digitalis, Digitalis Glycoside

1. History
   1. Derived from Foxglove (Digitalis) plant
   2. Originally used as herbal tea to cure "Dropsy"
   3. Best described by William Withering, England, 1775
2. Mechanism
   1. Inotropic effect (Increases myocardial contractility)
      1. Inhibits membrane-bound sodium potassium ATPase
         1. Increases calcium in sarcoplasmic reticulum
         2. Increases myocardial contractility
      2. Not affected by Beta Adrenergic Receptor antagonist
         1. Not dependent on endogenous Catecholamines
      3. Less Potent than parenteral inotropes
   2. Sinoatrial node and Atrioventricular Node effects
      1. Accelerates atrial conduction
      2. Depresses conduction through AV node
3. Indications
   1. Paroxysmal Supraventricular Tachycardia (PSVT)
      1. Hemodynamically stable patient
      2. Conversion to Normal Sinus Rhythm
   2. Chronic Congestive Heart Failure (Systolic Dysfunction)
   3. Atrial Fibrillation or Atrial Flutter
      1. Second line agent for Ventricular rate control
      2. Use in reduced ejection fraction
4. Contraindications
   1. Avoid in Diastolic Dysfunction
5. Drug Interactions
   1. Medications that increase Digoxin concentration
      1. Quinidine
      2. Verapamil
      3. Diltiazem
      4. Amiodarone
      5. Carvedilol
      6. Omeprazole (Prilosec)
      7. Propafenone
      8. Spironolactone (may yield falsely elevated levels)
   2. Medications that decrease Heart Rate and AV Conduction
      1. Verapamil
      2. Diltiazem
      3. Amiodarone
      4. Beta Blockers
      5. Propafenone
      6. Sotalol
   3. Medications that decrease Digoxin absorption
      1. Antacids (space administration 2 hours apart)
      2. Cholestyramine
      3. Colestipol
6. Pharmacokinetics
   1. Effects following intravenous dose
      1. Onset
         1. Intravenous: 5 to 30 minutes
         2. Oral: 30 minutes to 2 hours
      2. Peak: 1.5 to 3 hours
   2. Half-Life: 36 hours
7. Dose
   1. Indications to lower Digoxin dose by 50%
      1. Drug interactions (see above)
      2. Severe renal insufficiency (0.0625 mg daily)
   2. Chronic Congestive Heart Failure
      1. Dose: 0.125 mg po daily
   3. Rapid Atrial Fibrillation
      1. Load
         1. First Dose: 0.5 mg IV
         2. Second and Third Dose: 0.25 mg IV q6h for 2 doses
      2. Maintenance
         1. Dose: 0.125 to 0.375 mg IV or PO qd
8. Efficacy: Congestive Heart Failure (Stages C and D)
   1. Low doses (0.125 mg qd) are effective
      1. Digoxin Serum level 0.5 to 1.0 ng/ml
      2. Reduced morbidity
      3. Reduced Congestive Heart Failure signs and symptoms
      4. Neutral effect on mortality
      5. No benefit in acute Congestive Heart Failure
   2. RADIANCE trial (supports continued use of Digoxin)
      1. Packer (1993) N Engl J Med 329:1-7
      2. Smith (1993) N Engl J Med 329:51-53
9. Efficacy: Atrial Fibrillation
   1. Not recommended for Atrial Fibrillation Rate Control unless comorbid Congestive Heart Failure
   2. Not a great drug for rate control with activity
   3. Delayed onset of action
   4. Not first line for emergent rapid Atrial Fibrillation
   5. Higher mortality - see precautions below
10. Precautions
    1. Chronic Congestive Heart Failure
       1. Do not need to routinely follow Digoxin levels
       2. Check level if signs Digoxin Toxicity
    2. Acute Congestive Heart Failure management (not recommended)
       1. High Digoxin Toxicity risk in critically ill patient
       2. Parenteral inotropes are preferred over Digoxin
          1. More potent
          2. Less toxicity
    3. Atrial Fibrillation Rate Control (not recommended)
       1. Avoid Digoxin for Atrial Fibrillation Rate Control outside of comorbid CHF
       2. Increased mortaility when used for Atrial Fibrillation Rate Control
       3. Whitbeck (2012) Eur Heart J 10.1093/eurheartj/ehs348
          1. http://eurheartj.oxfordjournals.org/content/early/2012/11/14/eurheartj.ehs348.full