Digoxin

Derived from Foxglove (Digitalis) plant
1. Cardiac glycosides are also found in Lilly of the Valley
Originally used as herbal tea to cure "Dropsy"
First described by William Withering, England, 1775

Paroxysmal Supraventricular Tachycardia (PSVT)
1. Rarely used for PSVT, but can be considered in a hemodynamically stable patient
2. Conversion to Normal Sinus Rhythm
Chronic Congestive Heart Failure (Systolic Dysfunction)
1. Third-line adjunct for symptomatic chronic Systolic Dysfunction
2. Consider as adjunct if persistent symptoms despite ACE (or ARB), Beta Blocker, Diuretic and Aldosterone Antagonist
Atrial Fibrillation or Atrial Flutter
1. Third line agent for Ventricular rate control
2. Use in reduced ejection fraction

Digoxin is proarrhythmic
1. Dose cautiously in advanced age, comorbidity, Polypharmacy, impaired Renal Function and Electrolyte abnormalities
Chronic Congestive Heart Failure
1. Do not need to routinely follow Digoxin levels
2. See Indications for Digoxin levels below
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
Atrial Fibrillation Rate Control (not recommended for first line management)
1. Avoid Digoxin for Atrial Fibrillation Rate Control outside of comorbid CHF
2. Consider when Blood Pressure limits use of other rate control agents (e.g. Diltiazem, Metoprolol)
3. Increased mortaility when used for Atrial Fibrillation Rate Control
4. Whitbeck (2012) Eur Heart J 10.1093/eurheartj/ehs348
  1. http://eurheartj.oxfordjournals.org/content/early/2012/11/14/eurheartj.ehs348.full

Inotropic effect (Increases myocardial contractility)
1. Inhibits membrane-bound sodium Potassium ATPase pump
  1. Increases Calcium in Sarcoplasmic Reticulum
  2. Increased Calcium influx increases myocardial contractility
  3. Results in increased Cardiac Output and venous return
  4. Results in increased renal perfusion and secondary diuresis
2. Not affected by Beta Adrenergic ReceptorAntagonist
  1. Not dependent on endogenous Catecholamines
3. Less Potent than Parenteral inotropes
Sinoatrial Node and Atrioventricular Node effects
1. Accelerates atrial conduction
2. Depresses conduction through AV Node
  1. Increases AV Node sensitivity to Vagal Stimulation
Peripheral Vascular Resistance Increased
1. Increases venous return
2. May also increase myocardial workload and risk Myocardial Ischemia

Dosing is oral or IV
1. Do not use IM (risk of severe local reaction)
Indications to lower Digoxin dose by 50%
1. Drug Interactions (see above)
2. Severe Renal Insufficiency (0.0625 mg daily)
Chronic Congestive Heart Failure
1. Standard Dose: 0.125 mg orally daily (maximum dose 0.25 mcg daily)
2. Low Dose: 0.0625 mg daily or 0.125 mg every other day
  1. Elderly patients
  2. Underweight patients
  3. Chronic Kidney Disease
Rapid Atrial Fibrillation
1. Rarely used for Atrial Fibrillation Rate Control in 2014
  1. See precautions above
  2. Indicated only if refractory or intolerant of other preferred agents (Metoprolol, Diltiazem)
2. Load
  1. First Dose: 0.5 mg IV
    1. Impaired Renal Function: 0.25 IV
  2. Second and Third Dose: 0.25 mg IV every 6 hours for 2 doses
    1. Impaired Renal Function: 0.125 IV every 6 hours for 2 doses
  3. Total loading dose 10 to 15 mcg/kg IV or oral divided in 3 doses every 6 to 8 hours
    1. Impaired Renal Function: 6 to 10 mcg/kg divided into 3 doses
3. Maintenance
  1. Start: 0.125 IV or orally daily
  2. May titrate dose to 0.375 mg IV or orally daily
    1. Target Heart Rate <80 resting and <110 on exertion

Low dose Digoxin does not require routine level monitoring (unless otherwise indicated)
Indications
1. Digoxin Toxicity suspected
2. Elderly
3. Chronic Kidney Disease
4. Potential Drug Interactions (e.g. Amiodarone)
Target level
1. Targeting a specific drug level range is not typically indicated (outside of avoiding Digoxin Toxicity)
2. Target is the lowest effective dose to control Heart Rate in Atrial Fibrillation or symptoms in Congestive Heart Failure
3. Safe Digoxin range: 0.5 to 0.9 ng/ml

See Digoxin Toxicity
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)
Medications that decrease Heart Rate and AV Conduction (risk of AV Block)
Medications that decrease Digoxin absorption
1. Antacids (space administration 2 hours apart)
2. Cholestyramine
3. Colestipol

Half-Life: 36 hours
Protein Bound 25%
Excreted unchanged in urine
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

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
RADIANCE trial (supports continued use of Digoxin)
1. Packer (1993) N Engl J Med 329:1-7 [PubMed]
2. Smith (1993) N Engl J Med 329:51-53 [PubMed]

Not recommended for Atrial Fibrillation Rate Control unless comorbid Congestive Heart Failure
Not a great drug for rate control with activity
Delayed onset of action
Not first line for emergent rapid Atrial Fibrillation
Higher mortality - see precautions below