Unit Converter
Digitoxin
(Cardiac Glycoside – Therapeutic Drug Monitoring for Heart Failure & Arrhythmias)
Synonyms
- Digitoxin
- Digitalis toxin
- Cardiac glycoside (digitoxin type)
- Cardioactive steroid
- Gitoxin (older name)
Units of Measurement
- nmol/L
- µg/L
- µg/dL
- µg/100 mL
- µg%
- ng/mL
1 ng/mL = 1 µg/L
1 µg/dL = 0.01 µg/mL = 10 ng/mL
µg/100 mL = µg% = µg/dL
1 nmol/L = 0.764 ng/mL (using MW = 764.9 g/mol)
Description
Digitoxin is a cardiac glycoside derived from Digitalis purpurea (foxglove).
It increases cardiac contractility and decreases heart rate through:
- Inhibition of Na⁺/K⁺-ATPase → ↑ intracellular Ca²⁺
- Enhanced vagal tone → slowing of AV conduction
Digitoxin is used for:
- Congestive heart failure (historically)
- Supraventricular arrhythmias (especially atrial fibrillation)
Although digoxin is more commonly used today, digitoxin remains clinically relevant in certain regions and populations.
Digitoxin has:
- Longer half-life (5-7 days)
- Higher protein binding
- Hepatic metabolism
This makes it suitable for patients with renal insufficiency, unlike digoxin.
Physiological Role
Digitoxin has no physiological role; it is purely pharmacologic.
Mechanism:
- Blocks Na⁺/K⁺ ATPase
- Increases intracellular Na⁺
- Reduces Na⁺/Ca²⁺ exchange
- Increases intracellular Ca²⁺ storage in sarcoplasmic reticulum
- Enhances cardiac contractility (positive inotropy)
Clinical Significance
Elevated Digitoxin (Toxicity)
Digitoxin has a narrow therapeutic index.
Symptoms of Toxicity
Cardiac:
- PVCs
- AV block
- Bradycardia
- Ventricular tachycardia/fibrillation
Gastrointestinal:
- Nausea, vomiting
- Anorexia
- Abdominal pain
Neurologic:
- Confusion
- Delirium
- Visual disturbances (yellow/green halos)
Electrolytes:
- Hypokalemia → increases toxicity
- Hypercalcemia → increases toxicity
- Hypomagnesemia → increases toxicity
Digitoxin toxicity is life-threatening.
Low Digitoxin
- Subtherapeutic dosing
- Poor adherence
- Drug interactions that reduce absorption
- Malabsorption
Low levels reduce treatment efficacy.
Reference Intervals (Therapeutic Ranges)
(Tietz 8E + Cardiac Pharmacology + Mayo + ARUP)
Therapeutic Range
- 10 – 30 ng/mL (≈ 13–39 nmol/L)
- Optimal target: 15–25 ng/mL
Toxic Level
- > 35 ng/mL (≈ >46 nmol/L)
Levels correlate poorly with serum concentration in acute toxicity - interpret clinically.
Diagnostic Uses
1. Therapeutic Drug Monitoring
Digitoxin levels are measured to:
- Maintain safe therapeutic range
- Prevent toxicity
- Adjust dose in hepatic impairment
- Adjust dose in elderly
2. Assessing Toxicity
Indicated when:
- Arrhythmias
- GI symptoms
- Altered sensorium
- Electrolyte abnormalities
- Drug interactions (quinidine, verapamil, amiodarone)
3. Renal Impairment
Digitoxin preferred over digoxin due to:
- Hepatic metabolism
- Minimal renal excretion
Hence levels needed for dose titration.
4. Drug Interactions
Digitoxin levels increase with:
- Amiodarone
- Verapamil
- Quinidine
- Macrolides
- Azoles
- Tamoxifen
Levels decrease with:
- Rifampicin
- Phenytoin
Analytical Notes
- Serum samples preferred
- Collect 6–8 hours after last dose (trough)
- High protein binding → free digitoxin levels rarely measured
- Immunoassays commonly used
- Hemolysis minimal effect
- Monitor electrolytes, especially K⁺, Mg²⁺, Ca²⁺
Clinical Pearls
- Digitoxin is safer than digoxin in renal failure, but more dangerous in hepatic disease.
- Hypokalemia significantly increases digitoxin toxicity - always check potassium.
- ECG is often more sensitive for toxicity signs than serum levels.
- Digitoxin has a long half-life → toxicity develops slowly but also resolves slowly.
- Treatment of toxicity includes:
- Digoxin immune Fab (cross-reacts with digitoxin)
- Correct electrolytes
- Supportive care
- Digoxin immune Fab (cross-reacts with digitoxin)
Interesting Fact
Digitoxin and digoxin originate from the foxglove plant (Digitalis), discovered in 1785 by William Withering - one of the oldest drugs still in modern medicine.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Therapeutic Drug Monitoring.
- Cardiac Pharmacology Texts - Digitalis Glycosides.
- AHA/ACC Guidelines - Heart Failure & Arrhythmias.
- Mayo Clinic Laboratories - Digitoxin.
- ARUP Consult - Digitalis Toxicity.
- MedlinePlus / NIH - Digitalis Drugs.