Digitalis Toxicity Medication

Updated: Jan 04, 2017
  • Author: Vinod Patel, MD; Chief Editor: Jeffrey N Rottman, MD  more...
  • Print
Medication

Medication Summary

The goals of pharmacotherapy are to reduce toxic levels of digitalis, prevent complications, and reduce morbidity. Activated charcoal and binding resins can reduce gastrointestinal absorption of ingested digoxin and bind enterohepatically cycling digitalis.

Immunotherapy with digoxin Fab fragments has been an extremely valuable addition to the treatment of digoxin and digitoxin intoxication. In hemodynamically stable or unstable patients, it is a first-line therapy. Antidysrhythmic agents may be indicated in hemodynamically unstable patients.

Next:

Antidotes, Other

Class Summary

Activated charcoal is useful in limiting the absorption of ingested digoxin. It is most beneficial if administered within 4 hours of ingestion. Cholestyramine resin can bind drugs that are enterohepatically recycled. Upwards of 30% of a digoxin dose (higher in some individuals) and the majority of a digitoxin dose are enterohepatically recycled.

Digoxin immune Fab is used for the treatment of hemodynamic instability, refractory dysrhythmias, and severe or refractory hyperkalemia. This agent has reversed noncardiac digitalis-associated complications (eg, thrombocytopenia). [28, 29]

Digoxin immune Fab (DigiFab)

Digoxin immune Fab is an immunoglobulin fragment with specific and high affinity for digoxin and digitoxin molecules. A 50,000-Da molecule, Fab is derived from the IgG fragment of sheep antidigoxin antibodies produced in response to antigenic carrier proteins coupled to digoxin. This relatively pure Fab product is safe and extremely effective. It removes digoxin or digitoxin molecules from tissue-binding sites. Each vial contains 40 mg of purified digoxin-specific antibody fragments, which will bind approximately 0.6 mg of digoxin or digitoxin.

The advantages of digoxin-specific Fab compared with whole IgG antibodies include larger volume of distribution and more rapid onset of action. Onset of action ranges from 20-90 minutes, and digoxin is removed irreversibly from the myocardium and other specific binding sites. A complete response generally occurs within 4 hours.

Immediately following IV administration, digoxin-specific antibodies bind intravascular free digoxin. They then diffuse into the interstitial space, binding free digoxin there. A concentration gradient is established, which facilitates movement of intracellular digoxin and digoxin that is dissociated from its binding sites (external surface of Na+/K+-ATPase enzyme) in the heart into interstitial or intravascular spaces.

Intravascular concentration of inactive, antibody-bound digoxin rises substantially. The elimination kinetics of Fab antibody–bound digoxin depend on the patient's renal function and capacity for urinary elimination.

Fab binds free digoxin in vascular and interstitial space and decreases free plasma digoxin levels by binding intracellular digoxin from its binding sites in the heart and in interstitial and intravascular spaces. Fab raises intravascular levels of inactive antibody-bound digoxin to very high levels, which decrease over several days as it is excreted renally.

Complications of therapy include allergic reactions (relatively rare and more common in patients with allergic histories), worsening heart failure, tachyarrhythmias, and hypokalemia. Overall, the incidence of complications is very low.

Activated charcoal (Kerr Insta-Char, Actidose-Aqua, EZ-Char)

Activated charcoal prevents absorption by adsorbing drug in the intestine. A network of pores present in activated charcoal absorbs 100-1000 mg of drug per gram of charcoal. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption.

Theoretically, by constantly bathing the GI tract with charcoal, the intestinal lumen serves as a dialysis membrane for the reverse absorption of drug from the intestinal villous capillary blood into the intestine. The charcoal is supplied as an aqueous mixture or in combination with a cathartic (usually sorbitol 70%). It does not dissolve in water. For maximum effect, administer the charcoal within 30 minutes of poison ingestion.

Cholestyramine (Questran, Prevalite)

Cholestyramine forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts. It has been shown to decrease digoxin levels following therapeutic dosing and acute or chronic digitalis toxicity. However, this agent may not change the ultimate outcome, because a prolonged administration time is necessary.

Previous
Next:

Anticholinergic Agents

Class Summary

These agents may improve sinus and atrioventricular (AV) node conduction by inhibiting vagal activity. They are used as an alternative to digoxin immune Fab.

Atropine IV/IM (AtroPen)

Atropine increases the heart rate through vagolytic effects, causing an increase in cardiac output.

Previous
Next:

Anticonvulsants, Hydantoins

Class Summary

Phenytoin may reverse digitalis-induced prolongation of the action potential in myocardial cells and may suppress digitalis-induced tachydysrhythmias.

Phenytoin (Dilantin, Phenytek)

Phenytoin prolongs effective refractory period and depresses spontaneous depolarization in ventricular tissues.

Previous
Next:

Local Anesthetics, Amides

Class Summary

Class Ib antidysrhythmics 1b increase electrical stimulation threshold of ventricle by suppressing automaticity of conduction.

Lidocaine (Xylocaine-Cardiac)

Lidocaine is a class IB antiarrhythmic that increases the electrical stimulation threshold of the ventricle, suppressing the automaticity of conduction through the tissue. It combines with fast sodium channels and thereby inhibits recovery after repolarization, resulting in decreased myocardial excitability and conduction velocity.

Previous
Next:

Electrolyte Supplements, Parenteral

Class Summary

Magnesium is useful as a temporizing antiarrhythmic agent until digoxin Fab fragments are available. It may be a lifesaving adjunct in the treatment of digoxin-induced ventricular tachycardia or ventricular fibrillation.

Magnesium sulfate (MgSO4)

Magnesium sulfate possesses antidysrhythmic properties that are beneficial in treatment of digoxin toxicity. It slows the rate of sinoatrial node impulse formation and prolongs conduction time.

Previous