Digoxin Pharmacokinetics and Toxicity Overview

Digoxin

Cardiac glycoside used for heart conditions.

Mechanism of Action

Inhibits Na+-K+-ATPase, affecting ion transport.

Formulations

Available as injection, oral solution, tablets.

Volume of Distribution

5-7 L/kg, varies by patient factors.

Protein Binding

Digoxin is 25% protein bound in plasma.

Half Life

Approximately 38 hours for parent drug.

Time to Peak Effect (IV)

2-6 hours after intravenous administration.

Time to Peak Effect (Tablets)

1-4 hours after oral tablet administration.

Therapeutic Role in Atrial Fibrillation

Controls ventricular response rate in chronic cases.

Therapeutic Role in Heart Failure

Increases left ventricular ejection fraction.

Time to Onset of Effect (IV)

5-30 minutes after intravenous administration.

Time to Onset of Effect (Tablets)

0.5-2 hours after oral tablet administration.

Risk Factors for Toxicity

Kidney injury, age, electrolyte imbalance, fluid status.

Causes of Toxicity

Hypokalemia, hypercalcemia, hypomagnesemia increase toxicity.

Digoxin and Calcium

Enhances Ca++ absorption into cardiac myocytes.

Digitalis-Induced Arrhythmias

Sensitivity increases due to electrolyte imbalances.

Drug Interactions

Many drugs can alter digoxin concentration.

No P450 Interactions

Digoxin is not metabolized by P450 enzymes.

Steady State

Achieved in 7-10 days after consistent dosing.

Electrolyte Imbalance

Increases sensitivity to digoxin effects.

Fluid Status

Poor intake can lead to electrolyte imbalances.

Age Factor

Elderly patients often have decreased renal function.

Digoxin Elimination

Primarily eliminated by the kidneys.

Digoxin Toxicity Symptoms

Includes nausea, vomiting, and visual disturbances.

Digoxin Therapeutic Index

Narrow therapeutic index increases toxicity risk.

FDA Package Insert

Source of dosing and pharmacokinetic information.

Digoxin

A cardiac glycoside used for heart conditions.

Drug Interactions

Common drugs that affect digoxin efficacy.

Loop Diuretics

Medications that lower potassium levels, affecting digoxin.

Thiazide Diuretics

Diuretics that also decrease serum potassium levels.

Verapamil

Calcium channel blocker that alters digoxin excretion.

Diltiazem

Calcium channel blocker affecting digoxin pharmacokinetics.

Quinidine

Antiarrhythmic that increases digoxin serum levels.

Amiodarone

Antiarrhythmic that can raise digoxin levels.

Increased Serum Levels

Conditions leading to elevated digoxin concentrations.

Benzodiazepines

Sedatives that may increase digoxin toxicity risk.

Cyclosporine

Immunosuppressant affecting digoxin metabolism.

Hyperkalemia

High potassium levels, poor prognostic sign in toxicity.

Bradycardia

Slow heart rate, a symptom of digoxin toxicity.

Acute Toxicity Symptoms

Nausea, vomiting, abdominal pain, confusion.

Chronic Toxicity Symptoms

Subtle signs like confusion, drowsiness, and headache.

Visual Disturbances

Symptoms include blurred vision and yellow halos.

Hypokalemia

Low potassium levels, increases risk of arrhythmias.

Laboratory Analyses

Tests to interpret digoxin levels and electrolyte balance.

Mortality Risk

High mortality associated with hyperkalemia in toxicity.

Potassium Goals

Target potassium levels between 4.0-5.0 mEq/L.

Hypomagnesemia

Low magnesium may lead to refractory hypokalemia.

Antidote Indication

Antidote required when potassium exceeds 5 mEq/L.

Digoxin Distribution Phase

Initial phase affecting serum level readings.

Electrolyte Monitoring

Essential for managing digoxin toxicity.

Enhanced Pharmacodynamic Effects

Increased effects of digoxin due to certain drugs.

Antagonize Pharmacodynamic Effects

Drugs that reduce the effectiveness of digoxin.

Post-ingestion level

Initial level measured 4-6 hours after ingestion.

Unbound digoxin

Digoxin not bound to proteins in serum.

Fab fragments

Antibodies that bind digoxin for treatment.

Total digoxin

Sum of bound and unbound digoxin levels.

Digoxin toxicity diagnosis

Requires history, symptoms, EKG, levels, electrolytes.

Risk factors

Age and renal function affecting digoxin toxicity.

Acute overdose symptoms

Includes bradycardia, AV block, confusion, vomiting.

Chronic overdose symptoms

Insidious onset with visual changes and lethargy.

EKG findings

Arrhythmias and conduction abnormalities in toxicity.

Digoxin therapeutic range

0.5 - 2.0 ng/mL for safe levels.

Toxicity threshold

Toxic effects begin above 2.0 ng/mL.

Distribution phase

Digoxin levels high for 6-12 hours post-ingestion.

Electrolyte imbalances

Hypokalemia and hypomagnesemia increase toxicity risk.

Hypercalcemia effect

Enhances digitalis-induced inotropy and toxicity.

Decontamination methods

Activated charcoal can adsorb digoxin in gut.

Enhanced elimination

Dialysis ineffective due to digoxin's distribution.

DigiFab®

Digoxin-specific antibody treatment for toxicity.

Acute overdose treatment

Activated charcoal used for immediate digoxin removal.

Electrolyte monitoring

Critical for managing digoxin toxicity effects.

Signs of hyperkalemia

Elevated potassium levels indicating digoxin toxicity.

Visual symptoms

Photophobia and color vision changes in overdose.

Central nervous system signs

Delirium and confusion in chronic toxicity.

Gastrointestinal symptoms

Nausea, vomiting, and anorexia in digoxin toxicity.

Cardiac dysrhythmias

Bradycardia and tachydysrhythmias possible with toxicity.

Weight loss

Possible symptom of chronic digoxin overdose.

Seizures

Rare but possible in severe digoxin toxicity.

Digoxin levels misleading

Acute poisoning may not reflect true levels.

Renal function impact

Altered renal function affects digoxin clearance.