Medicine & USMLE

Class 3 Antiarrhythmics - Amiodarone

Antiarrhythmic Drugs (New)
  1. Adenosine
  2. Class 3 Antiarrhythmics - Dofetilide & Ibutilide
  3. Class 1A Antiarrhythmics
  4. Class 1B Antiarrhythmics
  5. Class 1C Antiarrhythmics
  6. Class 2 Antiarrhythmics
  7. Sotalol
  8. Class 3 Antiarrhythmics - Amiodarone
  9. Class 4 Antiarrhythmics
  10. Digoxin


Amiodarone is a class III antiarrhythmic drug. It works primarily on non-nodal heart tissue by blocking potassium channels. This markedly prolongs repolarization, increases the length of the ERP, and prolongs the AP duration. On EKG, this manifests as a prolonged QT interval. Amiodarone is also lipophilic and exhibits the effects of all classes of antiarrhythmics.

Clinically, amiodarone is used as an antiarrhythmic to treat A-Fib, where it is used for rhythm control. The drug may also be used to treat atrial flutter and ventricular arrhythmias.

Side effects of amiodarone include torsades de pointes, cardiovascular depression, pulmonary fibrosis, and neuropathy. Amiodarone acts as a hapten, which can lead to blue-gray skin deposits and photosensitivity, as well as corneal deposits that cause changes in vision.   The drug contains a large amount of iodine, which can lead to either hypothyroidism or hyperthyroidism depending on the patient.  Other side effects of amiodarone include constipation and liver damage. Lastly, Amiodarone also inhibits CYP450 enzymes, which can lead to drug interactions.

Key Points

  • Amiodarone
    • Drug Class
      • Class 3 Antiarrhythmic
        • Along with Ibutilide, Dofetilide, Sotalol, and Bretylium
    • Mechanism
      • Blocks Potassium (K+) channels
        • Prolongs phase 3 repolarization by blocking potassium outflow, mainly in non-nodal tissue
      • Increases AP duration
      • Increases effective refractory period (ERP)
      • Prolongs QT interval
        • Creates risk for early after-depolarizations and Torsades de Pointes
      • Lipophilic
        • Can dissolve across lipid membranes; can cross blood-brain barrier
      • Has class I, II, III, and IV effects
        • Class I, II, IV effects are seen with acute amiodarone administration
    • Clinical Use
      • Treats atrial flutter
      • Treats A-Fib (atrial fibrillation)
        • Used for rhythm control (e.g.pharmacologic cardioversion) and restoring of normal sinus rhythm
      • Treats ventricular tachycardia
        • Amiodarone is used in ACLS (along with epinephrine) for codes
    • Side Effects
      • Pulmonary fibrosis
      • Thyroid dysfunction
        • Can result in hyperthyroidism or hypothyroidism
        • AmIODarone is 40% IODine by weight
        • Serum TSH should be measured before starting and monitored during course
      • Hepatotoxicity
        • Elevated LFTs may be seen
      • Long QT (Torsades de Pointes risk)
        • All drugs that increase QT interval increase the risk of early after-depolarizations causing ventricular arrhythmias like Torsades de Pointes.
      • CYP450 inhibitor
        • Interacts with warfarin; both may be used in atrial fibrillation
      • Acts as hapten
        • corneal deposits
        • blue-gray skin discoloration leading to photosensitivity to light
        • Does not directly cause immunogenicity, but can when bound/attached to proteins
      • Neuropathy
      • Constipation
      • Cardiovascular depression (bradycardia, heart block, heart failure)