Antiarrhythmic drugs: Class 3 – Amiodarone and others

#Amiodarone Structure


Class 3 antiarrhythmic drugs are known for their ability to prolong action potentials, primarily by blocking potassium channels in cardiac muscle or enhancing inward currents through sodium channels. This article will focus on amiodarone and other Class 3 antiarrhythmic drugs, discussing their mechanism of action, cardiac and extracardiac effects, toxicity, pharmacokinetics, and therapeutic use.

Mechanism of Action

  • Action Potential Prolongation: Class 3 drugs like Amiodarone prolong action potentials, which can be both beneficial and risky. They exhibit “reverse use-dependence,” meaning they are less effective at fast heart rates where they are most needed.
  • QT Prolongation: These drugs often cause QT interval prolongation on the ECG, but this alone may not be the best predictor for the risk of torsades de pointes. Other factors like action potential stability and dispersion of repolarization time across the ventricles are also important.
#Amiodarone MOA

Cardiac Effects of Amiodarone

  • Broad Spectrum of Action: Amiodarone is effective against both ventricular and supraventricular arrhythmias due to its wide range of antiarrhythmic actions.
  • Action Potential Duration: Amiodarone prolongs the action potential duration uniformly over a wide range of heart rates, without reverse use-dependent action.
  • Additional Effects: Besides potassium channel blockade, Amiodarone also blocks inactivated sodium channels and has weak adrenergic and calcium channel-blocking actions.

Extracardiac Effects

  • Peripheral Vasodilation: Prominent after intravenous administration, possibly related to the action of the vehicle.


  • Pulmonary Toxicity: The most significant adverse effect, potentially leading to fatal pulmonary fibrosis.
  • Liver and Thyroid Effects: Regular monitoring of liver function tests and thyroid function is necessary.
  • Other Organ Systems: Effects have been described in virtually every organ system, requiring constant reevaluation of treatment.


  • Complex Elimination: Amiodarone has a complex half-life and can remain in the system for a long time even after discontinuation.
  • Drug Interactions: Amiodarone interacts with many other drugs, affecting their levels in the body.

Therapeutic Use

  • Broad Utility: Effective in maintaining normal sinus rhythm in atrial fibrillation patients and in preventing recurrent ventricular tachycardia.
  • ICD Adjuvant: Can be used alongside implanted cardioverter-defibrillators to reduce the frequency of uncomfortable discharges.

Amiodarone is a potent Class 3 antiarrhythmic drug with a broad spectrum of action, making it useful for treating a variety of arrhythmias. However, its complex pharmacokinetics and potential for toxicity require careful monitoring and consideration of drug interactions. Its broad utility and relatively lower risk of inducing torsades de pointes make it a valuable option in the antiarrhythmic arsenal.


Mechanism of Action

  • Structural analog of amiodarone with iodine atoms removed and a methanesulfonyl group added.
  • Multichannel actions, including blocking IKr, IKs, ICa, and INa, as well as β-adrenergic-blocking action.


  • Half-life of 24 hours, administered twice daily at a fixed dose of 400 mg.
  • Primarily nonrenal elimination.

Efficacy and Risks

  • Effective in a small percentage of patients with atrial fibrillation.
  • Black box warning against its use in acute decompensated or advanced (class IV) heart failure.


Mechanism of Action

  • Both β-adrenergic receptor-blocking (class 2) and action potential-prolonging (class 3) actions.


  • Not metabolized in the liver, predominantly excreted by the kidneys.
  • Half-life of approximately 12 hours.

Efficacy and Risks

  • Approved for life-threatening ventricular arrhythmias and maintenance of sinus rhythm in atrial fibrillation.
  • Risk of torsades de pointes at high doses.


Mechanism of Action

  • Class 3 action potential prolonging action through dose-dependent blockade of IKr.


  • 100% bioavailable, 80% eliminated unchanged by the kidneys.
  • Dosage must be based on estimated creatinine clearance.

Efficacy and Risks

  • Approved for the maintenance of normal sinus rhythm in patients with atrial fibrillation.
  • Relative contraindications include a baseline QTc of greater than 450 ms, bradycardia of less than 50 bpm, and hypokalemia.


Mechanism of Action

  • Slows cardiac repolarization by blockade of IKr.
  • Activation of slow inward sodium current also suggested.


  • Rapidly cleared by hepatic metabolism, half-life averages 6 hours.

Efficacy and Risks

  • Used for the acute conversion of atrial flutter and atrial fibrillation to normal sinus rhythm.
  • Risk of excessive QT-interval prolongation and torsades de pointes.


Class 3 antiarrhythmic drugs are known for their action potential prolonging effects, which can be both beneficial and risky. Each drug in this class has its own unique pharmacokinetic profile, efficacy, and associated risks, requiring careful consideration for appropriate use.

Note: This article is intended for educational purposes and should not be considered as medical advice. Always consult with a healthcare professional for medical advice and treatment.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the advice of a healthcare provider with any questions regarding a medical condition.

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