What is the mode of action of Flecainide (anti-arrhythmic medication)?

Flecainide Mode of Action

Flecainide is a Class IC antiarrhythmic agent that works primarily by blocking voltage-gated sodium channels in cardiac tissue, producing dose-dependent slowing of intracardiac conduction throughout the heart, with the most pronounced effects on the His-Purkinje system and ventricular conduction. 1

Primary Electrophysiologic Mechanisms

Sodium Channel Blockade:

• Flecainide inhibits inward sodium current through dose-dependent blockade of voltage-gated sodium channels within the cardiac membrane, which is the fundamental mechanism underlying all its antiarrhythmic effects 1, 2
• This sodium channel blockade produces membrane-stabilizing effects characteristic of Class IC antiarrhythmics, with local anesthetic activity 1, 3

Conduction Effects:

• The drug produces dose-related decreases in intracardiac conduction in all parts of the heart, with the greatest impact on the His-Purkinje system (H-V conduction) 1
• Effects on ventricular conduction velocity are more pronounced than effects on AV nodal conduction time or intra-atrial conduction 1
• Flecainide markedly prolongs conduction while having minimal effect on repolarization 3

Specific Cardiac Effects

ECG Manifestations:

• Prolongs the PR interval due to slowed AV conduction 1, 4
• Widens the QRS complex as a result of slowed ventricular conduction 1, 4
• May cause dose-related QRS widening that can progress to left bundle branch block with excessive dosing 2

Refractoriness and Rhythm Control:

• Produces significant effects on ventricular refractory periods, though effects on atrial refractoriness are less pronounced 1
• Selectively increases both anterograde and retrograde accessory pathway refractoriness, which is particularly relevant in treating supraventricular tachycardias 4
• Causes dose-related and plasma-level-related decreases in premature ventricular contractions and can suppress recurrence of ventricular tachycardia 1

Sinus Node Effects:

• Increases sinus node recovery times (corrected) following pacing and increases spontaneous cycle lengths 1
• This effect can become clinically significant in patients with pre-existing sinus node dysfunction 1

Hemodynamic Properties

• Flecainide demonstrates negative inotropic effects in animal models and isolated myocardium 1
• Decreases in ejection fraction consistent with negative inotropy have been observed after single doses of 200-250 mg in humans 1
• The drug does not usually alter heart rate, though bradycardia and tachycardia have been reported occasionally 1

Therapeutic Plasma Levels

• Plasma levels of 0.2 to 1 mcg/mL are needed to obtain maximal therapeutic effect for PVC suppression 1
• Trough plasma levels in patients successfully treated for recurrent ventricular tachycardia range between 0.2 and 1 mcg/mL 1
• Plasma levels above 0.7 to 1 mcg/mL are associated with higher rates of cardiac adverse effects such as conduction defects or bradycardia 1

Critical Safety Consideration Related to Mechanism

Proarrhythmic Risk:

• The same sodium channel blockade that provides antiarrhythmic effects can paradoxically cause proarrhythmic effects, particularly in patients with structural heart disease 5, 4
• Flecainide may inadvertently increase ventricular rate due to conversion of atrial fibrillation to atrial flutter with 1:1 AV conduction 5, 6
• This mechanism explains why flecainide is absolutely contraindicated in patients with structural heart disease, reduced left ventricular function, or history of myocardial infarction 6, 7, 8