Propafenone (Rythmol) exhibits predominantly class IC properties with conduction slowing due to sodium channel blockade. Additionally, propafenone is a weak β-receptor and L-type calcium channel blocker.
As with all members of its class, propafenone has its ma-jor effect on the fast inward sodium current. The IC agents depress Vmax over a wide range of heart rates and shift the resting membrane potential in the direction of hyperpolarization. The IC agents bind slowly to the sodium channel and dissociate slowly. Therefore, they exhibit rate-dependent block. Inhibition of the sodium channel throughout the cardiac cycle will result in a de-crease in the rate of ectopy and trigger ventricular tachycardia.
Propafenone causes sinus node slowing that could lead to sinoatrial block. It may lengthen the sinus node recovery time with minimal effects on sinus cycle length.
The action potential duration and ERP of atrial mus-cle are both prolonged by propafenone. The electrophys-iological effects persist beyond removal of the drug from the tissue. In patients with atrial flutter, fibrillation, or tachycardia, propafenone can slow the atrial rate, result-ing in a change from 2:1 or 4:1 A-V block to 1:1 A-V con-duction with a subsequent increase in the ventricular rate.
The IV administration of propafenone slows con-duction through the A-V node.
Propafenone slows conduction and inhibits auto-matic foci.
Propafenone causes dose-dependent increases in the PR and QRS intervals.
The IV administration of propafenone is accompanied by an increase in right atrial, pulmonary arterial, and pulmonary artery wedge pressures in addition to an in-crease in vascular resistance and a decrease in the car-diac index. A significant decrease in ejection fraction may be observed in patients with preexisting left ven-tricular dysfunction. In the absence of cardiac abnor-malities, propafenone has no significant effects on car-diac function.
The pharmacokinetic characteristics of propafenone:
Oral bioavailability : Nearly complete
Onset of action : 1 hour
Peak response : 2–3 hours
Duration of action : 8–12 hours
Plasma half-life : 2–10 hours
Primary route of metabolism : Hepatic
Primary route of excretion : 18.5–38% renal (unchanged)
Therapeutic serum concentration : <1/mL
Approved indications for propafenone include treatment of supraventricular arrhythmias and life-threatening ventricular arrhythmias in the absence of structural heart disease. Propafenone has been shown to increase mor-tality in patients with structural heart disease, and so ex-treme caution must be used in this subset of patients. As with flecainide, the patient should be hospitalized for initiation of therapy.
Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone.
As with other members of class IC, propafenone may interact in an unfavorable way with other agents that depress A-V nodal function, intraventricular con-duction, or myocardial contractility.
Overall, 21 to 32% of patients have adverse effects. The most common are dizziness or light-headedness, metallic taste, nausea, and vomiting; the most serious are proarrhythmic events.
Propafenone is contraindicated in the presence of se-vere or uncontrolled congestive heart failure; cardio-genic shock; sinoatrial, A-V, and intraventricular disor-ders of conduction; and sinus node dysfunction, such as sick sinus syndrome. Other contraindications include severe bradycardia, hypotension, obstructive pulmo-nary disease, and hepatic and renal failure. Because of its weak β-blocking action, propafenone may cause pos-sible dose-related bronchospasm. This problem is great-est in patients who are slow metabolizers.
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