| Indication |
Used to prolong the time to recurrence of paroxysmal atrial
fibrillation/flutter (PAF) associated with disabling symptoms in
patients without structural heart disease. Also used for the treatment
of life-threatening documented ventricular arrhythmias, such as
sustained ventricular tachycardia. |
| Pharmacodynamics |
Propafenone is a Class 1C antiarrhythmic drug with local
anesthetic effects, and a direct stabilizing action on myocardial
membranes. It is used in the treatment of atrial and ventricular
arrhythmias. It works by slowing the influx of sodium ions into the
cardiac muscle cells, causing a decrease in excitablity of the cells.
Propafenone has local anesthetic activity approximately equal to
procaine. |
| Mechanism of action |
The electrophysiological effect of propafenone manifests itself in
a reduction of upstroke velocity (Phase 0) of the monophasic action
potential. In Purkinje fibers, and to a lesser extent myocardial fibers,
propafenone reduces the fast inward current carried by sodium ions,
which is responsible for the drugs antiarrhythmic actions. Diastolic
excitability threshold is increased and effective refractory period
prolonged. Propafenone reduces spontaneous automaticity and depresses
triggered activity. At very high concentrations in vitro, propafenone
can inhibit the slow inward current carried by calcium but this calcium
antagonist effect probably does not contribute to antiarrhythmic
efficacy. |
| Absorption |
Nearly completely absorbed following oral administration (90%).
Systemic bioavailability ranges from 5 to 50%, due to significant
first-pass metabolism. This wide range in systemic bioavailability is
related to two factors: presence of food (food increases
bioavailability) and dosage (bioavailability is 3.4% for a 150-mg tablet
compared to 10.6% for a 300-mg tablet). |
| Volume of distribution |
|
| Protein binding |
97% |
| Metabolism |
Metabolized primarily in the liver where it is rapidly and
extensively metabolized to two active metabolites, 5-hydroxypropafenone
and N-depropylpropafenone. These metabolites have antiarrhythmic
activity comparable to propafenone but are present in concentrations
less than 25% of propafenone concentrations. |
| Route of elimination |
Approximately 50% of propafenone metabolites are excreted in the urine following administration of immediate release tablets. |
| Half life |
2-10 hours |
| Clearance |
Not Available |
| Toxicity |
Symptoms of propafenone overdose (usually most severe within the
first 3 hours) may include convulsions (rarely), heartbeat
irregularities, low blood pressure, and sleepiness. |
