Description
Propafenone hydrochloride is a class I anti-arrhythmic agent with basic local anaesthetic and membrane-stabilizing properties. Some P-adrenergic blocking action has also been described. Propafenone decreases the depolarization velocity and slows conduction in the His-Purkinje system with resultant increase in the PR interval and the QRS complex. Propafenone is used in the treatment of paroxysmal supraventricular tachycardias and ventricular arrhythmias.
Propafenone should not be used in uncontrolled cardiac failure, severe obstructive pulmonary disease or marked hypotension. Propafenone may worsen myasthenia gravis.
Chemical Properties
White Solid
Uses
A sodium channel protein inhibitor.
Uses
Antiarrhythmic;'Beta adrenergic antagonist
Uses
Sodium channel blocker. Antiarrhythmic (class IC)
Definition
ChEBI: A hydrochloride that is the monohydrochloride salt of propafenone. It is a class 1C antiarrhythmic drug with local anesthetic effects, and is used in the management of supraventricular and ventricular arrhythmias.
Brand name
Rythmol (Reliant).
Pharmacokinetics
Propafenone hydrochloride (Rythmol(R)) is similar in action to flecainide. It reduces the fast inward sodium current in Purkinje fibres and to a lesser extent in myocardial fibres. Unlike other class l drugs, propafenone has mild B-blocking effects. This may contribute to its overall effects on the conduction system. lt is also believed to have calcium channel-blocking effects, which may contribute to its mild negative inotropic effects.
Clinical Use
Anti-arrhythmic agent:
Ventricular arrhythmias
Paroxysmal supraventricular tachyarrhythmias,
(including paroxysmal atrial flutter or fibrillation,
and paroxysmal re-entrant tachycardias involving
the AV node or accessory pathway) where standard
therapy has failed or is unsuitable
Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: increased myocardial depression
with other anti-arrhythmics.
Antibacterials: increased metabolism with rifampicin
(reduced effect).
Anticoagulants: enhanced anticoagulant effect of
coumarins.
Antidepressants: increased risk of arrhythmias
with tricyclics; metabolism of propafenone possibly
inhibited by paroxetine (increased risk of toxicity).
Antihistamines: increased risk of ventricular
arrhythmias with mizolastine - avoid.
Antipsychotics: increased risk of ventricular
arrhythmias with antipsychotics that prolong the QT
interval.
Antivirals: concentration of propafenone increased
by saquinavir and ritonavir and possibly by
fosamprenavir, increased risk of ventricular
arrhythmias - avoid; use with caution with
telaprevir.
Beta-blockers: increased myocardial depression;
increased concentration of metoprolol and
propranolol.
Cardiac glycosides: increased digoxin concentration -
halve digoxin dose.
Ciclosporin: possibly increased ciclosporin
concentration.
Ulcer-healing drugs: levels increased by cimetidine.
Metabolism
Propafenone is hepatically metabolised mainly by
CYP2D6 isoenzyme but also to a small extent by
CYP1A2 and CYP3A4. This forms 2 active metabolites,
5-hydroxypropafenone and N-depropylpropafenone and
some inactive ones. Propafenone and its metabolites also
undergo glucuronidation. The extent of metabolism is
genetically determined.
Propafenone is excreted in the urine and faeces mainly in
the form of conjugated metabolites.
