Pharmacological action Propafenone
Propafenone Antiarrhythmic agent of class IC, sodium channel blocker. Reduces the maximum rate of depolarization of phase 0 of action potential and its amplitude predominantly in Purkinje fibers and ventricular contractile fibers, decreases automaticity. Highly effective in ventricular arrhythmias with supraventricular arrhythmias efficiency is somewhat lower. Propafenone has a poorly marked beta adrenoblokiruyuschee action.
Propafenone Pharmacokinetics
Pharmacokinetics of propafenone is characterized by significant individual differences.
After oral absorption of a rapid and almost complete – more than 90%, Cmax plasma levels reached after 1-3.5 h. Protein binding 97%. Subjected to intensive metabolism in the “first pass” through the liver to form two active metabolites – 5-gidroksipropafenona and N-despropilpropafenona which have antiarrhythmic activity comparable to the activity of propafenone, but are present in concentrations of 20% of the concentrations of propafenone.
T1 / 2 in patients with intense metabolism (more than 90% of cases) – 2-10 hours, with slow metabolizers (less than 10% of cases) – 10-32 hours is derived by the kidneys – 38% as metabolites, 1% – unchanged ; through the intestines – 53% as metabolites.
Indications Propafenone
Treatment and prevention of supraventricular and ventricular extrasystoles, paroxysmal arrhythmias (supraventricular tachycardia, including those with the syndrome WPW; ventricular tachycardia).
Dosing regimen Propafenone
When administered an initial dose – 450-600 mg / day, if necessary, increase the dose to 900 mg / day.
At iv drip of the initial dose – 500 mg / kg, if necessary, increase the dose to 1-2 mg / kg.
Side effects: Propafenone
With the cardiovascular system: possible bradycardia, slowing sinoatrial, AV and intraventricular conduction, decrease myocardial contractility (in predisposed patients), arrhythmogenic effect, while taking in high doses – orthostatic hypotension.
From the digestive system: when taking high doses of nausea, anorexia, feeling of heaviness in the epigastric pain, constipation, rarely – liver function abnormalities.
CNS: when receiving high-dose – headache, dizziness, rarely – visual impairment.
From the hemopoietic system: leucopenia, agranulocytosis, thrombocytopenia.
From the reproductive system: oligospermia.
Allergic reactions: seldom – a skin rash.
Contra Propafenone
Severe forms of chronic heart failure, severe hypotension, cardiogenic shock, marked bradycardia, SSS, AV-block II and III level, electrolyte derangement, myasthenia gravis, severe obstructive pulmonary disease, hepatic cholestasis, children’s age, sensitivity to propafenone.
Application of pregnancy and breastfeeding
Application of pregnancy is only possible if the intended benefits to the mother outweighs the potential risk to the fetus.
If necessary, use during lactation should solve the issue of termination of breastfeeding.
Cautions
With careful use in hepatic dysfunction, marked renal impairment, as well as in combination with other antiarrhythmics with similar electrophysiological parameters.
Treatment should begin in hospital as an increased risk of arrhythmogenic action associated with the use of propafenone. It is recommended that prior antiarrhythmic therapy was discontinued before the start of propafenone in a period equal to 2.5 half-life.
Propafenone is characterized by marked individual differences in concentrations of the active substance in the blood plasma, so we recommend careful selection of doses for each patient.
In the intravenous should be under the constant supervision of blood pressure, heart rate and electrocardiogram. If during the course of treatment or on the background / in the introduction notes the broadening of the QRS complex or QT interval by more than 20%, compared with the baseline values, reduce the dose or temporarily lift propafenone. In elderly patients, patients weighing less than 70 kg of propafenone in lower doses.
Effects on ability to drive vehicles and management mechanisms
With careful use in patients involved in potentially hazardous activities that require attention and quickness of psychomotor reactions.
Drug interactions Propafenone Propafenone
In an application with anticholinergics may increase anticholinergic action.
In an application with anticholinesterase agents (including with pyridostigmine) reduced the effectiveness of pyridostigmine in myasthenia gravis.
In an application with beta-blockers, tricyclic antidepressants, local anesthetics may increase antiarrhythmic action of propafenone in ventricular arrhythmias.
With the simultaneous application of propafenone may potentiate the effect of indirect anticoagulants.
In an application with phenobarbital increased excretion of propafenone from the body and reduces its concentration in blood plasma. It is believed that other barbiturates interact with propafenone in the same way.
In an application with ketoconazole described a case of cramps.
While the application may increase the plasma concentrations of propranolol, metoprolol, cyclosporine, digoxin.
In an application with rifampicin, the concentration of propafenone in plasma and significantly reduced its therapeutic efficacy. This is because rifampicin induces CYP3A4/1A2 isozymes and phase II glucuronidation of propafenone. Rifampicin has no effect on the metabolism of propafenone caused isoenzyme CYP2D6.
While the application describes cases increasing the concentration of theophylline in blood plasma and the development of toxic reactions.
Quinidine inhibits propafenone metabolism in the liver of patients with high levels of metabolism, which leads to a significant increase in its concentration in blood plasma. The effectiveness of propafenone does not change, because produce its active metabolite (5-gidroksipropafenona) simultaneously decreases by 2 times.
Quinidine increases the beta-blocking effects of propafenone in patients with a high level of metabolism in the liver, because Only the original active substance, and not the metabolites, has beta-blocking activity.
In an application with cimetidine possible small increase in the concentration of propafenone in plasma and the expansion of the QRS complex on ECG.
With the simultaneous application of erythromycin may inhibit the metabolism of propafenone.
