Effects Of Flecainide Acetate Research Articles

The effect of flecainide acetate on fetal heart rate variability: A case report

Fetal supraventricular tachycardia is most often treated by maternal application of digoxin. A drug used for second-choice therapy is flecainide acetate. For a case in which maternal digoxin therapy failed, flecainide caused a lowering of the fetal heart rate (FHR) but, simultaneously, variability and accelerations nearly disappeared. The fetus demonstrated a normal movement pattern. Fetal well-being during delivery was assessed by regular ultrasound observations of fetal movements. Flecainide was not continued after birth, and digoxin therapy was started when tachycardia reappeared. The heart rate changed into a reactive pattern 5 days after birth. Around that time, flecainide levels in the neonatal serum were below the limit of detection. Flecainide use can cause the absence of accelerations and poor variability in the FHR.

The antiarrhythmic effect of flecainide on halothane-epinephrine induced arrhythmias in dogs.

The antiarrhythmic effect of flecainide acetate (FCN), a newly developed class I antiarrhythmic drug, was evaluated on epinephrine (E)-halothane induced arrhythmias in dogs. The arrhythmogenic dose of E (ADE) under 1% of halothane was significantly increased from 0.71 +/- 0.08 to 1.08 +/- 0.11 and 1.84 +/- 0.23 micro g.kg(-1).min(-1) by the administration of 2 and 4 mg.kg(-1) of FCN, respectively. The arrhythmias induced by ADE in the absence of FCN were stopped by 1.78 +/- 0.29 mg.kg(-1) of FCN in bolus injections. These results suggest that FCN can be used for the treatment of arrhythmias that E contributes to under halothane anesthesia.

Clinical electrophysiologic effects of flecainide acetate.

Flecainide acetate depresses the rate of depolarization of action potential (Vmax), the so-called "membrane stabilizing action." In the intact heart it has a unique profile of substantial effect on conduction with modest effect on refractoriness. After intravenous administration, clinical electrophysiologic studies show that conduction through atrial myocardium, atrioventricular (AV) node, His-Purkinje system, and ventricular myocardium is depressed, the most prominent effect being on the His-Purkinje system. Refractorines of the normal atrial and AV nodal myocardium is not prolonged while that of the ventricular muscle is slightly increased. Atrial fibrillation (60% to 70%), atrial tachycardia (90% to 100%), and nodal and AV tachycardia (80% to 90%) are generally terminated, while flutter is usually slowed, but in a small proportion of patients (10% to 20%) might be terminated by the intravenous use of flecainide acetate. This drug has also been shown to be effective in terminating stable ventricular tachycardia (70%). However, it appears to be slightly less effective in suppressing inducibility of ventricular arrhythmias. Administered orally, flecainide is very effective in decreasing ventricular ectopic activity (80% to 95%) and nonsustained ventricular tachycardia. Thus, flecainide has a wide range of antiarrhythmic properties, making it a useful agent in the management of a variety of supraventricular and ventricular arrhythmias. In a small proportion of patients, however, its use can lead to apparent arrhythmogenic effects, the most dangerous being exacerbation of ventricular tachycardia.

Flecainide acetate in the treatment of tachycardias associated with Mahaim fibres.

Patients with Mahaim fibres are susceptible to tachycardias which can be refractory to conventional drug therapy, leading to treatment with surgery and catheter ablation. The effects of flecainide acetate were studied in 3 patients (61, 21 and 35 years of age) with Mahaim fibres presenting with tachycardias refractory to beta-blockers, quinidine and verapamil. One also had ophthalmic side-effects from amiodarone. Three types of tachycardias were induced: a reentrant tachycardia with left bundle branch block morphology (LBBBM) in all 3 patients, atrial flutter in one and atrial fibrillation in another. Intravenous flecainide acetate (2 mg kg-1) terminated reentrant tachycardia and abolished duality of atrioventricular conduction in patient 1. In patient 2, it abolished preexcitation during atrial flutter prior to termination. Atrial fibrillation could not be induced in patient 3 after flecainide acetate. In all patients, retrograde conduction was blocked, preexcitation was not present with atrial pacing and no tachycardia was induced after flecainide. All have remained asymptomatic on oral flecainide acetate (100 mg bd) for a mean follow-up period of 9 months. We conclude that (1) flecainide acetate is effective for the treatment of various tachycardias associated with Mahaim fibres; (2) since different mechanisms responsible for the tachycardia with LBBBM may be present in the same patient and difficult to determine in some, treatment with flecainide acetate which affects both the atrioventricular node and Mahaim fibre conduction may be appropriate for the condition and; (3) its use should be considered before more aggressive therapies.

Effects of flecainide acetate on ventricular tachyarrhythmia and fibrillation in dogs with recent myocardial infarction.

The antiarrhythmic and antifibrillatory actions of the class IC antiarrhythmic agent flecainide acetate were examined in urethane-anesthetized dogs with recent myocardial infarction. The intravenous administration of flecainide in a loading dose of 1.0 mg/kg (n = 7) or 2.0 mg/kg (n = 6), followed by a maintenance infusion of 1.0 mg/kg/h to achieve plasma drug concentrations considered clinically therapeutic, failed to significantly elevate the electrical threshold current required to provoke ventricular fibrillation at infarct zone, border zone and non-infarct zone stimulation sites in postinfarction dogs. In 8 dogs which responded to baseline programmed stimulation with inducible sustained ventricular tachycardia, flecainide administered as 1.0 or 2.0 mg/kg loading doses followed by a 1.0 mg/kg/h maintenance infusion failed to prevent ventricular tachycardia initiation in any animal tested, although the post-treatment ventricular tachycardia cycle lengths were prolonged compared to baseline values (pre: 178 +/- 11 ms vs post: 202 +/- 17 ms, p less than 0.05). Flecainide administration apparently facilitated the induction of newly sustained ventricular tachycardia in 3 previously noninducible postinfarction dogs. The development of acute posterolateral ischemia at a site remote from previous anterior myocardial infarction resulted in the development of ventricular fibrillation in 4 of 11 (36%) saline-treated postinfarction dogs vs a cumulative 10 of 12 (83%) flecainide-treated, baseline noninducible postinfarction dogs (p less than 0.05 vs saline-treated). The incidence of sudden ischemic ventricular fibrillation was 7 of 7 (100%) among flecainide-treated baseline inducible postinfarction dogs. These data suggest that flecainide acetate may have only limited efficacy in preventing ventricular tachycardia or ventricular fibrillation soon after myocardial infarction.

Effect of intravenous and oral flecainide on ventricular tachycardia

The effect of flecainide acetate, a class 1c antiarrhythmic agent, was examined in 15 patients with recurrent ventricular tachycardia. Intravenous flecainide was administered in a dose of 2 mg/kg at the time of intracardiac stimulation and recording studies. Oral flecainide was given to 10 15 patients and retesting was undertaken using an indwelling electrode. Intravenous flecainide terminated sustained stable tachycardia in 8 11 patients and prevented reinitiation of tachycardia in 5 10 patients. Oral therapy prevented induction of tachycardias in only 2 10 patients. Five patients had non-sustained tachycardia and three had slower sustained tachycardia. “New” non-clinical tachycardias could be induced in six patients after flecainide but five of these had had more than one type of induced tachycardia. Four of 10 patients remained free of tachycardias during follow-up. Withdrawal of oral treatment was necessary in three patients, one of whom had severe proarrhythmic effects. Two patients required additional antiarrhythmic therapy. Long-term suppression could not be predicted from the results of oral therapy, but testing after intravenous drug seemed to be a more useful prognostic indicator. In summary, intravenous flecainide is effective for slowing and termination of stable ventricular tachycardia. Oral therapy is also effective but caution should be exerted in patients with multimorphic tachycardias.

The effect of flecainide acetate, a new antiarrhythmic, on plasma digoxin levels.

The possible effect of oral flecainide acetate on steady-state digoxin levels was assessed in 15 healthy men. Each volunteer received digoxin 0.25 mg daily (8 AM) for 22 consecutive days and flecainide 200 mg bid (8 AM and 8 PM) on days 11 through 15. Plasma digoxin and flecainide levels were measured by radioimmunoassay and gas-liquid chromatography methods, respectively. Flecainide levels were within the range associated with suppression of premature ventricular contractions in patients. Mean plasma digoxin levels just before the 8 AM dose were 0.46 ng/mL on days 9 and 10 (baseline), 0.57 ng/mL (P less than .05) on day 13, and 0.49 ng/mL (not significant [NS]) on day 15. Compared with a mean six-hour postdose baseline digoxin level of 0.58 ng/mL, postdose levels were 0.62 ng/mL (NS) and 0.65 ng/mL (P less than .05) on days 13 and 15, respectively. On an average for each subject, predose and six-hour postdose digoxin levels increased by 24 +/- 35% and 13 +/- 19%, respectively, during coadministration. The changes in electrocardiographic intervals and vital signs that occurred during concomitant drug administration were not clinically significant although a slight prolongation of the PR interval was noted in some subjects. Unless plasma digoxin levels are in the upper end of the therapeutic range, changes in magnitude as observed in this study should be clinically inconsequential for most patients.

Haemodynamic and antiarrhythmic effects of intravenous flecainide acetate in chronic congestive heart failure.

The objective of this study was to evaluate the haemodynamic and antiarrhythmic effects of flecainide acetate in patients with heart failure. Flecainide acetate, a class Ic antiarrhythmic agent, was given intravenously to 9 patients with congestive heart failure and frequent ventricular arrhythmias with nonsustained ventricular tachycardia. The drug (2 mg/kg) was infused slowly over 60 minutes. The maximum plasma level achieved was 218 (range 142-350) ng/ml. Six of the 9 patients experienced a 90% suppression of their arrhythmias for an average of 6.5 (range 2-15) hours. Pre-ejection period control (PEPc, 148.8 +/- 3.6 msec) increased to 157 msec and pre-ejection period/ejection time (PEP/ET) [control 0.449 +/- 0.027] to 0.516 (p less than 0.005), while the ejection time index (ETI) did not change. Cardiac index (control 2.4 +/- 0.36 L/min/m2) decreased by 11% (p less than 0.02), and pulmonary wedge pressure (control 13.4 +/- 2.4mm Hg) increased by 23% (p less than 0.05). Stroke work index, arterial pressure and vascular resistance did not change significantly. The parameters returned to control values on completion of the infusion. Flecainide acetate can be safely administered at the usual dose of 2 mg/kg to patients with congestive heart failure, provided that the infusion time is doubled. Antiarrhythmic efficacy under these conditions is good even at lower plasma concentrations.