Disease relevance of flecainide

• Oral flecainide acetate for the treatment of ventricular arrhythmias [1].
• Ventricular tachycardia associated with flecainide [2].
• Flecainide-associated pneumonitis [3].
• Flecainide-associated interstitial pneumonitis [4].
• OBJECTIVE: To assess the short- and long-term safety and efficacy of oral flecainide therapy in patients with symptomatic tachycardia and an extranodal accessory pathway [5].

Psychiatry related information on flecainide

• Dysarthria and visual hallucinations due to flecainide toxicity [6].

High impact information on flecainide

• The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown [7].
• Flecainide thus appears to be a highly effective and well-tolerated antiarrhythmic agent with favorable pharmacokinetics [1].
• Hospital monitoring during initial therapy is recommended, and flecainide should be used with caution, if at all, in patients with structural heart disease [5].
• Adverse cardiac reactions (proarrhythmia or sinus node suppression) attributable to flecainide occurred in 11 of 63 patients (17%); in 9 (82%) of these 11 patients, events were detected during either in-hospital monitoring or the electrophysiologic study done before discharge [5].
• Isoproterenol reversed the effects of flecainide therapy in 11 of 21 patients; 7 of the 11 patients had spontaneous clinical recurrences of tachycardia or palpitations during the follow-up period, but these symptoms occurred in only 1 of 10 patients who did not show isoproterenol-induced reversal (P = 0.02) [5].

Chemical compound and disease context of flecainide

• OBJECTIVE: To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias [8].
• Increasing doses of heptanol (n = 10), potassium (n = 10), tetrodotoxin (n = 6), RP62719 (a new class III drug) (n = 4), flecainide (n = 5), and propafenone (n = 5) were administered to terminate ventricular tachycardia [9].
• Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST) [10].
• In the remaining 12 hearts (heptanol, n = 2; potassium, n = 3; tetrodotoxin, n = 2; RP62719, n = 2; flecainide, n = 1; and propafenone, n = 2), termination of ventricular tachycardia occurred by collision of the circulating impulse with a spontaneous antidromic wave front reflected within the circuit [9].
• This study assessed the safety and efficacy of combined flecainide and amiodarone therapy in controlling refractory tachyarrhythmias in infants [11].

Biological context of flecainide

• CONCLUSION: Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function [8].
• On the other hand, flecainide block of IK during an action potential would tend to prolong repolarization, but this effect may be obscured by concomitant block of plateau Na+ channels to produce little or no change in action potential duration, consistent with its class IC classification [12].
• Finally, the flecainide slowed symptomatic PSVT heart rates to 143 +/- 12 beats/min from 178 +/- 12 on placebo (p less than 0.02) in the seven patients who had events in the placebo and flecainide treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS)[13]
• At physiological membrane potentials (Vm) ([K+]o=5.4 micromol), 1 micromol flecainide decreased Vmax from 698+/-55 to 610+/-72 V/s (P=.003) and squared conduction velocity (theta2) from 2.11+/-1.1 to 1.72+/-0.9 (m/s)2 (P=.001) [14].
• No significant hemodynamic changes were observed compared with the control group except for those in the disopyramide and flecainide groups; that is, decrease in heart rate without changes in blood pressure compared with the control group was observed [15].

Anatomical context of flecainide

• On the other hand, the effect of flecainide on refractoriness in both normal and ischemic myocardia was negligible [16].
• METHODS AND RESULTS: The effects of flecainide were determined on ventricular tachycardia induced by programmed electrical stimulation in dogs with healing myocardial infarction 4 days after coronary artery occlusion [17].
• Beta-adrenergic augmentation of flecainide-induced conduction slowing in canine Purkinje fibers [14].
• Our data suggest that the presence of a prominent Ito in epicardium contributes the development of marked electrical heterogeneity in the ventricle after exposure to flecainide [18].
• These data suggest that flecainide has little direct effect on ectopic atrial automaticity but rather causes exit conduction slowing and block between transitional and atrial muscle fibers [19].

Associations of flecainide with other chemical compounds

• To gain insights into potential cellular mechanisms, we evaluated the response of human atrial action potentials to equimolar therapeutic concentrations of flecainide and quinidine and compared this response to that of guinea pig, rabbit, and dog atria [20].
• 4-Aminopyridine, a transient outward current (Ito) blocker, reversed the flecainide-induced marked abbreviation of APD in epicardium and abolished reentrant activity in all cases [18].
• The data indicate that propranolol, TTX, and flecainide, via their action to block sodium current, may exert opposite effects on action potential duration and refractoriness in cells spanning the ventricular wall [21].
• This drug interaction must be accounted for when amiodarone and flecainide are used concomitantly [22].
• Saline (control), disopyramide, lidocaine or flecainide was infused selectively into the cannula [23].

Gene context of flecainide

• CONCLUSIONS: The functional properties of Kv4.2, especially the flecainide sensitivity, resemble those of ITO in rat (and human) myocytes better than those of Kv1 [24].
• Na(+) channel blockers such as flecainide have found renewed usefulness in the diagnosis and treatment of two clinical syndromes arising from inherited mutations in SCN5A, the gene encoding the alpha subunit of the cardiac voltage-gated Na(+) channel [25].
• The CYP2D6 polymorphism did not appear to influence flecainide disposition kinetics or electrocardiographic effects at steady state [26].
• The ERP of the right ventricle increased from 251 +/- 27 ms during the control study to 267 +/- 34 ms on flecainide (P less than 0.01) [27].
• The binding of flecainide to open channels was further investigated in a non-inactivating mutant of Nav1 [28].

Analytical, diagnostic and therapeutic context of flecainide

• Drug therapy. Flecainide [29].
• Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide [30].
• At rest, the QRS duration after treatment with flecainide increased 12.1 +/- 10.0% compared with the pretreatment value, and with exercise, the QRS duration increased by a further 28.1 +/- 17.0% compared with the predrug value [31].
• Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group [32].
• In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide [30].

References