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Flecainide - PubMed

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Last Updated: 07 August 2022

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Common Structural Pattern for Flecainide Binding in Atrial-Selective Kv1.5 and Nav1.5 Channels: A Computational Approach.

A combination blockade of Nav1. 5 and Kv1. 5 ion channels, according to theoretical studies, gave a synergistic anti-arrhythmic effect without changes in ventricles. As a first step toward potential multi-target directed ligand design strategies, we concentrated on Kv1. 5 and Nav1. 5 to search for structural similarities in their binding site for flecainide. We present a computational workflow for a flecainide BS comparison in a flecainide-Kv1. 5 docking model and a fully working version of the flecainide-Nav1. 5 complex. Our results may lead to multi-target atrial-selective strategies for AF treatment since the simple MTDL model for AF is still incipient.

Source link: https://doi.org/10.3390/pharmaceutics14071356


How does flecainide impact RyR2 channel function?

Flecainide, a surface membrane sodium channel blocker, has been shown to reduce cardiac ryanodine receptor-mediated sarcoplasmic reticulum Ca2+ production by cardiac ryanodine receptor-mediated sarcoplasmic reticulum Ca2+ release. This Viewpoint primarily discusses flecainide's specific molecular behavior on isolated RyR2 channels in artificial lipid bilayers. Flecainide can bind to at least four separate inhibitory sites on RyR2 and one activation site, relative to its single NaV1. 5 pore binding site. Flemis can also prevent Ca2+ efflux by blocking counter currents within the pore, which would otherwise restrict SR membrane potential change during systolic Ca2+ efflux. This may lead to a decrease in Ca2+ efflux by blocking Ca2+ efflux rather than specifically blocking Ca2+ efflux. In summary, the antiarrhythmic effects of flecainide in CPVT seem to have involved several aspects of EC coupling and various actions on RyR2.

Source link: https://doi.org/10.1085/jgp.202213089


Efficacy of flecainide in bidirectional ventricular tachycardia and tachycardia-induced cardiomyopathy with Andersen-Tawil syndrome.

In only a few instances of Andersen-Tawil syndrome in particular, left ventricle function has been demonstrated. A 14-year-old female patient was admitted to our clinic from another center with documented arrhythmia and left ventricular systolic dysfunction. In a case of Andersen-Tawil syndrome with a novel mutation, we report the success of flecainide in bidirectional ventricular tachycardia and tachycardia-induced cardiomyopathy.

Source link: https://doi.org/10.1016/j.ejmg.2022.104499


Flecainide poisoning and prolongation of elimination due to alkalinization.

Following an intentional overdose, there are no reports on flecainide toxicokinetics despite established pharmacokinetic data from flecainide in therapeutic dosing. Flecainide can cause a variety of life-saving disorders, including sodium bicarbonate for stabilization and renal elimination of flecainide, but also reduced the renal elimination of flecainide, which could prolong the time of toxication.

Source link: https://doi.org/10.1016/j.ajem.2022.03.006


Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels.

In patients with AF, ventricular pro-arrhythmia, a common side effect of sodium channel blocker therapy, appears to be relatively common. Our findings reveal intrinsic differences between atrial and ventricular cardiac voltage-gated sodium currents, resulting in reduced maximum upstroke speed of action potential and slower conduction in left atria relative to ventricle. INa decreases atrial membrane potentials and is mainly caused by changes in sodium channel biophysical properties, not by NaV1. 5 protein expression. These differences may help to explain the relative safety of sodium channel blocker therapy in patients with atrial fibrillation.

Source link: https://doi.org/10.1016/j.yjmcc.2022.01.009


Moving in the right direction: elucidating the mechanisms of interaction between flecainide and the cardiac ryanodine receptor.

Flecainide's clinical effectiveness in this context is complicated due to multiple ion channels that may be affected by the disease state. However, ion fluxes across the SR membrane during heart contraction are bidirectional, and here, we explore experimental data proving that flecainide's key action on RyR2 involves the partial block of ion flow in the cytoplasm-to-lumen direction. Experimental studies have been suggested that may reveal new information on the mechanism of RyR2 block by flecainide.

Source link: https://doi.org/10.1111/bph.15718

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions