Editing Flecainide (section)

==Mechanism of action==
Flecainide works by blocking the [[Nav1.5]] [[sodium channel]] in the heart, slowing the upstroke of the [[cardiac action potential]].<ref name = Ramos>{{cite journal | vauthors = Ramos E, O'leary ME | title = State-dependent trapping of flecainide in the cardiac sodium channel | journal = The Journal of Physiology | volume = 560 | issue = Pt 1 | pages = 37–49 | date = October 2004 | pmid = 15272045 | pmc = 1665201 | doi = 10.1113/jphysiol.2004.065003 }}</ref> This thereby slows conduction of the electrical impulse within the heart, i.e. it "reduces excitability". The greatest effect is on the [[electrical conduction system of the heart|His-Purkinje system]] and ventricular [[myocardium]]. The effect of flecainide on the ventricular myocardium causes decreased contractility of the muscle, which leads to a decrease in the ejection fraction.

The effect of flecainide on the [[sodium channels]] of the heart increases as the heart rate increases; This is known as use-dependence and is why that flecainide is useful to break a [[tachyarrhythmia]].<ref name = Wang>{{cite journal | vauthors = Wang Z, Fermini B, Nattel S | title = Mechanism of flecainide's rate-dependent actions on action potential duration in canine atrial tissue | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 267 | issue = 2 | pages = 575–581 | date = November 1993 | pmid = 8246130 }}</ref>

Flecainide also inhibits [[ryanodine receptor 2]] (RyR2),<ref name="pmid25274603">{{cite journal | vauthors = Mehra D, Imtiaz MS, van Helden DF, Knollmann BC, Laver DR | title = Multiple modes of ryanodine receptor 2 inhibition by flecainide | journal = Molecular Pharmacology | volume = 86 | issue = 6 | pages = 696–706 | date = December 2014 | pmid = 25274603 | pmc = 4244595 | doi = 10.1124/mol.114.094623 }}</ref> a major regulator of [[Sarcoplasmic reticulum|sarcoplasmic]] release of stored calcium ions. It can reduce [[calcium sparks]] and thus arrhythmogenic calcium waves in the heart.<ref name="pmid19835880">{{cite journal | vauthors = Hilliard FA, Steele DS, Laver D, Yang Z, Le Marchand SJ, Chopra N, Piston DW, Huke S, Knollmann BC | display-authors = 6 | title = Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass | journal = Journal of Molecular and Cellular Cardiology | volume = 48 | issue = 2 | pages = 293–301 | date = February 2010 | pmid = 19835880 | pmc = 2813417 | doi = 10.1016/j.yjmcc.2009.10.005 }}</ref> While Flecainide therapy has been shown to suppress ventricular arrhythmias in patients with [[catecholaminergic polymorphic ventricular tachycardia]] (CPVT) and mouse models of this disease, the relative contribution from the inhibition of sodium channels and of RyR2 in this effect on CPVT is unclear.<ref name="pmid25858058">{{cite journal | vauthors = Smith GL, MacQuaide N | title = The direct actions of flecainide on the human cardiac ryanodine receptor: keeping open the debate on the mechanism of action of local anesthetics in CPVT | journal = Circulation Research | volume = 116 | issue = 8 | pages = 1284–1286 | date = April 2015 | pmid = 25858058 | doi = 10.1161/CIRCRESAHA.115.306298 | doi-access = free }}</ref>