title: Cardiac sodium channels and inherited electrophysiological disorders: an update on the pharmacotherapy.
abstract: BACKGROUND
  Since the recognition of inherited sodium (Na(+)) channel disease, the cardiac Na(+) channel has been extensively studied. Both loss-of-function and gain-of-function mutations of the cardiac Na(+) channel are associated with cardiac arrhythmia and sudden cardiac death. Pathophysiological mechanisms that may induce arrhythmia are unravelled and include alterations in biophysical properties due to the mutation in SCN5A, drug use and circumstantial factors. Insights into the mechanisms of inherited Na(+) channel disease may result in tailored therapy. However, due to the complexity of cardiac electrical activity and pathophysiological mechanisms, pharmacotherapy in cardiac Na(+) channel disease remains challenging.
  
  
  METHODS
  This review discusses various mechanisms involved in inherited Na(+) channel disorders, focussing on Brugada syndrome (Brs) and long QT syndrome type 3 (LQTS3). It aims to provide an overview of developments in pharmacotherapy, discussing both treatment and which drugs to avoid to prevent arrhythmia.
  
  
  CONCLUSIONS
  Altered biophysical properties of cardiac Na(+) channels are the basis of arrhythmias in patients with inherited Na(+) channel diseases such as BrS and LQTS3. The effects of such biophysical derangements are strongly modulated by concomitant factors. Tailored drug therapy is required to prevent arrhythmia and is best achieved by educating patients affected by Na(+) channel disorders.
authors.affiliation: University of Amsterdam, Academic Medical Center, Department of Cardiology , P.O. Box 22660, 1100 DD, Amsterdam , The Netherlands +0031 20 566 3264 ; +0031 20 566 9131 ; h.l.tan@amc.uva.nl.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: van Hoeijen
authors.forename: Marieke T
authors.initials: MT
authors.lastname: Blom
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
mesh_terms: D000200:Action Potentials; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D053840:Brugada Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D000075224:Cardiac Conduction System Disease; D006801:Humans; D008133:Long QT Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
chemical_list: D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels
keywords: Brugada syndrome; cardiac arrhythmias; cardiac sodium channel; long QT syndrome type 3; pharmacotherapy