Sodium channel blocker

Sodium channel blockers are agents used in the treatment of cardiac arrhythmia. They are classified as "Type I" in the Vaughan Williams classification.

Antiarrhythmic

The class I antiarrhythmic agents interfere with the (Na⁺) channel.Class I agents are grouped by what effect they have on the Na⁺ channel, and what effect they have on cardiac action potentials.Class 1 agents are called Membrane Stabilizing agents. The 'stabilizing' is the word used to describe the decrease of excitogenicity of the plasma membrane which is brought about by these agents. Also noteworthy is that a few class 2 agents like propranolol also have a membrane stabilizing effect.

Class Ia agents

Class Ia agents block the fast sodium channel.Blocking this channel depresses the phase 0 depolarization (reduces V_max), which prolongs the action potential duration by slowing conduction.Agents in this class also cause decreased conductivity and increased refractoriness.

Indications for Class Ia agents are supraventricular tachycardia, ventricular tachycardia, symptomatic ventricular premature beats, and prevention of ventricular fibrillation.

Procainamide can be used in the treatment of atrial fibrillation in the setting of Wolff-Parkinson-White syndrome, and in the treatment of wide complex hemodynamically stable tachycardias. Oral procainamide is no longer being manufactured in the US. Intravenous formulations are still available.

While procainamide and quinidine may be used in the conversion of atrial fibrillation to normal sinus rhythm, they should only be used in conjunction with an AV node blocking agent (ie: digoxin, verapamil, or a beta blocker), because procainamide and quinidine can increase the conduction through the AV node and may cause 1:1 conduction of atrial fibrillation, causing an increase in the ventricular rate.

Class Ia agents include quinidine, procainamide and disopyramide.

Class Ib agents

Class Ib antiarrhythmic agents are sodium channel blockers. Class Ib agents have fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. Class Ib agents shorten the action potential duration and reduce refractoriness. These agents will decrease V_max in partially depolarized cells with fast response action potentials. They either do not change the action potential duration, or they may decrease the action potential duration. Class Ib drugs tend to be much more specific for voltage gated Na channels than Ia. Lidocaine in particular is highly frequency dependent, in that it has more activity with increasing heart rates. This is because lidocaine selectively blocks Na channels in their open and inactive states and has little binding capability in the resting state.

Class Ib agents are indicated for the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation.

Class Ib agents include lidocaine, mexiletine, tocainide, and phenytoin.

Class Ic agents

Class Ic antiarrhythmic agents markedly depress the phase 0 depolarization (decreasing V_max). They decrease conductivity, but have a minimal effect on the action potential duration. Of the sodium channel blocking antiarrhythmic agents (the class I antiarrhythmic agents), the class Ic agents have the most potent sodium channel blocking effects.

Class Ic agents are indicated for life-threatening ventricular tachycardia or ventricular fibrillation, and for the treatment of refractory supraventricular tachycardia (ie: atrial fibrillation). These agents are potentially pro-arrhythmic, especially in settings of structural heart disease (e.g. post-myocardial infarction), and are contraindicated in such settings.

Class Ic agents include encainide, flecainide, moricizine, and propafenone. Encainide is not available in the US.

Other uses

Sodium channel blockers are also used as local anesthetics.

Sodium channel blockers have been proposed for use in the treatment of cystic fibrosis,cite journal |author=Hirsh AJ, Zhang J, Zamurs A, "et al" |title=Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4- [4-(2,3-dihydroxypropoxy)phenyl] butyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung disease |journal=J. Pharmacol. Exp. Ther. |volume=325 |issue=1 |pages=77–88 |year=2008 |month=April |pmid=18218832 |doi=10.1124/jpet.107.130443 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=18218832] but current evidence is mixed.cite web |url=http://www.cochrane.org/reviews/en/ab005087.html |title=Sodium channel blockers for cystic fibrosis |format= |work= |accessdate=]

ee also

* Sodium channel

References