Sodium channel blockers aredrugs which impair the conduction ofsodium ions (Na+) throughsodium channels.[1]
The following naturally-produced substances block sodium channels by binding to and occluding theextracellular pore opening of the channel:
Drugs which block sodium channels by blocking from theintracellular side of the channel include:
Sodium channel blockers are used in the treatment ofcardiac arrhythmia. They are classified as "Type I" in theVaughan Williams classification.
Class I antiarrhythmic agents interfere with the(Na+) channel.Class I agents are grouped by their effect on the Na+ channel, and by their effect on cardiacaction potentials.Class I agents are called Membrane Stabilizing Agents. 'Stabilizing' refers to the decrease of excitogenicity of the plasma membrane affected by these agents. A few class II agents,propranolol for example, also have amembrane stabilizing effect.
Class Ia agents block the fast sodium channel, which depresses the phase 0 depolarization (i.e. reduces Vmax), which prolongs the action potential duration by slowing conduction.Agents in this class also cause decreased conductivity and increasedrefractoriness.
Indications for Class Ia agents aresupraventricular tachycardia,ventricular tachycardia, symptomatic ventricular premature beats, and prevention ofventricular fibrillation.
Procainamide can be used to treatatrial fibrillation in the setting ofWolff–Parkinson–White syndrome, and to treat wide complex hemodynamically stabletachycardias. Oral procainamide is no longer being manufactured in the US, but intravenous formulations are still available.
While procainamide andquinidine may be used in the conversion of atrial fibrillation to normal sinus rhythm, they should only be used in conjunction with anAV node blocking agent such asdigoxin orverapamil, or abeta 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 includequinidine,procainamide anddisopyramide.
Class Ib antiarrhythmic agents are sodium channel blockers. They 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 Vmax 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 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 includelidocaine,mexiletine,tocainide, andphenytoin.
Class Ic antiarrhythmic agents markedly depress the phase 0 depolarization (decreasing Vmax). 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 supraventricular arrhythmias (i.e.atrial fibrillation) and as a last line treatment for refractory life-threatening ventricular tachycardia or ventricular fibrillation.[4] 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 includeencainide,flecainide,moricizine, andpropafenone. Encainide is not available in the United States.
Sodium channel blockers are also used aslocal anesthetics andanticonvulsants.[5]
Sodium channel blockers have been proposed for use in the treatment ofcystic fibrosis,[6] but current evidence is mixed.[7]
It has been suggested that the analgesic effects of someantidepressants may be mediated in part via sodium channel blockade.[8]
Voltage-gated sodium channel blockers are used asinsecticides, comprisingInsecticide Resistance Action Committee (IRAC)mechanism of action group 22. As of March 2020[update] these are two,indoxacarb (22A, theoxadiazines) andmetaflumizone (22B, thesemicarbazones).[9]
Selective blockers ofNav1.7 andNav1.8voltage-gated sodium channels, such asCNV1014802 andFunapide, are being investigated as novelanalgesics.[10][11][12]