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Sodium channel blockers are agents that impair conduction of sodium ions (Na+) through sodium channels.[1]

Extracellular[edit | edit source]

The following naturally produced substances block sodium channels by binding to and occluding the extracellular pore opening of the channel:

Intracellular[edit | edit source]

Drugs which block sodium channels by blocking from the intracellular side of the channel include:

Unknown mechanism[edit | edit source]

Antiarrhythmic[edit | edit source]

Sodium channel blockers are used in the treatment of cardiac arrhythmia. They are classified as "Type I" in the Vaughan 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 cardiac action potentials. Class I agents are called Membrane Stabilizing Agents. 'Stabilizing' refers to the decrease of excitogenicity of the plasma membrane effected by these agents. A few class II agents, propranolol for example, also have a membrane stabilizing effect.

Class Ia agents[edit | edit source]

File:Action potential class Ia.svg

Class Ia agent decreasing Vmax, thereby increasing action potential duration.

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 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 to treat atrial fibrillation in the setting of Wolff-Parkinson-White syndrome, and to treat wide complex hemodynamically stable tachycardias. Oral procainamide is no longer being manufactured in the US, but 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 such as digoxin or 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[edit | edit source]

File:Action potential Class Ib.svg

Effect of class Ib antiarrhythmic agents on the cardiac action potential.

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 include lidocaine, mexiletine, tocainide, and phenytoin.

Class Ic agents[edit | edit source]

File:Action potential class Ic.svg

Effect of class Ic antiarrhythmic agent on cardiac action potential.

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 life-threatening ventricular tachycardia or ventricular fibrillation, and for the treatment of refractory supraventricular tachycardia (i.e. 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[edit | edit source]

Sodium channel blockers are also used as local anesthetics and epilepsy treatments.[4]

Sodium channel blockers have been proposed for use in the treatment of cystic fibrosis,[5] but current evidence is mixed.[6]

It has been suggested that the analgesic effect of some antidepressants is due to sodium channel blockade.[7]

See also[edit | edit source]

References[edit | edit source]

  1. MeSH Sodium+Channel+Blockers
  2. Jarvis, Michael F., Prisca Honore and 35 additional coauthors (2007-05-27). A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. PNAS 104 (20): 8520–5.
  3. Habuchi Y, Tanaka H, Furukawa T, Tsujimura Y (Dec 1991). Caffeine-induced block of Na+ current in guinea pig single ventricular cells. Am J Physiol. 261 (6 Pt 2): H1855–63.
  4. Wood JN, Boorman J (2005). Voltage-gated sodium channel blockers; target validation and therapeutic potential. Curr Top Med Chem 5 (6): 529–37.
  5. Hirsh AJ, Zhang J, Zamurs A, et al. (April 2008). Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenylbutyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung disease]. J. Pharmacol. Exp. Ther. 325 (1): 77–88.
  6. Sodium channel blockers for cystic fibrosis.
  7. Dick IE, Brochu RM, Purohit Y, Kaczorowski GJ, Martin WJ, Priest BT (April 2007). Sodium channel blockade may contribute to the analgesic efficacy of antidepressants. J Pain 8 (4): 315–24.

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