Sodium channel blockers are drugs which impair conduction of sodium ions through
sodium channels. Extracellular
The following naturally-produced substances block sodium channels by
binding to and occluding the extracellular pore opening of the
channel: Alkaloids:
Saxitoxin Neosaxitoxin
Tetrodotoxin Intracellular
Drugs which block sodium channels by blocking from the intracellular side of
the channel include: Local anesthetics
Class I antiarrhythmic agents Various anticonvulsants
Unknown mechanism Calcium has been shown to block sodium
channels which explains the effects of hypercalcemia and hypocalcemia.
Caffeine has been shown to inhibit Na+ current in ventricular cells of guinea
pigs. Antiarrhythmic
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 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 =
Class Ia agents block the fast sodium channel, which depresses the phase 0
depolarization, 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 = 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 = Class Ic antiarrhythmic agents markedly
depress the phase 0 depolarization. They decrease conductivity, but have a
minimal effect on the action potential duration. Of the sodium channel blocking
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. These agents are
potentially pro-arrhythmic, especially in settings of structural heart disease,
and are contraindicated in such settings.
Class Ic agents include encainide, flecainide, moricizine, and propafenone.
Encainide is not available in the United States.
Other uses Sodium channel blockers are also used as
local anesthetics and anticonvulsants. Sodium channel blockers have been
proposed for use in the treatment of cystic fibrosis, but current evidence is
mixed. It has been suggested that the analgesic
effects of some antidepressants may be mediated in part via sodium channel
blockade. Future prospects
Selective blockers of Nav1.7 and Nav1.8 voltage-gated sodium channels, such as
CNV1014802 and TV-45070, are being investigated as novel analgesics.
See also Sodium channel
Conotoxin Raventoxin
Halcurin References