Sodium channel blocker
Encyclopedia
Sodium channel blockers are agents that impair conduction of sodium
ions (Na+) through sodium channels.
pore opening of the channel:
side of the channel include:
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 potential
s.
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
.
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 tachycardia
s. 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 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 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.
s and epilepsy treatments.
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 effect of some antidepressant
s is due to sodium channel blockade.
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
ions (Na+) through sodium channels.
Extracellular
The following naturally produced substances block sodium channels by binding to and occluding the extracellularExtracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
pore opening of the channel:
- AlkaloidAlkaloidAlkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
based toxins- tetrodotoxinTetrodotoxinTetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...
(TTX) - saxitoxinSaxitoxinSaxitoxin is a neurotoxin naturally produced by certain species of marine dinoflagellates and cyanobacteria Saxitoxin (STX) is a neurotoxin naturally produced by certain species of marine dinoflagellates (Alexandrium sp., Gymnodinium sp., Pyrodinium sp.) and cyanobacteria Saxitoxin (STX) is a...
(STX)
- tetrodotoxin
Intracellular
Drugs which block sodium channels by blocking from the intracellularIntracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
side of the channel include:
- Local anestheticLocal anestheticA local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
s - Class I antiarrhythmic agents
- Some anticonvulsantAnticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s
Unknown mechanism
- A-803467: specific blockade of Nav1.8 channels (SCN10ASCN10ASodium channel, voltage gated, type X, alpha subunit also known as SCN10A or Nav1.8 is a protein which in humans is encoded by the SCN10A gene.Nav1.8 is a sodium channel subunit.-Function:...
), developed by Icagen and Abbott LaboratoriesAbbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
- CaffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
has been shown to inhibit Na+ current in ventricular cellsVentricular SyncytiumThe ventricular syncytium is a network of cardiac muscle cells connected by gap junctions that lends to the coordinated contraction of the ventricles. Atrial syncytium refers to the same network in the atria....
of guinea pigGuinea pigThe guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
s.
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 (Na+) channel.
Class I agents are grouped by their effect on the Na+ channel, and by their effect on cardiac action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
s.
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
Membrane stabilizing effect
Membrane stabilizing effects involve the inhibition or total abolishing of action potential from being propagated across the membrane. This phenomenon is common in nerve tissues as they are the carrier of impulses from the periphery to the central nervous system. Membrane stabilization is the...
.
Class Ia agents
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
Supraventricular tachycardia
Supraventricular tachycardia is a general term that refers to any rapid heart rhythm originating above the ventricular tissue. Supraventricular tachycardias can be contrasted to the potentially more dangerous ventricular tachycardias - rapid rhythms that originate within the ventricular...
, ventricular tachycardia
Ventricular tachycardia
Ventricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...
, symptomatic ventricular premature beats, and prevention of ventricular fibrillation
Ventricular fibrillation
Ventricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest...
.
Procainamide
Procainamide
Procainamide INN is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.-History:...
can be used to treat atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
in the setting of Wolff-Parkinson-White syndrome
Wolff-Parkinson-White syndrome
Wolff–Parkinson–White syndrome is a disorder of the heart in which the ventricles of the heart contract prematurely due to an accessory pathway known as the bundle of Kent. This accessory pathway is an abnormal electrical communication from the atria to the ventricles...
, and to treat wide complex hemodynamically stable tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
s. Oral procainamide is no longer being manufactured in the US, but intravenous formulations are still available.
While procainamide and quinidine
Quinidine
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
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
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
or verapamil
Verapamil
Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...
, or a beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
), 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
Quinidine
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
, procainamide
Procainamide
Procainamide INN is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.-History:...
and disopyramide
Disopyramide
Disopyramide is an antiarrhythmic medication. It is a Class Ia antiarrhythmic used in the treatment of ventricular tachycardias...
.
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
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
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
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
, mexiletine
Mexiletine
Mexiletine belongs to the Class IB anti-arrhythmic group of medicines. It is used to treat arrhythmias within the heart, or seriously irregular heartbeats. It slows conduction in the heart and makes the heart tissue less sensitive. Dizziness, heartburn, nausea, nervousness, trembling, unsteadiness...
, tocainide
Tocainide
Tocainide is a class Ib antiarrhythmic agent. It is no longer sold in the United States.Quick look at the PharmacokineticsTocainide is a lidocaine analog, that does not have significant 1st pass metabolism. It is found in two enantiomers. The R isomer is 4x as potent as the S. Oral...
, and phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
.
Class Ic agents
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 qqthe 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
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
). These agents are potentially pro-arrhythmic, especially in settings of structural heart disease (e.g. post-myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
), and are contraindicated in such settings.
Class Ic agents include encainide
Encainide
Encainide is a class Ic antiarrhythmic agent. It is no longer used because its frequent proarrhythmic side effects....
, flecainide
Flecainide
Flecainide acetate is a class Ic antiarrhythmic agent used to prevent and treat tachyarrhythmias . It is used to treat a variety of cardiac arrhythmias including paroxysmal atrial fibrillation , paroxysmal supraventricular tachycardia Flecainide acetate is a class Ic antiarrhythmic agent used to...
, moricizine
Moricizine
Moricizine is a phenothiazine derivative with Vaughan Williams class Ic antiarrhythmic properties. It undergoes extensive first-pass metabolism, has a bioavailability of 34-38 percent, and is 95 percent bound to plasma proteins. Moricizine is extensively metabolized and may have pharmacologically...
, and propafenone
Propafenone
Propafenone is a class Ic anti-arrhythmic medication, which treats illnesses associated with rapid heart beats such as atrial and ventricular arrhythmias.-Mechanism of action:...
. Encainide is not available in the US.
Other uses
Sodium channel blockers are also used as local anestheticLocal anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
s and epilepsy treatments.
Sodium channel blockers have been proposed for use in the treatment of cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
, but current evidence is mixed.
It has been suggested that the analgesic effect of some antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
s is due to sodium channel blockade.