What do sodium channel blockers do

These drugs bind to and block the fast sodium channels that are responsible for the rapid depolarization phase 0 of fast-response cardiac action potentials. This type of action potential is found in non-nodal, cardiomyocytes e. In contrast, nodal tissue action potentials sinoatrial and atrioventricular nodes do not depend on fast sodium channels for depolarization; instead, phase 0 depolarization is carried by calcium currents.

Therefore, sodium-channel blockers have no direct effect on nodal tissue, at least through the blockade of fast sodium-channels. The principal effect of reducing the rate and magnitude of depolarization by blocking sodium channels is a decrease in conduction velocity in non-nodal tissue atrial and ventricular muscle, purkinje conducting system.

The faster a cell depolarizes, the more rapidly adjacent cells will become depolarized, leading to a more rapid regeneration and transmission of action potentials between cells. Therefore, blocking sodium channels reduces the velocity of action potential transmission within the heart reduced conduction velocity; negative dromotropy. This can serve as an important mechanism for suppressing tachycardias that are caused by abnormal conduction e. By depressing abnormal conduction, reentry mechanisms can be interrupted.

Besides affecting phase 0 of action potentials, sodium-channel blockers may also alter the action potential duration APD and effective refractory period ERP. These effects on ERP are not directly related to sodium channel blockade, but instead are related to drug actions on potassium channels involved in phase 3 repolarization of action potentials. The drugs in these subclasses also differ in their efficacy for reducing the slope of phase 0, with IC drugs having the greatest and IB drugs having the smallest effect on phase 0 IA drugs are intermediate in their effect on phase 0.

The following summarize these differences:. Increasing or decreasing the APD and ERP can either increase or decrease arrhythmogenesis, depending on the underlying cause of the arrhythmia.

Increasing the ERP, for example, can interrupt tachycardia caused by reentry mechanisms by prolonging the duration that normal tissue is unexcitable its refractory period. This can prevent reentry currents from re-exciting the tissue. On the other hand, increasing the APD can precipitate torsades de pointes , a type of ventricular tachycardia caused by afterdepolarizations.

By mechanisms not understood and unrelated to blocking fast sodium channels, Class I antiarrhythmics can suppress abnormal automaticity by decreasing the slope of phase 4, which is generated by pacemaker currents. The direct effect of Class IA antiarrhythmic drugs on action potentials is significantly modified by their anticholinergic actions.

By blocking these channels, these drugs reduce the heart rate and the speed of conduction in the heart. Class 5 antiarrhythmic drugs are agents that cannot be categorized into the above groups.

This article discusses the class 1 antiarrhythmic drugs in detail, along with a description of the salient features of individual drugs. Image : Drugs affecting the cardiac action potential. By Architha Srinivasan. Image : Basic cardiac action potential. The trajectory followed by the action potential will depend on the membrane potential of the cardiac cells, which varies between different parts of the heart. There is a normal rise followed by a fall in the action potential.

Phase 0 represents the rapid depolarization phase that occurs because of the influx of sodium. Phases 2 and 3 represent the repolarization phase. In both of these cases, there is the prominent efflux of potassium in addition to other ions.

In Phase 2, the potential, arising through the efflux of potassium, is balanced by the influx of calcium, thus causing the action potential to remain as a horizontal line. Sodium channel blockers comprise the class 1 antiarrhythmic compounds according to the Vaughan—Williams classification scheme. These drugs bind to and block the fast sodium channels that are responsible for the rapid depolarization phase 0 of fast-response cardiac action potentials.

This type of action potential is found in non-nodal cardiomyocytes e. Because the slope of phase 0 depends on the activation of fast sodium channels and the rapid entry of sodium ions into the cell, blocking these channels decreases the slope of phase 0, which also leads to a decrease in the amplitude of the action potential.

In contrast, nodal tissue action potentials in the SA node and the AV node do not depend on fast sodium channels for depolarization; instead, phase 0 depolarization is carried out by calcium currents. Therefore, sodium channel blockers have no direct effect on nodal tissue, at least through the blockade of fast sodium channels. Therefore, blocking sodium channels reduces the velocity of action potential transmission within the heart reduced conduction velocity; negative dromotropy.

This can serve as an important mechanism for suppressing tachycardias that are caused by abnormal conduction e. By decreasing abnormal conduction, re-entry mechanisms can be interrupted. The differences between the three subgroups within class 1 are that, in addition to affecting phase 0 of the action potentials, sodium channel blockers may also alter the action potential duration APD and effective refractory period ERP.

Because some sodium channel blockers increase the ERP class 1-A , while others decrease it class 1-B or have no effect on it class 1-C , the Vaughan—Williams classification recognizes these differences as subclasses of class 1 antiarrhythmic drugs. The effects on ERP are not directly related to the sodium channel blockade but instead are related to drug actions on potassium channels involved in phase 3 repolarization of action potentials.

The drugs in these subclasses also differ in their efficacy for reducing the slope of phase 0, with class 1-C drugs having the greatest and class 1-B drugs having the smallest effect on phase 0 class 1-A drugs are intermediate in their effect on phase 0.

Increasing or decreasing the APD and ERP can either increase or decrease arrhythmogenesis, depending on the underlying cause of the arrhythmia. Increasing the ERP, for example, can interrupt tachycardia caused by re-entry mechanisms class 1-A by prolonging the duration that normal tissue is unexcitable its refractory period. This can prevent re-entry currents from reexciting the tissue, as happens with Wolff—Parkinson—White syndrome WPW , which is caused by an aberrant pathway.

On the other hand, increasing the APD can precipitate torsades de pointes, a type of ventricular tachycardia caused by afterdepolarizations abnormal depolarizations of cardiac myocytes that interrupt phase 2, phase 3, or phase 4 of the cardiac action potential in the electrical conduction system of the heart.

Class 1 antiarrhythmic agents can suppress abnormal automaticity by decreasing the slope of phase 4, which is generated by pacemaker currents. The mechanism for this is not understood and is unrelated to blocking fast sodium channels. The anticholinergic effect seen with this group of drugs increases the conduction along the SA and AV pathways. Thus, in a patient with atrial flutter , although the ventricular rate will be reduced by their sodium blocking property, class 1 antiarrhythmics can lead to an increase in both the SA rate and the AV conduction, which can offset the direct effects of the drugs on these tissues.

Although a class 1-A drug may effectively decrease the atrial rate during flutter, it can lead to an increase in ventricular rate because of an increase in the number of impulses conducted through the AV node anticholinergic effect , thereby requiring concomitant treatment with a beta blocker or calcium channel blocker to slow the AV nodal conduction. These anticholinergic actions are most prominent at the SA and AV nodes because they are extensively innervated by vagal afferent nerves.

Different drugs within the class 1-A subclassification differ in their anticholinergic actions. Image : Atrial flutter with variable block between 3 and 4 to 1. By James Heilman, MD. All three classes of drugs are indicated for the treatment of ventricular tachyarrhythmias.

In addition, class 1-C drugs are very valuable in the life-threatening supraventricular tachyarrhythmias flecainide and propafenone.

Class 1-A drugs also have an effect on atrial fibrillation , along with flutter and supraventricular tachycardia. The side effects are discussed in detail for individual drugs. The increase or decrease in action potential duration and the effective refractory period can act as a double-edged sword. Both of these mechanisms prevent the re-entry circuits, but, at the same time, they increase the potential for causing torsades de pointes. The proarrhythmogenic potential is generally seen in this group of drugs.

In addition to the indications discussed above, important consideration needs to be given to those patients who have uncontrolled atrial fibrillation.

The administration of disopyramide will cause an increase in the AV nodal conduction, thereby increasing the ventricular rate in these patients. This effect also occurs with procainamide and quinidine. Treatment with beta blockers, digoxin, or a calcium channel blocker is required. Disopyramide is deemed safe in patients with hypertrophic cardiomyopathy and is shown to have beneficial effects.

Disopyramide has significant cardiac toxicity: It decreases the contraction of the heart negative inotropic effect and has the potential to cause arrhythmia. A common side effect of disopyramide is related to its anticholinergic effects.

This includes dryness of the mouth, hesitancy during urination, and constipation. In conditions in which cholinergic activity is already decreased such as in myasthenia gravis, in which antibodies against acetylcholine receptors are formed , the administration of this drug will aggravate the condition. License: CC BY 3. The other conditions in which caution needs to be exercised are acute angle closure glaucoma and urinary retention.

Although it is rare, hypoglycemia may occur with disopyramide therapy because disopyramide may induce inhibition of the K—ATP channels. In order to prevent the anticholinergic effect, the monitoring of serum concentrations of mono-N-dialkyl disopyramide is required in renally deranged patients. Although a decrease in contractility with disopyramide is self-limiting, short-term treatment with diuretics and an inotropic agent might be required. The anticholinergic effect can be counteracted by administering physostigmine and pyridostigmine, both of which increase the cholinergic activity.

QRS complex widening and prolongation of the QT interval require discontinuation of treatment with disopyramide. In patients who require treatment for prolongation of QT interval, intravenous magnesium sulfate may be required to stabilize the depolarization. One of the most important known side effects of procainamide is its potential to cause a lupus-like syndrome, which is especially common with long-term administration of the drug.

By Vertebro. License: Public domain. Similar to disopyramide, administration of procainamide results in a potential for prolongation of the QRS complex and the QT interval and the occurrence of ventricular arrhythmia. The drug also increases the risk of arrhythmias and is an arrhythmogenic agent. Bone marrow suppression is one of the dreaded side effects of procainamide; the possibility of this side effect leads to patients objecting to the routine use of this drug.

Pancytopenia and agranulocytosis occur in this condition. Their causes are not well delineated and might range from allergic to hypersensitivity reactions. The symptoms of a lupus-like syndrome occur in a very few patients, and even in those patients, it is self-limiting after the treatment is stopped.

Other alterations include considering alternatives like N-acetyl procainamide, which does not have the potential to cause lupus. The occurrence of bone marrow suppression warrants immediate discontinuation of the drug. Image : Chemical structure of quinidine. By Ymwang42 — Using ChemDraq License: CC0.