Three pillars of antiarrhythmic therapy
Based on electrophysiological mechanisms, there are three main approaches to the drug treatment of extrasystoles and tachyarrhythmias:
- Suppression of automaticity. Achieved by affecting pacemaker activity and phase 4 of the action potential.
- Suppression of conduction. Drugs purposefully slow down the propagation of the electrical impulse through heart tissues.
- Prolongation of the ERP (effective refractory period). The time during which the tissue remains unresponsive is increased. This is a universal strategy for rhythm disorders of any localization, as it reduces the risk of ventricular response to a premature stimulus.
Arrhythmias due to increased automaticity
Extrasystole is based on the untimely generation of an impulse. Due to tissue hypoxia, ischemia, or high potassium content in Purkinje fibers and contractile cardiomyocytes, local automaticity increases. An ectopic focus is formed, which begins to generate premature signals that spread to the ventricular myocardium.
- Pharmacological strategy: Action on slow diastolic depolarization (phase 4).
- Mechanism: Drugs prolong this phase, reducing the rate of spontaneous depolarization. As a result, the pathological automaticity of ectopic foci is suppressed.
Re-entry mechanism
Many arrhythmias arise due to the circulation of excitation (re-entry) through the His-Purkinje system. The anatomical and physiological basis for this is the presence of incomplete conduction blocks.
How a vicious circle forms:
- Normally, the impulse passes freely through both branches of the Purkinje fiber in the forward (orthodromic) direction, and ventricular excitation occurs synchronously.
- In pathology, a unilateral block occurs in one of the branches. The impulse cannot pass orthodromically, but passes through the neighboring healthy fiber. Reaching the distal end of the affected area, the action potential returns back (retrogradely).
- Since retrograde conduction is slow, by the time the impulse returns, the healthy tissue has time to emerge from the refractory period. The impulse enters it again, closing the circuit. Frequent rhythmic contractions occur.
Therapeutic effect: Under the influence of antiarrhythmic drugs, conduction is suppressed even further. A unilateral block converts into a complete (bilateral) block. The affected fiber loses the ability to conduct impulses both antegrade and retrograde. The circuit is broken, and the arrhythmia is terminated.
Note: The re-entry mechanism is universal. For example, in WPW syndrome, ordered macro-circulation occurs through an accessory pathway between the atria and ventricles. In the atria themselves, ordered circulation causes flutter, and disorganized circulation causes fibrillation.
Ion channels and receptors as targets
To achieve an antiarrhythmic effect, drugs act on specific phases of the action potential:
- Prolongation of phase 0 (depolarization) is achieved by blocking sodium channels.
- Prolongation of phase 3 (repolarization) is achieved by blocking potassium channels.
- Prolongation of phase 4 (spontaneous diastolic depolarization) is achieved by blocking both sodium and potassium channels.
The adrenergic system plays a distinct role. Blockade of $\beta_1$-adrenergic receptors leads to three effects: decreased automaticity, decreased conduction, and increased ERP.
Important clarification on pharmacodynamics: suppression of myocardial contractility (negative inotropic effect) is exclusively a side effect of antiarrhythmics, rather than the mechanism of treatment.
Briefly: answers to topical questions
What classes are antiarrhythmic agents divided into according to the Vaughan-Williams classification?
The cited sources explicitly indicate the following classes of antiarrhythmic agents according to the Vaughan-Williams classification:
- Class I — sodium channel blockers; subdivided into IA, IB, and IC.
- Class III — includes amiodarone and sotalol; drugs of this class block potassium channels and increase the effective refractory period.
The classification is based on clinical applications and mechanisms of action.
The three pillars of antiarrhythmic therapy are easy to remember by the acronym SCS: Suppression of automaticity, Suppression of conduction, Prolongation of ERP.
Class and exam questions
How do antiarrhythmic drugs interrupt re-entry?
They additionally suppress conduction in the affected area, converting a functional unilateral block into a complete bilateral block. This breaks the impulse re-entry circuit.
Is the reduction of cardiac contractility a treatment goal?
No, the negative inotropic effect (suppression of contractility) is a side effect of drugs, not a mechanism for eliminating arrhythmia.
How is the prolongation of phase 3 of the action potential achieved?
Prolongation of the repolarization phase (phase 3) is achieved through pharmacological blockade of potassium channels.
What else to study on this topic
- Anatomical variants of excitation macro-circulation (WPW syndrome)
- Differences between the mechanisms of atrial flutter and atrial fibrillation
- The impact of ischemia, hypoxia, and hyperkalemia on the formation of ectopic foci
- The role of sodium channels in phase 0 of the action potential
- Mechanisms of action of $\beta_1$-blockers in tachyarrhythmias
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