Three Pillars of Antiarrhythmic Therapy
Based on electrophysiological mechanisms, there are three main approaches to the pharmacological 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 the propagation of the electrical impulse through cardiac tissue.
- Prolongation of the ERP (Effective Refractory Period). The duration during which the tissue remains unexcitable is increased. This is a universal strategy for rhythm disturbances of any localization, as it reduces the risk of ventricular response to a premature stimulus.
Arrhythmias Due to Enhanced Automaticity
Extrasystoles are based on untimely impulse generation. Due to tissue hypoxia, ischemia, or elevated potassium levels in Purkinje fibers and contractile cardiomyocytes, local automaticity increases. An ectopic focus forms, which begins to generate premature signals that spread to the ventricular myocardium.
- Pharmacological Strategy: Action on slow diastolic depolarization (phase 4).
- Mechanism: Medications prolong this phase, decreasing the rate of spontaneous depolarization. As a result, the pathological automaticity of ectopic foci is suppressed.
Re-Entry Mechanism
Many arrhythmias arise due to impulse circulation (re-entry) within the His-Purkinje system. The anatomical and physiological basis for this is the presence of partial conduction blocks.
How a Vicious Cycle 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 adjacent healthy fiber. Reaching the distal end of the affected area, the action potential returns backward (retrogradely).
- Since retrograde conduction is slow, by the time the impulse returns, the healthy tissue has had time to exit the refractory period. The impulse re-enters it, closing the loop. Frequent rhythmic contractions occur.
Therapeutic Effect: Under the action of antiarrhythmic drugs, conduction is suppressed even further. A unilateral block is converted into a complete (bilateral) block. The affected fiber loses the ability to conduct impulses both forward and backward. The circuit is broken, and the arrhythmia is terminated.
Note: The re-entry mechanism is universal. For example, in Wolff-Parkinson-White (WPW) syndrome, organized macro-circulation occurs through an accessory pathway between the atria and ventricles. In the atria themselves, organized circulation causes flutter, while disorganized circulation causes fibrillation.
Ion Channels and Receptors as Targets
To achieve an antiarrhythmic effect, drugs target 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.
An independent role is played by the adrenergic system. Blockade of $\beta_1$-adrenergic receptors leads to three effects: decreased automaticity, decreased conduction, and increased ERP.
Important Pharmacodynamic Clarification: suppression of myocardial contractility (negative inotropic effect) is exclusively a side effect of antiarrhythmics, not a treatment mechanism.