The anti-arrhythmic medications have typically been categorized according to the Vaughan-Williams (VW) classification system. The system classifies the medications according to the main mechanism of action (although several of the agents retain properties from multiple classes). The VW classification is traditionally broken down into 4 main categories, with some references adding a fifth.
Sodium Channel Blockers prolong phase 0 (rapid sodium influx into the cell) of the cardiac action potential; effects on QTc are variable by subclass.
Beta-blockers decrease conduction velocity; slow conduction through the AV node.
Potassium channel blockers decrease rate of phase 3 of the cardiac action (potassium efflux out of the cell); phase 3 is the repolarization component of the action potential; by definition, all potassium channel blockers prolong the QTc interval
Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) decrease conduction velocity; slow conduction through the AV node.
The cardiac action potential is the cycle of ion movement which leads to successive depolarization and repolarization of the cardiac myocyte leading to muscle contraction. The resting phase of the cardiac myocyte has a resting membrane potential of negative 80 to negative 90 mV at baseline. The anti-arrhythmic medications essentially slow ion movement in various phases of the cardiac action potential and are broken down as follows.
Phase 0: "the depolarization" phase of the action potential; occurs by the rapid movement of sodium ions (Na+) into the cell along an electrochemical gradient which leads to a membrane potential of approximately positive 30 mV.
Phase 1: "The notch"; initial repolarization phase of the action potential. Involves potassium (K+) ion movement
Phase 2: "The plateau" phase; this phase is a balance of inward calcium movement and outward K+ movement
Phase 3: "The repolarization" phase of the action potential; this phase is primarily caused by the movement of K+ ions along their electrochemical gradient out of the cell, essentially taking the positive charge of the K+ ion out of the cell. Restores the negative potential of the cardiac myocyte
Phase 4: Restoration of the Na/K ATPase which restores the resting membrane potential of the cardiac myocyte.
The anti-arrhythmic medications have several areas of concern. First and foremost, most agents also have some degree of pro-arrhythmic potential. Practically speaking, while trying to suppress arrhythmias with the medications, the medications themselves, can lead to other (potentially more dangerous) arrhythmias. For example, the class Ia sodium channel blockers (quinidine, procainamide, and disopyramide) all effectively prolong the QTc interval and thus increase the risk of ventricular tachycardia (torsades de pointes). All K+ channel blockers share this potential side effect. The reason for this is quite simple if one compares the phases of the action potential to the ECG. The T wave on the ECG represents ventricular repolarization. Phase 3 of the action potential represents repolarization. If a K+ channel blocker is given, this prolongs phase 3 of the action potential in a charge over time manner. If the repolarization phase of the action potential is prolonged, the T-wave on the corresponding ECG is also prolonged, which creates an elongated QTc interval.
The clinical significance of the anti-arrhythmic medications lies in the type of arrhythmias that each drug or class can treat and what are the potential side effects of each overall classification or individual medication. The details of each are noted and discussed separately.
Each agent in the Vaughn Williams classification includes distinctive side effect profiles which must be viewed individually. For example, procainamide may induce a lupus-like syndrome, while quinidine is known to produce cinchonism. The benefit of the classification is in the primary mechanism of action, and the broad, predictable side effects brought about by the primary mechanism. An example would include the class III K+ channel blockers or "repolarization" blockers producing a prolonged phase 3 of the action potential and by definition also producing a prolonged QT interval on the corresponding ECG.