10.5: Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of the heart's electrical activity—is not always the best predictor of drug-induced torsades de pointes. Other factors, such as action potential stability, triangulation, reverse use dependence, and repolarization time dispersion, can also influence the occurrence of this condition.
Amiodarone is a well-known class III drug structurally similar to thyroxine and is used for severe ventricular and supraventricular arrhythmias. It blocks potassium channels (IKr and IKs), prolonging the heart rate. Amiodarone has side effects such as bradycardia, pulmonary toxicity, liver damage, skin discoloration, corneal microdeposits, visual disturbances, and thyroid dysfunction. Dronedarone is a shorter half-life analog of amiodarone without thyroxine effects. It blocks multiple channels (IKr, IKs, ICa, and INa) and should be taken with food. Sotalol is a unique class III drug with β-blocking and action potential prolonging properties. It treats life-threatening ventricular arrhythmias and maintains sinus rhythm but can cause torsades de pointes and worsen heart failure. Dofetilide blocks the rapid component of delayed rectifier potassium current and is eliminated unchanged by the kidneys. It helps maintain sinus rhythm in atrial fibrillation and requires hospital initiation with baseline measurements. Ibutilide blocks potassium channels and activates sodium current, slowing cardiac repolarization. It is rapidly cleared by the liver and kidneys. Intravenous ibutilide reverses atrial flutter or fibrillation but can cause excessive QT prolongation.
Class III antiarrhythmic drugs, while effective for certain arrhythmias, require careful dosage monitoring for clinical settings due to the risk of torsades de pointes and other side effects.
