10.3:
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Antiarrhythmic drugs treat dysrhythmias by restoring normal cardiac function. They are categorized based on their electrophysiological effects.
Class I antiarrhythmic drugs block open or inactivated voltage-sensitive Na+ channels in continuously depolarizing tissues. By reducing Na+ ion influx, they prevent auto-excitation and hinder action potential propagation.
Class I agents are subdivided based on their effects on the action potential duration and dissociation kinetics from the Na+ channel.
Class IA drugs feature intermediate dissociation kinetics and slow phase 0 depolarization. Additionally, they block K+ channels, prolonging the refractory period and action potential duration.
Class IB drugs exhibit fast dissociation kinetics. They do not affect phase 0 depolarization but shorten phase 3 depolarization and the action potential duration.
Class IC drugs possess slow dissociation kinetics, reducing phase 0 depolarization without affecting the action potential duration.
All class I drugs are proarrhythmic and show potential side effects like delayed conduction, tachycardia, and negative inotropy.
10.3:
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels, prolonging the duration of the action potential, and slowing down the conduction velocity in the heart. This group includes drugs such as quinidine, procainamide, and disopyramide. Class IA drugs may also exhibit some anticholinergic effects, resulting in decreased vagal tone and increased heart rate. Potential side effects of Class IA drugs include dizziness, blurred vision, and gastrointestinal disturbances. Physicians should carefully monitor patients for signs of drug-induced lupus or QT interval prolongation, which can lead to life-threatening arrhythmias. The dosage should be adjusted according to the patient's liver and renal function to minimize potential harm.
Class IB Antiarrhythmic Drugs: Class IB drugs, such as lidocaine and mexiletine, mildly block sodium channels. They preferentially target ischemic or depolarized tissues, decreasing the action potential duration and accelerating the repolarization phase. Class IB drugs have minimal effects on healthy cardiac tissue, making them particularly useful in treating ventricular arrhythmias associated with acute myocardial infarction. Common side effects include drowsiness, dizziness, and tremors. Caution should be exercised in patients with liver or renal dysfunction; dosage adjustments may be necessary to reduce the risk of adverse effects.
Class IC Antiarrhythmic Drugs: Class IC drugs like flecainide and propafenone have a potent sodium channel-blocking effect. They significantly slow conduction velocity without affecting the action potential duration or repolarization phase. Some Class IC drugs, like propafenone, exhibit additional beta-blocking properties, which can help control heart rate in certain arrhythmias. Potential side effects include dizziness, visual disturbances, and heart failure exacerbation. Class IC drugs should be used cautiously in patients with structural heart disease or a history of myocardial infarction due to the potential for proarrhythmic effects. Dosage adjustments are necessary for patients with impaired liver or renal function.