Pharmacology
Summary
Arrhythmias are caused by abnormal pacemaker activity or abnormal impulse propagation through the myocardium. They can be precipitated or exacerbated by a number of factors, including ischemia, hypoxia, acid-base disturbances, and electrolyte abnormalities. Antiarrhythmics are life-saving drugs that can decrease the automaticity of ectopic pacemakers, inhibit conduction, and reduce the excitability of cardiac tissue, being particularly useful in treating rhythms that can reduce cardiac output, like those that are too rapid, too slow, or too asynchronous. The antiarrhythmics are divided into classes, with class 1 being further split into subgroups Class 1A, Class 1B, and Class 1C.
Class 1A antiarrhythmics, such as quinidine and procainamide, block sodium channels, moderately slowing the upstroke of the action potential, and also block potassium channels. This allows the myocardium to stay depolarized longer, which prolongs the action potential and refractory period. Therefore, they are used to treat various atrial and ventricular arrhythmias including supraventricular tachyarrhythmias and Wolff-Parkinson-White syndrome.
Class 1B antiarrhythmics like lidocaine provide a minimal cumulative effect over multiple cardiac cycles, resulting in little use dependence and little effect on the phase 0 upstroke of the action potential. They are useful for treating ischemia-induced ventricular arrhythmias, being more selective for the ventricles and His-Purkinje system since these tissues have a longer action potential.
Class 1C antiarrhythmics, such as propafenone and flecainide, bind avidly to the fast sodium channel, which results in a drastic slowing of the action potential's phase 0 and hence, a more dramatic effect on QRS duration. They do not affect action-potential duration and are contraindicated in patients with any history of structural or ischemic heart disease especially post MI because of their proarrhythmic effects. Furthermore, they are used to treat both supraventricular and ventricular arrhythmias.
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FAQs
Class I antiarrhythmics primarily exert their effect by blocking sodium channels. This action decreases the steepness of the phase 0 upstroke in the cardiac action potential, which in turn slows conduction. Interestingly, this slowing is more pronounced in tissues that depolarize rapidly—a phenomenon termed "use-dependence." Class IA antiarrhythmics have an intermediate binding affinity for the Na+ channel, an intermediate use-dependence, and moderate slowing of the phase 0. Class IB antiarrhythmics have a low binding affinity for the Na+ channel, a low use-dependence, and a modest slowing of the phase 0. Class IC antiarrhythmics have a strong binding affinity for the Na+ channel, strong use-dependence, and drastic slowing of the phase 0 upstroke. On ECG, the slowing manifests as a widened QRS complex, reflecting reduced action potential conduction speed.
Class IA antiarrhythmics, such as quinidine, procainamide, and disopyramide, are characterized by their intermediate binding affinity for sodium channels. This leads to a moderate decrease in the phase 0 upstroke speed. Furthermore, they inhibit potassium channels, which prolongs phases 2 and 3 of the cardiac action potential, extending the refractory period. These combined effects make Class IA antiarrhythmics suitable for managing both supraventricular and ventricular arrhythmias, as well as conditions like Wolff-Parkinson-White (WPW) syndrome.
Class IA antiarrhythmics come with their share of potential side effects. Quinidine, for instance, may lead to cinchonism, presenting as tinnitus, headache, and dizziness, and is also associated with thrombocytopenia. Procainamide might precipitate a lupus-like syndrome in some patients. Disopyramide has the potential to worsen heart failure due to its negative inotropic effects. Additionally, a significant concern with Class IA antiarrhythmics is the potential for QT interval prolongation, which may progress to torsades de pointes.
Class IB antiarrhythmics, represented by agents like lidocaine, mexiletine, and to some extent, phenytoin, possess a low affinity for sodium channels. This results in only a modest reduction in the phase 0 upstroke speed. Notably, they also abbreviate phases 2 and 3 of the cardiac action potential, leading to a shortened refractory period. These drugs are particularly effective against ventricular arrhythmias, especially those originating in ischemic tissue. On the other hand, class IC antiarrhythmics, such as flecainide and propafenone, bind strongly to sodium channels. This binding profoundly slows the phase 0 upstroke, but without altering the duration of the cardiac action potential.
Class IC antiarrhythmics are versatile, being effective against both supraventricular and ventricular arrhythmias. They are also indicated in the treatment of atrial fibrillation and flutter, helping to restore and maintain normal sinus rhythm. However, they are contraindicated in patients with a history of structural or ischemic heart disease due to their proarrhythmic effects.
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