IGMG. Surya Chandra T, Pharmacology Dept., School of Medicine,
Udayana Univ. An arrhythmia is any abnormality in heart rate or rhythm of electrical conduction through the heart. Arrhythmias disturb the electrical activity of the heart and interrupt the normal sequence of atrial and ventricular activation and contraction. The physiologic consequences of arrhythmias are usually a decrease in cardiac output and blood pressure. In addition, the electrical disturbances can lead to life- threatening arrhythmias such as ventricular fibrillation and cardiac arrest. The type of arrhythmia depends on the location in the heart and the severity of the electrical disturbance. TYPES OF ARRHYTHMIAS The most common types of arrhythmias include tachycardias, premature contractions, flutters, and fibrillations. Arrhythmias that originate in the atria and atrioventricular (AV) nodal areas are referred to as supraventricular arrhythmias (above the ventrcles) Paroxysmal atrial tachycardia, atrial flutter, and atrial fibrillation The ventricles cannot keep up with the atria and contract at a slower rate. In atrial fibrillation the atrial rate is over 350 beats per minute and the ventricular rhythm is irregular. This predisposes the atria to the development of blood clots (thromboembolism). Arrhythmias that originate below the AV node are referred to as ventricular arrhythmias. Ectopic foci, areas of abnormal impulse generation, may appear when electrical impulses traveling through the conduction system are delayed or blocked. Ectopic foci that originate in the ventricles are referred to as premature ventricular contractions (PVCs). Ventricular tachycardia is a rapid ventricular rhythm where three or more PVCs occur consecutively. Ventricular tachycardia can cause significant circulatory impairment and may lead to ventricular fibrillation.
The most serious arrhythmia is
ventricular fibrillation, which constitutes a medical emergency. During fibrillation, the electrical activity of the ventricles is severely disturbed and the ventricles cannot contract efficiently enough to maintain adequate circulation. If not treated immediately, cardiac arrest and death will result. Electrophysiology of the Heart most important aspects of the heart is the function of several ions that regulate the electrophysiological properties of the heart. The ions are sodium (Na + ), potassium (K + ), and calcium (Ca 2+ ) During Phase 0 influx of Na+ ions depolarizes the cardiac membrane and generates an action potential. During Phases 13 the membrane is undergoing repolarization as K+ ions efflux out of the cardiac membrane. During Phase 2 (plateau) calcium channels open and Ca++ ions pass into the muscle cell and function in myocardial contraction. In Phase 4 the membrane potential has returned to its resting level and is ready for the next action potential Ventricular muscle does not normally display automaticity. However, it can develop automaticity when there is ischemia, excessive sympathetic stimulation, or other abnormal conditions. When this occurs ventricular muscle can depolarize and generate a premature ventricular contraction (PVC). Antiarrhythmic drugs that slow Phase 0, prolong Phases 13, or decrease Phase 4 automaticity produce effective antiarrhythmic actions. Most antiarrhythmic drugs affect the movement of one or more specific ions and exert their major antiarrhythmic action on a specific phase of the action potential. One cautionary note should be mentioned: all antiarrhythmic drugs have the potential to make any existing arrhythmia worse. In addition, antiarrhythmic drugs can cause new arrhythmias. Antiarrhythmic drugs are usually classified according to the Vaughn- Williams classification system, which organizes the antiarrhythmic drugs into four major classes based on their major mechanism of action CLASS 1 ANTIARRHYTHMIC DRUGS: SODIUM CHANNEL BLOCKERS The pri-mary effect of Class 1 antiarrhythmic drugs is to slow depolarization and conduction during Phase 0 of the action potential. Class IA antiarrhythmics also slow the efflux of K ions during repolarization, which prolongs the refractory period The Class I drugs are subdivided into three groups (IA, IB, IC) based on the degree to which they block Na ions during depolarization (Phase 0). IAs produce a moderate block; IBs, a mild block; ICs, a marked block of Na influx (Phase 0). Each Class I drug also produces a different effect on the refractory period Quinidine (IA) In the past quinidine has been used to treat supraventricular arrhythmias, and also ventricular arrhythmias. However, quinidine is a cardiac depressant that decreases myocardial contraction. In addition, quinidine produces anticholinergic and alpha-blocking effects. Consequently, quinidine can cause a wide range of adverse effects and potential toxicities and is rarely used Procainamide (Procanbid) (IA) procainamide produces similar antiarrhythmic actions as quinidine. However, produces less anticho-linergic and alpha-blocking actions than quinidine. Procainamide causes fewer adverse effects and toxicities and is the most fre- quently used IA antiarrhythmic drug Lidocaine ( Xylocaine ) (IB) widely used for ventricular arrhythmias, especially those resulting from a myocardial infarction or arrhythmias occurring during surgery. it does not depress normal impulse conduction. The main effect of lido-caine, prevention of ventricular arrhythmias, is attributed to its ability to depress automaticity Mexiletine ( Mexitil ) (IB) Mexiletine is a derivative of lidocaine that has been structurally modified so that it can be administered orally. is used for treatment of outpatient ventricular arrhythmias. Class 1C Antiarrhythmic Drugs Flecainide ( Tambocor ) and propafenone ( Rythmol ) depress cardiac conduction (Phase 0). Drug trials with the ICs have shown that these drugs can increase the risk of mortality in patients with preex-isting arrhythmias and other cardiac conditions. Also depress myocardial contractility and may cause heart failure. indicated for treatment of supraventricular arrhythmias CLASS 2 ANTIARRHYTHMIC DRUGS: BETA-BLOCKERS Frequently, in heart disease, there is increased sympathetic activity with increased release of norepinephrine and epinephrine. These NT increase heart rate, excitability, conduction, and automaticity, particularly of ventricular muscle. shorten the refractory period, all of which can contribute to the development of various arrhythmias Propranolol In addition to its beta-blocking effect, propranolol pro-duces a depressant effect on cardiac membranes that slows conduction and prolongs repolarization. Esmolol a selective beta-blocker that mainly affects beta-1 receptors in the heart CLASS 3 ANTIARRHYTHMIC DRUGS: POTASSIUM CHANNEL BLOCKERS The main antiarrhythmic action of the Class 3 drugs is to block potassium channels and interfere with the efflux of potassium ions (K+ ) during repolarization Phases 1 through 3. This action prolongs the refractory period of the heart and decreases the frequency of arrhythmias Amiodarone has multiple sites of action. In addition to blocking potassium channels, amiodarone blocks sodium (Class 1) and calcium (Class 4) channels. It also has blocking actions on both beta- (Class 2) and alpha-adrenergic receptors. Sotalol a nonselective beta-blocker that also has Class 3 antiarrhythmic activity. The main effects are prolonga-tion of the refractory period, slowed AV conduction, and decreased automaticity of the heart. Dofetilide and Ibutilide Whose actions are limited to blocking potassium channels. Dofetilide is administered orally; ibutilide is adminis-tered intravenously. CLASS 4 ANTIARRHYTHMIC DRUGS: CALCIUM CHANNEL BLOCKERS The Class 4 antiarrhythmic drugs are referred to as the calcium channel blockers. These drugs decrease the entry of calcium into cells whose electrophysiologic actions depend on the influx of calcium through the slow-type calcium channels. In the heart, the depolarization of SA and AV nodal cells is highly dependent on the influx of calcium ions. The effect of calcium channel blockers on the SA node is to slow depolarization and decrease the heart rate. The effect on the AV node is to slow conduction. These actions reduce the ventricular rate during fast supraventricular arrhythmias. The calcium channel blockers also affect the contraction of cardiac and smooth muscle. entry of calcium during Phase 2 of the action potential is important for regulating the force of myocardial contractions. Interference with calcium entry into cardiac muscle reduces myocardial contractility. This may precipitate heart failure in patients with CHF. The calcium channel blockers also relax smooth muscle and cause vasodilation While all calcium channel blockers produce vasodilation, only Verapamil and have direct actions on the heart and are used for their antiarrhyth-mic actions. Verapamil Verapamil decreases SA node activity, resulting in a slight decrease in heart rate. More important, verapamil decreases AV node conduction
Diltiazem The cardiac depres-sant effects of diltiazem are slightly less than those of verapamil, but diltiazem is generally considered to be a more potent vasodilator than verapamil.