Tiêu đề 21. ANTIARRHYTHMIC AGENTS.pdf ✅

PHARMD GURU Page 1 INTRODUCTION: Arrhythmia is a disease in which the rhythmic contraction of the heart is disturbed or altered. Rhythmic contractions are caused by a sequence of electrical activity propagating through the myocardial tissue that engulfs the heart. These contractions are controlled by the pacemaker cells of the heart, or by the sinoatrial (SA) node.  The SA node is at the junction of the right atrium and the superior vena cava, is solely responsible for the normal orderly maintenance of the sequence of events in the cardiac contraction.  Automaticity (spontaneous firing capacity) is one of its main characteristic features.  SA-node essentially possesses a normal firing frequency ranging between 60-100 impulses per minute.  Other tissues having this property are atreo-ventricular (AV) node, Purkinje fibres and bundle of His. On the release of the impulse from the SA node, the impulse spreads to the entire myocardium through specialized automatic fibers. This spreading of the impulse produces the characteristic electrocardiogram pattern that represents the changes in membrane action potentials brought about by alterations in the sodium, potassium, calcium and chloride ion concentrations within the cells. ANTIARRHYTHMIC AGENTS
PHARMD GURU Page 2 Cardiac action potential (cardiac electrical activity) has been divided into five phases:  Phase 0 represents depolarization and reversal of the transmembrane potential,  Phases 1–3 represent different stages of repolarization, and  Phase 4 represents the resting potential.  During phase 0, the permeability of the membrane for Na+ increases, and Na+ rapidly enters the cell, causing it to become depolarized. Phase 1 results from the ionic shift, which creates an electrochemical and concentration gradient that reduces the rate of Na+ influx but favours the influx of Cl− and efflux of K+ .  Phase 2, the plateau phase, results from the slow inward movement of Ca2+, which is triggered by the rapid inward movement of Na+ in phase 0. During this time, there also is an efflux of K+ that balances the influx of Ca2+, thus resulting in little or no change in membrane potential.  Phase 3 is initiated by a slowing of the Ca2+ influx coupled with a continued efflux of K+ . This continued efflux of K+ from the cell restores the membrane potential to normal resting potential levels.  During phase 4, the Na+/K+ -ATPase pump restores the ions to their proper local concentrations.  The action potential is a coordinated sequence of ion movements in which Na+ initially enters the cell, followed by a Ca2+ influx, and finally, a K+ efflux returns the cell to its resting state. Several anti-arrhythmic agents exert their effects by altering these ion fluxes.
PHARMD GURU Page 3 MECHANISM OF ARRHYTHMIAS: Cardiac arrhythmias can originate from a disturbed origin of the impulse, i.e., pacemaker cells. These cells may have altered automaticity, the rhythmic property to affect membrane depolarization at an optimal rate. Disturbed automaticity of pacemaker cells may arise from underlying diseases such as hypertension, atherosclerosis, hyperthyroidism, or lung disease. Other forms of arrhythmias may be caused by origination of impulses in cells other than pacemaker cells. These are called ectopic arrhythmias. The underlying causes of ectopic arrhythmias are myocardial ischemia, excessive myocardial catecholamine release, or toxicity of cardiac glycosides. Arrhythmias are also produced when the electrical impulse does not die down completely before the beginning of phase 0. In such circumstances, a fraction of previous impulse that remains at the end, re-enters and re-excites the heart muscles pre-maturely, resulting in asynchronous depolarization. This is the characteristic form of pre-mature heartbeat. Re-entrant arrhythmias are common in coronary atherosclerosis represented by following figure, (a) Normal conduction of impulses through triangular arrangement of cardiac fibres. (b)Unidirectional block on left arm of triangular section allows impulse to reenter the regional conducting system and recycle. CLASSIFICATION OF ARRHYTHMIA: 1. Abnormal heart pulse formation:  Sinus arrhythmia  Atrial arrhythmia