浙江大学医学院：《药理学》课程教学资源（PPT课件）抗心率失常药 Antiarrhythmic Drugs

Antiarrhythmic Drugs Huifang tang Department of pharmacology Zhejiang University School of medicine anghuitang@zju.edu.cn

Antiarrhythmic Drugs Huifang Tang Department of pharmacology Zhejiang University School of Medicine tanghuifang@zju.edu.cn

A Electrophysiological basis of arrhythmias B Electrophysiological effects and classification of antiarrhythmic drugs C Antiarrhythmic drugs D Proarrhythmic effects of antiarrhythmic drugs

A. Electrophysiological basis of arrhythmias B. Electrophysiological effects and classification of antiarrhythmic drugs C. Antiarrhythmic drugs D. Proarrhythmic effects of antiarrhythmic drugs

A normal rhythm Rs premature ventricular beat C paroxysmal supraventricular tachycardia (PSVT) D atrial fibrillation arrhythmias v-y E atrial flutter with variable Av conduction Too rapid +++++++++++4+++++ atrial flutter with 1: 1 AV conduction Too slow; G monomorphic ventricular tachycardia Asynchronous; Reduce cardiac output H Torsades de Pointes ventricular fibrillation

arrhythmias Too rapid; Too slow; Asynchronous; Reduce cardiac output

A Electrophysiological basis of arrhythmias 1. Normal cardiac electrophysiology Excitability: ability to produce action potentials maximal diastolic potentials(MDP) threshold levels Automaticity: pacemaker phase 4 slope Conductivity: conduction pathways a phase 0 amplitude

A. Electrophysiological basis of arrhythmias ◼ 1. Normal cardiac electrophysiology ◼ Excitability: ability to produce action potentials ◼ maximal diastolic potentials (MDP) ◼ threshold levels ◼ Automaticity: pacemaker ◼ phase 4 slope ◼ Conductivity: conduction pathways, ◼ phase 0 amplitude

inward outward 0 Phase 4 Na+ current Action Ca -type current T-type potential transient ITO1 (4-AP-sensitive) and ion outward current To2 (Ca2+-activated) transport delayed ctifiers p inward rectifier, Ik1 Fast response cell pacemaker current, If (…, see above Na*-Ca2+ exchange Na′,K+ ATPase

Action potential and ion transport Fast response cell

+20 ROH 4 00 绝对不应期 有效不应”1 动作电位时间 图224不应期与动作电位时间 局部去极化(局部性兴奋) 全面去极化(扩布性兴奋) Action potential and effective refractory period

Action potential and effective refractory period

atna ventricles 人- node conducting system Impulse generation and conduction in the heart endocardium ORS

Impulse generation and conduction in the heart

A. Electrophysiological basis of arrhythmias 2. Slow and fast response cells Slow response cells: pacemaker cells fast response cells: conduction and contraction cells Fast response Slow response phase 4 potential -90 mV 70 mV depolarization Na, 120 mV, 1-2 ms Ca+, 70 mV, 7 ms automaticity low( 0.02 V/s) high( 0.1 V/s) conduction fast( 200-1000 V/s) slow( 10 V/s) effects conduction pacemaker

◼ 2. Slow and fast response cells ◼ Slow response cells：pacemaker cells ◼ fast response cells：conduction and contraction cells Fast response Slow response phase 4 potential －90 mV －70 mV depolarization Na+ , 120 mV, 1-2 ms Ca2+, 70 mV, 7 ms automaticity low（0.02 V/s） high（0.1 V/s） conduction fast（200-1000 V/s） slow（10 V/s） effects conduction pacemaker A. Electrophysiological basis of arrhythmias

Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated and eCg). hase SA node Slow response AV node Phase Fast Tricuspid Purkinje Resting potential response Ventricle Action potential phases 1: Early-fast repolarization 2: Plateau 3: Repolarization ECG ECG

Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated and ECG). Slow response Fast response ECG

Interatrial pathway Cell A Atrioventricular (AV) nod Sinoatrial (SA)node atrum annum Faster rate of Intermodal Left depolarization pathway brar of bundle of His branch of bund! of His Len ventre ventrcle Purkinje Cell B Threshod Slower rate of depolarization Time (msec)