浙江大学医学院：抗心律失常药（PPT讲稿）Antiarrhythmic Drugs

所字 ZnsJiang University Antiarrhythmic Drugs Huifang Tang Department of pharmacology Zhejiang University School of Medicine tanghuifang⊙ ju. edu.cn

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

所字 ZnsJiang University 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 所字 ZnsJiang University premature ventricular beat 人人人入人 C paroxysmal supraventricular tachycardia (PSVT) D atrial fibrillation arrhythmias v-y E atrial flutter with variable Av conduction Too rapid; +++++++++++4+++++ F atrial flutter with 1: 1 AV conduction Too slow willow Asynchronous G monomorphic ventricular tachycardia 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 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

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

Action potential and ion transport Fast response cell

+20 60 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 ~- 所字 ZnsJiang University 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 hase 4 potential -90 mv -70mV depolarization Na*, 120 mv, 1-2 ms Caz*, 70 mv, 7 ms automaticity low(0.02 V/s) high(. 1 V/s conduction fast(200-1000V/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

933 Schematic representation of the heart and normal Jussy cardiac electrical activity(intracellular recordings from areas indicated and EcG) Phase 0 SA node Slow response AV node Phase Fast Tricuspid Resting potential response Mitral Ventricle ntial phases ECG 200ms

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 Fas eter 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)