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1、治疗心律失常药物 Antiarrhythmic agents,一、Basic Concept正常心率（窦性心律）：The electrical impulse that triggers a normal cardiac contraction originates at regular intervals in the sinoatrial node , usually at a frequency of 60-100 beats per minute. This impulse spreads rapidly through the atria and enters the atriove
2、ntricular node, then propagates over the His-Purkinje system and invades all parts of the ventricles.,心律失常：Arrhythmias consist of cardiac depolarizations that deviate from the above description in one or more aspectsie, there is an abnormality in the site of origin of the impulse, its rate or regula
3、rity, or its conduction 。,心律失常分类,总的可分快速型和过缓型（然后根据发生部位和性质再分） 快速型：房早，房速，房颤； 室早，室速，室颤过缓型（缓慢型）：房室传导阻滞，束支传导阻滞，窦性心动过缓等，阿托品，拟肾上腺素药物等有一定作用。,心律失常的治疗学分类,就临床治疗的观点，心律失常可分为三类： 良性（无器质性病变）benign arrhythmias: VPBs, sinus tachycardia using Anxiolytics and Sedatives 可能恶性（轻中度器质性病变）potential malignant arrhythmias： Paro
4、xysmal Supraventricular Tachycardia, monomorphic ventricular tachycardia, atrial fibrillation 恶性（重度器质性病变）malignant arrhythmias (life-threatening arrhythmias)：sustained ventricular tachycardia, polymorphic ventricular tachycardia, ventricular fibrillation,二、Pathophysiology,Arrhythmias develop because
5、 of abnormal impulse generation, abnormal propagation or both Bradyarrhythmias Which arise through abnormalities of intrinsic automatic behavior or conduction, principally within the atrioventricular node and the His-Purkinjes network.,Tachyarrhythmias Three mechanisms have been associated with many
6、 tachyarrhythmias Altered automaticity: Factors that increase automaticity include mechanical stretch beta-adrenergic stimulation hypokalemia Triggered automaticity: Early Afterdepolarization (EAD)早后除极which is associated with significant prolongation of the action potential duration. Factors that pr
7、edispose to EAD:bradycardia low extracellular K+ certain drugs, including some antiarrhythmics,Torsades de pointes, a polymorphic ventricular arrhythmia- associated with Prolongation of cardiac repolarization (prolonged Q-T interval) Possibly induced by early afterdepolarizations Delayed afterdepola
8、rization (DAD)迟后除极. Factors that predispose to DAD include:excessive adrenergic activity digitalis toxicity high intracellular Ca2+ reentry: Most clinically significant tachyarrhythmias are probably due to reentry.,Afterdepolarizations and triggered activity,Symptoms and Signs Palpitations (awarenes
9、s of the heartbeat) are often disagreeable and may arise equally from increased force of contraction and from rhythm disturbance. They should be investigated to define the cause and to allay anxiety. Arrhythmias that cause hemodynamic upset are usually sustained bradycardias or tachycardias and may
10、be life threatening. Resulting dizziness and syncope are common. These arrhythmias require urgent attention and, often, hospitalization.,Some arrhythmias cause few or no symptoms but are associated with an adverse prognosis. Much evidence suggests that prognosis is not necessarily improved by their
11、suppression. Other arrhythmias, although symptomatic, are benign. The nature and severity of underlying heart disease are often of greater prognostic significance than is the arrhythmia itself.,Treatment,Most cardiac arrhythmias cause no symptoms, have no hemodynamic importance, and have no prognost
12、ic significance but may cause anxiety in a patient who becomes aware of them. Some patients with benign arrhythmias remain disabled despite reassurance. Behavior modification therapy often helps when reassurance has failed. In rare cases, a precipitating factor may be identified and modified (eg, ex
13、cessive intake of caffeine or alcohol).,Drug treatment: Antiarrhythmic drug therapy is the mainstay of management for most important arrhythmias. There is no universally effective drug; all have important safety limitations and can aggravate or promote arrhythmias (arrhythmogenesis, proarrhythmia).
14、Drug selection is difficult and often involves trial and error.,抗心律失常药物分类,Willams分类法分为四类：类：钠通道阻断剂，又再分为a,b,c三亚类 类：beta-受体阻断剂 类：钾通道阻断剂（动作电位时程延长药） 类：钙通道阻断剂 其它类：强心苷、腺苷、镁，等,分类 阻断钠通道 抑制0相Vmax 延长APD 阻钾外流a类 + + + +b类 + + - -c类 + + - -,Class I drugs are Na channel blockers, including older antiarrhythmic dru
15、gs (eg, quinidine). All reduce the maximal rate of depolarization of the action potential and thereby slow conduction. They are subclassified based on the kinetics of their receptor effects: class Ia-drugs with intermediate onset and offset; class Ib-drugs with short effects; class Ic-drugs with pro
16、longed effects.,第类药钠通道阻滞药a类代表药 主要有奎尼丁（quinidine）、普鲁卡因胺(procainamide) b类代表药 主要有利多卡因（lidocaine）、苯妥英钠(phenytoin sodium)、美西律（mexiletine） c类代表药 主要有心律平（普罗帕酮，propafenone），氟卡尼(flecainide，氟卡胺)，恩卡尼(encainide，恩卡胺),奎尼丁（quinidine）a类代表药药理作用：阻钠内流，阻钾外流， A传导：抑制0相，减慢传导，P-R延长。 B自律性：抑制4相钠内流除极，降低自律性，抑制异位节律 C时程：延长APD，ERP，QRS增宽另外，通过钠钙交换降低细胞内钙，抑制心肌收缩，阻断受体降血压 应用：为广谱抗心律失常药，对房性，室性，早搏、心动过速均有效。,不良反应： 较严重的为心律失常：多相性室性心动过速（尖端扭转性室速，torsade de points）,可演变成室颤。 低血压扩张血管，抑制心肌 金鸡钠反应：头痛，头晕，耳鸣，视听力减退。,
