1、Chapter28 抗心绞痛药抗心绞痛药Anti-angina Pectoris DrugsTeaching goals1.列举抗心绞痛药物分类及代表药。列举抗心绞痛药物分类及代表药。2.简述硝酸甘油抗心绞痛作用及机理。简述硝酸甘油抗心绞痛作用及机理。3.分析硝酸酯类与分析硝酸酯类与 R 阻断药合用治阻断药合用治 疗心绞痛是否合理。疗心绞痛是否合理。I.Introduction(概述概述)Angina pectoris(心绞痛心绞痛)is a common symptom of coronary artery(冠状动脉冠状动脉)disease caused by transient(短暂短暂)
2、episodes(发作发作)of myocardial ischemia(缺血缺血)and anoxia(缺氧缺氧).An attack of angina pectoris occurs when the need of the myocardium for oxygen exceeds the amount delivered to it by the coronary circulation.【Classification of Angina Pectoris】Stable angina pectoris(稳定型、劳累型心绞痛稳定型、劳累型心绞痛)：冠脉粥样硬化，激动、劳累时发作冠脉粥样
3、硬化，激动、劳累时发作Unstable angina pectoris(不稳定型心绞痛不稳定型心绞痛)：（非典型性或梗死前心绞痛非典型性或梗死前心绞痛）冠脉粥样硬化，血栓，可发展为心梗冠脉粥样硬化，血栓，可发展为心梗 或猝死，也可恢复为稳定型心绞痛。或猝死，也可恢复为稳定型心绞痛。Variant angina pectoris(变异型心绞痛变异型心绞痛)：冠脉痉挛所致，夜间或休息时发作。冠脉痉挛所致，夜间或休息时发作。【发病机理发病机理】Determinants of myocardial oxygen consumption(决定心肌耗氧量主要因素决定心肌耗氧量主要因素):Ventricul
4、ar wall tension(室壁张力室壁张力)Heart rate(心率心率)Ventricular contractility(心室收缩力心室收缩力)Ejection time(射血时间射血时间)Angina pectoris results from an imbalance(失衡失衡)between oxygen supply-demand relationship in ischemic(缺血的缺血的)regions of the myocardium(心肌心肌).Normal Oxygen supplyOxygen demandAngina 供氧供氧耗氧耗氧冠脉冠脉硬化硬化痉挛痉
5、挛栓塞栓塞射血时间射血时间心室容积心室容积收缩力收缩力HR Principles of treatment(治疗原则治疗原则)：耗氧耗氧室壁张力室壁张力心率心率心肌收缩力心肌收缩力心脏负荷心脏负荷冠脉血流量冠脉血流量侧枝循环侧枝循环心舒张时间心舒张时间供氧供氧 To recover the balance between oxygen supply and oxygen consumption.(恢复氧供需平衡恢复氧供需平衡)【Classification of anti-angina pectoris】(抗心绞痛药物分类抗心绞痛药物分类)1）Organic nitrates(硝酸酯类硝酸酯类
6、)2）R blockers 3）Calcium channel blockers(钙拮抗剂钙拮抗剂)II.Organic nitrates(硝酸酯类硝酸酯类)Nitroglycerin(硝酸甘油硝酸甘油)【Pharmacokinetics】1.Because of marked first-pass elimination it can not be given orally,and usually given sublingually(舌下舌下).（首过消除明显首过消除明显,口服无效，舌下含服口服无效，舌下含服）2.可透皮吸收可透皮吸收【pharmacological actions】1.R
7、eduction of myocardial oxygen consumption （降低心肌耗氧量降低心肌耗氧量）Dilation of veins(扩扩V)myocardial oxygen consumption心肌耗氧量心肌耗氧量cardiac preload(心心脏前负荷脏前负荷)Dilation of arteries(扩扩A)Cardiac afterload(心脏后负荷心脏后负荷)Note:HR、心肌收缩力、心肌收缩力耗氧耗氧why2.Dilate coronary artery,increase the blood flow in ischemic areas.(扩张冠脉，扩
8、张冠脉，缺血区血流缺血区血流)Nitroglycerin舒张侧枝血管舒张侧枝血管血流重血流重新分布新分布 从非从非 缺血缺血 区经侧枝流向缺血区区经侧枝流向缺血区缺血区血供缺血区血供3.Increase the blood flow in subendocardial area.(心内膜下区域血供心内膜下区域血供)Nitroglycerin 硝酸甘油硝酸甘油扩扩VLVEDP扩心外膜大血管扩心外膜大血管扩侧支血管扩侧支血管心内膜心内膜下缺血下缺血区血区血 供供4.保护缺血的心肌细胞，减轻缺血损伤保护缺血的心肌细胞，减轻缺血损伤mechanism【clinical uses】1.All types
9、 of angina pectoris(各型心绞痛各型心绞痛 ):急性发作首选急性发作首选,舌下舌下(sublingually)给药给药 2.Acute myocardial infarction(急性心肌梗死急性心肌梗死)3.Congestive heart failure(充血性心衰充血性心衰)【Adverse reactions】1.Vasodilation(扩血管扩血管)：面部潮红、搏动性头痛、面部潮红、搏动性头痛、体位性低血压、眼压体位性低血压、眼压、颅内压、颅内压2.Tolerance(耐受性耐受性)：间歇给药：间隔：间歇给药：间隔8小时以上小时以上 补充含巯基药：卡托普利等补充含
10、巯基药：卡托普利等硝酸异山梨醇酯硝酸异山梨醇酯 III.R BlockersPropranolol(普萘洛尔普萘洛尔)【Anti-angina pectoris effects】(抗心绞痛作用抗心绞痛作用)1.Reduce the myocardial oxygen consumption.(降低心肌耗氧量降低心肌耗氧量)(-)RHRforce of contraction(心肌收缩力心肌收缩力)BPoxygen consumption耗氧量耗氧量Note：force of contraction(心肌收缩力心肌收缩力)Ventricular ejection time(射血时间射血时间)Ve
11、ntricular volume(心容积心容积)耗氧耗氧2.Improvement of blood supply in ischemic areas （改善心肌缺血区供血改善心肌缺血区供血）1）HR 舒张期舒张期 血流从心外膜进入内膜血流从心外膜进入内膜 2）增加缺血区侧支循环）增加缺血区侧支循环【Clinical uses】1.Stable angina pectoris(稳定型心绞痛稳定型心绞痛)：Especially for the patients with hypertension and arrhythmia.(对伴高血压或心律失常者尤佳对伴高血压或心律失常者尤佳)2.Cardi
12、ac infarction(心肌梗死心肌梗死)：Note:变异型心绞痛不用变异型心绞痛不用whyIV.Calcium Channel Blockers（钙通道阻断药钙通道阻断药）Nifedipine(硝苯地平硝苯地平,心痛定心痛定)Verapamil(维拉帕米，异搏定维拉帕米，异搏定)Diltiazem(地尔硫卓，硫氮卓酮地尔硫卓，硫氮卓酮)【Mechanism】阻钙内流阻钙内流2.Dilation of coronary vessels(扩张冠脉扩张冠脉)3.Protection of ischemic myocardial cell (保护缺血心肌细胞保护缺血心肌细胞)：防止：防止C 内内
13、Ca2+超负荷超负荷4.Inhibition of platelet aggregation (抑制血小板聚集抑制血小板聚集)【Anti-angina pectoris effects】(抗心绞痛作用抗心绞痛作用)1.Reduction of oxygen consumption(降低氧耗降低氧耗)：心力心力、HR、血管扩张、血管扩张、BP、心负荷、心负荷【Clinical uses】1.Variant angina(变异性心绞痛变异性心绞痛)：首选：首选2.Stable or unstable angina(稳定型或不稳定型稳定型或不稳定型)：心肌收缩力心肌收缩力Propranolol冠状动脉冠状动脉室壁张力室壁张力HRNitroglycerin舒张舒张收缩收缩射血时间射血时间BP
