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Chapter28抗心绞痛药Anti-anginaPectorisDrugsTeachinggoals1.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。3.分析硝酸酯类与－R阻断药合用治疗心绞痛是否合理。I.Introduction(概述)Anginapectoris(心绞

痛)isacommonsymptomofcoronaryartery(冠状动脉)diseasecausedbytransient(短暂)episodes(发作)ofmyocardialischemia(缺血)andanoxia(缺氧).Anatta

ckofanginapectorisoccurswhentheneedofthemyocardiumforoxygenexceedstheamountdeliveredtoitbythecoronarycirculation.【Classific

ationofAnginaPectoris】Stableanginapectoris(稳定型、劳累型心绞痛)：冠脉粥样硬化，激动、劳累时发作Unstableanginapectoris(不稳定型心绞痛)：（非典型性或梗死前心绞痛）

冠脉粥样硬化，血栓，可发展为心梗或猝死，也可恢复为稳定型心绞痛。Variantanginapectoris(变异型心绞痛)：冠脉痉挛所致，夜间或休息时发作。【发病机理】Determinantsofmyocardialoxygenconsumption(决定心肌耗氧量主要因素

):Ventricularwalltension(室壁张力)Heartrate(心率)Ventricularcontractility(心室收缩力)Ejectiontime(射血时间)Anginapectorisresultsfromanimbala

nce(失衡)betweenoxygensupply-demandrelationshipinischemic(缺血的)regionsofthemyocardium(心肌).NormalOxygensupplyOxygendemandAngina供氧耗氧冠脉硬化痉挛栓塞射血时间↑心室容积↑收缩

力↑HR↑Principlesoftreatment(治疗原则)：耗氧室壁张力心率心肌收缩力心脏负荷冠脉血流量侧枝循环心舒张时间供氧〓Torecoverthebalancebetweenoxygensupp

lyandoxygenconsumption.(恢复氧供需平衡)【Classificationofanti-anginapectoris】(抗心绞痛药物分类)1）Organicnitrates(硝酸酯类)2）－Rbl

ockers3）Calciumchannelblockers(钙拮抗剂)II.Organicnitrates(硝酸酯类)Nitroglycerin(硝酸甘油)【Pharmacokinetics】1.Becauseofmarkedfirst-passeliminationitcannotbeg

ivenorally,andusuallygivensublingually(舌下).（首过消除明显,口服无效，舌下含服）2.可透皮吸收【pharmacologicalactions】1.Reductionofmyoca

rdialoxygenconsumption（降低心肌耗氧量）Dilationofveins(扩V)myocardialoxygenconsumption心肌耗氧量cardiacpreload(心脏前负荷)

Dilationofarteries(扩A)Cardiacafterload(心脏后负荷)Note:HR↑、心肌收缩力↑→耗氧↑why2.Dilatecoronaryartery,increasethebloodflowinische

micareas.(扩张冠脉，↑缺血区血流)Nitroglycerin→舒张侧枝血管→血流重新分布→从非缺血区经侧枝流向缺血区→缺血区血供↑3.Increasethebloodflowinsubendocardial

area.(↑心内膜下区域血供)Nitroglycerin硝酸甘油扩V→LVEDP↓扩心外膜大血管扩侧支血管心内膜下缺血区血供↑4.保护缺血的心肌细胞，减轻缺血损伤mechanism【clinicaluses】1.Alltypesofa

nginapectoris(各型心绞痛):急性发作首选,舌下(sublingually)给药2.Acutemyocardialinfarction(急性心肌梗死)3.Congestiveheartfailure(充血性心衰)【Adversereactions

】1.Vasodilation(扩血管)：面部潮红、搏动性头痛、体位性低血压、眼压↑、颅内压↑2.Tolerance(耐受性)：间歇给药：间隔8小时以上补充含巯基药：卡托普利等硝酸异山梨醇酯III.－RBlo

ckersPropranolol(普萘洛尔)【Anti-anginapectoriseffects】(抗心绞痛作用)1.Reducethemyocardialoxygenconsumption.(降低心肌耗

氧量)(-)－RHR↓forceofcontraction(心肌收缩力)↓BP↓oxygenconsumption耗氧量Note：forceofcontraction(心肌收缩力)Ventricularejectiontime(射血时间)Ventricular

volume(心容积)耗氧2.Improvementofbloodsupplyinischemicareas（改善心肌缺血区供血）1）HR↓→舒张期↑→血流从心外膜进入内膜↑2）增加缺血区侧支循环【Clinicaluses】1.Stableanginapecto

ris(稳定型心绞痛)：Especiallyforthepatientswithhypertensionandarrhythmia.(对伴高血压或心律失常者尤佳)2.Cardiacinfarction(心肌梗死)：Note:变异型心绞痛不用whyIV.Calci

umChannelBlockers（钙通道阻断药）Nifedipine(硝苯地平,心痛定)Verapamil(维拉帕米，异搏定)Diltiazem(地尔硫卓，硫氮卓酮)【Mechanism】阻钙内流2

.Dilationofcoronaryvessels(扩张冠脉)3.Protectionofischemicmyocardialcell(保护缺血心肌细胞)：防止C内Ca2+超负荷4.Inhibitionofplateletaggregation(抑制血小板聚集)【Anti-anginape

ctoriseffects】(抗心绞痛作用)1.Reductionofoxygenconsumption(降低氧耗)：心力↓、HR↓、血管扩张、BP↓、心负荷↓【Clinicaluses】1.Variantangina(变异性心绞痛)：首选2.Stableoruns

tableangina(稳定型或不稳定型)：心肌收缩力Propranolol冠状动脉室壁张力HRNitroglycerin舒张收缩↓↑↑↑↓↓射血时间↓↑BP↓↓