抗心绞痛药.ppt

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1、Antianginal Drugs抗心绞痛药抗心绞痛药Objectives Know the major classes of drugs used to treat angina and their mechanisms of action 抗心绞痛药分类、代抗心绞痛药分类、代表药及其作用机制表药及其作用机制What is Angina pectoris?冠脉供氧不足引起的冠脉供氧不足引起的暂时性急剧心肌缺血暂时性急剧心肌缺血所致所致的临床综合征，表现的临床综合征，表现为胸骨后疼痛，并可为胸骨后疼痛，并可放射放射到左臂。是冠状动脉到左臂。是冠状动脉粥样硬化性心脏病粥样硬化性心脏病（冠心（冠心

2、病的常见症状。病的常见症状。It is the principle symptom of ischemic heart diseaseThe condition is characterized by sudden,severe substernal pain or pressureOxygen supply Oxygen demand coronary atherosclerosis 冠状动脉硬化，冠状动脉硬化，95%coronary artery spasm 冠状动脉痉挛冠状动脉痉挛coronary thrombosis 冠状动脉血栓形成冠状动脉血栓形成myocardial contrac

3、tility心肌收缩力心肌收缩力HR心率心率Sports,mood modification运动、情绪改变运动、情绪改变Angina pectoris patterns变异型心绞痛变异型心绞痛（Variant angina）不稳定型心绞痛不稳定型心绞痛（Unstable angina）稳定型心绞痛稳定型心绞痛（Stable or classic angina）The mechanism of antianginal drugsDecease myocardial oxygen consumption减少心肌耗氧减少心肌耗氧Increase myocardial blood and oxygen

4、 supply增加心肌供血增加心肌供血Antiplatelet,antithrombosis抗血小板、抗血栓形成抗血小板、抗血栓形成Factors affecting myocardial oxygen demand and oxygen supplyOxygen demandOxygen supply=Coronary blood flow冠脉血流冠脉血流Regional myocardial Distribution网状血管区域心肌分布网状血管区域心肌分布Ventricular Volume心室容积心室容积LV pressure左室压左室压wall tension室壁张力室壁张力Contr

5、actily心肌收缩力心肌收缩力heart rate心率心率 aortic pressure主动脉压主动脉压Coronary vascular resistance冠脉阻力冠脉阻力normalischemiaanainal symptomsAV oxygen differenceAV血氧差血氧差Classification of antianginal drugsNitrate esters 硝酸酯类硝酸酯类 receptor blockers 受体阻断药受体阻断药Calcium channel blockers钙通道阻滞药钙通道阻滞药Novel drugs:pFOX inhibitors部分

6、脂肪酸氧化酶抑制剂部分脂肪酸氧化酶抑制剂 ATP-sensitive potassium channel opener ATP敏感钾离子通道开放剂敏感钾离子通道开放剂Nitrate esters,Organic nitratesNitroglycerin(NGT)硝酸甘油硝酸甘油Pentaerithrityl tetranitrate戊四硝酯戊四硝酯，长效硝酸甘油，长效硝酸甘油 Amyl nitrate亚硝酸异戊酯亚硝酸异戊酯 Isosorbide dinitrate(ISDN)硝酸异山梨酯（消心痛）硝酸异山梨酯（消心痛）5-Isosorbide mononitrate(5-ISMN)5-单硝

7、酸异山梨酯单硝酸异山梨酯Chemical structures of two nitratesNitroglycerine硝酸甘油硝酸甘油Isosorbide dinitrate硝酸异山梨酯硝酸异山梨酯Pharmacological mechanismOrganic nitrates NO guanylyl cyclase(鸟苷酸环化酶鸟苷酸环化酶)GTP cGMPcGMP dependent protein kinase intracellular Ca2+vascular smooth muscle relaxationOxygen demand venous relaxation 静脉舒

8、张静脉舒张artery relaxation（large dose)动脉舒张动脉舒张(大剂量大剂量)venous return回心血量回心血量preload前负荷前负荷ventricular end-diastolic volume心室舒张末期容积心室舒张末期容积ventricular wall tension心室壁张力心室壁张力VET心室射血时间心室射血时间afterload后负荷后负荷Oxygen demand耗氧量耗氧量TPR总外周阻力总外周阻力Oxygen supply ventricular wall tension心室壁张力心室壁张力coronary blood flow (esp

9、ecially the ischemic myocardium)冠脉供血冠脉供血(特别是缺血区心肌特别是缺血区心肌)coronary artery relaxation冠脉舒张冠脉舒张Oxygen supply ventricular wall tension心室壁张力心室壁张力subendocardial vascular resistance 心内膜下血管阻力心内膜下血管阻力ventricular pressure 心室内压心室内压blood flow from the epicardial to ischemic zone of endocardial血液从心外膜流向心内膜缺血区血液从心

10、外膜流向心内膜缺血区non-ischemic coronary forced flow to ischemic area,improving the blood supply of ischemic area.迫使非缺血区冠脉血流更多迫使非缺血区冠脉血流更多地分流到缺血区，改善缺血地分流到缺血区，改善缺血区血供区血供to relax large transport vessels,narrow coronary and collateral vessels selectively,while relax resistance vessels weakly 选择性舒张心外膜较大的输选择性舒张心外

11、膜较大的输送血管心外膜血管、狭窄的送血管心外膜血管、狭窄的冠脉和侧枝血管，而对阻力冠脉和侧枝血管，而对阻力血管舒张作用较弱血管舒张作用较弱coronary steal 冠脉窃血冠脉窃血Pharmacokinetic Properties of NitratesPropertyNGTISDN5-ISMNHalf-life(min)310280Plasma clearance(L/min)5040.1Oral bioavailability(%)820100Routes of AdministrationAmyl nitrate is a gas at room temperatures and

12、can be administered by inhalation-Rapid onset,short duration(3-5 min)亚硝酸异戊酯亚硝酸异戊酯室温为气体，室温为气体，可吸入给药，起效快，维可吸入给药，起效快，维持短持短，副作用较多，少用。，副作用较多，少用。GTN can be administered by sublingually,inhalation,transdermal or buccal.Its not suitable for maintenance therapy.IV nitrogylcerin can be used to treat severe re

13、current unstable angina.GTN可吸入、颊部、透皮或舌下含服；可吸入、颊部、透皮或舌下含服；作用时间短，不适合维持治疗作用时间短，不适合维持治疗;静注用于不稳定型的严重复发。静注用于不稳定型的严重复发。bidQd5-ISMN is not subject to first-pass metabolism and is 100%available after oral administration.slowly onset,long duration.口服生物利用度高，口服生物利用度高，起效慢，维持久起效慢，维持久Clinical Uses can quickly ease

14、 the onset of various types of angina pectoris 能迅速缓解各类心绞痛的发作能迅速缓解各类心绞痛的发作 used for the prevention of angina pectoris.用于心绞痛发作的预防用于心绞痛发作的预防angina心绞痛心绞痛 to improve the blood supply to ischemic areas,reduce infarct area 改善缺血区的供血，缩小梗塞范围改善缺血区的供血，缩小梗塞范围 anti-platelet aggregation and adhesion 抗血小板聚集和粘附抗血小板聚

15、集和粘附AMI急性心梗急性心梗 vascular smooth muscle relaxation 扩张血管扩张血管pulmonary hypertension 肺高压肺高压（CHF时时）Adverse Effects of Nitrovasodilatorsdue to excessive vasodilation由于血管过度舒张由于血管过度舒张Orthostatic hypotension,Syncope 体位性低血压，晕厥体位性低血压，晕厥BPTachycardia,angina 心动过速心动过速，诱发心绞痛诱发心绞痛Severe throbbing headache,Dizziness

16、 搏动性头痛，头晕搏动性头痛，头晕Skin of face and neck flushing 面、颈皮肤潮红面、颈皮肤潮红Elevated intracranial pressure 颅内压增高颅内压增高Increased intraocular pressure 眼内压增高眼内压增高 NGT maybe cause methemoglobinemia when admistreated it with long-term and large dose.长期大剂量应用长期大剂量应用NGT可致高铁血红蛋白血症可致高铁血红蛋白血症Tolerance and Dependence with NitrovasodilatorsContinuous or frequent exposure to nitrovasodilators can lead to the development of complete tolerance-Transdermal GTN may provide therapeutic levels of drug for 24 hours or more,but eff