药理antianginaldrugs

ANTIANGINAL DRUGS,抗心绞痛药,Whats the Angina Pectoris ?,分型 classifications,劳累性心绞痛：可分为稳定型、初发型及恶化型心绞痛；自发性心绞痛 包括：卧位型、变异型、中间综合征和梗死后心绞痛；混合性心绞痛,We should know the physiological characterization of the heart .,Oxygen delivery,Oxygen utilization,The heart have something wrong!,Oxygen delivery,Oxygen utilization,The pathophysiology underlying angina pectoris,major determinants of myocardial oxygen consumption:,myocardial basic metabolismheart ratecontractility wall tensionejection timeblood pressure (peripheral resistance),ventricular volume ventricular pressure,The mechanism of antianginal drugs,O2 increase supply and/or lower demandMyocardial O2 supply: Coronary blood flow, regional flow distribution Myocarial O2 demand: amount of energy required to support the work of the heartCardiac work influenced by: heart rate, heart contractility, myocardial wall tension,Section 2 Organic nitrates,1.Drugs: Nitroglycerin (硝酸甘油) ,isosorbide dinitrate(硝酸异山梨酯)isosorbide mononitrate(单硝酸异山梨酯),硝酸甘油 nitroglycerin,发展简史化学结构体内过程,1998，Furchgott, Ignarro and Murad,2.Pharmacological mechanism,Organic nitrates NO guanylyl cyclase cGMPcGMP dependent protein kinase intracellular Ca2+ vascular smooth muscle relaxation,硝酸甘油 nitroglycerin,血管平滑肌舒张,3. Pharmacological action,(1) decrease myocardiac oxygen consumption dilate venous decrease blood returning to heart decrease ventricular end-diastolic volume and pressure (large dose) dilate arterial decrease peripheral resistance decrease afterload(2) increase blood supply to ischemia area,3. Pharmacological action,(3) redistribution of coronary blood flow(4) Inhibition of platelet aggregation, increase the release of PGI2 and CGRP,4.Clinical uses,(1) all types of angina(2) acute myocardia infarction(3) CHFisosorbide dinitrate used in prophylaxis attack and CHF after myocardia infarction,5. adverse effects and tolerance,tachycardia, flushing, throbbing headache, orthostatic hypotension, methemoglobinemia,硝酸甘油 nitroglycerin,不良反应,头、颈、面部皮肤发红、发热血管搏动性头痛反射性心率加快体位性低血压大剂量还可引起高铁血红蛋白血症,section 3. -adrenoceptor blocking drugs,1.The mechanism of antiangina decrease myocardial oxygen consumption block -adrenoceptor inhibit myocardial contractility and heart rateimprove blood and oxygen supply to ischeamia area lower heart rate, prolong diastolic perfusion time, increase endocardium flow promote oxygen to dissociate from HbO2,2.cilinical uses stable and unstable angina myocardia infarction3.contraindication variant angina, bronchial asthma, bradycardia, 4.the combined use with nitroglycerin,-受体阻断药,稳定型心绞痛：可用不稳定型心绞痛：慎用变异型心绞痛：忌用,有效量个体差异较大，应从小量开始。 久用停药时，会加剧心绞痛的发作或心梗， 应逐渐减量。,心脏功能抑制 心动过缓、低血压、严重心功能不全者禁用 哮喘/慢阻肺禁用,硝酸甘油与普萘洛尔合用,普萘洛尔可取消硝酸甘油所致的反射性心率加快和心肌收缩力增强，而硝酸甘油却可缩小普萘洛尔所致的心室容积扩大和心室射血时间延长，二者合用可增强疗效，减少不良反应。,Section 4 calcium antagonists,1.mechanism of antiangina (1) dilate coronary arterial (2) reduction in peripheral vascular resistance(3) negative chronotropic and inotropic, decrease myocardiac oxygen consumpation (4) protect cardiac myocytes(5) antiatherosclerosis,2.clinical usedVariant angina, Stable angina, Unstable angina,3.compare with -adrenoceptor blocking drugs,section4 other antiagina drugs,carvedilol nicorandil molsidomine sodium tanshinon-A silate,Lipidemic modulating drugsAntiatherosclerotic agents,High blood cholesterolHigh blood pressureSmokingObesityLack of physical activity,Causes,section 1 introduction,1.atherosclerosis 2.the composition of blood lipidcholesteryl esters(CE, 胆固醇酯)triglycerides (TG，甘油三酯), cholesterol, (Ch 胆固醇)phospholipids (PL磷脂）apolipoproteins（载脂蛋白）,3. major lipoprotein classes:chylomicron VLDL IDL LDL HDL4. the action of lipoprotein in atherosclerosis formationVLDL, LDL, IDL, apoB HDL, apoA,4. forms of hyperlipoproteinemia,section 2 lipidemic-modulating drugs,Drugs which lower the TC and LDL 1.inhibitors of HMG-CoA reductase Drugs: mevastatin(美伐他汀) lovastatin(洛伐他汀) pravastatin(普伐他汀) simvastatin(辛伐他汀) fluvastatin(氟伐他汀),drugs which lower the TC and LDL,2.Bile acid-binding resins (胆汁酸结合树脂)Drugs : cholestyramine (考来烯胺) colestipol (考来替泊),drugs which lower the TG and VLDL,Phenyloxygen acid (fibrates) Drugs: gemfibrozil (吉非贝齐) benzafibrate(苯扎贝特) fenofibrate (非诺贝特),Drugs which lower the TG and VLDL,Nicotinic acid (烟酸)Pharmacological action(1) decrease VLDL, TG, LDL; increase HDL (2) inhibit platelet aggregation(3) dilate vessel,section 3 Antioxidants,Probucol(普罗布考)1.pharmacological actiondecrease TC, LDL-c, HDL-cprotect LDL from hydroperoxidation.2.Clinical use hypercholesterylemia,section 4 polyunsaturated fatty acids (polyenoic fatty acids),n-3 type polyenoic fatty acids eicosapentaenoic acid(EPA, 二十二碳五烯酸), docosahexaenoic acid (DHA,二十二碳六烯