上海交通大学：《药理学》课程教学资源（课程讲稿）抗心绞痛药 ANTIANGINAL DRUGS

ANTIANGINAL DRUGS 抗心纹痛药

ANTIANGINAL DRUGS 抗心绞痛药

What's the Angina Pectoris Angina a type of temporary chest pain, pressure or discomfort. Narrowed artery Stress HIschemia Gan Hialre Heart muscle is not You Sick receiving enough oxygen due to a namowed coronary artery

What’s the Angina Pectoris ?

分型 classifications ①劳累性心绞痛：可分为稳定型、初 发型及恶化型心绞痛； ②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 ③混合性心绞痛

分型 classifications  ①劳累性心绞痛： 劳累性心绞痛：可分为稳定型、初 可分为稳定型、初 发型及恶化型心绞痛； 发型及恶化型心绞痛；  ②自发性心绞痛 包括：卧位型、变异 包括：卧位型、变异 型、中间综合征和梗死后心绞痛； 型、中间综合征和梗死后心绞痛；  ③混合性心绞痛

We should know the physiological characterization of the heart Oxygen utilization Oxygen delivery

We should know the physiological characterization of the heart . Oxygen utilization Oxygen delivery

The pathophysiology underlying angina pectoris Contractile AV state OXYGEN OXYGEN Oxygen Difference DEMAND SUPPLY Heart Regional Rate Myocardial Distribution Wall ↑ ISCHEMIA Tension Coronary Blood Flow LV Ventricular Coronary Aortic Vascular Pressure Volume Pressure Resistance

The pathophysiology underlying angina pectoris OXYGEN DEMAND OXYGEN SUPPLY Contractile state Heart Rate Wall Tension ISCHEMIA AV Oxygen Difference Regional Myocardial Distribution Coronary Blood Flow LV Pressure Ventricular Volume Coronary Vascular Resistance Aortic Pressure

major determinants of myocardial oxygen consumption: > myocardial basic metabolism heart rate > contractility ventricular volume wall tensionventricr ejection time blood pressure (peripheral resistance)

major determinants of myocardial oxygen consumption:  myocardial basic metabolism  heart rate  contractility  wall tension  ejection time  blood pressure (peripheral resistance) ventricular volume ventricular pressure

The mechanism of antianginal drugs 02 increase supply and/or lower demand Myocardial 02 supply:Coronary blood flow, regional flow distribution Myocarial 02-demand:amount of energy required to support the work of the heart Cardiac work influenced by:heart rate, heart contractility,myocardial wall tension

The mechanism of antianginal drugs O2 increase supply and/or lower demand  Myocardial O2 supply: Coronary blood flow, regional flow distribution  Myocarial O2 –demand: amount of energy required to support the work of the heart  Cardiac work influenced by: heart rate, heart contractility, myocardial wall tension

Section 2 Organic nitrates 1.Drugs: 口Nitroglycerin(硝酸甘油) isosorbide dinitrate(硝酸异山梨酯) 口isosorbide mononitrate(单硝酸异山梨酯)

Section 2 Organic nitrates 1.Drugs: 1.Drugs:  Nitroglycerin ( Nitroglycerin (硝酸甘油) ,  isosorbide isosorbide dinitrate dinitrate (硝酸异山梨酯 )  isosorbide isosorbide mononitrate mononitrate (单硝酸异山梨酯 单硝酸异山梨酯 )

硝酸甘油nitroglycerin 口发展简史 1998,Furchgott,Ignarro and Murad 化学结构 口体内过程 CH2-O-NO CH- O-NO CH,-O-NO

硝酸甘油 nitroglycerin 发展简史 化学结构 体内过程 C H 2 C H C H 2 O N O 2 O N O 2 O N O2 1998，Furchgott, Ignarro and Murad

2.Pharmacological mechanism Organic nitrates NO guanylyl cyclase cGMP↑ cGMP dependent protein kinase intracellular Ca2+ vascular smooth muscle relaxation

2.Pharmacological mechanism Organic nitrates Organic nitrates NO guanylyl guanylyl cyclase cyclase cGMP cGMPdependent protein dependent protein kinase intracellular Ca intracellular Ca2+ 2+ vascular smooth muscle relaxation vascular smooth muscle relaxation