1、Part 6 Antianginal Drugs,Organic nitrates receptor blockers Calcium channel blockers,第一页，共三十一页。,Coronary vessels:blood supply for the heart,1.OVERVIEW,第二页，共三十一页。,Coronary atherosclerosis:cause of cardiac ischemia,第三页，共三十一页。,Distribution of coronary arteries in the heart,第四页，共三十一页。,Ischemia(angina pe
2、ctoris):imbalance between oxygen demand and supply,第五页，共三十一页。,Classification of angina pectoris:Exertional angina(劳累(loli)性心绞痛)Stable angina(稳定性心绞痛)Initial onset angina(初发型心绞痛)Accelerated angina(恶化性心绞痛)Spontaneous angina(自发性心绞痛)Angina decubitus(卧位型心绞痛)Variant or vasospastic angina(变异性痉挛性心绞痛)Acute co
3、ronary insufficiency(急性冠脉功能不全)Postinfarction angina(梗死后心绞痛)Mixed angina(混合性心绞痛)Unstable angina(不稳定性心绞痛),1.OVERVIEW,第六页，共三十一页。,Myocardial oxygen demand is chiefly determined by:Contractility Heart rate Wall tension Preload(venous return)Afterload(arteriolar resistance),1.OVERVIEW,preload,afterload,第七
4、页，共三十一页。,Myocardial oxygen demand is diminished by:Reducing contractility Reducing heart rate Reducing the preload Reducing the afterload,1.OVERVIEW,Wall tension,第八页，共三十一页。,1.OVERVIEW,Myocardial oxygen supply is chiefly determined by:AV oxygen difference Regional myocardial distribution coronary blo
5、od flow:vascular resistance,artery pressure,第九页，共三十一页。,Effects of antianginal drugs:Reducing oxygen demands Reducing heart rate and contractility Dilating systemic arteries and veins(wall tension by lowering heart loads)Increasing oxygen supply Dilating conduct coronary arteries(coronary blood flow)
6、Promoting regional distribution(in ischemic regions)Others:Anti-platelet coagulation and thrombus formation,1.OVERVIEW,第十页，共三十一页。,2.1 NitratesNitroglycerin(硝酸甘油)A.Pharmacological actions Dilating vessels and reducing heart loads wall tension;reflex tachycardia Redistribution of coronary circulation
7、dilating conduct artery:collateral circulation reducing wall tension:blood flow in ischemic subendocardial area,2.Antianginal drugs,第十一页，共三十一页。,Influence of organic nitrates and dipyridamole on the blood supply of ischemic area,2.Antianginal drugs,第十二页，共三十一页。,Mechanism of the effect of nitroglycerin
8、 and other nitrates,2.Antianginal drugs,第十三页，共三十一页。,Mechanism of the effect of nitroglycerin and other nitrates,第十四页，共三十一页。,B.Clinical uses Angina pectoris:all kinds,especially stable type Heart failure：reducing heart loads due to vasodilationC.Adverse reactions Increase in heart rate and contractil
9、ity Symptoms due to vasodilation:headache,flash,postural hypotension,collapse,ect.Others:methaemoglobinaemia高铁血红蛋白(xuhng dnbi)Tolerance:avoiding steady-state plasma concentration;supplement of agents containing SH(captopril),2.Antianginal drugs,第十五页，共三十一页。,2.1 Other nitrates Isosorbide dinitrate(硝酸(
10、xio sun)异山梨酯)Isosorbide-5-mononirate(5-硝酸异山梨酯)Compared with nitroglycerin:Similar but weaker effect Acting slowly but lasting longer Larger individual variation and more adverse effects,2.Antianginal drugs,第十六页，共三十一页。,第十七页，共三十一页。,2.2 receptor blockersA.Pharmacological action Reducing oxygen demand:h
11、eart rate and contractility Increasing oxygen supply:diastolic period:perfusion time vascular tone in normal regions:blood flow in ischemic regions Others:Improving myocardial metabolism Inhibiting coagulation of platelets,2.Antianginal drugs,第十八页，共三十一页。,B.Clinical uses stable and unstable pectoris,
12、especially associated with hypertension or arrhythmias,even with myocardial infarction;but not used for variant angina pectorisC.Notes Dose individualization:starting from small dose Withdraw gradually and slowly:symptom rebound Combination with nitroglycerin,2.Antianginal drugs,第十九页，共三十一页。,2.3 Calc
13、ium channel blockers,2.Antianginal drugs,第二十页，共三十一页。,2.3 Calcium channel blockersA.Pharmacological actions Reducing myocardial oxygen remand:heart loads:nifedipine heart rate and contractility:verapamil and diltiazem Increasing myocardial blood supply Protecting ischemic myocardial cells Inhibiting
14、coagulation of platelets,2.Antianginal drugs,第二十一页，共三十一页。,Actions of calcium channel blockers,第二十二页，共三十一页。,B.Clinical uses stable and variant type:nifedipine,verapamil,diltiazem unstable type:verapamil,diltiazem,2.Antianginal drugs,Actions of DHP(like nifedipine)are similar to those of nitroglycerin
15、Actions of verapamil and diltiazem are similar to those of blockers,第二十三页，共三十一页。,2.4 Other drugsACEIs 血管紧张(jnzhng)素转化酶抑制药Treating hypertension and preventing ischemic heart disease Reducing heart loadsInhibiting cardial remodeling Nicorandil 尼可地尔 Opening ATP-sensitive K+channel(KATP)Lowering intrace
16、llular Ca2+Providing NO(like nitroglycerin)Inducing ischemic preconditioning,2.Antianginal drugs,第二十四页，共三十一页。,Molsidomine 吗多明Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregationPromoting collateral circulation after long-term useDipyridamole 双嘧达莫，潘生丁 Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregationPromoting collateral circulation after long-term use,2.Antianginal drugs,第二十五页，共三十一页。,nitroglycerin blockers Ca2+antagonists combination*Hear
