医学资料Antianginal-Drugs(抗心绞痛药)

1、Part 6 Antianginal Drugs Organic nitrates receptor blockers Calcium channel blockers2021/7/19 星期一Coronary vessels: blood supply for the heart1. OVERVIEW2021/7/19 星期一Coronary atherosclerosis: cause of cardiac ischemia2021/7/19 星期一Distribution of coronary arteries in the heart2021/7/19 星期一Ischemia (an

2、gina pectoris ): imbalance between oxygen demand and supply2021/7/19 星期一Classification of angina pectoris:Exertional angina (劳累性心绞痛) 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

3、性痉挛性心绞痛) Acute coronary 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. OVERVIEW2021/7/19 星期一Myocardial oxygen demand is chiefly determined by: Contractility Heart rate Wall tension Preload (venous return ) Afterload (arteriolar resistance) 1.

4、 OVERVIEWpreloadafterload2021/7/19 星期一Myocardial oxygen demand is diminished by: Reducing contractility Reducing heart rate Reducing the preload Reducing the afterload1. OVERVIEWWall tension 2021/7/19 星期一1. OVERVIEWMyocardial oxygen supply is chiefly determined by: AV oxygen difference Regional myoc

5、ardial distribution coronary blood flow: vascular resistance, artery pressure 2021/7/19 星期一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

6、coronary arteries ( coronary blood flow) Promoting regional distribution ( in ischemic regions)Others: Anti- platelet coagulation and thrombus formation 1. OVERVIEW2021/7/19 星期一2.1 NitratesNitroglycerin (硝酸甘油)A. Pharmacological actions Dilating vessels and reducing heart loads wall tension ; reflex

7、tachycardia Redistribution of coronary circulation dilating conduct artery: collateral circulation reducing wall tension: blood flow in ischemic subendocardial area 2. Antianginal drugs2021/7/19 星期一Influence of organic nitrates and dipyridamole on the blood supply of ischemic area2. Antianginal drug

8、s2021/7/19 星期一Mechanism of the effect of nitroglycerin and other nitrates2. Antianginal drugs2021/7/19 星期一Mechanism of the effect of nitroglycerin and other nitrates2021/7/19 星期一B. Clinical uses Angina pectoris: all kinds, especially stable type Heart failure：reducing heart loads due to vasodilation

9、C. Adverse reactions Increase in heart rate and contractility Symptoms due to vasodilation: headache, flash, postural hypotension, collapse, ect. Others: methaemoglobinaemia（高铁血红蛋白） Tolerance : avoiding steady-state plasma concentration; supplement of agents containing SH (captopril) 2. Antianginal

10、drugs2021/7/19 星期一2.1 Other nitrates Isosorbide dinitrate (硝酸异山梨酯) 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 effects2. Antianginal drugs2021/7/19 星期一2021/7/19 星期一2.2 receptor

11、 blockersA. Pharmacological action Reducing oxygen demand: heart 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 platelets2. Antiangin

12、al drugs2021/7/19 星期一B. Clinical uses stable and unstable pectoris, 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 reboun

13、d Combination with nitroglycerin2. Antianginal drugs2021/7/19 星期一2.3 Calcium channel blockers2. Antianginal drugs2021/7/19 星期一2.3 Calcium channel blockersA. Pharmacological actions Reducing myocardial oxygen remand: heart loads : nifedipine heart rate and contractility : verapamil and diltiazem Incr

14、easing myocardial blood supply Protecting ischemic myocardial cells Inhibiting coagulation of platelets2. Antianginal drugs2021/7/19 星期一Actions of calcium channel blockers2021/7/19 星期一B. Clinical uses stable and variant type: nifedipine, verapamil, diltiazem unstable type: verapamil, diltiazem2. Ant

15、ianginal drugsActions of DHP (like nifedipine) are similar to those of nitroglycerinActions of verapamil and diltiazem are similar to those of blockers2021/7/19 星期一2.4 Other drugsACEIs （血管紧张素转化酶抑制药）Treating hypertension and preventing ischemic heart disease Reducing heart loadsInhibiting cardial rem

16、odeling Nicorandil （尼可地尔） Opening ATP-sensitive K+ channel (KATP) Lowering intracellular Ca2+ Providing NO (like nitroglycerin)Inducing ischemic preconditioning 2. Antianginal drugs2021/7/19 星期一Molsidomine （吗多明）Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregationPromoting

17、 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 use2. Antianginal drugs2021/7/19 星期一 nitroglycerin blockers Ca2+ antagonists combination*Heart rate Cont

18、ractility /Wall tension / /Oxygen demand Blood pressure : increase, : markedly increase; : decrease, : markedly decrease; : variable according to the dose and effect of each drug ; * blockers combined with nitroglycerin or Ca2+ antagonists (nifedipine; combination with verapamil/diltiazem not be rec

19、ommendated)Caution: Combination may potentiate the antianginal effects, but may induce severe hypotension3. Summary of antianginal drugs2021/7/19 星期一SammaryCardiovascular pharmacology2021/7/19 星期一Overview of Cardiovascular DiseasesCommon Cardiac DiseasesAbnormal contractility：Heart failuresAbnormal

20、rhythms：ArrhythmiasAbnormal blood supply：Ischemic heart diseases Myocardial disordersCommon vascular diseasesAbnormal systematic resistance：HypertensionDysfunction of coronary vessels：Coronary vascular diseasesDysfunction of cerebral vessels：Cerebral ischemia, hemorrhageDysfunction of pulmonary vessels：Pulmonary hypertensionDysfunction of peripheral vessels: Peripheral vascular disorderArteriosclerosis: basis of most CVS diseases2021/7/19 星期一Overview of Cardiovascular Drugs Classification based on target o