1、Part 6 Antianginal Drugs Organic nitrates receptor blockers Calcium channel blockersCoronary vessels: blood supply for the heart1. OVERVIEWCoronary atherosclerosis: cause of cardiac ischemiaDistribution of coronary arteries in the heartIschemia (angina pectoris ): imbalance between oxygen demand and

2、 supplyClassification of angina pectoris:Exertional angina (勞累性心絞痛) Stable angina (穩(wěn)定性心絞痛) Initial onset angina (初發(fā)型心絞痛) Accelerated angina (惡化性心絞痛)Spontaneous angina (自發(fā)性心絞痛) Angina decubitus (臥位型心絞痛) Variant or vasospastic angina (變異性痙攣性心絞痛) Acute coronary insufficiency (急性冠脈功能不全) Postinfarction a

3、ngina (梗死后心絞痛)Mixed angina (混合性心絞痛) Unstable angina (不穩(wěn)定性心絞痛)1. OVERVIEWMyocardial oxygen demand is chiefly determined by: Contractility Heart rate Wall tension Preload (venous return ) Afterload (arteriolar resistance) 1. OVERVIEWpreloadafterloadMyocardial oxygen demand is diminished by: Reducing c

4、ontractility Reducing heart rate Reducing the preload Reducing the afterload1. OVERVIEWWall tension 1. OVERVIEWMyocardial oxygen supply is chiefly determined by: AV oxygen difference Regional myocardial distribution coronary blood flow: vascular resistance, artery pressure Effects of antianginal dru

5、gs: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) Promoting regional distribution ( in ischemic regions)Others: Anti- platelet

6、 coagulation and thrombus formation 1. OVERVIEW2.1 NitratesNitroglycerin (硝酸甘油)A. Pharmacological actions Dilating vessels and reducing heart loads wall tension ; reflex tachycardia Redistribution of coronary circulation dilating conduct artery: collateral circulation reducing wall tension: blood fl

7、ow in ischemic subendocardial area 2. Antianginal drugsInfluence of organic nitrates and dipyridamole on the blood supply of ischemic area2. Antianginal drugsMechanism of the effect of nitroglycerin and other nitrates2. Antianginal drugsMechanism of the effect of nitroglycerin and other nitratesB. C

8、linical uses Angina pectoris: all kinds, especially stable type Heart failure：reducing heart loads due to vasodilationC. Adverse reactions Increase in heart rate and contractility Symptoms due to vasodilation: headache, flash, postural hypotension, collapse, ect. Others: methaemoglobinaemia（高鐵血紅蛋白）

9、Tolerance : avoiding steady-state plasma concentration; supplement of agents containing SH (captopril) 2. Antianginal drugs2.1 Other nitrates Isosorbide dinitrate (硝酸異山梨酯) Isosorbide-5-mononirate (5-硝酸異山梨酯) Compared with nitroglycerin: Similar but weaker effect Acting slowly but lasting longer Large

10、r individual variation and more adverse effects2. Antianginal drugs2.2 receptor 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:

11、Improving myocardial metabolism Inhibiting coagulation of platelets2. Antianginal drugsB. 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: star

12、ting from small dose Withdraw gradually and slowly: symptom rebound Combination with nitroglycerin2. Antianginal drugs2.3 Calcium channel blockers2. Antianginal drugs2.3 Calcium channel blockersA. Pharmacological actions Reducing myocardial oxygen remand: heart loads : nifedipine heart rate and cont

13、ractility : verapamil and diltiazem Increasing myocardial blood supply Protecting ischemic myocardial cells Inhibiting coagulation of platelets2. Antianginal drugsActions of calcium channel blockersB. Clinical uses stable and variant type: nifedipine, verapamil, diltiazem unstable type: verapamil, d

14、iltiazem2. Antianginal drugsActions of DHP (like nifedipine) are similar to those of nitroglycerinActions of verapamil and diltiazem are similar to those of blockers2.4 Other drugsACEIs （血管緊張素轉化酶抑制藥）Treating hypertension and preventing ischemic heart disease Reducing heart loadsInhibiting cardial re

15、modeling Nicorandil （尼可地爾） Opening ATP-sensitive K+ channel (KATP) Lowering intracellular Ca2+ Providing NO (like nitroglycerin)Inducing ischemic preconditioning 2. Antianginal drugsMolsidomine （嗎多明）Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregationPromoting collateral

16、circulation after long-term useDipyridamole （雙嘧達莫，潘生?。?Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregationPromoting collateral circulation after long-term use2. Antianginal drugs nitroglycerin blockers Ca2+ antagonists combination*Heart rate Contractility /Wall tension /

17、 /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 recommendated)Caution: Combi

18、nation may potentiate the antianginal effects, but may induce severe hypotension3. Summary of antianginal drugsSammaryCardiovascular pharmacologyOverview of Cardiovascular DiseasesCommon Cardiac DiseasesAbnormal contractility：Heart failuresAbnormal rhythms：ArrhythmiasAbnormal blood supply：Ischemic h

19、eart 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 diseasesOverview of Cardiovascular Drugs Classification based on target organs/tissues