Drugs acting on cardiovascular system(CVS) Chapter 6. Drugs acting on cardiovascular system(CVS)

Part 1. Drugs Acting Ion Channels in CVS(作用心血管离子通道的药物) Part 2. Antiarrhythmic Drugs(抗心律失常药) Part 3. Drugs for Treatment of Chro-nic Cardiac Dysfunction Part 3. Drugs for Treatment of Chro-nic Cardiac Dysfunction Part 4. Antianginal Drugs(抗心绞痛药) Part 4. Antianginal Drugs(抗心绞痛药) Part 5. Antiatheroscleotic drugs(抗动脉粥样硬化药) Part 5. Antiatheroscleotic drugs(抗动脉粥样硬化药) Part 6. Antihypertensive Drugs(抗高血压药)

Part 4 Antianginal Drugs (抗心绞痛药)

Contents ▲ Overview A. Organic nitrates B.  receptor blockers C. Calcium channel blockers D. Combination of antianginal drugs

▲ OVERVIEW

Classification of angina pectoris: ▲ OVERVIEW Classification of angina pectoris: (1)Stable angina pectoris: associated with sympathetic nervous system activity. (2)Unstable angina pectoris： initial onset type; accelerated type; spontaneous type. associated with atheroscleorsis plaque and thrombus formation. (3)Variant angina pectoris: associated with spasm of coronary arteries.

The causes of angina pectoris ▲ OVERVIEW The causes of angina pectoris The need of the myocardium for oxygen. Amount delivered for oxygen to myocar-dium by the coronary circulation.

▲ OVERVIEW Myocardial oxygen consumption is chiefly determined by: (1)Preload(venous return); (2)Afterload(arteriolar resistance); (3)Heart rate.

Myocardial oxygen consumption diminished by: ▲ OVERVIEW Myocardial oxygen consumption diminished by: (1)Avioding the provocative exercise; (2)Reducing the preload; (3)Reducing the afterload; (4)Reducing the heart rate.

Principle of antianginal drugs: ▲ OVERVIEW Principle of antianginal drugs: (1)Dilating systemic arteries, especially coronary arteries; (2)Dilating systemic veins; (3)Anti-platelet coagulation & thrombus formation.

A. Organic nitrates(硝酸酯类)

1. Pharmacological effects: A. Organic nitrates Nitroglycerin(硝酸甘油) 1. Pharmacological effects: (1)Dilating systemic vessels, and anticoaqulation of platelets; (2)Redistribution of coronary circul-ation: subendocardial area(心内膜区); epicardial vessels(心外膜血管); collateral circulation(侧枝循环);  blood supply of ischemic area.

Mechanism of dilating vessels: Nitroglycerin Mechanism of dilating vessels: Nitrates NO GC activated cGMP  [Ca2+]i  Vascular smooth muscle dilated and nticoagulation of platelets Sensitivity of contractive protein to Ca2+ 

Nitroglycerin Influence of organic nitrates and dipyridamole on the blood supply of ischemic area

2. Clinical uses: 3. Adverse effects: Nitroglycerin (1)Angina pectoris: All types, especially stable type. (2)Heart failure. 3. Adverse effects: Symptoms due to vasodilation: headache,  intraocular pressure, postural hypotension, collapse; Allergy; Methemoglobinemia; Tolerance.

Isosorbide dinitrate(硝酸异山梨酯) Isosorbide mononirate(单硝酸异山梨酯) A. Organic nitrates Other organic nitrates(其他硝酸酯类): Isosorbide dinitrate(硝酸异山梨酯) Isosorbide mononirate(单硝酸异山梨酯) Compared with nitroglycerin: (1)Slow exertion; (2)Weaker effect; (3)Longer acting term.

B.  receptor blockers

1. Pharmacological effects: B.  receptor blockers 1. Pharmacological effects: blocking  receptor of heart: (1)Myocardial contractility and oxygen consumption; (2)Increasing blood supply to ischemic area and increasing oxygen supply to tissues; (3)Inhibitng coagulation of platelets.

2. Therapeutic uses: 3. Notices: B.  receptor blockers stable and unstable type, especi-ally associated with hypertension or arrhythmias, even with myocardial infarction. 3. Notices: (1)Begin with small dose; (2)Withdraw gradually(because of rebound phenomenon); (3)Had better combine with nitro-glycerin.

C. Calcium channel blockers

C. Calcium channel blockers 1. Pharmacological effects: (1)Decrease myocardial oxygen con-sumption; (2)Increase myocardial blood supply; (3)Protect ischemic myocardial cell; (4)Inhibit coagulation of platelets. 2. Clinical uses: (1)stable and variant type (nifedipine, verapamil, diltiazem) (2)unstable type (verapamil, diltiazem)

D. Combination of antianginal drugs

C. Combination of antianginal drugs 心肌氧供需决定 因素 硝酸酯类 受体阻断药 钙拮抗药 室壁张力  ± 心室容积  心室压力 心脏体积 心率 收缩性 心内外膜 血流比率 侧枝血流量

C. Combination of antianginal drugs 作用 硝酸酯类 受体阻断药 硝酸酯类+ 动脉压    心率 (反射性) 心肌收缩力 抑制或不变 射血时间  不变 舒张期灌流时间 延长 左室舒张末压 不变或降低 心室容积 不变或缩小

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Part 5 Antiatheroscleotic drugs (抗动脉粥样硬化药)

Atherosclerosis (动脉粥样硬化)

Drugs used in treatment of atheroscleosis 1. Modulating plasma lipids: ①HMG CoA reductase inhibitors: lovastatin(洛伐他汀), etc. ②Bile acid binding resins: colestryramine(考来烯胺), etc. ③Nicotinic acids: nicotinic acid(烟酸) ④Fibric acids: gemfibrozil(吉非贝齐) 2. Other drugs: ①Antioxdants: probucol(普罗布考), vit E; ②Polyenoic acids(多烯脂肪酸类); ③Protective agents for arterial endothe-lium(保护动脉内皮药).

Drugs used in treatment of atheroscleosis HMG CoA reductase inhibitors 3-羟-3-甲基戊二酰辅酶A还原酶抑制剂 Lovastatin(洛伐他汀) Simvastatin(辛伐他汀) Pravastatin(普伐他汀) Fluvastatin(氟伐他汀) Mevastatin(美伐他汀) Atorvastatin(阿伐他汀) Cerivastatin(西伐他汀)

HMG CoA reductase inhibitors (美伐他汀) (洛伐他汀) (辛伐他汀) (普伐他汀) (氟伐他汀) (阿伐他汀) (西伐他汀) HMG CoA reductase inhibitors (羟甲戊酸)

(羟甲戊酸) (类异戊二烯) (角鲨烯) (胆固醇)

HMG CoA reductase inhibitors 1. Pharmacological effects: (1)plasma LDL and total cholesterol: to inhibit atherosclerosis forma-tion. (2)Other effects: can inhibit hypertrophy of arterial smooth muscles, inflammation, free radicals

HMG CoA reductase inhibitors 2. Clinical uses: Hypercholesterolemia. to prevent cardiovascular diseases and cerebrovascular diseases. 3. Adverse effects: GI reactions Hepatotoxicity Myopathy

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