Cardiovascular pharmacology Chapter 32 Antianginal drugs China Medical University

Angina  Angina is a specific type of pain in the chest caused by inadequate blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).  So coronary flow does not meet the metabolic needs of the heart, a radiating chest pain --- anginal pain –results.

 The heart as pump Left anterior descending

Coronary Blood Flow Oxygen Supply Oxygen Demand Systolic BP LV Volume Contractility Heart Rate LV Wall Tension Arrhythmias Ischemia LV Dysfunction Chest Pain pathology

Causes of angina Coronary atherosclerosis Coronary artery spasm Transient platelet aggregation and coronary thrombosis Endothelial injury causing the accumulation of vasoconstrictor substances. Coronary vasoconstriction following adrenergic stimulation

 Stable or classical angina is due to fixed stenosis 狭窄 of the coronary arteries, and is brought on by exercise and stress.  Unstable angina can occur suddenly at rest, and becomes progressively worse, with a increase in the number and severity of attacks.  Variant angina occurs at rest, at the same time each day, and usually due to coronary artery spasm. Classification of angina :

Nitrate esters : Nitroglycerin Isosorbide dinitrate (IDN) 硝酸异山梨酯  receptor blocker : Propranolol Atenolol Metoprolol Calcium channel blockers: Verapamil Diltiazem Nifedipne Unstable angina is treated with: Aspirin (reduces platelet aggregation) Classifications of treatment medicine

Nitrate esters CH 2 2 O NO 2 O 2 O 2 Nitroglycerin 硝酸甘油 CH 2 2 O NO 2 2 O O CH 2 2 O NO 2 O H O O Isosorbide Dinitrate 硝酸异山梨酯 Isosorbide -5-Mononitrate 5’- 单硝酸异山梨酯

Nitroglycerin 硝酸甘油  Dilatation of the coronary arteries increases blood flow and oxygen delivery to the myocardium. Pharmacological Function :  Dilatation of the veins and artery decreases preload and afterload thus the oxygen demand of the heart Increase the heart rate

Nitroglycerin are prodrugs, decomposing to form nitric oxide (NO), which activates guanylyl cyclase (GC),thereby increasing the levels of cyclic guanosine monophosphate (cGMP). Protein kinase G is activated and contractile proteins are phosphorylated. Mechanism of action: active Ca 2+ inner cell VSM dilation NO cGMP dependent PK- PKG SMC or EC （ GC ） cGMP Nitrate esters active Inhibit platelet aggregation and adhesion

Nitroglycerin is administered sublingually, and can be given by intravenous infusion or from patches. Nitroglycerin is given for the prophylaxis 预 防 and treatment of angina － Stable angina Route of administration: Indication:

The side effects of nitroglycerin include postural hypotension, tachycardia, headache,flushing and dizziness. To avoid nitrate tolerance, a drug-free period of approximately 8 hours is needed. Adverse effects ： Therapeutic notes:

 -receptor blocker Propranolol 普奈洛尔 Pindolol 吲哚洛尔 Timolol 噻吗洛尔 Metoprolol 美托洛尔 Atenolol 阿替洛尔

Pharmacological Function:  -blockers  -blockers block  1- adrenoreceptors in the heart. this causes a decrease in heart rate (slowing of phase 4) in systolic blood pressure in cardiac contractile activity and in myocardial oxygen demand. 1

2) Improve the myocardial metabolism 3) Increases blood flow and oxygen of The ischemia region 4) Promote the oxygen release from the Hb Inhibit platelet aggregation

Clinical utilization: Stable or classical angina (specially to patient who concurring the fast heart rate and hypertension ) Unstable angina not suitable to Variant angina  receptor （一） α receptor will be predominate coronary artery spasm To

Contraindications and notes Related to heart: Bradycardia, hypotention, AV block, and CHF Asthmatic 哮喘 β1 receptor up-regulation So slowly reduce the doses

Calcium-channel blockers Verapamil Diltiazem Nifedipine Examples of calcium-channel blockers include block L-type calcium channels, thereby reducing calcium entry into cardiac and vascular cells block L-type calcium channels in vascular cells,

This decrease in intracellular calcium → reduces cardiac contractility and causes vasodilatation, which results in several effects:  Reduced preload due to the reduced venous pressure;  Reduced afterload due to the reduced arteriolar pressure; Increased coronary blood flow;  Reduced cardioc contractility  decreased heart rate  anti-sympathetic activity reduced myocardial oxygen consumption Pharmacological Function:

Coronary vascular dilatation promote the opening of side branch Inhibit platelet aggregation Increase the supply of blood Protect the ischemic myocardial Treatment of angina Variant angina Verapamil is given for Clinical uses supraventricular arrhythmias

others Dipyridamole 双嘧达莫 潘生丁 Nicorandil 尼可地尔 Dipyridamol causes inhibition of adenosine uptake, resulting in the accumulation of adenosine within the tissue. Adenosine is an endogenous vasodilator--- the effect is pronounced on arterioles Nicorandil increase the cGMP ， active the channel of potassium,dilate the coronary vessels

conjunction use Nitrate esters + Calcium-channel blockers Amlodipine 氨氯地平 络活喜  -receptor blocker ＋ Calcium-channel blockers Nitrate esters+  -receptor blocker

N- Nitrate esters B - β -receptor blocker Notes ： ↑= increase ， ↓=decrease ， →= no change ， ↓↑= unsure

FactorNitrate esters  -receptor blocker Calcium-channel blockers Wall Tenson 室壁张力 ↓±↓ LV volume 心室容量 ↓↑± Ventricular pressure 心室压力 ↓↓↓ rate 心 率 ↑↓± contractility 收缩性 ↑↓± 心内膜 / 心外膜 blood ratio 血 流比率 ↑↑↑ the flow of side branch 侧枝血流 ↑→↑

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