1. Part 6 Antianginal Drugs
Organic nitrates
 receptor blockers
Calcium channel blockers

2. 1. OVERVIEW
Coronary vessels: blood supply for the heart

3. Coronary atherosclerosis:
cause of cardiac ischemia

4. Distribution of coronary arteries in the heart

5. Ischemia (angina pectoris ):
imbalance between oxygen demand and supply

6. 1. OVERVIEW 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): link of stable angina and myocardial infarction

7. 1. OVERVIEW Myocardial oxygen demand is chiefly determined by:
Contractility
Heart rate
Wall tension
Preload (venous return )
Afterload (arteriolar resistance)
afterload
preload

8. 1. OVERVIEW Myocardial oxygen demand is diminished by:
Reducing contractility
Reducing heart rate
Reducing the preload
Reducing the afterload
Wall tension 

9. 1. OVERVIEW Myocardial oxygen supply is chiefly determined by:
AV oxygen difference
Regional myocardial
distribution
coronary blood flow:
vascular resistance, artery pressure

10. 1. OVERVIEW 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)
Promoting regional distribution (  in ischemic regions)
Others:
Anti-platelet coagulation and thrombus formation

11. 2. Antianginal drugs 2.1 Nitrates Nitroglycerin (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 flow in ischemic subendocardial area 

12. 2. Antianginal drugs Influence of organic nitrates and dipyridamole
on the blood supply of ischemic area

13. Mechanism of the effect of nitroglycerin and other nitrates
[Ca2+]i 
Mechanism of the effect of nitroglycerin and other nitrates

14. 2. Antianginal drugs B. Clinical uses C. Adverse reactions
Angina pectoris: all kinds, especially stable type
Heart failure：reducing heart loads due to vasodilation
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)

15. 2. Antianginal drugs 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:
Orally active
Similar but weaker effect
Acting slowly but lasting longer
Larger individual variation and more adverse effects

17. 2. Antianginal drugs 2.2  receptor blockers A. 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 platelets

18. 2. Antianginal drugs B. Clinical uses C. Notes
stable and unstable pectoris, especially associated with hypertension or arrhythmias, even with myocardial infarction; but not used for variant angina pectoris
C. Notes
Dose individualization: starting from small dose
Withdraw gradually and slowly: symptom rebound
Combination with nitroglycerin but without verapamil
Contraindicated in heart depression, asthma, and so on

19. 2. Antianginal drugs
2.3 Calcium channel blockers

20. 2. Antianginal drugs 2.3 Calcium channel blockers
A. 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 coagulation of platelets

21. Actions of calcium channel blockers

22. Selective calcium channel blockers
Dihydropyridines (二氢吡啶类):
nifedipine 硝苯地平 rapid, hypotension, reflex tachycardia
amlodipine 氨氯地平 high bioavailability, t1/ h, long-acting, less influences on heart rate and blood pressure
Phenylalkylamines (苯烷胺类):
verapamil 维拉帕米 reducing oxygen demands, antiarrhythmia
Benzothiazepines (苯硫卓类):
diltiazem 地尔硫卓 weaker for heart depression and vasodilation; suitable for variant angina pectoris

23. 2. Antianginal drugs B. Clinical uses stable and variant type:
nifedipine, verapamil, diltiazem
unstable type:
verapamil, diltiazem
Actions of DHP (like nifedipine) are similar to those of nitroglycerin
Actions of verapamil are similar to those of  blockers
Actions of diltiazem are intermedial in both above drugs

24. 3. Summary of antianginal drugs
nitroglycerin  blockers Ca2+ antagonists combination*
Heart rate    
Contractility    /
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 recommendated)
Caution: Combination may potentiate the antianginal effects, but may induce severe hypotension

25. 2. Antianginal drugs 2.4 Other drugs ACEIs （血管紧张素转化酶抑制药）
Treating hypertension and preventing ischemic heart disease
Reducing heart loads
Inhibiting cardiac remodeling
Nicorandil （尼可地尔）
Opening ATP-sensitive K+ channel (KATP)
Lowering intracellular Ca2+
Providing NO (like nitroglycerin)
Inducing ischemic preconditioning

26. 2. Antianginal drugs Molsidomine （吗多明） Dipyridamole （双嘧达莫，潘生丁）
Promoting collateral circulation
Similar to nitroglycerin
Used in stable angina
Dipyridamole （双嘧达莫，潘生丁）
Inhibiting adenosine uptake and cAMP degradation
Inhibiting pletelet aggregation
Small doses, long-term oral administration

27. Cardiovascular pharmacology
Summary

28. Overview of Cardiovascular Diseases
Common Cardiac Diseases
Abnormal contractility：Heart failures
Abnormal rhythms：Arrhythmias
Abnormal blood supply：Ischemic heart diseases
Myocardial disorders
Common vascular diseases
Abnormal systematic resistance：Hypertension
Dysfunction of coronary vessels：Coronary vascular diseases
Dysfunction of cerebral vessels：Cerebral ischemia, hemorrhage
Dysfunction of pulmonary vessels：Pulmonary hypertension
Dysfunction of peripheral vessels: Peripheral vascular disorder
Arteriosclerosis: basis of most CVS diseases

29. Overview of Cardiovascular Drugs
Classification based on target organs/tissues
Heart：Heart failures, arrhythmias, cardiac ischemia
Vessels：Vasodilatation, vasoconstriction, arteriosclerosis
Classification based on the mechanisms
Ion channels：Ca2+, Na+, K+ channels
Receptors：Adrenoceptors, AT1 receptors, etc.
Enzymes：ACEI, Na+-K+-ATPase, HMG-CoA reductase
Others：Diuretics

30. Cardiovascular Drugs Antiarrhthemic drugs Antihypertensive drugs
Classification; Typical drugs and their properties
Antihypertensive drugs
Classification; Properties of 6 main drug classes
Drugs for treating heart failure
Classification; ACEIs,  blockers, cardiac glycoide
Antiatheroscleotic drugs
HMG CoA reductase inhibitors (statins)
Antianginal drugs
Nitroglycerin;  blockers; Ca2+ antagonists