Part 6 Antianginal Drugs

• Organic nitrates
•  receptor blockers
• Calcium channel blockers
 1. OVERVIEW

Coronary vessels: blood supply for the heart

Coronary atherosclerosis:
cause of cardiac ischemia
Distribution of coronary arteries in the heart
Ischemia (angina pectoris ):
imbalance between oxygen demand and supply
 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)
 1. OVERVIEW
Myocardial oxygen demand is chiefly
determined by:

• Contractility
• Heart rate
• Wall tension
• Preload (venous return )
• Afterload (arteriolar resistance)

afterload preload
 1. OVERVIEW

Myocardial oxygen demand is

diminished by:
• Reducing contractility
• Reducing heart rate
• Reducing the preload
Wall tension 
• Reducing the afterload
1. OVERVIEW

•Myocardial oxygen
supply is chiefly
determined by:

• AV oxygen difference
• Regional myocardial
distribution
• coronary blood flow:
• vascular resistance, artery pressure
 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
 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 
 2. Antianginal drugs

Influence of organic nitrates and dipyridamole

on the blood supply of ischemic area
 2. Antianginal drugs

Mechanism of the effect of nitroglycerin and other nitrates

Mechanism of the effect of nitroglycerin and other nitrates
 2. Antianginal drugs
B. Clinical uses
• 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)
 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:
• Similar but weaker effect
• Acting slowly but lasting longer
• Larger individual variation and more adverse effects
 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
 2. Antianginal drugs

B. Clinical uses
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
 2. Antianginal drugs

2.3 Calcium channel blockers

 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
Actions of calcium channel blockers
 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 and diltiazem are similar to those of  blockers
 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 cardial remodeling

Nicorandil （尼可地尔）
• Opening ATP-sensitive K+ channel (KATP)
• Lowering intracellular Ca2+
• Providing NO (like nitroglycerin)
•Inducing ischemic preconditioning
 2. Antianginal drugs

Molsidomine （吗多明）
•Inhibiting adenosine uptake and cAMP degradation
•Inhibiting pletelet aggregation
•Promoting collateral circulation after long-term use

Dipyridamole （双嘧达莫，潘生丁）
• Inhibiting adenosine uptake and cAMP degradation
•Inhibiting pletelet aggregation
•Promoting collateral circulation after long-term use
 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
Cardiovascular
pharmacology

Sammary
 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
 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
 Cardiovascular Drugs
• Antiarrhthemic 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