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抗心绞痛药
Antianginal Drugs
Overview
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What’s Angina pectoris
Cause and the classification of angina pectoris :
Atheromatous obstruction of the large coronary vessels (atherosclerotic
angina, classic angina);
劳累性心绞痛：稳定型，初发型，恶化型
Transient spasm of localized portions of the large coronary vessels
(angiospastic or variant angina);
自发性心绞痛：卧位型，变异型，急性冠脉功能不全，梗死后心绞痛
Both causes
混合性心绞痛
Unstable angina pectoris:
initial onset type; accelerated type; spontaneous type
associated with atheroscleosis plaque and thrombus formation
may lead to myocardial infarction
Overview
Coronary vessels: blood supply for the heart
Overview
Coronary atherosclerosis:
cause of cardiac ischemia
Distribution of coronary arteries in the heart
Overview
oxygen requirement 
oxygen supply 
imbalance
• Primary cause of angina pectoris:
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In classic angina, the imbalance occurs when
the myocardial oxygen requirement increases;
“angina of effort”
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In variant angina, oxygen delivery decreases as
a result of reversible coronary vasospasm.
“vasospastic or Prinzmetal's angina”
afterload
preload
Overview
Myocardial oxygen demand is diminished by:
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Reducing contractility
Reducing heart rate
Reducing the preload
Reducing the afterload
Wall tension 
Myocardial oxygen supply is increased by:
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Dilating conduct coronary arteries
(  coronary blood flow)
Promoting regional distribution
(  in ischemic regions)
Treatments:
• Non-drug treatment:经皮冠状动脉成形术(percutaneous
transluminal coronary angioplasty, PTCA), 冠脉搭桥术
( coronary artery bypass graft surgery, CABG )
• Drug treatment
Antianginal Drugs
Effects of antianginal drugs:
• Reducing oxygen demands
• Increasing oxygen supply
• Others: Anti- platelet coagulation and
thrombus formation
Antianginal drugs:
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Organic nitrates
 receptor blockers
Calcium channel blockers
Anti-platelet agents
ACEIs
Fish oil
Nitrates & Nitrites
nitroglycerin
• Quick tolerance and cross-tolerance;
• Pharmacokinetic factors determine the selection;
Nitrates & Nitrites
- Pharmacokinetics
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Low oral bioavailability (eg, nitroglycerin and isosorbide
dinitrate, typically < 10–20%).
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Sublingual is normally used. Transdermal and buccal
absorption from slow release preparations.
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Amyl(戊基) nitrite and related nitrites can be used with
inhalation route.
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Duration of effect is very brief (Unchanged nitrate t1/2=2-8
minutes, partially denitrated metabolites longer t1/2= 3 hrs). So
micro-pump is very common in hospital usage.
Nitrates: Nitroglycerin (硝酸甘油)
- 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 
• Alleviating ischemic injury
• Anti- platelet coagulation
Nitrates: Nitroglycerin (硝酸甘油)
Influence of organic nitrates and dipyridamole
on the blood supply of ischemic area
Mechanism of the
effect of
nitroglycerin and
other nitrates
Intracellular Ca2+ release↓，extracellular Ca2+ influx↓
Intracellular [Ca2+] ↓
The production of PGE or PGI2 and membrane hyper-polarization may also be
involved.
Nitrates: Nitroglycerin (硝酸甘油)
- Clinical uses
• Angina pectoris: all kinds, especially stable type
• Heart failure
- Adverse reactions
• Symptoms due to vasodilation: headache, postural
hypotension, etc.
• Increase in heart rate and contractility
• Others: methaemoglobinaemia（高铁血红蛋白）
• Tolerance : avoiding steady-state plasma concentration;
supplement of agents containing –SH
(captopril, NAC), VitC
Nitrates
Other nitrates
Isosorbide dinitrate (硝酸异山梨酯)
Isosorbide-5-mononirate (5-硝酸异山梨酯)
Compared with nitroglycerin:
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Similar but weaker effect
Acting slowly but lasting longer
Larger individual variation and more adverse effects
 receptor blockers
- 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
Increase oxygen supply
Inhibiting coagulation of platelets
 receptor blockers
- Clinical uses
stable and unstable pectoris, especially associated with
hypertension or arrhythmias, even with myocardial infarction; but not
used for variant angina pectoris
- Notes
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Dose individualization: starting from small dose
Withdraw gradually and slowly: symptom rebound
Cardiac depression
Inducing asthma
Combination with nitroglycerin
Calcium channel blockers
- Pharmacological actions
• Reducing myocardial oxygen remand:
heart loads : nifedipine
heart rate and contractility : verapamil and diltiazem
• Increasing myocardial blood supply
• Inhibiting coagulation of platelets
• Protecting ischemic myocardial cells
- Clinical uses
stable and variant type:
nifedipine, verapamil, diltiazem
unstable type:
verapamil, diltiazem
Calcium channel blockers
- Toxicity
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Cardiac depression, including cardiac arrest, bradycardia,
atrioventricular block, and heart failure.
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Relatively short-acting calcium channel blockers have the potential to
enhance the risk of adverse cardiac events.
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Slow-release and long-acting vasoselective calcium channel blockers
are usually well tolerated.
Patients receiving -adrenoceptor-blocking drugs are more
sensitive to
the cardiodepressant effects of calcium channel blockers.
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• Tolerable toxicity: flushing, dizziness, nausea, constipation, and
peripheral edema.
Other drugs
Angiotensin converting enzyme inhibitors (ACEI)
Nicorandi (尼可地尔)
• a potassium channel opener
Molsidomine （吗多明）
• Producing NO → stimulate guanylyl cyclase (GC)
→increase cGMP → relaxes vascular smooth muscle
Dipyridamole （双嘧达莫，潘生丁）
• Inhibiting adenosine uptake and cAMP degradation
• Inhibiting pletelet aggregation
Summary of antianginal drugs
nitroglycerin
Heart rate
Contractility
Wall tension
Oxygen demand
Blood pressure
 blockers Ca2+ antagonists combination*
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: 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
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