Download Drugs anti

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
Reducing the afterload
Wall tension 
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
Heart rate
Contractility
Wall tension
Oxygen demand
Blood pressure
 blockers Ca2+ antagonists combination*








/

/
/








: 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