This document summarizes different drugs used to treat angina. It first defines angina as chest pain caused by inadequate blood flow to the heart muscle. The main drugs discussed are: 1. Nitrate esters like nitroglycerin, which work by dilating blood vessels to increase blood flow and decrease workload on the heart. 2. Beta-blockers like propranolol, which work by blocking beta-1 receptors to reduce heart rate, blood pressure, and cardiac workload. 3. Calcium channel blockers like verapamil, which work by blocking calcium channels in heart and blood vessels to reduce contraction and dilate vessels, also reducing workload on the heart. These

1. Cardiovascular pharmacology
Chapter 32 Antianginal drugs
China Medical University

2. 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 .

3.  The heart as pump
Left anterior descending

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

5. 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

9. 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 :

10. • 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

11. Nitrate esters CH
2
CH
2
CH
O NO
2
O NO2
O NO2
Nitroglycerin
硝酸甘油
CH2 CH CH CH CH CH2
O NO2
O NO
2
O
O
CH2 CH CH CH CH CH2
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

12. Nitroglycerin 硝酸甘油
 Dilatation of the coronary arteries
increases blood flow and oxygen
delivery to the myocardium.
Pharmacological Function:
CH2
CH
CH2
O NO2
O NO2
O NO2
 Dilatation of the veins
and artery decreases preload
and afterload thus the oxygen
demand of the heart
Increase the heart rate

13. 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
Ca2+ inner cell
VSM dilation
NO
cGMP dependent PK-
PKG
SMC or EC（GC）
cGMP
Nitrate
esters
active
Inhibit platelet aggregation and adhesion

15. 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:

16. 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:

17. -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

18. Pharmacological Function:
-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

19. 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

20. 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

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

22. 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,

23. 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:

24. 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

25. 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

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

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

28. Factor Nitrate 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 ↑ → ↑

29. end