Transcript receptor blocker

China Medical University
Chapter 32 Antianginal drugs
Cardiovascular pharmacology
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 .
 The heart as pump
Left anterior descending
pathology
Contractility
Coronary
Oxygen
Oxygen
Blood Flow
Supply
Demand
Heart Rate
LV Wall Tension
Systolic
LV
BP
Volume
Ischemia
LV Dysfunction
Chest Pain
Arrhythmias
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
Classification of angina :
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 .
Classifications of treatment medicine
• 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)
Nitrate esters
Nitroglycerin
硝酸甘油
CH
2
O
NO
2
CH
O
NO 2
CH
2
O
NO 2
O
Isosorbide Dinitrate
硝酸异山梨酯
CH2
Isosorbide -5-Mononitrate
5’-单硝酸异山梨酯
CH2
O
NO2
CH
CH
CH
CH
O
O
O
O
NO
2
CH
CH
CH
CH2
CH
O
O
H
CH2
NO2
Nitroglycerin
硝酸甘油
Pharmacological Function:
CH2
O
 Dilatation of the veins
CH
O
and artery decreases preload
O
and afterload thus the oxygen CH2
demand of the heart
 Dilatation of the coronary arteries
increases blood flow and oxygen
delivery to the myocardium.
Increase the heart rate
NO2
NO2
NO2
Mechanism of action:
Nitrate
Nitroglycerin are prodrugs,
esters
NO
decomposing to form nitric
active
oxide (NO), which activates
SMC or EC（GC）
guanylyl cyclase (GC) ,thereby
increasing the levels of cyclic
cGMP
active
guanosine monophosphate
cGMP dependent PK(cGMP). Protein kinase G is
PKG
activated and contractile
2+ inner cell
Ca
proteins are phosphorylated.
Inhibit platelet aggregation and adhesion
VSM dilation
Route of administration:
Nitroglycerin is administered sublingually ,
and can be given by intravenous infusion or
from patches.
Indication:
Nitroglycerin is given for the prophylaxis预
防
and treatment of angina－ Stable angina
Adverse effects：
The side effects of nitroglycerin include postural
hypotension, tachycardia, headache ,flushing and
dizziness.
Therapeutic notes:
To avoid nitrate tolerance, a drug-free period
of approximately 8 hours is needed.
-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
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
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
To
•
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
Contraindications and notes
• Related to heart:
Bradycardia, hypotention, AV
block, and CHF
• Asthmatic 哮喘
•β1 receptor up-regulation
So slowly reduce the doses
Calcium-channel blockers
Examples of calcium-channel blockers include
Verapamil
Diltiazem
Nifedipine
block L-type calcium channels,
thereby reducing calcium entry
into cardiac and vascular cells
block L-type calcium channels
in vascular cells,
Pharmacological Function:
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
Coronary vascular dilatation
promote the opening of side branch
Inhibit platelet aggregation
Increase the supply of blood
Protect the ischemic myocardial
Clinical uses
Treatment of angina
Variant angina
Verapamil is given for
supraventricular arrhythmias
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
conjunction use
Nitrate esters + Calcium-channel blockers
Amlodipine 氨氯地平 络活喜
-receptor blocker ＋ Calcium-channel blockers
Nitrate esters+ -receptor blocker
N- Nitrate esters
B -β -receptor blocker
Notes：↑= increase，↓=decrease，→= no change，↓↑= unsure
Factor
Nitrate esters
-receptor
blocker
Calcium-channel
blockers
Wall Tenson室壁张力
↓
±
↓
LV volume
↓
↑
±
Ventricular
pressure心室压力
↓
↓
↓
rate心 率
↑
↓
±
contractility收缩性
↑
↓
±
心内膜/心外膜blood ratio
↑
↑
↑
↑
→
↑
心室容量
血流比率
the flow of side branch侧枝血流
end