Chapter 4
Drugs acting on the blood and
blood-forming organs
Drugs affecting the blood and bloodforming organs
Coagulation
- bleeding
 Anticoagulant drugs（抗凝血药）
 Antiplatelet drugs （抗血小板药）
 Thrombolytic drugs （溶栓药）
 Drugs for treatment of bleeding （止血药）
Blood cell
growth
 Drugs for treatment of anemia（抗贫血药）
 Hematopoietic growth agents（造血细胞药）
Blood
volume
Drugs for treatment of hypovolemia（血容量
扩充药）
A. Anticoagulant drugs
A. Anticoagulant drugs
 Heparin 肝素
 Low molecular weight heparin 低分子肝素
 Coumarins 香豆素类
 warfarin 华法林


dicoumarol 双香豆素
acenocoumarol 醋硝香豆素
Thrombosis injures vital organs
外源性 （组织损伤）
内源性 （血管壁损伤）
Stage I
Stage II
Stage III
II
I
IIa
Ia
Major reactions of blood coagulation
Coumarins
A. Anticoagulant drugs
Heparin
肝素
Molecular weights: 3~30 kDa; mean 15 kDa
A. Anticoagulant drugs
 1. Pharmacological effects
 (1) Anticoagulation

Increasing the activity of AT III: The AT III
inhibiting the activity of the activated IIa, VIIa, IXa,
Xa, XIIa, etc.
Rapid and short (2~4 h)

Effective both in vitro and in vivo.

more
rapid
Example of the effect of heparin
A. Anticoagulant drugs
 (2) Anti –atherosclerosis
blood lipids 

protecting endothelial cells

inhibiting the hypertrophy of smooth muscle

cells
 (3) Other effects:
Antiinflammatory, antioxydant effects, etc.

A. Anticoagulant drugs
 2. Clinical uses
 (1) Thrombosis: pulmonary emboli, deep vein thrombosis,
cardiac infraction, etc.
 (2) Cardiac ischemia: high-risk patients
 (3) Disseminated intravascular coagulation (DIC):
early use.
 (4) Prevention of coagulation in vitro: cardiovascular
surgery, hemodialysis, cardiac canula, etc.
A. Anticoagulant drugs
 3. Adverse effects
 (1) Bleeding (at higher doses)


Protamine is the inhibitor of heparin.
1 mg (protamine 鱼精蛋白) = 100 U (heparin)
 (2) Thrombocytopenia (血小板减少): warfarin should
be substituted if the platelet count falls
 (3) Others: allergy, local necrosis, long-term use:
alpecia (脱发), osteoporosis (骨质疏松), etc.
A. Anticoagulant drugs
 Low molecular weight heparin


Mean MW = 1～12 kDa
Features:




Stronger effects on Xa, XIIa than on IIa
Stronger in inhibiting thrombosis/coagulation
High bioavailability; Longer half -life
Weak bleeding effects
A. Anticoagulant drugs
Warfarin
华法林
A. Anticoagulant drugs
 1. Pharmacological effects
 (1) Mechanisms of action:

antagonizing vitamine K, inhibiting of carboxylation of the
glutamic acid residues of the factors II, VII, IX, X , and
reducing the activated II, VII, IX, X
 (2) Properties:

slowly and longer duration: effect appears after p.o. 1~3
days, and lasts for 4 days

effective only in vivo
Sites of
warfarin action
Factor II,
VII, IX, X
warfarin action
Activated factor
II, VII, IX, X
COO-
氢醌型Vit K
环氧型Vit K
A. Anticoagulant drugs
 2. Clinical uses
 Anticoagulation in vivo
 3. Adverse effects
 (1) Bleeding: vitamine K may antagonize the
reaction; interrelaction with other agents


(2) Necrosis of skin and parenchyma (软组织)
(3) Liver injury
4. Drug interactions
Plasma protein binding
replacement
Hepatic metabolism:
inhibition
potentiation
B. Antiplatelet drugs
B. Antiplatelet drugs
Inhibition of platelet metabolisms
Inhibitors of cyclic nucleotide phosphodiesterase:
dipyridamole 双嘧达莫 (潘生丁)
COX inhibitors: aspirin 阿司匹林
TXA2 receptor antagonists and TXA2 synthetase inhibitors:
ridogrel 利多格雷, picotamide 匹可托安
Activators of adenosine cyclase: epoprostenol 依前列醇
Inhibition of ADP-induced platelet activation
ticlopidine 噻氯匹定
Gp IIb/IIIa receptor antagonists
abciximab 阿昔单抗 (C7E3Fab)
B. Antiplatelet drugs
Aspirin 阿司匹林
Acetylsalicylic acid 乙酰水杨酸
COOH
O
O
C
Aspirin
阿司匹林
CH3
B. Antiplatelet drugs

small doses (30～100 mg/d): inhibiting TXA2
synthesis, preventing thrombosis.
used to treat ischemic heart disease, reduce the

mortality of myocardiac infarction, and prevent
cerebral thrombosis.




larger doses: inhibiting PGI2 synthesis,
promoting thrombosis.
PGI2: vasodilation and platelet depolymerization (血小板
解聚).
The mechanism of
aspirin:
Target enzymes
acetylated
C. Thrombolytic drugs
C. Thrombolytic
drugs
C. Thrombolytic drugs
 Streptokinase（SK）(T1/2 = 23 min; )
 Urokinase（UK） (T1/2 = 15 min; )
 Tissue plasminogen activator ( t-PA，组织
纤溶酶原激活剂 )

i.v. T1/2 = 3~8 min
t-PA
(+)
Action of thrombolytic drugs
C. Thrombolytic drugs
 Common adverse effects
bleeding

antidotes: antifibrinolytic drugs

Thrombolysis
Bleeding
D. Drugs for treatment
of bleeding
D. Drugs for treatment of bleeding
 Vitamine K
 Carboxylation of the glutamic acid
residues of factors II, IIV, IX, X, protein C.
 Preventing bleeding with vitamine K
deficiency or warfarin-induced bleeding
Vitamin K
Vitamin K
D. Drugs for treatment of bleeding
 Thrombin-like agents




thrombin,
prothrombin complex,
used for various bleeding
D. Drugs for treatment of bleeding
 Drugs preventing activation of
antifibrinolytics




aprotinin (抑肽酶）
tranexamic acid (AMCHA, 氨甲环酸)
p-aminomethylbenzoic acide (PAMBA, 氨甲
苯酸）
used for preventing the activation
fibrinolysis and resultant bleeding
Inhibiting plasminogen activation
E. Drugs for treatment
of anemia
E. Drugs for treatment of anemia
 Anemia may result from the excess destruction of
erythrocytes, and nutritional deficiencies (iron,
minerals, cobalt, vitamin B12, folic acid, ascorbic
acid, riboflavin, copper, zinc, etc.
 Iron:

anemia due to loss of erythrocytes and iron deficiency
 Folic acid and vitamin B12:

megaloblastic anemia
 Erythropoietin (EPO)

promoting red cell proliferation and differentiation
E. Drugs for treatment of anemia
 Iron


ferrous sulfate 硫酸亚铁
ferric ammonium citrate 枸橼酸铁铵
 1. Interaction with other drugs or diet in the GI




tract
2. Used for anemia due to loss of erythrocytes and
iron deficiency
3. Adverse effects: GI reactions, hypersensitivity
Acute intoxication: severe CVS and GI reactions
- treated with deferoxamine（去铁敏）
E. Drugs for treatment of anemia
 Folic acid






1. Pharmacological effects
Regulating nucleic acid, amino acid metabolism
2. Clinical uses
Megaloblastic anemia; MTX-induced anemia
3. Adverse effects
Rarely reported
 Vitamin B12
 Co-factor of folic acid
 Important in maintaining neuron myelination
E. Drugs for treatment of anemia
 Erythropoietin (EPO)





rhEPO
1. Pharmacological effects
Promoting red cell proliferation and differetiation
2. Clinical uses
Anemia due to chronic renal failure with
hemodialysis, radiotherapy, chemotherapy, AIDS,
etc.
 3. Adverse effects
 Hypertension, epilepsy, thrombosis, etc.
Effect of EPO on red cell proliferation and differentiation
F. Hematopoietic
growth agents
F. Hematopoietic growth agents
 Granulaocyte colony-stimulating factor G-CSF
粒细胞集落刺激因子
 Granulaocyte/macrophage colony-stimulating
factor GM-CSF 粒细胞/巨噬细胞集落刺激因子
 Used for neutropenia (chemotheapy or radiotherapy),
autologous bone marrow transplantation,
myelodysplasia, aplastic anemia, AIDS-associated
neutropenia
 Allergy, GI and hepatic injuries, local irritation, etc.
G. Drugs for treatment
of hypovolemia
G. Drugs for treatment of hypovolemia
 Dextran 右旋糖酐（葡聚糖）
 Hydroxyethyl starch 羟乙基淀粉
 Increasing blood volume
 Inhibiting platelet aggregation (~ MW 40,000)
 Osmotic diuretic effects
hydroxyethyl starch 羟乙基淀粉
Enzymatic degradation and excretion of hydroxyethyl starch