Drugs affecting blood and
blood-forming organs
(作用于血液和造血系统药物)
Tang Huifang (汤慧芳)
Dept. of Pharmacology,
School of Medicine, Zhejiang University
Email: [email protected]
General concept
Drugs affecting the blood and
blood-forming organs
Coagulationbleeding
Anticoagulant drugs(抗凝血药)
Antiplatelet drugs(抗血小板药)
Fibrinolytic drugs(纤维蛋白溶解药)
Hemostatic drugs(止血药)
 Antianemic drugs(抗贫血药)
Hematopoietic growth agents
agents (促白细胞生长药)
Blood volume • Drugs for treatment of
hypovolemia (血容量扩充剂)
Blood cell
growth
Part 1. Anticoagulants 抗凝血药
 凝血酶间接抑制剂：
 Heparin（肝素）
 Low molecular weight heparin （低分子量肝素）
 Fondaparinux (磺达肝癸钠)
 Oral direct Factor X inhibitors：Apixaban （阿派沙班）、
Rivaroxaban(利伐沙班)
 凝血酶直接抑制剂（direct thrombin inhibitors，DTIs)：
 ORAL DTIs: Dabigatran (达比加群)
 Factor II inhibitor: Lepirudin（重组水蛭素/来匹卢定）、
desirudin （地西卢定）、bivalirudin(比伐卢定)、Argatroban
（阿加曲班）
 Vitamin K antagonists: Coumarins 香豆素类
Warfarin（华法林）、dicoumarol（双香豆素）、
acenocoumarol（醋硝香豆素）
Anticoagulant drugs
Heparin（肝素）
MW of 5～30 kD(mean 12 kD).
化学：强酸性，具强负电荷（抗凝作用基础）
特效解毒剂：鱼精蛋白（碱性，强正电荷）
Ⅺa、Ⅸa、Ⅹa、Ⅻa
 Heparin accelerates inactivation of coagulation
factors by antithrombin.
Anticoagulant drugs
1. Pharmacological effects
(1)Anticoagulation:
1)Heparin increase the activity of AT Ⅲ
The AT Ⅲ may inhibit the activity of the
activated Ⅱa、Ⅺa、Ⅸa、Ⅹa、Ⅻa, to cause
anticoagulation.
2)Characteristics of anticoagulation
①It is effective in vitro and in vivo ;
②Its effects are rapid(iv) (<10min)and
short(3～4 h): activated partial thromboplastin
time(APTT) ↑
Anticoagulant drugs
(2)Anti-atherosclerosis:
1)Regulating blood lipids: VLDL
2)Protecting endothelial cells;
3)Inhibiting the proliferation of smooth
muscle cells.
4)Inhibits platelet aggregation
(3)Other effects:
Anti-complement, anti-inflammation,
and  blood viscosity（血液粘度）.
Anticoagulant drugs
2. Pharmacokinetics
(1)Heparin is not absorbed
by GI.
It need iv. or sc.
(2)plasma protein binding
rate: 80%
(3)t1/2: 1～2 hr.
It’s metabolised in
liver, and partially
degraded heparin appears
in the urine.
Anticoagulant drugs
3. Clinical uses
(1)Anticoagulation
Such as: pulmonary emboli; deep vein
thrombosis; cardiac infarction, etc.
(2)Heart ischemia
Prevent emboli in coronary artery——
early use.
(3)DIC(disseminated intravascular
coagulation, 弥散性血管内凝血)
Such as: certain surgical procedures,
hemodialysis, cardiac catheterization, etc.
(4)Prevent coagulation in vitro
Anticoagulant drugs
4. Adverse effects
(1)Bleeding(5%～10%)
Protamine sulfate（硫酸鱼精蛋白）is the antagonist
of heparin. 1mg protamine=100U heparin.
(2) Heparin-induced thrombocytopenia(血小板
减少症) (HIT)
5%～6%, Warfarin should be substi-tuted if the
platelet count falls.
(3)Others
Allergy(过敏反应);
Local necrosis(局部坏死), when sc;
Increased loss of hair and reversible alopecia(脱发);
Osteoporosis(骨质疏松).
(4) Contraindicated in patients with bleeding
risk
Anticoagulant drugs
Low molecular weight heparin
(LMWH, 低分子肝素)
FatcorⅩa
 常用LMWH：
 enoxaparin (依诺肝素)
 Tedelparin (替地肝素)
 Fraxiparin （弗希肝素）
 Logiparin（洛吉肝素）
 Lomoparin （洛莫肝素）
Mean MW = 1～12 kD
Stronger Effects on Ⅹa, Ⅻa than on Ⅱa
FatcorⅩa
Anticoagulant drugs
Coumarins(香豆素类)
Warfarin(华法林); Dicoumarol(双香豆素);
Acenocoumarol(醋硝香豆素)
双香豆素
苯茚二酮
华法林
Anticoagulant drugs
1. Pharmacological effects
(1)Properties:
Slowly and longer duration:
The effect appears after p.o. 1~3 days,
and lasts for 4 days
Effective only in vivo.
(2)Mechanisms of action:
Antagonizes vitamin K.
It inhibits carboxylation of the gluta-mic
acid residues of the factors Ⅱ、Ⅶ、Ⅸ、Ⅹ,
to decrease the activation of factors Ⅱ、Ⅶ、
Ⅸ、Ⅹ.
Mechanism of Coumarins
Anticoagulant drugs
2. Clinical uses
Anti-coagulation in vivo(such as deep vein
thrombosis, pulmonary emboli, and cardiac
infarction, etc).
3. Adverse effects
(1)Bleeding(9%～10%)
Can affect all organs in body.
Vitamin K1 may antagonist this reaction,
can treat with fresh blood or plasma and prothrombin
complex(凝血酶原复合物).
(2)Necrosis of skin and parenchyma(皮肤和软组织坏死).
(3)Liver injury(warfarin).
4. Drug interactions
(1)Plasma protein binding
replacement
(2)Hepatic metabolism:
enzyme inhibition
enzyme induction
Part 2. Antiplatelet drugs(抗血小板药)
→
PGI2
PGI2
受体
GPⅡb/Ⅲa 受体
TXA2
受体
ADP
受体
Thrombus formation at the site of the damaged vascular wall (EC, endothelials cell) and the role of platelets and
clotting factors. Platelet membrane receptors include the glycoprotein (GP) Ia receptor, binding to collagen (C);
GP Ib receptor, binding von Willebrand factor (vWF); and GP IIb/IIIa, which binds fibrinogen and other
macromolecules. Antiplatelet prostacyclin (PGI2) is released from the endothelium. Aggregating substances
released from the degranulating platelet include adenosine diphosphate (ADP), thromboxane A2 (TXA2),
and serotonin (5-HT).
Antiplatelet drugs(抗血小板药)
Types
Drugs
Remarks
Cyclooxygenase inhibitor, TXA2
 Clinical use: Angina, infarction
Dipyridmole(双嘧达莫, Reversibly inhibits PDE, cAMP ,
潘生丁)
 platelet reactivity , t1/2: 12 hr,

Clinical use: Thrombosis,
Ridogrel(利多格雷),
TXA2 synthase inhibitor
picotamide(匹可托安)
TXA2 receptor blocker,
Clinical use: Thrombosis
Epoprostenol(依前列醇) AC activitor cAMP ,
Clinical use: Thrombosis
Ticlopidine(噻氯匹定)  Selectively i n h i b i t A D P i n d u c e d
Clopidogrel (氯吡格雷) activation of platelet function
Clinical use: substituded for aspirin
Aspirin(阿司匹林)
1. Platelet
metabolism
inhibitor
2. Platelet
activation
inhibitor
3. Platelet
GpⅡb/Ⅲa
receptor
antigonist
in ischemic heart, brain disorders
Abciximab
阿昔单抗)
(C7E3Fab
Competitive
Platelet GpⅡb/Ⅲa receptor antigonist
Clinical use: angina, infarction
The class of antiplatelet drugs
Inhibition of AA metabolism in platelets
Irreversible cyclooxygenase inhibitors(COX inhibitor)： Aspirin (阿司匹林) 、
Triflusal (三氟柳)
Thromboxane synthase inhibitors and Thromboxane receptor antagonists：
Ridogrel(利多格雷), picotamide(匹可托安) 、Ozagrel、Seratrodast （塞曲司特）
Increase intracellular cAMP
Phosphodiesterase inhibitors(PDE inhibitor)： Cilostazol (西洛他唑)
Adenosine reuptake inhibitors： Dipyridamole (双嘧达莫, 潘生丁)
Activators of adenosine cyclase: epoprostenol （依前列醇）
Platelet activation inhibitor
Adenosine diphosphate (ADP) receptor inhibitors(P2Y12 inhibitor)：
 Clopidogrel (氯吡格雷) 、Prasugrel (普拉格雷) 、Ticagrelor (替卡格雷)
Ticlopidine (噻氯匹定)
Protease-activated receptor-1 (PAR-1) antagonists: Vorapaxar (沃拉帕沙)
Glycoprotein IIB/IIIA inhibitors ：
Intravenous use only: Abciximab (阿昔单抗)、Eptifibatide (依替巴肽)、
Tirofiban (替罗非班)、
Oral use: Xemilofiban（珍米洛非班）、Fradafiban（夫雷非班）、
Anti-platelet drugs
Aspirin(阿司匹林)
Acetylsalicylic acid(乙酰水杨酸)
COOH
O
O
C
CH3
It is a cyclooxygenase inhibitor, inhibiting TXA2 synthesis.
Mechanism:
Target enzymes
(cyclooxygenase)
are acetylated
and inactive.
Anti-platelet drugs
Aspirin
Small doses (30～100 mg/day):
inhibiting TXA2 synthesis, preventing
thrombosis.
used to treat ischemic heart
disease, reduce the mortality of
myocardiac infar-ction, and prevent
cerebral thrombosis.
Larger doses (  500 mg/day):
inhibiting PGI2 synthesis, promoting
thrombosis.
—— PGI2: vasodilation and platelet
depolymerization(血小板解聚).
Anti-platelet drugs
Dipyridamole(双嘧达莫,
Persantin, 潘生丁)
Reversibly inhibits phosphadiesterase
(PDE) of platelet,  cAMP , 
platelet reactivity , t1/2 12 hr.
Clinical uses: Prevent thrombosis.
Ticlopidine(噻氯匹定)
Selectively interferes ADP induced
platelet activation
Inhibits platelet function.
Clinical uses: Prevent cerebral
apoplexy (中风) and cardiac
infarction, etc.
Part 3. Fibrinolytic drugs 纤维蛋白溶解药
纤溶酶原
阿替普酶
尿激酶
+
链激酶
-
+
纤溶酶
阿尼普酶
凝血酶
纤维蛋白原
Fibrinolytic drugs
Alteplase
(Tissue plasminogen activator
t-PA, 组织型纤溶酶原激活剂)
1. Effect:
Local action on the thrombotic fibrin (血
栓纤维蛋白) to produce fibrinolysis;
iv. t1/2=3～8 min, effect 1～3 hr.
A potentially important agent in treating
thromboembolic disease.
2. ADR: bleeding.
Fibrinolytic drugs
Urokinase(尿激酶, UK)
1. Effect:
Plasminogen activator,
t1/2=15 min;
2. Clinical use:
Severe pulmonary emboli, and
deep vein thrombosis.
3. Adverse reaction:
(1)systemic fibrinolytic state,
(2)bleeding.
Fibrinolytic drugs
Streptokinase(链激酶, SK)
1. Pharmacological effect:
plasminogen(纤溶酶原) activator,
t1/2 = 23 min;
2. Clinical Use:
Severe pulmonary emboli, and
deep vein thrombosis
3. Adverse reaction:
Systemic fibrinolytic state which can
lead to bleeding problems(5%);
Antigenicity——allergy.
Fibrinolytic drugs
Anistreplase(阿尼普酶)
It is a streptokinase-plasminogen
complex, in which lys-plasminogen is
acylated at its catalyicsite serine.
The acyl group is hydrolyzed in vivo,
allowing the complex to bind to fibrin prior
to activation, and this modification confers
some specificity toward clots on the
fibrinolytic process.
It is used coronary thrombolysis also.
Adverse effects
The thrombolytic agents do not
distinguish between the fibrin of an
unwanted thrombus and the fibrin of a
beneficial hemostatic plug.
Hemorrhage is a major side effect.
Antidotes: fibrinolytic inhibitors (PAMBA
氨甲苯酸, AMCHA氨甲环酸)
Part 4. Hemostatic drugs
(Haemostats, 促凝血药, 止血药)
Vitamin K
1. Carboxylation of the glutamic acid
residues of II, VII, IX, X, protein C.
2. To prevent bleeding with vitamin K
deficiency.
3. Response to vitamin K is slow, the
severe hemostasis patients should be
infused with fresh plasma immediately.
Haemostats
Thrombin-like agents
(凝血酶制剂)
Thrombin(凝血酶, factor Ⅱ)
Prothrombin complex(凝血酶原复合物,
factor Ⅱ、Ⅶ、Ⅸ、Ⅹ)
used for various bleeding.
Globulin anti-hemophilia
(factor Ⅷ, 抗血友病球蛋白)
used for treatment for hemophilia.
Haemostats
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
Part 5. Antianemic drugs
抗贫血药
1. Cause of anemia:
(1)Anemia may result from the excess
destruction of erythrocytes;
(2)Anemia may result from nutritional
deficiencies, including: iron, minerals,
vitamins (B12 and folic acid), ascorbic acid,
riboflavin, etc.
2. Drugs for treatment of anemia:
Iron preparations;
Folic acid and vitamin B12;
Erythropoietin(EPO), and rhEPO
(Reconbanant human EPO)
Antianemic drugs
Iron preparations(铁制剂)
铵)
Ferrous sulfate(硫酸亚铁),
Ferric ammonium citrate(枸橼酸铁
Iron dextran(右旋糖酐铁),
Iron sorbitex(山梨醇铁)
1. Clinical Uses
Iron deficiency anemia.
2. ADRs
GI reactions: nausea, vomiting,
and diarrhea.
Acute intoxication: severe CNS
symptoms and GI reactions.
In this time, treatment with
deferoxamine(去铁胺).
Antianemic drugs
Folic acid(叶酸) & Vitamin B12
Both Folic acid(叶酸) and Vitamin B12 are
essential for the synthesis of DNA, this
process is impaired in patients with
megaloblastic anemia(巨幼红细胞贫血).
1. Pharmacological effects
Regulating nucleic acid & amino acid
metabolism.
2. Clinical uses
Megaloblastic anemia.
3. Adverse reaction
Rare reports
Antianemic drugs
Erythropoietin(EPO, 红细胞生成素)
rhEPO(重组人红细胞生成素)
1. Pharmacological effects
promoting red cell proliferation and
differentiation
2. Clinical uses
anemia due to chronic renal failure
with hemodialysis, radiotherapy, chemotherapy, AIDS, etc.
3. Adverse effects
etc.
Hypertension, epilepsy, thrombosis,
Part 6. Haemopoietic growth factors
促白细胞生成药
非格司亭（filgrastim,G-CSF:粒细胞集落刺激因子)
沙格司亭（sargramostim，GM-CSF:粒细胞/巨噬细
胞集落刺激因子, 生白能)
1. Effects and mechanism of effects
(1)Stimulates the formation of macrophage,
granulocyte colony;
(2)Stimulates proliferation, differentiation
and maturity of blood stem cell;
(3)Promotes the release of blood cell from
bone marrow
(4)Strenghtens the function of granulocyte
Haemopoietic growth factors
2. Clinical uses
Bone marrow suppression from
chemotherapy and radiotherapy of
neoplasm.
3. Adverse effects
GI reactions,
liver injury,
fever,
myalgia(肌肉痛).
Part 7. Agents correcting blood
volume(血容量扩充剂)
Dextran(右旋糖酐): (C6H10O5)n
Dextran-10; Dextran-40; Dextran-70
1. Pharmacological effects:
(1)Blood volume ,
(2)blood viscosity , platelet binding and
aggregation ;
(3)osmotic diuretic effects.
2. Clinical Use:
Anti-shock, maintain blood volume.
3. ADRs:
hypersensitivity, bleeding.
Reference
 Mega
JL1,
Simon
T2.
Pharmacology
of
antithrombotic drugs: an assessment of oral
antiplatelet and anticoagulant treatments. Lancet.
2015 Mar 11. pii: S0140-6736(15)60243-4. doi:
10.1016/S0140-6736(15)60243-4

Thanks!