1、Chapter 36Drugs acting on the blood and blood-forming organs,Drugs affecting the blood and blood-forming organs,Anticoagulant drugs Antiplatelet drugs Thrombolytic drugs Drugs for treatment of bleeding,Drugs for treatment of anemia Hematopoietic growth agents,Drugs for treatment of hypovolemia,Coagu

2、lation - bleeding,Blood cell growth,Blood volume,Heparin 肝素 Low molecular weight heparin 低分子肝素 Coumarins 香豆素類 warfarin 華法林 dicoumarol 雙香豆素 acenocoumarol 醋硝香豆素,A. Anticoagulant drugs,Thrombosis: injury in vital organs,Coumarins,Stage I,Stage II,Stage III,A. Anticoagulant drugs,Heparin 肝素,A. Anticoagu

3、lant drugs,1. Pharmacological effects (1) Anticoagulation Increasing the activity of AT III: The AT III inhibiting the activity of the activated XIIa, XI, Xa, IXa,a, IIa, etc. Rapid and short (24 h) Effective both in vitro and in vivo (2) Anti atherosclerosis blood lipids protecting endothelial cell

4、s inhibiting the hypertrophy of smooth muscle cells (3) Other effects: Antiinflammatory, antioxydant effects, etc.,Effect of heparin,A. Anticoagulant drugs,2. Clinical uses (1) Thrombosis: pulmonary emboli, deep vein thrombosis, cardiac infraction, etc. (2) Cardiac ischemia: high-risk patients (3) P

5、revention of coagulation in vitro: cardiovascular surgery, hemodialysis, cardiac canula, etc. (4) Disseminsted intravascular coagulation (DIC): early use.,A. Anticoagulant drugs,3. Adverse effects (1) Bleeding (at higher doses) Protamine is the inhibitor of heparin. 1 mg (protamine 魚精蛋白) = 100 U (he

6、parin) (2) Thrombocytopenia (血小板減少): warfarin should be substituted if the platelet count falls (3) Others: allergy, local necrosis, long-term use: alpecia (脫發(fā)), osteoporosis (骨質(zhì)疏松), etc.,A. Anticoagulant drugs,Low molecular weight heparin Mean MW = 112 kD Features: Stronger effects on Xa, XIIa than

7、 on IIa Stronger anticoagulants Longer half -life Weak bleeding effects,A. Anticoagulant drugs,Warfarin 華法林,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 , a

8、nd inducing the activated II, VII, IX, X (2) Properties: slowly and longer duration: effect appears after p.o. 13 days, and lasts for 4 days effective only in vivo,Sites of warfarin action,A. Anticoagulant drugs,2. Clinical uses Anticoagulation in vivo 3. Adverse effects (1) Bleeding: vitamine K may

9、 antagonite the reaction; Interrelaction with other agents (2) Necrosis of skin and parenchyma (軟組織) (3) Liver injury,4. Drug interactions Plasma protein binding replacement Hepatic metabolism: inhibition stimulation,B. Antiplatelet drugs,Inhibition of platelet metabolisms Inhibitors of cyclic nucle

10、otide phosphodiesterase: dipyridamole 雙嘧達(dá)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 recepto

11、r antagonists abciximab 阿昔單抗 (C7E3Fab),B. Antiplatelet drugs,Aspirin 阿司匹林 Acetylsalicylic acid 乙酰水楊酸,Aspirin 阿司匹林,B. Antiplatelet drugs,small doses (30100 mg/d): inhibiting TXA2 synthesis, preventing thrombosis. used to treat ischemic heart disease, reduce the mortality of myocardiac infarction, and

12、 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,Streptokinase（SK）(T1/2 = 23 min; ) Urokinase（UK） (T1/

13、2 = 15 min; ) Tissue plasminogen activator ( t-PA ) i.v. T1/2 = 38 min,Action of thrombolytic drugs,C. Thrombolytic drugs,Common adverse effects bleeding antidotes: antifibrinolytic drugs,Bleeding,Thrombolysis,D. Drugs for treatment of bleeding,Vitamine K Carboxylation of the glutamic acid residues

14、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 a

15、ctivation of antifibrinolytics aprotinin, tranexamic acid (AMCHA, 氨甲環(huán)酸) p-aminomethylbenzoic acide (PAMBA, 氨甲苯酸） used for preventing the activation fibrinolysis and resultant bleeding,E. Drugs for treatment of anemia,Anemia may result from the excess destruction of erythrocytes, and nutritional defi

16、ciencies (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 differetiation,E. Drugs for

17、 treatment of anemia,Iron ferrous sulfate 硫酸亞鐵 ferric ammonium citrate 枸櫞酸鐵銨 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 CNS, GI reactions - tr

18、eated with deferoxamine（去鐵敏）,E. Drugs for treatment of anemia,Folic acid and vitamin B12 1. Pharmacological effects Regulating nucleic acid, amino acid metabolism 2. Clinical uses Megaloblastic anemia 3. Adverse effects Rare reports,Folic acid metabolism and the effect of vitamin B12,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, ep