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1、Chapter 36Drugs acting on the blood and blood-forming organsDrugs affecting the blood and blood-forming organsAnticoagulant drugsAnticoagulant drugsAntiplateletAntiplatelet drugs drugsThrombolyticThrombolytic drugs drugsDrugs for treatment of bleeding Drugs for treatment of bleeding Drugs for treatm
2、ent of anemiaDrugs for treatment of anemia HematopoieticHematopoietic growth agents growth agentsDrugs for treatment ofDrugs for treatment of hypovolemia hypovolemiaCoagulation - bleedingBlood cell growthBlood volumeHeparin 肝素肝素肝素肝素Low molecular weight heparin 低分子肝素低分子肝素低分子肝素低分子肝素Coumarins 香豆素类香豆素类香
3、豆素类香豆素类 warfarin warfarin 华法林华法林华法林华法林 dicoumarol dicoumarol 双香豆素双香豆素双香豆素双香豆素 acenocoumarol acenocoumarol 醋硝香豆素醋硝香豆素醋硝香豆素醋硝香豆素A. Anticoagulant drugsThrombosis: injury in vital organsCoumarinsStage IStage IStage IIStage IIStage IIIStage IIIA. Anticoagulant drugsHeparin 肝素肝素A. Anticoagulant drugs1. Ph
4、armacological effects(1) Anticoagulation(1) Anticoagulation Increasing the activity of AT III: Increasing the activity of AT III: The AT III inhibiting The AT III inhibiting the activity of the activatedthe activity of the activated XIIa XIIa, XI, XI, Xa Xa, , IXa IXa, ,a, a, IIa IIa, , etc.etc. Rap
5、id and short (24 h) Rapid and short (24 h) Effective both Effective both in vitroin vitro and and in vivoin vivo(2) Anti (2) Anti atherosclerosisatherosclerosis blood lipids blood lipids protecting endothelial cells protecting endothelial cells inhibiting the hypertrophy of smooth muscle cells inhib
6、iting the hypertrophy of smooth muscle cells(3) Other effects:(3) Other effects: Antiinflammatory Antiinflammatory, , antioxydantantioxydant effects, effects, etc. etc. Effect of heparinA. Anticoagulant drugs2. Clinical uses(1) Thrombosis:(1) Thrombosis: pulmonary emboli, deep vein thrombosis, pulmo
7、nary emboli, deep vein thrombosis, cardiac infraction, cardiac infraction, etcetc. .(2) Cardiac (2) Cardiac ischemiaischemia: : high-risk patientshigh-risk patients(3) Prevention of coagulation (3) Prevention of coagulation in vitroin vitro: : cardiovascular cardiovascular surgery, surgery, hemodial
8、ysishemodialysis, cardiac , cardiac canulacanula, , etc.etc.(4)(4) Disseminsted intravascular Disseminsted intravascular coagulation (DIC): coagulation (DIC): early use.early use.A. Anticoagulant drugs3. Adverse effects(1) (1) Bleeding (at higher doses)Bleeding (at higher doses) ProtamineProtamine i
9、s the inhibitor of heparin. is the inhibitor of heparin. 1 mg (1 mg (protamineprotamine 鱼精蛋白鱼精蛋白鱼精蛋白鱼精蛋白) = 100 ) = 100 U (heparin)U (heparin)(2) (2) ThrombocytopeniaThrombocytopenia ( (血小板减少血小板减少血小板减少血小板减少): ): warfarinwarfarin should be substituted if the platelet count fallsshould be substituted
10、if the platelet count falls(3) Others:(3) Others: allergy, local necrosis, long-term use: allergy, local necrosis, long-term use: alpeciaalpecia ( (脱发脱发脱发脱发), ), osteoporosis (osteoporosis (骨质疏松骨质疏松骨质疏松骨质疏松), ), etc.etc. A. Anticoagulant drugsLow molecular weight heparin Mean MW = 112 kD Features: S
11、tronger effects on Stronger effects on XaXa, , XIIaXIIa than on than on IIaIIa Stronger anticoagulantsStronger anticoagulants Longer half -life Longer half -life Weak bleeding effects Weak bleeding effectsA. Anticoagulant drugsWarfarin 华法林华法林A. Anticoagulant drugs1. Pharmacological effects(1) Mechan
12、isms of action:(1) Mechanisms of action: antagonizing antagonizing vitaminevitamine K, K, inhibiting of inhibiting of carboxylationcarboxylation of the of the glutamicglutamic acid residues of the acid residues of the factorsfactors II, VII, IX, XII, VII, IX, X , and , and inducing the activated II,
13、 VII, IX, X inducing the activated II, VII, IX, X (2) Properties:(2) Properties: slowly and longer duration:slowly and longer duration: effect appears after effect appears after p.o.p.o. 13 13 days, and lasts for 4 daysdays, and lasts for 4 days effective only effective only in vivoin vivoSites of w
14、arfarin actionA. Anticoagulant drugs2. Clinical uses Anticoagulation Anticoagulation in vivoin vivo 3. Adverse effects(1) (1) Bleeding:Bleeding: v vitamine K may antagonite the reaction; Interrelaction with other agents(2) Necrosis of skin and parenchyma(2) Necrosis of skin and parenchyma ( ( ( (软组织
15、软组织软组织软组织) ) ) )(3) Liver injury(3) Liver injury4. Drug interactionsPlasma protein binding replacementHepatic metabolism: inhibition inhibition stimulation stimulationB. Antiplatelet drugsInhibition of platelet metabolismsInhibition of platelet metabolismsInhibitors of cyclic nucleotideInhibitors of
16、 cyclic nucleotide phosphodiesterase phosphodiesterase: : dipyridamoledipyridamole 双嘧达莫双嘧达莫双嘧达莫双嘧达莫 ( ( ( (潘生丁潘生丁潘生丁潘生丁) ) ) ) COX inhibitors:COX inhibitors: aspirin aspirin 阿司匹林阿司匹林阿司匹林阿司匹林TXATXA2 2 receptor antagonists and TXA receptor antagonists and TXA2 2 synthetasesynthetase inhibitors: inhibi
17、tors: ridogrel ridogrel 利多格雷利多格雷利多格雷利多格雷, , picotamidepicotamide 匹可托安匹可托安匹可托安匹可托安 Activators of adenosineActivators of adenosine cyclase cyclase: : epoprostenol epoprostenol 依前列醇依前列醇依前列醇依前列醇Inhibition of ADP-induced platelet activationInhibition of ADP-induced platelet activation ticlopidineticlopid
18、ine 噻氯匹定噻氯匹定噻氯匹定噻氯匹定Gp IIbGp IIb/ /IIIaIIIa receptor antagonists receptor antagonists abciximab abciximab 阿昔单抗阿昔单抗阿昔单抗阿昔单抗 (C7E3Fab(C7E3Fab) ) ) )B. Antiplatelet drugsAspirin 阿司匹林阿司匹林Acetylsalicylic acid 乙酰水杨酸乙酰水杨酸Aspirin Aspirin 阿司匹林阿司匹林阿司匹林阿司匹林B. Antiplatelet drugs small doses (30small doses (3010
19、0 mg/d):100 mg/d): inhibiting TXA inhibiting TXA2 2 synthesis, preventing thrombosis.synthesis, preventing thrombosis. used to treat used to treat ischemic ischemic heart disease, reduce the heart disease, reduce the mortality ofmortality of myocardiac myocardiac infarction, and prevent infarction,
20、and prevent cerebral thrombosis.cerebral thrombosis. larger doses:larger doses: inhibiting PGI inhibiting PGI2 2 synthesis, synthesis, promoting thrombosis.promoting thrombosis. PGIPGI2 2: : vasodilation vasodilation and platelet and platelet depolymerizationdepolymerization ( (血小板解聚血小板解聚血小板解聚血小板解聚)
21、. ).The mechanism of The mechanism of aspirin:aspirin:Target enzymes Target enzymes acetylatedacetylatedC. Thrombolytic drugsC. Thrombolytic drugsStreptokinase（SK）(T(T1/21/2 = 23 min; ) = 23 min; )Urokinase（UK） (T(T1/21/2 = 15 min; ) = 15 min; )Tissue plasminogen activator ( t-PA ) i.v. i.v. T T1/21
22、/2 = 38 min = 38 minAction of Action of thrombolytic thrombolytic drugsdrugsC. Thrombolytic drugsCommon adverse effectsCommon adverse effects bleeding bleeding antidotes:antidotes: antifibrinolyticantifibrinolytic drugs drugsBleedingBleedingThrombolysisThrombolysisD. Drugs for treatment of bleeding
23、Vitamine KCarboxylationCarboxylation of the of the glutamic glutamic acid residues of acid residues of factors II, IIV, IX, X, protein C.factors II, IIV, IX, X, protein C.Preventing Preventing bleeding bleeding with with vitaminevitamine K K deficiency deficiency or or warfarinwarfarin-induced bleed
24、ing-induced bleedingVitamin KVitamin KVitamin KVitamin KD. Drugs for treatment of bleedingThrombin-like agents thrombin, prothrombin complex, used for various bleedingD. Drugs for treatment of bleedingDrugs preventing activation of antifibrinolytics aprotinin, tranexamic acid (AMCHA, 氨甲环酸氨甲环酸) p-ami
25、nomethylbenzoic acide (PAMBA, 氨氨甲甲苯酸）苯酸） used for preventing the activation fibrinolysis and resultant bleeding E. Drugs for treatment of anemiaAnemia may result from the excess destruction of Anemia may result from the excess destruction of erythrocytes, and nutritional deficiencies (iron, erythroc
26、ytes, and nutritional deficiencies (iron, minerals, cobalt, vitamin Bminerals, cobalt, vitamin B1212, folic acid, ascorbic , folic acid, ascorbic acid, riboflavin, copper, zinc, etc.acid, riboflavin, copper, zinc, etc. Iron: anemia due to loss of erythrocytes and iron deficiency anemia due to loss o
27、f erythrocytes and iron deficiency Folic acid and vitamin B12: megaloblastic megaloblastic anemiaanemia Erythropoietin (EPO) promoting red cell proliferation and promoting red cell proliferation and differetiationdifferetiationE. Drugs for treatment of anemiaIron ferrous sulfateferrous sulfate 硫酸亚铁硫
28、酸亚铁硫酸亚铁硫酸亚铁 ferric ammonium citrateferric ammonium citrate 枸橼酸铁铵枸橼酸铁铵枸橼酸铁铵枸橼酸铁铵 1. 1. Interaction with other drugs or diet in the GI Interaction with other drugs or diet in the GI tracttract2. Used for anemia due to loss of erythrocytes 2. Used for anemia due to loss of erythrocytes and iron deficie
29、ncy and iron deficiency 3. Adverse effects:3. Adverse effects: GI reactions, hypersensitivity GI reactions, hypersensitivityAcute intoxication:Acute intoxication: severe CNS, GI reactions severe CNS, GI reactions- treated with - treated with deferoxaminedeferoxamine（去铁敏）去铁敏）去铁敏）去铁敏）E. Drugs for trea
30、tment of anemiaFolic acid and vitamin B121. 1. Pharmacological effectsPharmacological effectsRegulating nucleic acid, amino acid metabolismRegulating nucleic acid, amino acid metabolism2. 2. Clinical usesClinical usesMegaloblastic Megaloblastic anemiaanemia3. 3. Adverse effectsAdverse effectsRare re
31、portsRare reportsFolic acid metabolism Folic acid metabolism and the effect of and the effect of vitamin Bvitamin B1212E. Drugs for treatment of anemiaErythropoietin (EPO) rhEPOrhEPO1. 1. Pharmacological effectsPharmacological effectspromoting red cell proliferation andpromoting red cell proliferati
32、on and differetiation differetiation2. 2. Clinical usesClinical usesAnemia due to Anemia due to chronic renal failure with chronic renal failure with hemodialysishemodialysis, , radiotherapy, chemotherapy, AIDS, radiotherapy, chemotherapy, AIDS, etc.etc.3. 3. Adverse effectsAdverse effectsHypertensi
33、on, epilepsy, thrombosis, Hypertension, epilepsy, thrombosis, etc.etc.Effect of EPO on red cell proliferation and differentiationEffect of EPO on red cell proliferation and differentiationF. Hematopoietic growth agentsGranulaocyte colony-stimulating factor G-CSF G-CSF 粒细胞集落刺激因子粒细胞集落刺激因子粒细胞集落刺激因子粒细胞集
34、落刺激因子Granulaocyte/macrophage colony-stimulating factor GM-CSF GM-CSF 粒细胞粒细胞粒细胞粒细胞/ /巨噬细胞集落刺激因子巨噬细胞集落刺激因子巨噬细胞集落刺激因子巨噬细胞集落刺激因子Used for Used for neutropenianeutropenia ( (chemotheapychemotheapy or or radiotherapy), radiotherapy), autologous autologous bone marrow bone marrow transplantation, transplant
35、ation, myelodysplasiamyelodysplasia, , aplastic aplastic anemia, anemia, AIDS-associated AIDS-associated neutropenianeutropeniaAllergy, GI and hepatic injuries, local irritation, Allergy, GI and hepatic injuries, local irritation, etc.etc.G. Drugs for treatment of hypovolemiaDextran 右旋糖酐（葡聚糖右旋糖酐（葡聚糖右旋糖酐（葡聚糖右旋糖酐（葡聚糖）Hydroxyethyl starch 羟乙基淀粉羟乙基淀粉羟乙基淀粉羟乙基淀粉Increasing blood volumeIncreasing blood volumeInhibiting platelet aggregation ( MW 40,000)Inhibiting platelet aggregation ( MW 40,000)Osmotic diuretic effectsOsmotic diuretic effects
