《基础医学各论I：血液系统药物》由会员分享，可在线阅读，更多相关《基础医学各论I：血液系统药物（59页珍藏版）》请在金锄头文库上搜索。
1、Drugs acting on the blood and blood-forming organsDrugs affecting the blood and blood-forming organsAnticoagulant drugs Anticoagulant drugs ( (抗凝药抗凝药抗凝药抗凝药) )Antiplatelet drugs Antiplatelet drugs ( (抗血小板药抗血小板药抗血小板药抗血小板药) )Thrombolytic drugs Thrombolytic drugs ( (纤溶药纤溶药纤溶药纤溶药) )Drugs for treatment of
2、 bleeding Drugs for treatment of bleeding ( (止血药止血药止血药止血药) )Drugs for treatment of anemia Drugs for treatment of anemia ( (抗贫血药抗贫血药抗贫血药抗贫血药) ) Hematopoietic growth agentsHematopoietic growth agentsn nDrugs for treatment of hypovolemiaDrugs for treatment of hypovolemia ( (血容量扩充药血容量扩充药血容量扩充药血容量扩充药) )C
3、oagulation - bleedingBlood cell growthBlood volumeheparin 肝素肝素肝素肝素 low molecular weight heparinlow molecular weight heparin 低分子量肝素低分子量肝素低分子量肝素低分子量肝素dermatan sulfate 硫酸皮肤素硫酸皮肤素硫酸皮肤素硫酸皮肤素lepirudin 重组水蛭素重组水蛭素重组水蛭素重组水蛭素coumarins 香豆素类香豆素类香豆素类香豆素类 warfarin warfarin 华法林华法林华法林华法林 dicoumarol dicoumarol 双香豆素双
4、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Anticoagulant drugsheparin 肝素肝素肝素肝素( (凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药) ) low molecular weight heparin low molecular weight heparin 低分子量肝素低分子量肝素低分子量肝素低分子量肝素dermatan sulfate 硫酸皮肤素硫酸皮肤素硫酸皮肤素硫酸皮肤素( (凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药) )lepirudin
5、 重组水蛭素重组水蛭素重组水蛭素重组水蛭素 ( (凝血酶直接抑制药凝血酶直接抑制药凝血酶直接抑制药凝血酶直接抑制药) )coumarins 香豆素类香豆素类香豆素类香豆素类( (维生素维生素维生素维生素KK拮抗药拮抗药拮抗药拮抗药) ) 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Anticoagulant drugsStage IStage IStage IIStage IIStage IIIStage
6、 IIIIIIIaIIa外源性外源性外源性外源性 （组织损伤）（组织损伤）（组织损伤）（组织损伤）内源性内源性内源性内源性 （血管壁损伤）（血管壁损伤）（血管壁损伤）（血管壁损伤）AT IIIMajor reactions of blood coagulationMajor reactions of blood coagulationThrombosis injures vital organsCoumarinsAnticoagulant drugsHeparin 肝素肝素Molecular weights:Molecular weights: 330 kDa; mean 15 kDa330
7、kDa; mean 15 kDa1. Pharmacological effects(1) Anticoagulation(1) Anticoagulation Increasing the activity of AT III(Increasing the activity of AT III(抗凝血酶抗凝血酶抗凝血酶抗凝血酶III):III): The AT III The AT III inhibiting the activity of the activated IIa, inhibiting the activity of the activated IIa, IXa, Xa, X
8、Ia , XIIa IXa, Xa, XIa , XIIa. . Activating HCII Activating HCII( (肝素辅助因子肝素辅助因子肝素辅助因子肝素辅助因子) ) Enhancing the release of t-PA Enhancing the release of t-PA（组织纤溶酶原激活剂组织纤溶酶原激活剂组织纤溶酶原激活剂组织纤溶酶原激活剂） and TFPIand TFPI( ( ( (组织因子通路抑制物组织因子通路抑制物组织因子通路抑制物组织因子通路抑制物) ) ) ) Rapid action, short duration (24 h)Rapid
9、 action, short duration (24 h) Effective both Effective both in vitroin vitro and and in vivoin vivo. . Heparin 肝素肝素more rapidExample of the effect of heparin(2) Anti atherosclerosis(2) Anti atherosclerosis blood lipids blood lipids protecting endothelial cells protecting endothelial cells inhibitin
10、g the hypertrophy of smooth muscle cells inhibiting the hypertrophy of smooth muscle cells(3) Other effects: (3) Other effects: Anti-inflammatory, anti-oxidant effects, Anti-inflammatory, anti-oxidant effects, etc. etc. Heparin 肝素肝素2. Clinical uses(1) Thrombosis:(1) Thrombosis: pulmonary emboli, dee
11、p vein pulmonary emboli, deep vein thrombosis, cardiac infraction, thrombosis, cardiac infraction, etcetc. .(2) Cardiac ischemia:(2) Cardiac ischemia: high-risk patientshigh-risk patients(3) Disseminated intravascular coagulation (3) Disseminated intravascular coagulation (弥散弥散性血管内凝血，性血管内凝血，DIC):DIC
12、): early use.early use.(4) Prevention of coagulation (4) Prevention of coagulation in vitroin vitro: : cardiovascular surgery, hemodialysis(cardiovascular surgery, hemodialysis(血透血透血透血透), cardiac ), cardiac canula(canula(心导管心导管心导管心导管), ), etc.etc.Heparin 肝素肝素3. Adverse effects(1) (1) Bleeding (at la
13、rger doses)Bleeding (at larger doses) Protamine is the inhibitor of heparin.Protamine is the inhibitor of heparin. 1 mg (protamine 1 mg (protamine 鱼精蛋白鱼精蛋白鱼精蛋白鱼精蛋白) 100 U (heparin) 100 U (heparin)(2) Thrombocytopenia(2) Thrombocytopenia ( (血小板减少血小板减少血小板减少血小板减少): ): warfarin should be warfarin should
14、 be substituted if the platelet count fallssubstituted if the platelet count falls(3) Others:(3) Others: allergy, local necrosis, long-term use: allergy, local necrosis, long-term use: alpecia (alpecia (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. 4. Contraindication Hepa
15、rin 肝素肝素Low molecular weight heparin MW 7 kDa Features: Stronger effects on Xa than on IIa Stronger effects on Xa than on IIa Stronger in inhibiting thrombosis/coagulation Stronger in inhibiting thrombosis/coagulation High bioavailability; Longer half life (200-300 min) High bioavailability; Longer
16、half life (200-300 min) Weak bleeding effects Weak bleeding effectsHeparin 肝素肝素Fondaparinux：合成肝素衍生物，引起血小板减少症的风险降低。合成肝素衍生物，引起血小板减少症的风险降低。heparin 肝素肝素肝素肝素 low molecular weight heparinlow molecular weight heparin 低分子量肝素低分子量肝素低分子量肝素低分子量肝素dermatan sulfate 硫酸皮肤素（硫酸皮肤素（硫酸皮肤素（硫酸皮肤素（activate HC II, activate
17、HC II, Heparin-cofactor IIHeparin-cofactor II）lepirudin 重组水蛭素（重组水蛭素（重组水蛭素（重组水蛭素（thrombin inhibitorthrombin inhibitor）coumarins 香豆素类香豆素类香豆素类香豆素类 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Anticoagulant drugsheparin 肝素肝素肝素肝素( (
18、凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药) ) low molecular weight heparin low molecular weight heparin 低分子量肝素低分子量肝素低分子量肝素低分子量肝素dermatan sulfate 硫酸皮肤素硫酸皮肤素硫酸皮肤素硫酸皮肤素( (凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药凝血酶间接抑制药) )lepirudin 重组水蛭素重组水蛭素重组水蛭素重组水蛭素 ( (凝血酶直接抑制药凝血酶直接抑制药凝血酶直接抑制药凝血酶直接抑制药) )coumarins 香豆素类香豆素类香豆素类香豆素类( (维生素维生素维生素
19、维生素KK拮抗药拮抗药拮抗药拮抗药) ) 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Anticoagulant drugsAnticoagulant drugsWarfarin 华法林华法林1. Pharmacological effects(1) Mechanisms of action:(1) Mechanisms of action: antagonizing vitamine K,antagon
20、izing vitamine K, inhibiting of carboxylation of the inhibiting of carboxylation of the glutamic acid residues of the glutamic acid residues of the factorsfactors II, VII, IX, XII, VII, IX, X , and , and reducing the activated II, VII, IX, Xreducing the activated II, VII, IX, XWarfarin 华法林华法林Sites o
21、f warfarin actionwarfarin actionFactor II, Factor II, VII, IX, XVII, IX, XActivated factor Activated factor II, VII, IX, XII, VII, IX, X氢醌型氢醌型氢醌型氢醌型Vit KVit K环氧型环氧型环氧型环氧型Vit KVit KCOO-1. Pharmacological effects(1) Mechanisms of action:(1) Mechanisms of action: antagonizing vitamine K,antagonizing vi
22、tamine K, inhibiting of carboxylation of the inhibiting of carboxylation of the glutamic acid residues of the glutamic acid residues of the factorsfactors II, VII, IX, XII, VII, IX, X , and , and reducing the activated II, VII, IX, Xreducing the activated II, VII, IX, X(2) Properties:(2) Properties:
23、 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 vivoWarfarin 华法林华法林2. Clinical uses Anticoagulation Anticoagulation in vivoin vivo 3. Adverse
24、effects(1) (1) Bleeding:Bleeding: v vitamine K may antagonize the reaction; interreaction with other agents(2) Necrosis of skin and parenchyma(2) Necrosis of skin and parenchyma ( ( ( (软组织软组织软组织软组织) ) ) )(3) Liver injury(3) Liver injury(4) (4) Serious birth defectSerious birth defect Warfarin 华法林华法林
25、4. Drug interactionsPlasma protein binding replacementHepatic metabolism: inhibitioninhibition potentiationpotentiationAntiplatelet drugsticlopidineAntiplatelet drugs Inhibition of platelet metabolismsInhibition of platelet metabolismsInhibitors of cyclic nucleotide phosphodiesterase:Inhibitors of c
26、yclic nucleotide phosphodiesterase: dipyridamole dipyridamole 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: aspirinaspirin 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 synthetase inhibitors:synthetase inhibitors: ridogrel ridogre
27、l 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 adenosine cyclase:Activators of adenosine cyclase: epoprostenol epoprostenol 依前列醇依前列醇依前列醇依前列醇( ( ( (PGIPGI2 2) ) ) ) Inhibition of ADP-induced platelet activation Inhibition of ADP-induced platelet activation ticlopidineticlop
28、idine 噻氯匹定噻氯匹定噻氯匹定噻氯匹定 Gp IIb/IIIa receptor antagonistsGp IIb/IIIa receptor antagonists abciximab abciximab 阿昔单抗阿昔单抗阿昔单抗阿昔单抗 (c7E3Fab(c7E3Fab) ) ) )Major reactions of blood coagulationMajor reactions of blood coagulationAntiplatelet drugsAspirin 阿司匹林阿司匹林Acetylsalicylic acid 乙酰水杨酸乙酰水杨酸Aspirin Aspirin
29、 阿司匹林阿司匹林阿司匹林阿司匹林 small doses (40small doses (4080 mg/d):80 mg/d): inhibiting TXA inhibiting TXA2 2 synthesis, preventing thrombosis.synthesis, preventing thrombosis. used to treat ischemic heart disease, reduce the used to treat ischemic heart disease, reduce the mortality of myocardiac infarction,
30、 and prevent mortality of myocardiac infarction, and prevent cerebral thrombosis.cerebral thrombosis. larger doses:larger doses: inhibiting PGI inhibiting PGI2 2 synthesis, synthesis, promoting thrombosis.promoting thrombosis. PGIPGI2 2: : vasodilation and platelet depolymerization (vasodilation and
31、 platelet depolymerization (血小板血小板血小板血小板 解聚解聚解聚解聚). ).Aspirin 阿司匹林阿司匹林The mechanism of The mechanism of aspirin:aspirin:Target enzymes Target enzymes acetylatedacetylatedThrombolytic drugs (纤溶药纤溶药)Thrombolytic drugsStreptokinase（SK）(T(T1/21/2 = 23 min; ) = 23 min; )Urokinase（UK） (T(T1/21/2 = 15 min;
32、 ) = 15 min; )Tissue plasminogen activator ( t-PA，组组组组织织织织纤溶酶原激活剂纤溶酶原激活剂纤溶酶原激活剂纤溶酶原激活剂 ) i.v. i.v. T T1/21/2 = 38 min = 38 minAction of thrombolytic drugsAction of thrombolytic drugst-PAt-PA(+)(+)Thrombolytic drugsCommon adverse effects bleeding antidotes: antifibrinolytic drugsBleedingBleedingThrom
33、bolysisThrombolysisDrugs for treatment of bleeding Vitamine KCarboxylation of the glutamic acid Carboxylation of the glutamic acid residues of factors II, IIV, IX, X, protein C.residues of factors II, IIV, IX, X, protein C.Preventing Preventing bleeding bleeding with with vitamine vitamine K K defic
34、iency or warfarin-induced bleedingdeficiency or warfarin-induced bleedingVitamin KVitamin KVitamin KVitamin KDrugs for treatment of bleedingThrombin-like agents thrombin prothrombin complex used for various bleedingDrugs for treatment of bleedingDrugs preventing activation of fibrinolysis Drugs prev
35、enting activation of fibrinolysis (antifibrinolytics)(antifibrinolytics) aprotinin aprotinin ( (抑肽酶）抑肽酶）抑肽酶）抑肽酶） tranexamic acid tranexamic acid (AMCHA, (AMCHA, 氨甲环酸氨甲环酸氨甲环酸氨甲环酸) ) p-aminomethylbenzoic acidep-aminomethylbenzoic acide (PAMBA, (PAMBA, 氨甲苯酸）氨甲苯酸）氨甲苯酸）氨甲苯酸） used forused for preventing t
36、he activation fibrinolysis preventing the activation fibrinolysis and resultant bleedingand resultant bleeding Inhibiting plasminogen activationInhibiting plasminogen activationDrugs for treatment of anemiaAnemia may result from the excess destruction of Anemia may result from the excess destruction
37、 of erythrocytes, and nutritional deficiencies (iron, erythrocytes, and nutritional deficiencies (iron, minerals, cobaltminerals, cobalt钴钴钴钴, vitamin B, vitamin B1212, folic acid, ascorbic , folic acid, ascorbic acid, riboflavinacid, riboflavin核黄素核黄素核黄素核黄素, copper, zinc, etc., copper, zinc, etc. ) )
38、Iron: anemia due to loss of erythrocytes and iron deficiency anemia due to loss of erythrocytes and iron deficiency Folic acid and vitamin B12: megaloblastic anemia megaloblastic anemia （巨红细胞性贫血巨红细胞性贫血巨红细胞性贫血巨红细胞性贫血 ）Erythropoietin (EPO) promoting red cell proliferation and differentiation promoting
39、 red cell proliferation and differentiationIron ferrous sulfateferrous sulfate 硫酸亚铁硫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 tractInteraction with other drugs or diet in the GI tract2. Used for anemia due to l
40、oss of erythrocytes and 2. Used for anemia due to loss of erythrocytes and iron deficiency iron deficiency 3. Adverse effects:3. Adverse effects: GI reactions, hypersensitivity GI reactions, hypersensitivityAcute intoxication:Acute intoxication: severe CVS and GI reactions severe CVS and GI reaction
41、s- treated with deferoxamine- treated with deferoxamine（去铁敏）（去铁敏）（去铁敏）（去铁敏）Vit B12Folic acid1. 1. Pharmacological effectsPharmacological effects Regulating nucleic acid, amino acid metabolism Regulating nucleic acid, amino acid metabolism2. 2. Clinical usesClinical uses Megaloblastic anemia; MTX( Me
42、galoblastic anemia; MTX(甲氨蝶呤甲氨蝶呤甲氨蝶呤甲氨蝶呤)-induced anemia)-induced anemia3. 3. Adverse effectsAdverse effects Rarely reported Rarely reportedVitamin B12Co-factor of folic acidCo-factor of folic acidImportant in maintaining neuron myelinationImportant in maintaining neuron myelinationEffect of EPO on
43、red cell proliferation and differentiationEffect of EPO on red cell proliferation and differentiationErythropoietin (EPO) rhEPOrhEPO1. 1. Pharmacological effectsPharmacological effects Promoting red cell proliferation and differetiation Promoting red cell proliferation and differetiation2. 2. Clinic
44、al usesClinical uses Anemia due to Anemia due to chronic renal failure with chronic renal failure with hemodialysis,hemodialysis, radiotherapy, chemotherapy, AIDS radiotherapy, chemotherapy, AIDS3. 3. Adverse effectsAdverse effects Hypertension, epilepsy, thrombosis, Hypertension, epilepsy, thrombos
45、is, etc.etc.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 (chemotherapy
46、or (chemotherapy or radiotherapy), autologous bone marrow radiotherapy), autologous bone marrow transplantation, myelodysplasia(transplantation, myelodysplasia(脊髓发育不良脊髓发育不良脊髓发育不良脊髓发育不良 ), ), aplastic anemia(aplastic anemia(再生障碍性贫血再生障碍性贫血再生障碍性贫血再生障碍性贫血 ), AIDS-associated ), AIDS-associated neutropeni
47、aneutropeniaAllergy, GI and hepatic injuries, local irritation, Allergy, GI and hepatic injuries, local irritation, etc.etc.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）Increasing blood volume (MW 70, 40, 10kD)Increasing blood volume (MW 70, 40, 10kD)Inhibiting platelet
48、 aggregation (MW 40,10kD)Inhibiting platelet aggregation (MW 40,10kD)Osmotic diuretic effects (MW 40, 10kD)Osmotic diuretic effects (MW 40, 10kD)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 volume (MW 70, 40, 10kD
49、)Increasing blood volume (MW 70, 40, 10kD)Inhibiting platelet aggregation (MW 40,10kD)Inhibiting platelet aggregation (MW 40,10kD)Osmotic diuretic effects (MW 40, 10kD)Osmotic diuretic effects (MW 40, 10kD)hydroxyethyl starch 羟乙基淀粉羟乙基淀粉Enzymatic degradation and excretion of hydroxyethyl starchEnzymatic degradation and excretion of hydroxyethyl starchThanks!
