血液系统药物专家讲座

Drugsactingonthebloodandblood-formingorgans

Yun-BiLu,PhD

卢韵碧

Dept.ofPharmacology,

SchoolofMedicine,ZhejiangUniversity

yunbi@血液系统药物第1页Drugsaffectingthebloodandblood-formingorgansAnticoagulantdrugs(抗凝药)Antiplateletdrugs(抗血小板药)Thrombolyticdrugs(纤溶药)DrugsfortreatmentofbleedingDrugsfortreatmentofanemia

HematopoieticgrowthagentsDrugsfortreatmentofhypovolemiaCoagulation-bleedingBloodcellgrowthBloodvolume血液系统药物第2页heparin

肝素lowmolecularweightheparin

低分子量肝素dermatansulfate硫酸皮肤素lepirudin重组水蛭素coumarins

香豆素类

warfarin华法林dicoumarol双香豆素acenocoumarol醋硝香豆素Anticoagulantdrugs血液系统药物第3页Thrombosisinjuresvitalorgans血液系统药物第4页血液系统药物第5页StageIStageIIStageIIIIIIIaIIa外源性（组织损伤）内源性（血管壁损伤）血液系统药物第6页Majorreactionsofbloodcoagulation血液系统药物第7页Coumarins血液系统药物第8页AnticoagulantdrugsHeparin

肝素Molecularweights:

3~30kDa;mean15kDa血液系统药物第9页1.Pharmacologicaleffects(1)Anticoagulation

IncreasingtheactivityofATIII:

TheATIIIinhibitingtheactivityoftheactivatedIIa,IXa,Xa,XIa,XIIa.

Rapidaction,shortduration(2~4h)

Effectivebothinvitroandinvivo.Heparin

肝素血液系统药物第10页morerapidExampleoftheeffectofheparin血液系统药物第11页(2)Anti–atherosclerosisbloodlipidsprotectingendothelialcellsinhibitingthehypertrophyofsmoothmusclecells(3)Othereffects:Anti-inflammatory,anti-oxidanteffects,etc.Heparin

肝素血液系统药物第12页2.Clinicaluses(1)Thrombosis:

pulmonaryemboli,deepveinthrombosis,cardiacinfraction,etc.(2)Cardiacischemia:

high-riskpatients(3)Disseminatedintravascularcoagulation(DIC):

earlyuse.(4)Preventionofcoagulationinvitro:

cardiovascularsurgery,hemodialysis,cardiaccanula,etc.Heparin

肝素血液系统药物第13页3.Adverseeffects(1)Bleeding(atlargerdoses)

Protamineistheinhibitorofheparin.

1mg(protamine鱼精蛋白)=100U(heparin)(2)Thrombocytopenia

(血小板降低):

warfarinshouldbesubstitutediftheplateletcountfalls(3)Others:

allergy,localnecrosis,long-termuse:alpecia(脱发),osteoporosis(骨质疏松),etc.

Heparin

肝素血液系统药物第14页Lowmolecularweightheparin

MW<7kDa

Features:StrongereffectsonXathanonIIaStrongerininhibitingthrombosis/coagulationHighbioavailability;Longerhalf–life(200-300min)WeakbleedingeffectsHeparin

肝素血液系统药物第15页Fondaparinux：合成肝素衍生物血液系统药物第16页heparin

肝素lowmolecularweightheparin

低分子量肝素dermatansulfate硫酸皮肤素（activateHCII,Heparin-cofactorII）lepirudin重组水蛭素（thrombininhibitor）coumarins

香豆素类

warfarin华法林dicoumarol双香豆素acenocoumarol醋硝香豆素Anticoagulantdrugs血液系统药物第17页AnticoagulantdrugsWarfarin

华法林血液系统药物第18页1.Pharmacologicaleffects(1)Mechanismsofaction:

antagonizingvitamineK,inhibitingofcarboxylationoftheglutamicacidresiduesofthefactors

II,VII,IX,X,andreducingtheactivatedII,VII,IX,X(2)Properties:

slowlyandlongerduration:effectappearsafterp.o.1~3days,andlastsfor4days

effectiveonlyinvivoWarfarin

华法林血液系统药物第19页Sitesofwarfarinaction血液系统药物第20页warfarinactionFactorII,VII,IX,XActivatedfactorII,VII,IX,X氢醌型VitK环氧型VitKCOO-血液系统药物第21页1.Pharmacologicaleffects(1)Mechanismsofaction:

antagonizingvitamineK,inhibitingofcarboxylationoftheglutamicacidresiduesofthefactors

II,VII,IX,X,andreducingtheactivatedII,VII,IX,X(2)Properties:

slowlyandlongerduration:effectappearsafterp.o.1~3days,andlastsfor4days

effectiveonlyinvivoWarfarin

华法林血液系统药物第22页2.Clinicaluses

Anticoagulationinvivo

3.Adverseeffects(1)Bleeding:

vitamineKmayantagonizethereaction;interreactionwithotheragents(2)Necrosisofskinandparenchyma

(软组织)(3)Liverinjury(4)Seriousbirthdefect

Warfarin

华法林血液系统药物第23页4.DruginteractionsPlasmaproteinbindingreplacementHepaticmetabolism:

inhibition

potentiation血液系统药物第24页AntiplateletdrugsInhibitionofplateletmetabolismsInhibitorsofcyclicnucleotidephosphodiesterase:

dipyridamole

双嘧达莫(潘生丁)

COXinhibitors:

aspirin

阿司匹林TXA2receptorantagonistsandTXA2synthetaseinhibitors:

ridogrel利多格雷,picotamide

匹可托安

Activatorsofadenosinecyclase:

epoprostenol依前列醇InhibitionofADP-inducedplateletactivation

ticlopidine

噻氯匹定GpIIb/IIIareceptorantagonistsabciximab阿昔单抗(c7E3Fab)血液系统药物第25页血液系统药物第26页血液系统药物第27页AntiplateletdrugsAspirin阿司匹林Acetylsalicylicacid乙酰水杨酸Aspirin阿司匹林血液系统药物第28页血液系统药物第29页

smalldoses(40～80mg/d):inhibitingTXA2synthesis,preventingthrombosis.usedtotreatischemicheartdisease,reducethemortalityofmyocardiacinfarction,andpreventcerebralthrombosis.

largerdoses:inhibitingPGI2synthesis,promotingthrombosis.

PGI2:

vasodilationandplateletdepolymerization(血小板解聚).Aspirin阿司匹林血液系统药物第30页Themechanismofaspirin:Targetenzymesacetylated血液系统药物第31页Thrombolyticdrugs血液系统药物第32页ThrombolyticdrugsStreptokinase（SK）(T1/2=23min;)Urokinase（UK）(T1/2=15min;)Tissueplasminogenactivator(t-PA，组织纤溶酶原激活剂)i.v.T1/2=3~8min血液系统药物第33页Actionofthrombolyticdrugst-PA(+)血液系统药物第34页ThrombolyticdrugsCommonadverseeffectsbleeding

antidotes:

antifibrinolyticdrugs血液系统药物第35页BleedingThrombolysis血液系统药物第36页Drugsfortreatmentofbleeding

VitamineKCarboxylationoftheglutamicacidresiduesoffactorsII,IIV,IX,X,proteinC.PreventingbleedingwithvitamineKdeficiencyorwarfarin-inducedbleeding血液系统药物第37页VitaminKVitaminK血液系统药物第38页DrugsfortreatmentofbleedingThrombin-likeagents

thrombinprothrombincomplex

usedforvariousbleeding血液系统药物第39页DrugsfortreatmentofbleedingDrugspreventingactivationofantifibrinolyticsaprotinin(抑肽酶）tranexamicacid(AMCHA,氨甲环酸)

p-aminomethylbenzoicacide

(PAMBA,氨甲苯酸）

usedfor

preventingtheactivationfibrinolysisandresultantbleeding

血液系统药物第40页Inhibitingplasminogenactivation血液系统药物第41页DrugsfortreatmentofanemiaAnemiamayresultfromtheexcessdestructionoferythrocytes,andnutritionaldeficiencies(iron,minerals,cobalt,vitaminB12,folicacid,ascorbicacid,riboflavin,copper,zinc,etc.

)Iron:anemiaduetolossoferythrocytesandirondeficiency

FolicacidandvitaminB12:megaloblasticanemia

Erythropoietin(EPO)promotingredcellproliferationanddifferentiation血液系统药物第42页血液系统药物第43页Iron

ferroussulfate

硫酸亚铁ferricammoniumcitrate

枸橼酸铁铵1.

InteractionwithotherdrugsordietintheGItract2.Usedforanemiaduetolossoferythrocytesandirondeficiency3.Adverseeffects:GIreactions,hypersensitivityAcuteintoxication:severeCVSandGIreactions-treatedwithdeferoxamine（去铁敏）血液系统药物第44页血液系统药物第45页Folicacid1.PharmacologicaleffectsRegulatingnucleicacid,aminoacidmetabolism2.ClinicalusesMegaloblasticanemia;MTX-inducedanemia3.AdverseeffectsRarelyreportedVitaminB12Co-factoroffolicacidImportantinmaintainingneuronmyelination血液系统药物第46页EffectofEPOonredcellproliferationanddifferentiation血液系统药物第47页Erythropoietin(EPO)

rhEPO1.PharmacologicaleffectsPromotingredcellproliferationanddifferetiation2.ClinicalusesAnemiaduetochronicrenalfa