血液系統(tǒng)藥物專家講座

Drugsactingonthebloodandblood-formingorgans

Yun-BiLu,PhD

盧韻碧

Dept.ofPharmacology,

SchoolofMedicine,ZhejiangUniversity

yunbi@血液系統(tǒng)藥物第1頁Drugsaffectingthebloodandblood-formingorgansAnticoagulantdrugs(抗凝藥)Antiplateletdrugs(抗血小板藥)Thrombolyticdrugs(纖溶藥)DrugsfortreatmentofbleedingDrugsfortreatmentofanemia

HematopoieticgrowthagentsDrugsfortreatmentofhypovolemiaCoagulation-bleedingBloodcellgrowthBloodvolume血液系統(tǒng)藥物第2頁heparin

肝素lowmolecularweightheparin

低分子量肝素dermatansulfate硫酸皮膚素lepirudin重組水蛭素coumarins

香豆素類

warfarin華法林dicoumarol雙香豆素acenocoumarol醋硝香豆素Anticoagulantdrugs血液系統(tǒng)藥物第3頁Thrombosisinjuresvitalorgans血液系統(tǒng)藥物第4頁血液系統(tǒng)藥物第5頁StageIStageIIStageIIIIIIIaIIa外源性（組織損傷）內(nèi)源性（血管壁損傷）血液系統(tǒng)藥物第6頁Majorreactionsofbloodcoagulation血液系統(tǒng)藥物第7頁Coumarins血液系統(tǒng)藥物第8頁AnticoagulantdrugsHeparin

肝素Molecularweights:

3~30kDa;mean15kDa血液系統(tǒng)藥物第9頁1.Pharmacologicaleffects(1)Anticoagulation

IncreasingtheactivityofATIII:

TheATIIIinhibitingtheactivityoftheactivatedIIa,IXa,Xa,XIa,XIIa.

Rapidaction,shortduration(2~4h)

Effectivebothinvitroandinvivo.Heparin

肝素血液系統(tǒng)藥物第10頁morerapidExampleoftheeffectofheparin血液系統(tǒng)藥物第11頁(2)Anti–atherosclerosisbloodlipidsprotectingendothelialcellsinhibitingthehypertrophyofsmoothmusclecells(3)Othereffects:Anti-inflammatory,anti-oxidanteffects,etc.Heparin

肝素血液系統(tǒng)藥物第12頁2.Clinicaluses(1)Thrombosis:

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

high-riskpatients(3)Disseminatedintravascularcoagulation(DIC):

earlyuse.(4)Preventionofcoagulationinvitro:

cardiovascularsurgery,hemodialysis,cardiaccanula,etc.Heparin

肝素血液系統(tǒng)藥物第13頁3.Adverseeffects(1)Bleeding(atlargerdoses)

Protamineistheinhibitorofheparin.

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

(血小板降低):

warfarinshouldbesubstitutediftheplateletcountfalls(3)Others:

allergy,localnecrosis,long-termuse:alpecia(脫發(fā)),osteoporosis(骨質(zhì)疏松),etc.

Heparin

肝素血液系統(tǒng)藥物第14頁Lowmolecularweightheparin

MW<7kDa

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

肝素血液系統(tǒng)藥物第15頁Fondaparinux：合成肝素衍生物血液系統(tǒng)藥物第16頁heparin

肝素lowmolecularweightheparin

低分子量肝素dermatansulfate硫酸皮膚素（activateHCII,Heparin-cofactorII）lepirudin重組水蛭素（thrombininhibitor）coumarins

香豆素類

warfarin華法林dicoumarol雙香豆素acenocoumarol醋硝香豆素Anticoagulantdrugs血液系統(tǒng)藥物第17頁AnticoagulantdrugsWarfarin

華法林血液系統(tǒng)藥物第18頁1.Pharmacologicaleffects(1)Mechanismsofaction:

antagonizingvitamineK,inhibitingofcarboxylationoftheglutamicacidresiduesofthefactors

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

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

effectiveonlyinvivoWarfarin

華法林血液系統(tǒng)藥物第19頁Sitesofwarfarinaction血液系統(tǒng)藥物第20頁warfarinactionFactorII,VII,IX,XActivatedfactorII,VII,IX,X氫醌型VitK環(huán)氧型VitKCOO-血液系統(tǒng)藥物第21頁1.Pharmacologicaleffects(1)Mechanismsofaction:

antagonizingvitamineK,inhibitingofcarboxylationoftheglutamicacidresiduesofthefactors

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

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

effectiveonlyinvivoWarfarin

華法林血液系統(tǒng)藥物第22頁2.Clinicaluses

Anticoagulationinvivo

3.Adverseeffects(1)Bleeding:

vitamineKmayantagonizethereaction;interreactionwithotheragents(2)Necrosisofskinandparenchyma

(軟組織)(3)Liverinjury(4)Seriousbirthdefect

Warfarin

華法林血液系統(tǒng)藥物第23頁4.DruginteractionsPlasmaproteinbindingreplacementHepaticmetabolism:

inhibition

potentiation血液系統(tǒng)藥物第24頁AntiplateletdrugsInhibitionofplateletmetabolismsInhibitorsofcyclicnucleotidephosphodiesterase:

dipyridamole

雙嘧達莫(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阿昔單抗(c7E3Fab)血液系統(tǒng)藥物第25頁血液系統(tǒng)藥物第26頁血液系統(tǒng)藥物第27頁AntiplateletdrugsAspirin阿司匹林Acetylsalicylicacid乙酰水楊酸Aspirin阿司匹林血液系統(tǒng)藥物第28頁血液系統(tǒng)藥物第29頁

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

largerdoses:inhibitingPGI2synthesis,promotingthrombosis.

PGI2:

vasodilationandplateletdepolymerization(血小板解聚).Aspirin阿司匹林血液系統(tǒng)藥物第30頁Themechanismofaspirin:Targetenzymesacetylated血液系統(tǒng)藥物第31頁Thrombolyticdrugs血液系統(tǒng)藥物第32頁ThrombolyticdrugsStreptokinase（SK）(T1/2=23min;)Urokinase（UK）(T1/2=15min;)Tissueplasminogenactivator(t-PA，組織纖溶酶原激活劑)i.v.T1/2=3~8min血液系統(tǒng)藥物第33頁Actionofthrombolyticdrugst-PA(+)血液系統(tǒng)藥物第34頁ThrombolyticdrugsCommonadverseeffectsbleeding

antidotes:

antifibrinolyticdrugs血液系統(tǒng)藥物第35頁BleedingThrombolysis血液系統(tǒng)藥物第36頁Drugsfortreatmentofbleeding

VitamineKCarboxylationoftheglutamicacidresiduesoffactorsII,IIV,IX,X,proteinC.PreventingbleedingwithvitamineKdeficiencyorwarfarin-inducedbleeding血液系統(tǒng)藥物第37頁VitaminKVitaminK血液系統(tǒng)藥物第38頁DrugsfortreatmentofbleedingThrombin-likeagents

thrombinprothrombincomplex

usedforvariousbleeding血液系統(tǒng)藥物第39頁DrugsfortreatmentofbleedingDrugspreventingactivationofantifibrinolyticsaprotinin(抑肽酶）tranexamicacid(AMCHA,氨甲環(huán)酸)

p-aminomethylbenzoicacide

(PAMBA,氨甲苯酸）

usedfor

preventingtheactivationfibrinolysisandresultantbleeding

血液系統(tǒng)藥物第40頁Inhibitingplasminogenactivation血液系統(tǒng)藥物第41頁DrugsfortreatmentofanemiaAnemiamayresultfromtheexcessdestructionoferythrocytes,andnutritionaldeficiencies(iron,minerals,cobalt,vitaminB12,folicacid,ascorbicacid,riboflavin,copper,zinc,etc.

)Iron:anemiaduetolossoferythrocytesandirondeficiency

FolicacidandvitaminB12:megaloblasticanemia

Erythropoietin(EPO)promotingredcellproliferationanddifferentiation血液系統(tǒng)藥物第42頁血液系統(tǒng)藥物第43頁Iron

ferroussulfate

硫酸亞鐵ferricammoniumcitrate

枸櫞酸鐵銨1.

InteractionwithotherdrugsordietintheGItract2.Usedforanemiaduetolossoferythrocytesandirondeficiency3.Adverseeffects:GIreactions,hypersensitivityAcuteintoxication:severeCVSandGIreactions-treatedwithdeferoxamine（去鐵敏）血液系統(tǒng)藥物第44頁血液系統(tǒng)藥物第45頁Folicacid1.PharmacologicaleffectsRegulatingnucleicacid,aminoacidmetabolism2.ClinicalusesMegaloblasticanemia;MTX-inducedanemia3.AdverseeffectsRarelyreportedVitaminB12Co-factoroffolicacidImportantinmaintainingneuronmyelination血液系統(tǒng)藥物第46頁EffectofEPOonredcellproliferationanddifferentiation血液系統(tǒng)藥物第47頁Erythropoietin(EPO)

rhEPO1.PharmacologicaleffectsPromotingredcellproliferationanddifferetiation2.ClinicalusesAnemiaduetochronicrenalfa