血液系统药物Drugsaffectingthebloodandblood-formingorgansheparin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ThrombosisinjuresvitalorgansStageIMajorreactionsofbloodcoagulationCoumarinsAnticoagulantdrugs1.Pharmacologicaleffects(1)AnticoagulationIncreasingtheactivityofATIII:TheATIIIinhibitingtheactivityoftheactivatedIIa,IXa,Xa,XIa,XIIa.Rapidaction,shortduration(2~4h)Effectivebothinvitroandinvivo.morerapid(2)Anti–atherosclerosisbloodlipidsprotectingendothelialcellsinhibitingthehypertrophyofsmoothmusclecells(3)Othereffects:Anti-inflammatory,anti-oxidanteffects,etc.2.Clinicaluses(1)Thrombosis:pulmonaryemboli,deepveinthrombosis,cardiacinfraction,etc.(2)Cardiacischemia:high-riskpatients(3)Disseminatedintravascularcoagulation(DIC):earlyuse.(4)Preventionofcoagulationinvitro:cardiovascularsurgery,hemodialysis,cardiaccanula,etc.3.Adverseeffects(1)Bleeding(atlargerdoses)Protamineistheinhibitorofheparin.1mg(protamine鱼精蛋白)=100U(heparin)(2)Thrombocytopenia(血小板减少):warfarinshouldbesubstitutediftheplateletcountfalls(3)Others:allergy,localnecrosis,long-termuse:alpecia(脱发),osteoporosis(骨质疏松),etc.LowmolecularweightheparinMW<7kDaFeatures:StrongereffectsonXathanonIIaStrongerininhibitingthrombosis/coagulationHighbioavailability;Longerhalf–life(200-300min)WeakbleedingeffectsFondaparinux：合成肝素衍生物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Anticoagulantdrugs1.Pharmacologicaleffects(1)Mechanismsofaction:antagonizingvitamineK,inhibitingofcarboxylationoftheglutamicacidresiduesofthefactorsII,VII,IX,X,andreducingtheactivatedII,VII,IX,X(2)Properties:slowlyandlongerduration:effectappearsafterp.o.1~3days,andlastsfor4dayseffectiveonlyinvivoSitesofwarfarinactionwarfarinaction1.Pharmacologicaleffects(1)Mechanismsofaction:antagonizingvit