《药理学》英文课件 Drugs Affecting Blood

DrugsAffectingBloodthreeimportantdysfunctionsofbloodthrombosis,bleeding,andanemia.Thrombosis--theformationofanunwantedclotwithinthebloodvesselsorheart.BleedingdisordersinvolvingfailureofhemostasisarelesscommonthanthromboembolicdiseasesandincludehemophiliaandvitaminKdeficiency.Anemiascausedbynutritionaldeficienciescanbetreatedwitheitherdietaryorpharmaceuticalsupplementation.NORMALRESPONSETOVASCULARTRAUMAPhysicaltraumatothevascularsystem,suchasapunctureorcut,initiatesacomplexseriesofinteractionsbetweenplatelets,endothelialcells,andthecoagulationcascade.Thisresultsintheformationofaplatelet-fibrinplug.A.FormationofaclotClotformationrequiresplateletactivationandaggregation,followedbyformationofthrombin.RoleofplateletsPlateletsrespondtovasculartraumaby"activation"processes,whichinvolvethreesteps:adhesiontothesiteofinjury,releaseofintracellulargranules,andaggregationoftheplatelets.RoleoffibrinLocalstimulationofthecoagulationcascadebyfactorsreleasedfromtheinjuredtissueandplateletsresultsintheformationofthrombin(FactorII).Inturn,thrombin,aserineprotease,catalyzestheconversionoffibrinogentofibrin,whichisincorporatedintotheplug.ThrombusversusembolusAclotthatadherestoavesselwalliscalledathrombus,whereasanintravascularclotthatfloatswithinthebloodistermedanembolus.Thus,adetachedthrombusbecomesanembolus.Fibrinolysis

Duringplateletplugformation,thefibrinolyticpathwayislocallyactivated.Plasminogenisenzymaticallyprocessedtoplasmin(fibrinolysin)byplasminogenactivatorspresentinthetissue.Plasmininterferesinclotpropagationanddissolvesthefibrinnetworkaswoundsheal.ANTICOAGULANTSHeparinisaninjectable,rapidly-actinganticoagulantthatisoftenusedacutelytointerferewiththeformationofthrombi.MechanismofactionHeparinactsindirectlybybindingtoantithrombinIlltocausearapidanticoagulanteffect.MaximalanticoagulationoccurswithinminutesafterintravenousheparininjectionTherapeuticusesHeparinlimitstheexpansionofthrombibypreventingfibrinformation.Heparinisthemajorantithromboticdrugforthetreatmentofdeepveinthrombosisandpulmonaryembolism.Itdecreasestheincidenceofrecurrentthromboembolicepisodes.Clinically,heparinisusedprophylacticallytopre-ventpostoperativePharmacokineticsAbsorption:Heparinmustbegivenparenterallyeitherinadeepsubcutaneoussiteorintravenously,becausethedrugdoesnotreadilycrossmembranes.Fate:Intheblood,heparinbindstomanyproteinsthatneutralizeitsactivityandcancauseresistancetothedrug.Althoughgenerallyrestrictedtothecirculation,heparinistakenupbythereticuloendothelialsystemandundergoesdepolymerizationtoinactiveproducts.Adverseeffects:Bleedingcomplications:Hypersensitivityreactions:Thrombocytopenia:DRUGSUSEDTOTREATBLEEDINGBleedingproblemsmayhavetheirorigininnaturallyoccurringpathologicconditionssuchashemophilia,orasaresultoffibrinolyticstatesthatmayariseaftergastrointestinalsurgeryorprostatectomy.VitaminKThatvitaminK1administrationcanstembleedingproblemsduetotheoralanticoagulants,TheresponsetovitaminKisslow,requiringabout24hours;thusifimmediatehemostasisisrequired,freshfrozenplasmashouldbeinfused.AGENTSUSEDTOTREATANEMIAAnemiaisdefinedasabelow-normalplasmahemoglobinconcentrationresultingfromadecreasednumberofcirculatingredbloodcellsoranabnormallylowtotalhemoglobincontentperunitofbloodvolume.Anemiacanbecausedbychronicbloodloss,bonemarrowabnormalities,increasedhemolysis,infections,malignancy,endocrinedeficiencies,andanumberofotherdiseasestates.IronFolicacidCyanocobalamin(vitaminB12)vitaminB12DeficienciesofvitaminB12canresultfromeitherlowdietarylevelsor,morecommonly,frompoorabsorptionofthevitaminduetothefailureofgastricparietalcellstoproduceintrinsicfactor(asinperniciousanemia)ortoalossofactivityofthereceptorneededforintestinaluptakeofthevitamin.vitaminB12NonspecificmalabsorptionsyndromesorgastricresectioncanalsocausevitaminB12deficiency.Thevitaminmaybeadmin