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    ANTI TROMBANTI TROMBTI COSTI COSANTI COAGULANTES,ANTI COAGULANTES,

    ANTI PLAQUETANTI PLAQUET RI OS ERI OS E

    FI BRI NOLFI BRI NOLTI COSTI COSProf a. Christianne Brtas Vieira ScaramelloProf a. Christianne Brtas Vieira Scaramello

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    ANTI COAGULANTES,ANTI COAGULANTES,

    ANTI PLAQUETANTI PLAQUET RI OS & FI BRI NOLRI OS & FI BRI NOLTI COSTI COSFrmacos que impedem a f ormao de

    trombos

    Anticoagulantes:retardam ou impedem a coagulao

    sangunea

    Antiplaquetrios:inibem a agregao plaquetria

    Fibrinolticos:dissolvem trombos patolgicos e depsitos de

    fibrina

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    PrevenPreveno da perdao da perdade sanguede sangue

    HemostaseHemostase

    Leso vascular

    Vasoconstrio Agregaoplaquetria

    Coagulaosangunea

    Tampo hemosttico

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    Coagulao FibrinFibrinliseliseAgregaoplaquetaria

    HemorragiaHemorragia

    TrombogneseTrombognese

    Formao indesejada de um tampo hemosttico

    (condio patolgica resultante de hipercoagulao)

    TromboseArtria

    Necrose I squmia

    Tr omboseVeia

    Tecidos drenados

    Edema e inf lamaoVeia profundaembolia pulmonar

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    Coagulao sangunea

    Via ExtrVia Extrnsecanseca

    Ca++

    Trauma tecidualTrauma tecidual

    Fator tecidualFator tecidual

    XX XaXaVIIVII VIIaVIIa** Ca

    ++

    TrombinaTrombinaCa++

    ProtrombinaProtrombina

    Fosfolipidos plaquetFosfolipidos plaquetriosrios Ca++VaVa VV

    Via IntrVia Intrnsecanseca

    FosfolipFosfolipdosdosplaquetplaquetriosrios

    Ca++

    SuperfSuperfciecieexternaexterna

    PrPr--calicrecalicrenana

    calicrecalicrenana

    XIIXII XIIaXIIa

    XIXI XIaXIa

    IXIX IXaIXa**

    VIVI

    IIII

    VIIIaVIIIa

    XX XaXa

    XaXa

    Rede de fibrinaRede de fibrina

    AtivaAtivaooplaquetplaquetriaria

    Tempo de tromboplastinaparcial ativada

    Tempo de protrobina

    ZI MOGNI OS

    Fatores inativos f ormados no f gado.

    A TI VA O (I I , VI I , I X , X )

    carboxilao do resduo de cidoglutmico

    cof ator - vit K reduzida

    (restaurada pela vit K redutase)

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    2 antiplasmina

    (-)

    TrombinaTrombinaFibrinognioFibrinognio Monmeros deMonmeros de

    fibrinogniofibrinognio

    Rede de fibras de fibrinaRede de fibras de fibrina

    Fibras de fibrinaFibras de fibrina

    TrombinaTrombina

    fator estabilizador de fibrina (XIIIa)fator estabilizador de fibrina (XIIIa)

    Ca++

    PlasminaPlasminognio

    (-)

    tPA

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    Endotlio

    Subendotlio

    Fator de vonWillebram

    Complexo2b 3(antigo GpI I b- I I I a)

    f ibrinognio

    PlaquetaGpI b

    Adeso&

    agregao plaquetrias

    f ibras de colgeno

    TxA2ADP

    Plaquetas

    vWFvWF: Fator von Willebrand

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    Colagno

    Adesoplaquetria:Plaquetas unidaspor f ibrinognio

    Seqncia decoagulao extrnseca

    vWF

    Exposio do fatortecidual ligado

    membrana

    Favorecem a tromboseFavorecem a trombose

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    Inativa a trombina, fatores Xa, IXa

    Protelise de Va, VIIIa

    Ptn C ativa Ptn C

    Antitrombina III

    trombina PGI2, NO

    agregaoplaquetria

    Trombomodulina EndotlioMolcula semelhante heparina

    I nibem a tromboseI nibem a trombose

    (-)

    S

    + ativador tecidual de plaminognio (tPA)

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    ANT I COAGULANT ES

    ?ao dos fatores de coagulao

    HeparinaHeparinas de baixo peso

    molecular

    Enoxaparina

    DalteparinaCertoparina

    Antagonistas da trombina

    Hirudina Hirulog Lepirudina

    Anticoagulantes orais

    VarfarinaDicumarol

    Femprocumom

    Classif icaClassif icao dos Antitrombo dos Antitrombticosticos

    ANTI PLAQUETRI OS

    Inibio da formao de TXA2

    Inibidor COX

    Aspirina

    Inibidor TXA2 sintase

    Dazoxiben

    RidogrelAntagonista TXA2

    Ridogrel

    GR32191

    Inibidores dos receptores

    2b 3 (GpIIb / IIIa)Abciximab

    Tirofiban

    FI BRI NOL TI COS

    Catalisam converso de

    plasminognio em plasminaEstreptoquinase

    Uroquinase

    Inibidor de PDE

    DipiridamolAntagonista do

    receptor para ADP

    Ticlopidina

    Clopidogrel

    Anlogos PGI2Epoprostenol

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    ANT I COAGULANT ES PARENTERAI SANT I COAGULANT ES PARENTERAI S

    HEPARI NASHEPARI NAS

    (McLean, 1916)

    Fontes: mucosa intestinal suna, pulmo bovino

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    MECANI SMO DE AO

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    Usos clnicos Ef eitos indesejados

    Profilaxia e tratamentodo tromboembolismo

    venoso

    Angina instvel (+ AAS)Infarto agudo do

    miocrdio

    Hemodilise

    Hemorragia

    Trombocitopenia

    Leses cutneas

    Osteoporose

    Hipoaldosteronismo

    Hipercalemia

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    Farmacocintica

    2 4 6 8 10 h

    Administrao subcutnea

    t1/2

    = 40 90 min

    35000 UI / 8 12 h

    [H]

    5000 UI

    1200 - 1600 UI

    Infuso contnua

    Janela teraputica: 0,3 0,7 U / mL

    [H]

    Superdosagem:sulfato de protamina 1 %

    No atravessa a placenta

    Monitorizao laboratorial

    TTPa = Tempo de Tromboplastina parcial ativada

    Avaliao da via intrnseca

    Sangue calcificado + fosfolipdeos

    Coagulao

    Normal 26 33 segundos

    heparina 1,5 a 2,5 x maior

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    LMWH:LMWH: Biodisponibilidade SC; efeito previsvel; auto-administrao; baixo

    ndice de trombocitopenia; risco de sangramento e osteopenia

    DANAPARDANAPARIDEIDE (Orgaran)::contra fator Xa, s/ antdoto, monitorar c/ anti-Xa

    84% heparan

    12% dermatan

    4% condroitina sulfato

    LEPIRUDINALEPIRUDINA (Refludan): fator IIa- s/antdoto, ac anti-hirudina, cuidado c/

    insuficincia renal

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    ANTI COAGULANTESANTI COAGULANTES

    ORAI SORAI S

    EUA, 1920

    Derivados de 4-OH

    cumarinas: Varfarin (Marevan)

    Dicumarol

    Derivados de indan-1,3-

    diona:

    Anisindiona

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    MECANI SMO DE AO

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    t1/2de protenas dependentes de vitamina K:

    Protena Tempo (h)

    Fatores de coagulao

    Fator VII 6

    Fator IX 24

    Fator X 36

    Protrombina 50

    Protenas anticoagulantes

    Protena C 8

    Protena S 30

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    Usos clnicos Ef eitos indesejados

    Profilaxia e tratamento do

    tromboembolismo venoso

    Valvopatias e prteses

    valvares

    Infarto agudo do

    miocrdio Fibrilao atrial

    no valvar

    Hemorragia

    Distrbios GI

    Necrose cutnea (ptn C)

    Prpura

    Dermatite urticariforme

    Alopecia

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    Farmacocintica

    Biodisponibilidade VO 80 100 % (ou IV)

    99 % ligao a albumina plasmtica (interao AAS)

    Metabolismo heptico

    Fase I CYP2C9

    variantes allicos 10 a 20 % caucasianos menor dose

    Interaes: ? [varfarina] - Cimetidina, cloranfenicol

    ?J[varfarina] - Barbitricos, carbamazepina

    Fase II - glicuronidao

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    Superdosagem:administrao de vitamina K, plasma fresco

    Monitorizao laboratorial

    TP = Tempo de Protrombina

    Avaliao da via extrnseca

    Sangue calcificado + tromboplastina

    coagulao

    Normal 12 14 segundos

    Varfarin ndice normalizado Internacional (INR)

    INR = TP paciente

    TP controle = 2 a 4

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    ANTI PLAQUETANTI PLAQUET RI OSRI OS

    AAS(160 320 mg / dia VO)Indicaes: Acidente vascular cerebral

    Aps cirurgia de derivao coronarianaNova estenose aps angioplastia ou trombliseInfarto do miocrdioCrise isqumica transitria

    t1/2= 2 3 h; ligao a protenas plasmticas = 50 70 %

    TI ENOPI RI DI NASTiclopidina (Ticlid)dose de ataque 500 mg; dose usual 250 mg / 2x dia; t

    1/2= 30 h

    Clopidrogrel (Plavix)dose de ataque 300 mg; dose usual 75 mg / diaProvavelmente pr-frmacosIndicaes: Acidente vascular cerebral; Angioplastia (+ AAS)Efeitos indesejados: Neutropenia reversvel, trombocitopenia, nuseas, vmitos, diarria,rashes cutneos

    I nibidores do receptor I I b/ I I I aTirofibam (Aggrastat) t1/2= 30 min - Abciximab (Reopro) - Eptifibatide (Integrelin)

    Indicaes: Angioplastia, anginaPreveno de restenoseInfarto do miocrdio (+AAS e heparina)

    Efeitos indesejados: Hemorragia, trombocitopenia

    Efeitos indesejados:Irritao GI dose-dependenteHipersensibilidade

    Sindrome de Reye em crianas

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    AAS

    AAS +clopidogrel

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    FI BRI NOLFI BRI NOLTI COSTI COS

    Usos clnicos: IAM, trombose

    venosa profunda, embolia

    pulmonar (IV)

    t1/ 2

    0 10 20 90

    AnistreplaseAnistreplase

    EstreptoquinaseEstreptoquinase

    UroquinaseUroquinase

    tt--PAPA

    Ativao doplasminognioAnistreplaseAnistreplase

    Estreptoquinase (Strptase)Estreptoquinase (Strptase)

    Uroquinase (Abbokinase)Uroquinase (Abbokinase)

    tt--PA (Alteplase)PA (Alteplase)

    Antigenicidade

    AnistreplaseAnistreplase

    EstreptoquinaseEstreptoquinase

    UroquinaseUroquinase

    tt--PAPA

    Efeitos indesejados:Hemorragia, reaes de hipersensibilidadeSuperdosagem:cido aminocaprico e cido tranexmico

    Contra-indicaes:Cirurgia (< 10 dias), trauma, ressucitao cardiopulmonar,sangramento GI (< 3 meses), hipertenso, sangramento / hemorragia, AVC prvio,

    disseco artica, pericardite aguda

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