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ANTITROMBTICOS

ANTICOAGULANTES,
ANTIPLAQUETRIOS E
FIBRINOLTICOS
Profa. Christianne Brtas Vieira Scaramello
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ANTICOAGULANTES,
ANTIPLAQUETRIOS & FIBRINOLTICOS
Frmacos que impedem a formao 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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Preveno da perda
de sangue

Hemostase

Leso vascular

Vasoconstrio

Coagulao
sangunea

Agregao
plaquetria

Tampo hemosttico
TOMBOGNESE HEMOSTASE
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Hemorragia

Agregao Coagulao
plaquetaria

Fibrinlise

Trombognese
Formao indesejada de um tampo hemosttico
(condio patolgica resultante de hipercoagulao)
Veia

Trombose
Artria

Trombose

Tecidos drenados
Veia profunda
embolia pulmonar

Edema e inflamao

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Necrose Isqumia

Coagulao sangunea

Via Intr
Intrnseca

Superf
Superfcie
externa

Via Extr
Extrnseca

Pr
Prcalicre
calicrena

Tempo de protrobina

Tempo de tromboplastina
parcial ativada

calicre
calicrena
XII

Trauma tecidual

XIIa
XI

XIa
IX

IXa *

Fator tecidual
Ca++
VII

VIIa *
X

VI
II

Ca++

VIIIa

Fosfolip
Fosfolipdos
plaquet
plaquetrios
Ca++

Xa

Xa

Xa
ZIMOGNIOS

Fosfolipidos plaquet
plaquetrios

Va

Ca++

Fatores inativos formados no fgado.


ATIVAO (II, VII, IX, X)
carboxilao do resduo de cido
glutmico
cofator - vit K reduzida

Protrombina
Ca++

Trombina

(restaurada pela vit K redutase)


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Rede de fibrina
Ativa
Ativao
plaquet
plaquetria

Fibrinognio

Trombina

Monmeros de
fibrinognio
Ca++
Fibras de fibrina
Trombina

fator estabilizador de fibrina (XIIIa)


Rede de fibras de fibrina
(-)
Plasminognio

tPA

Plasmina
(-)
2 antiplasmina

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Adeso
&
agregao plaquetrias

Plaquetas
ADP
TxA2

vWF
fibras de colgeno
vWF: Fator von Willebrand
GpIb
Complexo 2b 3

(antigo GpIIb-IIIa)

Plaqueta
fibrinognio

Endotlio

Subendotlio
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Fator de von
Willebram

Favorecem a trombose
Seqncia de
coagulao extrnseca

Adeso
plaquetria:
Plaquetas unidas
por fibrinognio

vWF

Exposio do fator
tecidual ligado
membrana

Colagno

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Inibem a trombose
Inativa a trombina, fatores Xa, IXa
Protelise de Va, VIIIa
Ptn C ativa

Ptn C

agregao
plaquetria

Antitrombina III

(-)
trombina

Molcula semelhante
heparina

Trombomodulina

PGI2, NO

Endotlio

+ ativador tecidual de plaminognio (tPA)

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Classificao dos Antitrombticos


ANTICOAGULANTES

ANTIPLAQUETRIOS

Inibidor de PDE

?
ao dos fatores de coagulao

Inibio da formao de TXA2

Heparina

Dipiridamol

Inibidor COX

Heparinas

de

baixo

peso Aspirina

Antagonista do
receptor para ADP

molecular

Inibidor TXA2 sintase

Enoxaparina

Ticlopidina

Dazoxiben

Dalteparina

Clopidogrel

Ridogrel

Certoparina

Anlogos PGI2

Antagonista TXA2

Antagonistas da trombina

Epoprostenol

Ridogrel

Hirudina Hirulog Lepirudina

GR32191

FIBRINOLTICOS

Anticoagulantes orais

Inibidores dos receptores

Catalisam converso de

Varfarina

2b 3 (GpIIb / IIIa)

plasminognio em plasmina

Dicumarol

Abciximab

Femprocumom

Tirofiban

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Estreptoquinase
Uroquinase

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ANTICOAGULANTES PARENTERAIS
HEPARINAS
(McLean, 1916)

Fontes: mucosa intestinal suna, pulmo bovino

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MECANISMO DE AO

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Usos clnicos

Efeitos indesejados

Profilaxia e tratamento

Hemorragia

do tromboembolismo

Trombocitopenia

venoso

Leses cutneas

Angina instvel (+ AAS)

Osteoporose

Infarto agudo do

Hipoaldosteronismo

miocrdio

Hipercalemia

Hemodilise

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Farmacocintica
35000 UI / 8 12 h
[H]

No atravessa a placenta
Monitorizao laboratorial
TTPa = Tempo de Tromboplastina parcial ativada
2 4

10

Administrao subcutnea
t1/2 = 40 90 min

Avaliao da via intrnseca


Sangue calcificado + fosfolipdeos
Coagulao

5000 UI

Normal 26 33 segundos

[H]

heparina 1,5 a 2,5 x maior


1200 - 1600 UI
Infuso contnua
Janela teraputica: 0,3 0,7 U / mL
Superdosagem: sulfato de protamina 1 %
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LMWH: Biodisponibilidade SC; efeito previsvel; auto-administrao; baixo


ndice de trombocitopenia; risco de sangramento e osteopenia
DANAPARIDE (Orgaran): contra fator Xa, s/ antdoto, monitorar c/ anti-Xa
84% heparan
12% dermatan
4% condroitina sulfato
LEPIRUDINA (Refludan): fator IIa- s/antdoto, ac anti-hirudina, cuidado c/
insuficincia renal
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ANTICOAGULANTES
ORAIS
EUA, 1920
Derivados de 4-OH
cumarinas: Varfarin (Marevan)
Dicumarol
Derivados de indan-1,3diona:
Anisindiona

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MECANISMO DE AO

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t1/2 de protenas dependentes de vitamina K:


Protena

Tempo (h)

Fatores de coagulao
Fator VII

Fator IX

24

Fator X

36

Protrombina

50

Protenas anticoagulantes
Protena C

Protena S

30

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Usos clnicos

Efeitos indesejados

Profilaxia e tratamento do Hemorragia


tromboembolismo venoso
Valvopatias

prteses Necrose cutnea (ptn C)

valvares
Infarto

Prpura
agudo

do Dermatite urticariforme

miocrdio Fibrilao atrial


no valvar

Distrbios GI

Alopecia
Teratogenicidade

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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
Excreo renal (t = 25 60 h)
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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
Superdosagem: administrao de vitamina K, plasma fresco
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ANTIPLAQUETRIOS
Efeitos indesejados:
AAS (160 320 mg / dia VO)
Irritao GI dose-dependente
Indicaes: Acidente vascular cerebral
Hipersensibilidade
Aps cirurgia de derivao coronariana
Nova estenose aps angioplastia ou tromblise Sindrome de Reye em crianas
Infarto do miocrdio
Crise isqumica transitria
t1/2 = 2 3 h; ligao a protenas plasmticas = 50 70 %
TIENOPIRIDINAS
Ticlopidina (Ticlid) dose de ataque 500 mg; dose usual 250 mg / 2x dia; t1/2 = 30 h
Clopidrogrel (Plavix) dose de ataque 300 mg; dose usual 75 mg / dia
Provavelmente pr-frmacos
Indicaes: Acidente vascular cerebral; Angioplastia (+ AAS)
Efeitos indesejados: Neutropenia reversvel, trombocitopenia, nuseas, vmitos, diarria,
rashes cutneos
Inibidores do receptor IIb/ IIIa
Tirofibam (Aggrastat) t1/2 = 30 min - Abciximab (Reopro) - Eptifibatide (Integrelin)
Indicaes: Angioplastia, angina
Preveno de restenose
Infarto do miocrdio (+AAS e heparina)
Efeitos indesejados: Hemorragia, trombocitopenia
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AAS

AAS + clopidogrel

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FIBRINOLTICOS
Ativao do
plasminognio

Anistreplase
Usos clnicos: IAM, trombose
venosa

profunda,

embolia

pulmonar (IV)

Estreptoquinase (Strptase)
Uroquinase (Abbokinase)
t-PA (Alteplase)

Anistreplase

Anistreplase

Estreptoquinase

Estreptoquinase
Uroquinase

Uroquinase
t-PA
0

t1/2

t-PA

Antigenicidade

10
20
90
Efeitos indesejados: Hemorragia, reaes de hipersensibilidade
Superdosagem: 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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