antiplatelets, anti-thrombotics Flashcards

1
Q

event in platelet activation & aggregation

A

1 (normal). intact endothelium releases PGI2 into plasma, which binds to platelet membrane –> synthesis of cAMP –> inhibit release of granules containing aggregating agents

2 (inhibited by aspirin). thrombin, TXA2 (also synthsized in platelet), exposed collagen –> release of arachidonic acid from platelet membrane –> platelet synthesize more TXA2

  1. TXA2 binds to receptors on toher platelets –> initiate release of additional aggregating agents (propagation)

balance b/w PGI2 and TXA2 influences whether platelets aggregate or circulate freely

serotonin, ADP increases platelet aggregation

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2
Q

aspirin

A

anti-platelet NSAID

irreversible inhibitor of COX –> effect lasts the life of platelet –> 7-10 days

uses:
- prophylactic tx of transient cerebral ischemia
- reduce incidence of recurrent myocardial infarction
- decrease mortality of post-MI pt

AE: bleeding (PGI2 > TXA2), gastric ulcer (PGE2 v), GI bleeding

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3
Q

platelet GPIIB/IIIA receptor blockers

A

antiplatelet

  • used to prevent restenosis after coronary angioplasty, acute coronary syndromes

abciximab – monoclonal Ab (IV route) directed against IIb/IIIa complex –> reversibly inhibits binding of fibrinogen and other ligands to GPIIB/IIIA

eptifibatide –> analog of part of fibrinogen –> competitive inhibitor

tirofiban –> small molecule (oral route) blocker of GPIIB/IIIA

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4
Q

GP IIB/IIIA receptor

A

platelet membrane glycoprotein complex involved in platelet cross-linking

receptor for fibrinogen, fibronectin, vitronectin, von willebrand factor (clotting factors)

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5
Q

ADP receptor blocker

A

ticlopidine
antiplatelet

prevents release of ADP which increases platelet aggregation

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6
Q

PDE inhibitor

A

dipyridamole
antiplatelet

inhibits conversion of cAMP to 5’ AMP

increase intra-platelet [cAMP], increased effect of cAMP to prevent degranulation of granules containing ADP and serotonin

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7
Q

actions of thrombin (factor IIa)

A

-activated upstream proteins –> further thrombin generation

cleaves fibrinogen –> fibrin

activates factor XIII, a fibrinoligase –> strengthen fibrin-to-fibrin links

causes platelet aggregation

stimulate cell proliferation

modulate smooth muscle contraction

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8
Q

antithrombin III (ATIII)

A

endogenous anticlotting protein

irreversibly inactivates clotting factor proteases (esp thrombin, IXa, Xa)

forms stable complexes

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9
Q

heparin

A

anticoagulant

PK: IV, subcutaneous
CANNOT GIVE IM –> haematoma

family of sulfated GAG (mucopolysaccharides)

low m.w. heparins –> longer duration of action, but only increases action of ATIII on Xa, not thrombin

uses
- deep vein thrombosis, pulm embolism, acute MI
- when MUST use an anticoagulant in pregnancy
- in combi w thrombolytics for revascularisation (restore blood flow in aa/vv)
- in combi w GPIIb/IIIa inhibitors during angioplasty, placement of coronary stents

AE:

haemorrhage –> stop heparin, use protamin sulfate (bind to heparin)

thrombosis (blood clot), thrombocytopenia (low platelet count) –> immune mediated response

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10
Q

action of heparin

A

heparin binds to ATIII –> ATIII active site exposed –> more rapid interaction w proteases

heparin need bind to ATIII and thrombin to inhibit thrombin

only need to bind to ATIII to inhibit factor X (LMWHs)

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11
Q

vit K

A

-fat soluble vitamin essential for formation of clotting factors 2, 7, 9, 10

reduced vit K essential co-factor in gamma carboxylation of glutamate residues
- reduced vit K regenerated by vit K reductase

uses:
- tx/prevention of bleeding from anticoagulant drug use eg warfarin, prevent haemorrhagic disease in newborns
- vit k deficiency

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12
Q

warfarin

A

anticoagulant
pk: small, lipid soluble – oral route
- small vol of distribution – >99% bound to plasma albumin
- elimination depends on metab by CYP450 (drug interactions)

vit k reductase inhibitor
- reduced vit K cannot regenerate –> less clotting factors

uses: same as heparin BUT CANNOT USE IN PREGNANCY

AE: bleeding

PREGNANCY: crosses placenta – hemorrhagic disorder in fetus

fetal proteins in bone and blood may be affected

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13
Q

thrombolytic agents

A

IV, intracoronary injection

t-PA, urokinase, streptokinase, anistreplase

all increases conversion from plasminogen to plasmin –> dissolve fibrin

uses: emergency tx of coronary aa thrombosis (intracoronary inj), peripheral aa thrombosis, emboli

ischaemic stroke (<4.5h window)

AE: bleeding

Contraindication: delayed wound healing, pregnancy

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