Anti-thrombotic Agents (antiplatelets) Flashcards
Name the 3 types of anti-clotting drugs:
- Anti-platelet
- Anti-coagulants
- Thrombolytics/Fibrinolytics
What kind of anti-clotting drug is aspirin?
Anti-platelet drug
What kind of anti-clotting drug is clopidogrel?
Anti-platelet drug
What kind of anti-clotting drug is Abciximab?
Anti-platelet drug
What kind of drugs are heparin and warfarin?
Anti-coagulants
Haemostasis process:
- Vasoconstriction/ vascular spasm
- Platelet adhesion, activation, aggregation
- Fibrin formation
- Network of fibrin
What is the lifespan of a platelet?
7-10days
- so inhibitory effect of aspirin which lasts for life of platelet also lasts for 7-10 days
Adverse effects of anti-thrombotics, anti-platelets:
- Bleeding (PGI2)
- Gastric upset & ulcers (PGE2)
- GIT bleeding
Clinical uses of Aspirin:
Prevention of arterial thrombosis (e.g. myocardial infarction, stroke)
- prophylactic treatment of transient cerebral ischemia
- reduce incidence of recurrent MI
- decrease mortality in postmyocardial infarction patients
What allows the cross-linking of fibrinogen?
GP IIB/IIA (glycoprotein 2B 3A)
- platelet membrane surface protein
- which allows fibrinogen cross-linking of platelets
Pg 7 of slides
How is heparin delivered?
- intravenously or subcutaneously
- CANNOT be given intramuscularly (will form haematomas!)
Adverse effects of heparin:
- Haemorrhage
- to stop heparin therapy + start on treatment w protamin sulfate
- protamin sulfare binds to heparin due to opposite charge -> isolates heparin - Thrombosis & thrombocytopenia
Which anti-thrombotic drug is not contraindicated in pregnancy?
Heparin
(Only antithrombotic drug in pregnancy)
MOA of Aspirin as an anti-platelet?
- Irreversible COX inhibitor
- Inhibits TXA2 synthesis in platelets => inhibits platelet aggregation
MOA of Clopidogrel?
- Pro-drug: converted to active metabolite by CYP2C19
- P2Y 12 receptor irreversible antagonist => inhibit ADP-induced platelet aggregation
MOA of Abcimiximab:
Abcimiximab: Fibrinogen Receptor Antagonist
- Humanised Fab (antigen-binding fragment) mAb
- Fibrinogen receptor antagonist => inhibit platelet aggregation
Name the newer P2Y 12 receptor antagonists:
- Prasugrel: pro-drug, irreversible, fast onset
- Ticagrelor: direct, reversible
MOA of Unfractionated Heparin (UFH)
- anticoagulant
- Binds & activates AT-III (plasma protease inhibitor)
- Enhance AT-III interaction w clotting factors (IIa, IXa, Xa) by 1000 folds => form inactive complexes
- Conformational change of AT-II
- Stimulate TFPI release from endothelium
MOA of Low-MW Heparin (LWMH)
Anticoagulant
- Bind & activate AT-III
- Inhibit Factor Xa more, Factor IIa less
- fractionation of UFH
- more homogenous than UFH
MOA of Vitamin K Antagonist - Warfarin
- Inhibit Vit K Epoxide Reductase => decreased Vit K formation
- Decreases Vit K co-factor for activation of Factors II, VII, IX, X by γ-Caboxylase
- racemic mixture of equal amounts of optical isomers
-> S-warfarin: 4x more potent
-> R-warfarin
MOA of Direct Anticoagulants - Rivaroxaban, Dabigatran
- Rivaroxaban : Factor Xa inhibitor
- Dabigatran: Thrombin IIa inhibitor
List the 4 types of Anticoagulants:
- Unfractionated Heparin (UFH)
- Low-MW Heparin (LWMH)
- Vitamin K Antagonist (Warfarin)
- Direct Anticoagulants (Rivaroxaban, Dabigatran)
Which Anticoagulant cannot be given during pregnancy?
Warfarin.
- crosses placenta
- Teratogen => can cause Fetal Warfarin syndrome, birth defects, haemorrhagic foetus, abortion
What is a Teratogen?
- substance that interferes with normal fetal development and causes congenital disabilities.
