Coagulation - Antiplatelets Flashcards
Platelets have ___ but not _____
organelles and secretory granules
but no nucleus
First step of platelet activation
Adhesion and shape change
- GP1a -> Collagen
- GP1b –> vWF
Shape change facilitates receptor binding
____ secretes prostacyclin to inhibit thrombogenesis
IN-TACT endothelial cells
Second step of platelet activation
Secretion, Degranulation
- ADP
- TXA2
- 5HT
These activate other platelets (all) and are vasoonstrictors (TXA and 5HT only)
Third step of platelet activation
Aggregation
ADP/5HT/TXA2 induces GP2b3a receptors to bind fibrinogen.
*Temporary hemostatic plug is formed.
Aspirin MOA
irrev. acetylation of platelet’s COX-1
- Inhibits TXA2 formation (also PG synthesis if high dose)
- Interferes with bleeding time, NOT PT
Inhibition of COX by aspirin is ____ and is maximally effective at a dose of _____
permanent (no nucleus to regenerate)
50-320mg
Indication for ASA
Prophylaxis and treatment of arterial thromboembolic disorders
P2Y1 receptor pathway
Gq coupled receptor
–>PLC, IP3, Ca++ pathway
P2Y12 pathway
Coupled to Gi and inhibition of adenylyl cyclase
Activation of _____ is required for platelet activation by ADP
Both P2Y1 and P2Y12
P2Y12 inhibitors
Ticlopidine - no longer used d/t TTP
Clopidogrel - Lower tox profile
Effects for days (irrev. inhibition)
Uses: ACS, post-AMI, PVDz, PCI prodecure
Ticlopidine, Clopidogrel, and Prasugrel are ______
prodrugs that inhibit P2Y12
Prasugrel vs Clopidogrel
Prasugrel = Faster onset, increased potency due to rapid CYP450 metabolism
Protease that cleaves circulating vWF
Drug that blocks this process (as an AE)?
ADAMTS13
Ticlid induces antibodies against ADAMTS13 = reduced proteolytic activity = excessie platelet aggregation
P2Y12 receptor antagonists that act on platelet surface, and need NO METABOLISM to work
These drugs are ____
Ticagrelor
Cangrelor
Both are REVERSIBLE
CYP metabolism of Clopidogrel and Prasugrel
C = 2C19
P = 3A4, 2D6
Eptifibatide MOA
- Has what structural component?
- ROA?
- Use?
Inhibits fibrinogen binding to GP2b3a –> decrease platelet agg.
- has RGD motif
- Delivered IV because its a peptide
- Use to prevent TE in unstable angina and PCI
Tirofiban MOA
- ROA
- T1/2
- Use?
Reversible inhibitor of fibrinogen binding to GP2b3a
- IV in dilute soln
- 2 hrs
- Combo with HEPARIN for ACS
Abciximab structural makeup?
MOA?
PK and implications of this?
Fab fragment of chimeric monoclonal Ab
Binds to GP2b3a receptor to inhibit agg.
LONG duration of action = increased risk of bleed
PDE3 inhibitors
Dypyridamole
Cilostazol
Platelet aggregation inhibition. Action related to cAMP PDE inhibition & inhibition of Adenosine uptake
Dipyridamole use
combo with warfarin (prevent Embol. from prosthetic valves)
Combo with ASA to prevent ischemic stroke
Cilostazol use
intermittent claudication
Protease activated receptor inhibitors
Vorapaxar, Atopaxar
Thrombin activates platelets
Proteolytic cleavage of PAR-1 receptors on surface of platelet
(PAR’s are GPCR’s that release Ca++)
Reversible PAR1 receptor antagonist
Use?
Contrainications?
Another thing to consider regarding lasting effects?
Vorapaxar
- Combo with ASA or clopidogrel
- CI = Stroke/TIA history
- Antiplatelet effects last for DAYS after discontinuation
