Antiplatelet agents Flashcards
Antiplatelet agents are used for prevention and treatment of:
thrombotic disease (CVA, MI)
How is ASA different from other NSAIDs?
Irreversibly bind and inhibits COX enzyme for life of the platelet (7-10days)
What is the MOA of COX inhibitors?
Inhibit the COX enzyme which inhibits TxA2 which usually causes platelet aggregation
(also inhibits prostacyclin, which has a natural antiplt effect, in endothelial cells. Endothelial cells are able to synthesize new COX enzymes)
COX inhibitors include:
NSAIDs, ASA
What is the MOA of ADP Receptor Inhibitors?
Irreversibly inactivates or antagonizes the platelet P2Y (ADP) receptors which inhibits platelet activation
ADP Receptors Inhibitors include:
Ticlodipine (Ticlid)
Clopidogrel (Plavix)
Prasurgurel (Effient)
Ticragrelor (Brillanta)
All prodrugs and irreversible except Ticragrelor
Can be used with ASA
Ticlodipine (Ticlid):
ADP Receptor Inhibitor
- Prodrug
- Maximal plt inhibition within 8-11days, or 4-7 days with ASA
- Loading dose often given
- AE: neutropenia, thrombocytopenia, TTP
- Monitor CBC frequently
- Less tolerable and slower onset than clopidogrel
Clopidogrel (Plavix)
ADP Receptor Inhibitor
-Prodrug
**Metabolized to its active form by CYP 2C19
(poor met by genetic predisposition=less effective; drugs like omeprazole can inhibit CYP2C19= can’t activate prodrug)
-Loading dose often given
-Less AE
-GI AE similar to ASA
**Omeprazole inhibits CYP induction, Rotonavir induces
Prasugrel (Effient)
ADP receptor inhibitor
- Prodrug
- More complete inhibition of P2Y(ADP) receptor; efficiently metabolized=higher concentration of active drug= increased risk of bleeding
Ticagrelor (Brilinta)
ADP Receptor Inhibitor
- Active form (not a prodrug) with active metabolites
- Reversible and noncompetitive inhibition of P2Y (ADP) receptors (recovery of plt function depends on serum concentration of drug and its active metabolites)
- Metabolized by CYP 3A4
What is the MOA of GPIIb/IIIa Antagonists?
Inhibit the GPIIb/IIIa receptors on platelets which link together to cause aggregation (final pathway/step)
What is the route of administration of GPIIb/IIIa antagonists?
IV
The most common AE of GPIIb/IIIa antagonists:
Bleeding
Abciximab: Class, AE
GPIIb/IIIa antagonist
Bleeding: Irreversible, fresh platelet infusion needed
Eptifibatide, tirofiban: Class, AE
GPIIb/IIIa antagonists
Bleeding: Reversible, drug greatly outnumbers receptors. Wait for drug clearance, do not immediately transfuse platelets = drug will attach to new platelets as well.
What is the MOA of Phosphodiesterase inhibitors?
Inhibit breakdown of cAMP which decreases platelet activation. These drugs are uses in combination with another antiplatelet therapy
Dipyridamole:
Phosphodiesterase inhibitor
Weak plt inhibitor
Vit K is required for normal hepatic synthesis of what coagulation factors and proteins?
Factors, II, VII, IX, X
Protein C and S (body’s natural anticoagulants- balance)
Vit K in its inactive form is activated or regenerated by what and how is this related to warfarin’s MOA?
Epoxide reductase
Warfarin inhibits the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex
Warfarin can also be called a____ _______.
Vit K antagonist
Degree of depression of VKORCI is dependent on:
Dosage
Patient’s VKORC1 genotype: sensitive/resistant
What are the half life of the clotting factors and proteins that warfarin affects?
Factor II: 60hrs Factor VII: 4-6hrs Factor IX: 24hrs Factor X: 48hrs Protein C: 8hrs Protein S: 30hrs
What is warfarin’s onset, peak, and duration of a single dose?
Onset: 24 hours
Peak: 72-96 hours
Duration of single dose: 2-5 days
Roughly how many days should you wait to check a warfarin level after a dose has been changed?
4 days