module 9 antiplatelet meds Flashcards
antiplatelet agents/classes
COX inhibitors
phosphodiesterase inhibitors
ADP receptor pathway inhibitors
GPIIb/IIIa antagonists
platelet adhesion
fibrinogen
- connects platelets together for aggregation
- site of Rx
Activation sites of Rx
ADP
Thromboxane A2
Normal pathway of prostaglandin and platelet aggregation synthesis
- arachidonic acid is converted to prostaglandins by cycloxygenase (COX) : site of action
- prostaglandins converted to prostacylin by PGI2, and thromboxane A2 by TxA2 synthase.
prostacylin
vasodilator
inhibits platelet aggregation by increases cAMP
COX inhibitors
aspirin: irreversible
NSAID: reversible
thomboxane a2
produced by activated platelets
prothrombotic properties
- stimulates activation of new platelets and increases aggregation
COX inhibitors MOA
prevent the production of prostaglandins and in turn thromboxane A2 -> dec. platelet activation and aggregation
aspirin
irreversible binding
-> continued inhibition for 7-10 even after stopping the med d/t life of platelet.
ADP receptor inhibitors
ticlopidine clopidogrel prasugrel ticagrelor - call all be used in combo with ASA
ADP receptor inhibitor MOA
irreversibly inactivate or antagonize the platelet P2Y(ADP) receptors -> inhibition of aggregation
ADP receptors
activation causes platelets to undergo a shape change and aggregate to other platelets.
ticlopidine
ADP receptor inhibitor prodrug binds irreversibly maximal platelet inhibition within 8-11 days, 4-7 w/ ASA - loading dose
ticlopidine AE
neutropenia
thrombocytopenia
TTP
-> monitor CBC freq.
clopidogrel
prodrug binds irreversibly metabolized to active form by CYP2C19 - drugs that inhibit 2C19: omeprazole, esomeprazole loading dose lack of significant hematologic effects
clopidogrel AE
GI adverse effects
prasugrel
prodrug more complete inhibition of P2Y(ADP) receptor binds irreversibly - more efficiently metabolized - inc. concentration of active drug - inc. risk of bleeding
ticagrelor
not a prodrug, drug is active form, also has active metabolites
reversible and non-competitive inhibition of P2Y(ADP)
Metabolized by CYP3A4
GPIIb/IIIa antagonist
eptifibatide
abciximab
tirofiban
- administered IV
GPIIb/IIIa
part of final common pathway of platelet aggregation
abciximab AE
irreversible
- will need FFP infusion to stop bleeding
thrombocytopenia
eprifibatide, tirofiban AE
reversible, but drug greatly out numbers receptors
- have to await drug clearance. New platelets will bind to free drug
thrombocytopenia
dipyridamole
very weak platelet inhibitor
