antiplatelet drugs Flashcards
(55 cards)
antiplatelet drugs inhibit what functions
primary hemostatic plug formation, aggregation, activation and release mechanisms.
Platelet Aggregation Assay
- prepare PRP
- activate platelets (PRP+ ADP, TRAP, epinephrine,
5-HT, collagen, ristocetin, AA) - measure Light transmittance (low= no aggregration, high = aggregation)
Light (alpha) granule release products:
a. Platelet factor 4 (aka heparin co-factor)
b. Beta-thromboglobulin
c. Platelet-derived growth factor (PDGF)
Dark (beta) granule release products:
a. Ca+2
b. Serotonin
c. ATP/ADP
Products formed during platelet activation and endothelial interaction:
prostaglandin derivatives, endoperoxides, thromboxanes.
advantages of antiplatelet drugs vs heparins and anticoagulants
These drugs are effective in the arterial circulation, where anticoagulants such as heparin and oral anticoagulants have relatively little effect.
types of antiplatelet drugs
- Aspirin
- Cyclooxygenase (COX) inhibitors (COX1 and COX2 inhibitors)
- Propionic acid derivatives (NSAIDs)
- ADP Receptor inhibitors
- Dipyridamole (Persantine®) a coronary vasodilator
- Cilostazol (Pletal®) – used for the management of intermittent claudication
- GPIIb/IIIa Inhibitors
- Prostacyclin analogue (Iloprost®)
what drugs belong to the ADP Receptor inhibitors group
Ticlopidine (Ticlid), Clopidogrel (Plavix), Prasugrel (Effient), Ticagrelor (Brilinta) and Cangrelor (Kengreal)
which drugs belong to GPIIb/IIIa Inhibitors group
abciximab, ReoPro®;
tirofiban, Aggrastat®, and
eptifabatide, Integrilin®
Dipyridamole (Persantine®) MOA
coronary artery dilator (used for coronary artery surgeries)
Aspirins MOA
COX-1 and COX-2 inhibitor
aspirins dosing for antiplatelet effects
Aspirin is used as a single low dose 81 mg/daily for antiplatelet actions
aspirin resistance
many pts do no respond to the normal daily dose of 81 mg per day leading to theurapeutic failure. Increasing the dose can restore the antiplatelet effect.
may be the cause of recurrent ischemic vascular events in patients taking asprin.
may be due to COX polymorphism
clopidogrens MOA
selectively inhibits ADP binding to its platelet receptor, preventing subsequent platelet aggregation
clopidogrel vs. Prasugrel
both inhibit platelet aggreation.
clopidogrel has a large amount of variation in responses within the population while prasurgrel has less variation and is therefore effective for a larger % of people.
Dual Antiplatelet Therapy
Aspirin/ADP receptor inhibitors
Aspirin/GP IIb/IIIa inhibitor
Aspirin/Dipyridamol
Triple Antiplatelet Therapy
Aspirin/ADP receptor inhibitor/ Cilostazol
not commonly used
GP IIb-IIIa inhibitors MOA
after platelets are activated they express GP IIb/IIIa, the GP IIb/IIIa inhibitor binds to the active site preventing fibrinogen from binding
clinical uses for antiplatelet drugs
- Cerebrovascular disease:
a. Transient ischemic attack (TIA)
b. Complete stroke - Coronary artery disease:
a. Acute myocardial infarction
b. Unstable Angina - Saphenous vein coronary artery bypass grafts:
- Peripheral vascular disease:
a. Venous thrombosis
b. Peripheral arterial disease (PAOD, intermittent claudication) - Small vessel disease
a. **Thrombotic thrombocytopenic purpura - Prevention of thrombus formation on artificial surfaces
Drug Interactions with Antiplatelet Agents
Thrombolytic agents (urokinase, streptokinase and tissue plasminogen activator).
- Heparin/LMW Heparin/oral anticoagulants
- Warfarin
- Antithrombin agents (hirudin, bivalirudin and argatroban).
all increase the antiplatelet effect and risk of bleeding
Arachidonic Acid is released from
membrane phospolipids
Arachidonic Acid is used to make
Leukotrienes, Thromboxanes, Prostacyclins, Prostaglandins
aspirin and NSAIDs block thromboxanes, prostacyclins, and prostaglandins
arachidonic acid is metabolized by which 2 pathways
Cyclooxygenase pathway
-Prostaglandins, thromboxanes, prostacyclins
Lipoxygenase pathway
- Leukotrienes
Cyclooxygenase Pathway
Cycloxygenase represents constitutive (COX-1) and inducible (COX-2) enzymes.
Aspirin inhibits both COX-1 and COX-2 thereby limiting the production of prostaglandins.
In particular, thromboxane formation in platelets is inhibited.
This is the main mechanism by which aspirin mediates its therapeutic effects.
