4. Antiplatelet Drugs Flashcards
Platelets do not have a nucleus. (T/F)
True
Where do platelets originate?
megakaryocytes from the bone marrow
What is the life span of a platelet?
~ 10 days
What is a normal platelet count?
150,000 – 450,000 / μL
What are the 4 main mechanisms that activate platelets?
- underlying disease
- endothelial injury
- collagen
- von Willebrand factor
Agonists bind to platelet receptors that initiate a signaling cascade that results in:
- platelet shape change
- granule release
- thromboxane A2 generation
- GP IIb/IIIa receptor activation
What are the platelet receptors that initiate activation?
glycoprotein IIb/IIIa
What are potent platelet activation agonists?
- binding to collagen after vascular damage
- thrombin
What are weak platelet activation agonists?
- ADP
- TxA2
- Epinephrine
Platelets are activated by what G proteins?
- q and i
- G (12/13) families
Platelets are inhibited by what G proteins?
s
Platelet granule release occurs after ______.
adhesion
What are the 3 types of granules?
- alpha
- dense
- lysosomal
What is platelet adhesion?
Platelets bind to damaged area via GP Ib and GP VI
What is platelet aggregation?
fibrinogen binds to activated GP IIb/IIIa receptors
Platelets meshed in fibrin is called what?
hemostatic plug
What is a hemostatic plug made up of?
platelets and fibrin mesh
What are the indications for antiplatelet agents?
- cerebrovascular disease
- ACS/ unstable angina
- PAD
- CABG or PCI
What are the antiplatelet agents?
- ASA
- thienopyridines
- GP IIb/IIIa antagonists
- Phosphodiesterase inhibitors
What are the thienopyridine agents?
- clopidogrel (Plavix)
- prasugrel (Effient)
What are the GP IIb/IIIa inhibitors?
- abciximab (Reopro)
- eptifibatide (Integrilin)
- tirofiban (Aggrastat)
What is the MOA of ASA?
Acetylation at Ser529 results in irreversible inhibition of COX-1 for the life of the platelet.
High doses of ASA inhibit what?
both COX-1 and COX-2
Why are lower doses of ASA effective for antiplatelet response?
- inhibition of platelet COX-1 occurs at lower doses than inhibition of COX-2 in the vessel wall
- platelets have no nucleus
What is the onset of action for platelet inhibition with ASA?
~ 5 minutes
What is the duration of antiplatelet action with ASA?
7-10 days
What are the ADRs with ASA?
- GI upset
- bleeding
ASA therapy in combination with _______ can inhibit the site of action for ASA and reduce its antiplatelet effects.
other NSAIDs
What is the MOA of thienopyridines?
- irreversible antagonist of platelet P2Y12 ADP receptors
- the P2Y12 receptor couples to Gi to inhibit adenylyl cyclase
What is the route of administration of clopidogrel?
oral
Maximal platelet inhibition occurs within _______ of oral administration of clopidogrel.
5-7 days
Antiplatelet effects of clopidogrel persist for _______ after discontinuing.
4-8 days
Clopidogrel is a prodrug. (T/F)
True
Clopidogrel is a preferred agent because it has very little variation among patients. (T/F)
False: variability is an issue with clopidogrel
Prasugrel is a prodrug. (T/F)
True
What is the route of administration of prasugrel?
oral
Prasugrel requires hepatic conversion to an active metabolite. (T/F)
True
Which thienopyridine has the quickest onset of action?
prasugrel
Clopidogrel is considered more efficacious for ACS than Ticagrelor. (T/F)
False: ticagrelor is considered more efficacious
Ticagrelor requires hepatic conversion to an active metabolite. (T/F)
False: no required metabolic activation
What is the route of administration of ticagrelor?
oral
Ticagrelor is not a thienopyridine. (T/F)
True
Ticagrelor irreversibly binds to the platelet P2Y12 receptor. (T/F)
False: reversibly
Cangrelor is a reversible P2Y12 receptor antagonist. (T/F)
True
What is the route of administration of cangrelor?
IV
Cangrelor is not a thienopyridine. (T/F)
True
Cangrelor requires hepatic activation. (T/F)
False
The antiplatelet effects of cangrelor are reversed ________(slowly/quickly) after stopping infusion.
quickly
What is cangrelor FDA approved for?
Adjunct during PCI to reduce thrombosis
What is the MOA of GP IIb/IIIa antagonists?
Inhibits binding of fibrinogen to the activated GP IIb/IIIa receptor to prevent platelet aggregation.
Monoclonal antibody that binds GP IIb/IIIa receptor
abciximab
reversible RGD-mimetic peptide that binds GP IIb/IIIa receptor
eptifibatide
reversible non peptide RGD-mimetic that binds GP IIb/IIIa receptor
tirofiban
What is the route of administration for GP IIb/IIIa inhibitors?
IV
What is the onset of action for GP IIb/IIIa inhibitors?
minutes
What is the duration of action for GP IIb/IIIa inhibitors?
abciximab: up to 72 hours
eptifibatide and tirofiban 4-6 hours
GP IIb/IIIa inhibitors are often used in combination with _______ during PCI.
clopidogrel
What is the main ADR of GP IIb/IIIa inhibitors?
bleeding
GP IIb/IIIa inhibitors are available as oral formulation. (T/F)
False
What are the anticoagulant phosphodiesterase inhibitor agents?
- Aggrenox
- Persantine
- Cilostazol
What are the components of Aggrenox?
- aspirin 25 mg
- dipyridamole ER 200 mg
What is Aggrenox indicated for?
ischemic stroke and TIA
What are the components of Persantine?
dipyridamole only: not effective antiplatelet
What is Cilostazol approved for?
intermittent claudication
What is the MOA for Vorapaxar?
protease-activated receptor-1 (PAR-1) antagonist
What is Vorapaxar approved for?
reduce trombosis in patients with previous MI or PAD
What is the route of administration of Vorapaxar?
oral
Why is Vorapaxar considered to have irreversible effects?
While the antagonism is reversible, the half-life is so long (8 days) that it is considered to be irreversible because the life span of a platelet is 8-9 days.
What are the contraindications for Vorapaxar?
- history of stroke or TIA
- intracranial hemorrhage
- current active bleeding
