Antiplatelet Medications Flashcards
What are the 3 functions of platelets?
- activation
- adhesion
- aggregation
Which clotting factors promote platelet adhesion to damaged vascular walls?
- factor VIII and vWF
What is the most common inherited coagulation defect?
- vonWillebrand’s disease
What factor activates the platelet?
- thrombin (factor IIa)
What 2 mediators promote platelet aggregation?
- ADP
- thromboxane A2
They uncover the fibrinogen receptor, which links PLT’s together
What clotting factor causes platelet aggregation?
- fibrinogen (factor I)
- attaches to receptors and links platelets together
What are the 4 types of platelet aggregation inhibitors?
- aspirin
- NSAIDS
- platelet glycoprotein (GP IIb/IIIa) receptor inhibitors
- thienopyridine ADP-receptor antagonists
Name 4 thienopyridine ADP-receptor antagonists
- clopidogrel (Plavix)
- prasugrel (Effient)
- ticagrelor (Brilinta)
- ticlopidyne (Ticlid)
What is the mechanism of action of thienopyridine ADP-receptor antagonists?
- bind selectively and non-competitively to low affinity ADP receptor binding site on surface of platelets
- causes inhibition of ADP binding to the receptor and inhibits activation of platelet glycoprotein complex necessary for fibrinogen platelet binding
- receptor is irreversibly modified by these drugs
How long should plavix be stopped prior to surgery?
- 7 days
- platelet aggregation and bleeding time return to baseline values within 5 days
True or False
Platelets exposed to Plavix or Effient are affected for the remainder of their lifespan.
- true
How long does it take for plavix to reach a steady state in the blood?
- 40-60% inhibition after the first day of therapy
- steady state reached in 3-7 days
What medication can normalize prolonged bleeding time within 2 hours in patients being treated with ticlid?
- methylprednisolone
- platelet transfusion can also be used to reverse the effects (avoid in patients with TTP).
When should ticagrelor (Brilinta) be stopped prior to surgery?
- 5 days
When should prasugrel (Effient) be stopped prior to surgery?
- 7 days
True or False
Brilinta is not reversible.
- false
Brilinta is a __________ substrate.
- CYP3A4
How long will it take for a patient to return to baseline after Effient is discontinued?
- 5-9 days
How long does it take for Effient to reach steady state in the body?
- half of platelets are inhibited within 1 hour
- steady state in 3-5 days
What are the adverse effects of plavix, Effient and Brilinta?
- bleeding
- diarrhea
- N/V
- rash
- thrombotic thrombocytopenia purpura
- severe neutropenia
What are the adverse effects of Ticlid?
- greater than 50% of patients have diarrhea or rash
- agranulocytosis
- aplastic anemia
- bleeding
- severe neutropenia
- thrombotic thrombocytopenia purpura
True or False
Cangrelor (Kengreal), a platelet aggregation inhibitor, should not be administered with a GIIb/IIIa inhibitor.
- true
What is measured by VerifyNow P2Y12?
- measures the percentage of platelet inhibition
- used to monitor antiplatelet therapy
- can be used to help determine when it is safe to proceed with surgery or regional anesthesia (<20% inhibition)
What are 3 assays that can be used to measure platelet inhibition?
- VerifyNow aspirin
- VerifyNow IIb/IIIa
- VerifyNow P2Y12
What is the mechanism of action of platelet glycoprotein IIb/IIIa receptor inhibitors?
- interact with platelet glycoprotein IIb/IIIa to inhibit fibrinogen binding to activated platelets
- leads to inhibition of platelet aggregation and clot retraction
What are indications for use of platelet glycoprotein IIb/IIIa receptor inhibitors?
- acute ischemic complications of percutaneous coronary intervention
- unable angina
- non Q-wave MI
What are adverse effects associated with platelet glycoprotein IIb/IIIa receptor inhibitors?
- anaphylaxis
- bleeding
- hypotension
- N/V
- thrombocytopenia
What GI med can cause stent failure if given with plavix?
Prilosec
plavix is a prodrug. If you give a CYP2C9 it inhibits the prodrug activation. Prilosec is a 2C9
What is the only ADP receptor antagonist that is reversible?
ticagrelor (Brilinta)
vonWillebrand’s factor (Factor VIII:vWF) is manufactured and released from _______
endothelial cells
MOA of aspirin
Renders cyclooxygenase nonfunctional for the life of the PLT (8-12 days)
MOA of NSAID’s
Depression of thromboxane-A2 production by platelets is only temporary (approx. 24-48 hours).
What is cyclooxygenase?
Rate-limiting enzyme in the conversion of arachidonic acid to thromboxane-A2
Without thromboxane-A2, platelet aggregation is impaired
What is the most widely used ADP receptor antagonist?
Plavix
Name 3 platelet GIIb/IIIa receptor inhibitors
Abciximab (ReoPro®)
Eptifibatide (Integrilin ®)
Tirofiban (Aggrastat ®)
These work OUTSIDE of the platelet
T/F
With the exception of Ticagrelor (Brilinta®), all other ADP receptor antagonists are irreversible
True
ADP receptors antagonists are ____, _____, _____
selective
noncompetitive
irreversible
Which ADP receptor inhibitor has the longest hold time prior to surgery?
Ticlopidine (Ticlid ®) Needs to be held 14 days
What can be done to reverse ADP inhibitors
basically just give PLT’s and blood products
What is the only IV P2Y12 inhibitor?
Cangrelor
Is cangrelor reversible?
yes, PLT’s return to normal after 1 HOUR of stopping infusion
With VerifyNow, it safe to proceed with surgery or regional anesthesia if PLT inhibition is ____
less than 20%
What anti-platelet med is not effective when used alone, only when combine with an anticoagulant or PLT aggreagation inhibitor?
Dipyridamole (Persantine®)
What med is a combination of dipyridamole and ASA?
Aggrenox
Used in CVA patients
what is the major drawback to Vorapaxar (Zontivity ®)?
Long half life of 5-13 days
Which GIIb/IIIA antagonist is not rapidly reversible?
Abciximab (Reopro)
All of them are reversible, this med just takes longer (48hrs)
Emily stressed in the lecture that this is the important thing to know about GIIb/IIIa inhibitors
T/F
SQ Heparin is a contraindication to the use of neuraxial techniques
FALSE
If on heparin > days, just check PLT count first to r/o HIT
