Antiplatelets and Fibrinolytics- Austin

What are the 4 classes of antiplatelets?

What are the 4 classes of antiplatelets?

1. Cyclooxygenase (COX) inhibitors aka NSAIDs

2. Phosphodiesterase inhibitors (PDE)

3. ADP receptor pathway inhibitors (ADP)

4. Glycoprotein IIb/IIIa antagonists

What is the ONLY NSAID used for antiplatelet therapy?

aspirin

Which of the following are PDE inhibitors?

SATA

a. Dipyridamole

b. Cilostazole

c. Abciximab

d. Clopidogrel

a,b

What are the 3 ADP receptor pathway inhibitors?

• Clopidogrel

• Prasugrel

• Ticagrelor

Note: all have “grel” in the name

What are the 3 Glycoprotein IIb/IIIa antagonists?

• Abciximab

• Eptifibatide

• Tirofiban

Which COX isoform deals with platelets?

a. COX1

b. COX2

a

Inhibiting COX1 will do what do platelet function? (increase/decrease)

decrease

What is the MOA of Aspirin?

covalently (irreversibly) binds to active site of COX1 and COX2

__________________ in cAMP leads to decrease in platelet activation and aggregation. (increase/decrease)

increase

• think of cAMP as brakes to platelet aggregation

How can we increase cAMP?

inhibit platelet phosphodiesterases

(exactly why our drug class is called “Phosphodiesterase Inhibitors”)

Which PDE Inhibitor has an ADR of coronary steal syndrome?

Dipyridamole

Which PDE inhibitor can also be used for intermittent claudication?

Cilostazol

Which PDE inhibitor is contraindicated in heart failure?

Cilostazol

Which PDE inhibitor has a weak antiplatelet effect and is always combined with warfarin or aspirin?

Dipyridamole

Which PDE inhibitor has a high chance of CYP interactions?

Cilostazol

ADP receptor pathway inhibitors work by blocking what receptor?

P2Y₁₂

If we block the P2Y₁₂ receptor what happens?

ADP can’t bind= AC less inhibited= more cAMP= less platelet activation

What is the boxed warning on Clopidogrel (ADP Inhibitor)?

patients with 2C19 polymorphisms may have increased risk of CV events

Why can the 2C19 polymorphisms increase risk of CV events?

If your 2C19 doesn’t activate the drug, you have a clotting possibility

Boxed warning of Prasugrel and Ticagrelor:

bleeding risk-avoid in patients with history of TIA/stroke, active bleeding, severe hepatic impairment

Clopidogrel ____ a prodrug. Ticagrelor ______ a prodrug.

a. is, is

b. is, isn’t

c. isn’t, isn’t

d. isn’t, is

b

Which ADP inhibitors covalently(irreversibly) bind to the P2Y₁₂ and which are competitive inhibitors?

Covalent- Clopidogrel, Prasugrel

Competitive- Ticagrelor

GP IIb/IIIa antagonists are all ___________________.

a. oral

b. parental

b

MOA of Abciximab (GP IIb/IIIa antagonist):

irreversibly bind GPIIb/IIIa receptor

• uses steric effects

  • like “sitting on” on the GP IIb/IIIa receptor

What are the contraindications of Abciximab?

• active internal bleeding

• recent bleeding

• thrombocytopenia

• history of stroke

• recent trauma/surgery

• severe, uncontrolled HTN

Eptifibatide and Tirofiban bind _________________. (reversibly/irreversibly)

reversibly