Antithrombotic agents

Question 1

How does aspirin function as an antiplatelet drug?

Answer 1

Blocks thromboxane and PGI2 production for prevention of arterial thrombosis
- Thromboxane promotes platelet aggregation, can only be restored by new platelet formation in 1-2 weeks
- PGI2 inhibits platelet aggregation, can be restored by synthesis of new COX enzyme due to presence of endothelial cell nuclei to make new COX enzymes
Once aspirin bonds irreversibly to COX, more TXA production is blocked than PGI2 as it can be regenerated via cell nuclei, effect of platelet aggregation inhibition is more dominant.

Question 2

Mechanism of action of clopidogrel

Answer 2

Pro-drug P2Y12 receptor irreversible antagonist to inhibit ADP-induced platelet aggregation
Inhibits platelet lifespan

Question 3

How is prasugrel different from clopidogrel?

Answer 3

Prasugrel is also a pro-drug and irreversible, but has a faster onset

Question 4

How is ticagrelor different from clopidogrel?

Answer 4

Ticagrelor is a direct reversible antagonist

Question 5

Mechanism of action of abciximab

Answer 5

GP IIb/IIIa fibrinogen receptor antagonist which decreases ischemic complications and narrowing of blood vessels

Question 6

AE of abciximab

Answer 6

Bleeding and thrombocytopenia

Question 7

How does unfractionated heparin function as an anticoagulant?

Answer 7

1. Inhibits activity of IIa, IXa and Xa
2. Promotes release of TFPI, which blocks conversion of X to Xa
3. Binds to plasma protease inhibitor III, changing its conformation to enhance interaction with clotting factors by 1000x to form inactive complexes that prevents fibrin formation

Question 8

Heparin antidote

Answer 8

Protamine sulfate

Question 9

Difference between unfractionated and low molecular weight heparin?

Answer 9

LMW heparin inhibits more Xa and less IIa
LMW heparin route via subcutaneous only, unfractionated can be via subc or IV
LMW heparin has better bioavailability and longer plasma half life
Similar risk of bleeding but LMW has less thrombocytopenia and osteoporosis

Question 10

Mechanism of action of warfarin

Answer 10

Inhibits vitamin K epoxide reductase, preventing the gamma-carboxylase from synthesising II, VII, IX and X

Question 11

What is rivaroxaban?

Answer 11

Oral direct Xa inhibitors

Question 12

What is argatroban and dabigatran?

Answer 12

Oral direct IIa inhibitors

Question 13

Which antithrombotic agents are contraindicated in pregnancy?

Answer 13

Aspirin (3rd trimester)

Warfarin

Question 14

Which antithrombotic agent, when used with warfarin, will enhance its anticoagulant effects?

Answer 14

Heparin

Question 15

How do fibrinolytics work?

Answer 15

Cleaves plasminogen to plasmin, which degrades the fibrin matrix of thrombus

Question 16

When are fibrinolytics used?

Answer 16

Acute myocardial infarction, ischemic stroke, acute pulmonary embolism