Antiplatelet Agents

Question 1

Which drugs affect hemostasis?

Answer 1

1. Heparin-like
2. Oral agents
   - warfarin
   - direct acting IIa and Xa inhibitors
3. Antiplatelet agents
   - aspirin
   - clopidogrel
   - GP inhibitors (angioplasty)
4. Medical devices

Question 2

What drugs affect thrombolysis?

Answer 2

Plasminogen activators

• alteplase

Question 3

What is the goal of anticoagulation?

Answer 3

To diminish the activity of Factors Xa and IIa (thrombin)

Question 4

What are examples of antithrombin III catalysts??

Answer 4

• heparin
• enoxaparin
• fondaparinux

Question 5

What are examples of thrombin inhibitors?

Answer 5

• dabigatran
• rivaroxaban
• apixaban

Question 6

What is an inhibitor of clotting factor synthesis?

Answer 6

warfarin

Question 7

What’s the difference between fractionated and unfractionated heparin?

Answer 7

unfractionated = larger

fractionated = smaller

Question 8

What is the pH of heparin?

Answer 8

acidic

made from porcine intestine or bovine lung

Question 9

Antithrombin III catalysts MOA

Answer 9

Activate anti thrombin III so that it can bind to and inactivate factors IIa and Xa clotting factors.

Question 10

True/false: heparin is NOT consumed in the reaction (binding to antithrombin III)

Answer 10

True. It is NOT consumed. It is a catalyst

Question 11

Unfractionated heparin MOA

Answer 11

accelerates the reaction. Can bridge thrombin/antithrombin molecules, which speeds up the reaction of ATIII and IIa

Question 12

LMW heparin MOA

Answer 12

No bridge. Can accelerate the interaction of ATIII with Xa.

Question 13

Fondaparinux MOA

Answer 13

Pentasaccharide that binds to ATIII, inhibits Xa activity.

Question 14

Which of the heparins requires routine monitoring?

Answer 14

heparin

Question 15

True/false: heparin does not cross the placenta.

Answer 15

True

Question 16

Heparins: adverse effects

Answer 16

BLEEDING

hypersensitivity

thrombocytopenia

Question 17

What is the best way to monitor the anticoagulant action of heparin?

Answer 17

aPTT (increase)

maintain 2x control time

Question 18

What is Heparin-induced thrombocytopenia? (HIT)

Answer 18

Antibodies againsed heparin-platelet factor 4 complexes. Bind to Fc receptors on adjacent platelets >> aggregation. = antibody mediated thrombocytopenia with paradoxical thrombosis

Question 19

True/False: warfarin is contraindicated in HIT.

Answer 19

True.

A direct thrombin inhibitor is preferred, fondaparinux or argatroban.

Question 20

Contraindication for heparin

Answer 20

• hypersensitivity
• active bleeding
• threatened abortion
• infective endocarditis
• surgical procedures

Question 21

What is the heparin antagonist?

Answer 21

protamine sulfate

ion pairs with heparin to form a stable complex. BE CAUTIOUS: excess PS has anticoagulant activity. Adverse effects = dyspnea, bradycardia, hypotension

Question 22

Indications for LMW heparin

Answer 22

• DVT, clots

- CONTRAINDICATED in HIT

Question 23

Indications for Fondaparinux

Answer 23

• PE, DVT
• thromboprophylaxis for hip/knee surgery

- use for HIT

Question 24

Thrombin inhibitors MOA

Answer 24

Agents that bind to and directly inhibit the activity of key clotting factors.

Question 25

Warfarin MOA

Answer 25

decreases synthesis of **active coagulation factors** ## Footnote *_inhibits addition of the gamma-carboxy groups to the clotting factors_* *_= **inactive factors**_*

Question 26

What is warfarin's MOA in relation to **vitamin K?**

Answer 26

It blocks the enzyme VKORCI, which is key to recycling (reduction) of vitamin K.

Question 27

What is important to know about the time frame for using warfarin clinically?

Answer 27

It takes time, 8-12 hrs for the drug to act; full activity takes several days.

Question 28

Warfarin Adverse effects

Answer 28

1. BLEEDING 2. Fetal hemorrhage; abn bone formation 3. I**nhibition of protein C and S \>\> procoagulant states**

Question 29

Vitamin K and Warfarin

Answer 29

Warfarin = structural analog of vit. K **(isomers)** ## Footnote **S form is 4x more active**

Question 30

Warfarin **drug interactions**

Answer 30

metabolized by **CYP2C9** ## Footnote **Vitamin K-large doses can reverse warfarin action**

Question 31

**Dabigatran** **Rivaroxaban** **Apixaban**

Answer 31

orally direct acting inhibitors

Question 32

Dabigatran

Answer 32

Prodrug \>\> hydrolysis **Adverse effects** = _BLEEDING_ (esp GI), slightly higher MI risk **Drug interactions**: p-glycoprotein transport (ketocon**azole** + **rifampin**)

Question 33

Are there antidotes to **dabigtran** and **rivaroxaban**?

Answer 33

NO \*also very expensive drugs

Question 34

Rivaroxaban

Answer 34

**Adverse effect** = _BLEEDING_ **Drug interactions**: p-glycoprotein and **_Cyp 3A4_**

Question 35

Desirudin MOA

Answer 35

**_D_**irect acting thrombin inhibitor - *no need for ATIII* * - one to one complex with thrombin* ***was lepirudin***

Question 36

Bivalrudin MOA

Answer 36

20 AA direct inhibitor

Question 37

Argatroban MOA

Answer 37

must be **IV** blocks catalytic site of thrombin (reversible) **_use in HIT_**

Question 38

Abciximab MOA

Answer 38

blocks GP IIB/IIIa receptors - an integrin, receptor for fibrinogen and vWF adjunctive for angioplasty

Question 39

Clopidogrel (&prasugrel) MOA

Answer 39

Antiplatelet ADP pathway: **P2Y1 and P2Y12 receptors** activated at the same time \>\> activate platelets **Clopidogrel inhibits activation P2Y12 _irreversibly_** \*\*alternative for apteints who cannot tolerate aspirin (no effect on prostaglandin pathway)

Question 40

What happens when you combin **clopidogrel and aspirin**?

Answer 40

synergy

Question 41

What is unique about the metabolism of heparin?

Answer 41

metabolized by the RES

Question 42

What is unique about the metabolism of dabigatran?

Answer 42

Is NOT **metabolized** ## Footnote **renal excretion**

Question 43

Prasugrel

Answer 43

newer member of class contraindicated in **cerebrovascular** disease

Question 44

Adverse effect of Clopidogrel

Answer 44

rash, diarrhea, abdominal pain, dyspepsia, bleeding