L33 Antiplatelet Drugs

Question 1

During platelet aggregation and release reactions, what happens?

Answer 1

Pharmacologically active substances are released from granules. In addition, many of the prostaglandin derivatives such as thromboxanes are formed.

Question 2

Describe a platelet aggregation assay.

Answer 2

1. Prepare PRP
2. Activate platelets (ADP, TRAP, EPI, 5-HT, collagen, ristocetin, AA)
3. Measure light transmittance (more aggregation, more light)

You are looking for indication of platelet dysfunction (lack of aggregation)

Question 3

What is an antiplatelet agent?

Answer 3

A drug that decreases platelet adhesion, activation, and aggregation, thereby inhibiting thrombus formation

Question 4

Where are antiplatelet agents effective?

Answer 4

In arterial circulation (where anticoagulants such as heparin and warfarin have little effect)

Question 5

What are the 8 main antiplatelet agents/categories?

Answer 5

1. Aspirin
2. COX inhibitors
3. Propionic acid derivatives (NSAIDs)
4. ADP receptor inhibitors
5. Dipyridamole (coronary vasodilator)
6. Cilostazol (intermittent claudication)
7. GP 2b3a inhibitors
8. Prostacyclin analogues

Question 6

What is the main COX inhibitor?

Answer 6

Celebrex

Question 7

What are the main NSAIDs?

Answer 7

Ibuprofen, naproxen

Question 8

What are the 5 major ADP receptor inhibitors?

Answer 8

Ticlopidine, Clopidogrel (Plavix), Prasugrel, Ticagrelor, Cangrelor

Question 9

What are the 3 GP 2b3a inhibitors?

Answer 9

1. Abciximab
2. Tirofiban
3. Eptifabatide

Question 10

___ may be a cause of recurrent ischemic vascular events in patients taking aspirin.

Answer 10

Aspirin resistance

Question 11

What may be the cause of aspirin resistance?

Answer 11

COX polymorphism

Question 12

What is the MOA of ADP receptor inhibitors?

Answer 12

The drug binds to the ADP receptor on the platelet, preventing subsequent platelet aggregation

Question 13

___ has high interpopulation variation.

Answer 13

Clopidogrel

Question 14

What is the MOA of GP 2b3a inhibitors?

Answer 14

The drug binds to the GP 2b3a receptor and inhibitors platelet aggregation.

Question 15

What are the # clinical applications of antiplatelet drugs?

Answer 15

1. Cerebrovascular disease (transient ischemic attack, complete stroke)
2. Coronary artery disease (acute myocardial infarction, unstable angina)
3. Saphenous vein coronary artery bypass grafts
4. Peripheral vascular disease (venous thrombosis, peripheral arterial disease)
5. Small vessel disease (TTP)
6. Prevention of thrombus formation on artificial surfaces

Question 16

What are the important drug interactions with antiplatelet agents?

Answer 16

1. Thrombolytic agents
2. Heparin
3. Warfarin
4. Antithrombin agents

Question 17

Describe the metabolism of arachadonic acid.

Answer 17

AA is released by phospholipase A2. It is then converted via COX to cycloendoperoxides and then to thromboxanes (platelets), prostacyclins (endothelium), and prostaglandins (smooth muscle)

OR

via 5-LO to leukotrienes

Question 18

What is the MOA of aspirin?

Answer 18

Inhibition of COX, which inhibits thromboxane formation and inhibits platelet aggregation

Question 19

What are the different effects caused by thromboxane and by prostacyclin?

Answer 19

Thromboxane: vasoconstriction and platelet aggregation

Prostacyclin: vasodilation and platelet disaggregatino

Question 20

What is an inhibitor of lipoxygenase?

Answer 20

Zileuton (treatment of asthma)

Question 21

What are 2 leukotriene antagonists?

Answer 21

Montelkast (asthma/seasonal allergies), Zaririukast (asthma)

Question 22

What are the active ingredients in omega-3 fatty acids?

Answer 22

1. Alpha-linolenic acid
2. Eicosaphentaenoic acid
3. Docosahexaenoic acid

Question 23

What is the mechanism of fish oil?

Answer 23

Antiplatelet via membrane effects and thromboxane A3 (inactive) formation

Question 24

What are the two phosphodiesterase inhibitors?

Answer 24

1. Dipyridamole

2. Cilostazol