H. Anti-Platelet Drugs

Front 1

What are 5 antiplatelet drugs?

Back 1

-Aspirin
-Dipyridamole
-Ticlopidine
-Clopidogrel
-Abciximab

Front 2

What is the major role of platelets in vascular injury?

Back 2

They provide the initial hemostatic plug at the injury site.

Front 3

What are 3 pathologic thromotic processes in which platelets participate?

Back 3

-MI
-Stroke
-DVT

Front 4

What causes platelets to adhere to exposed subendothelium of a damaged blood vessel?

Back 4

GP1a/2a - Collagen receptor
GPIb - vWF receptor

Front 5

What 2 receptors are initially responsible for platelets aggregating?

Back 5

PAR1/PAR4
P2Y1/P2Y12

Front 6

What is the ligand for PAR1/PAR4 receptor on platelets?

Back 6

Thrombin

Front 7

What is the ligand for P2Y1/P2Y12 receptor on platelets?

Back 7

ADP

Front 8

What happens when PAR1/PAR4 and P2Y1/P2Y12 are stimulated?

Back 8

They activate GPIIb/IIIa and Cox-1 to promote platelet aggregation and secretion.

Front 9

What is GbIIb/IIIa?

Back 9

Platelet Fibrinogen-binding protein.

Front 10

What is the result of GB2b/3a being activated?

Back 10

Fibrinogen binding results in cross-linking of adjacent platelets.

Front 11

What is the result of Cox-1 being activated?

Back 11

TxA2 is synthesized which also stimulates platelet aggregation.

Front 12

What is the product of Cox-1 in endothelial cells? What is its function?

Back 12

Prostacyclin - inhibits platelet activation to prevent overdoing the platelet aggregation.

Front 13

What is the mechanism of Aspirin in preventing platelet aggregation?

Back 13

Irreversible inhibition of platelet cyclooxygenase

Front 14

How does aspirin inhibit Cox-1?

Back 14

By acetylating a serine residue near the active site of the enzyme.

Front 15

What is not formed as a result of inhibiting cox-1 in platelets?

Back 15

Thromboxane - hence no platelet aggregation.

Front 16

How is Aspirin administered?

Back 16

Orally

Front 17

What are the 2 adverse effects of Aspirin but what is good about when it's used to prevent platelet aggregation?

Back 17

-Gi upset
-GI bleeding
Aspirin doses for this are usually low, so these effects won't be severe.

Front 18

What are the acute uses of Aspirin?

Back 18

-Acute MI (alone or in combo with a thrombolytic)
-Ischemic stroke
-Unstable angina

Front 19

What are 3 chronic/prophylactic uses of Aspirin?

Back 19

-MI prophylaxis
-Stroke prophylaxis
-Preeclampsia prophylaxis

Front 20

What are 2 actions of Dipyridamole?

Back 20

1. A PDE inhibitor
2. Inhibits the uptake of adenosine by RBCs/EC's

Front 21

What results from Dipyridamole -inhibiting PDE?
-Inhibiting adenosine uptake?

Back 21

-Increased cAMP
-Decreased ADP

Front 22

And what does increased cAMP and decreased ADP result in?

Back 22

Inhibition of platelet aggregation

Front 23

How is Dipyridamole administered?

Back 23

Orally

Front 24

What are 3 side effects of Dipyridamole?

Back 24

-Headache
-GI upset
-Dizziness

Front 25

What is the main therapeutic use of Dipyridamole?

Back 25

Prevention of thromboembolism in patients with prosthetic heart valves

Front 26

How is Dipyridamole almost always used?

Back 26

With Warfarin

Front 27

What are Ticlopidine and Clopidogrel? How do they work?

Back 27

Anti-platelet drugs that act through P2Y1-P2Y12 receptors to inhibig ADP-induced plt aggregation

Front 28

What are the Gproteins that are coupled to the P2y1/P2y12 receptors? What effector mechanism results?

Back 28

P2y12 = Gi - decreases adenyl cyclase, decreases cAMP
P2y1 = Gq - increases PLC, increases calcium

Front 29

What happens when Ticlopidine and Clopidogrel bind the P2y1/P2y12 receptors?

Back 29

They prevent ADP from binding so that it can't induce platelet aggregation.

Front 30

What are the 2 clinical manifestations of Blocking ADP induced platelet aggregation with Ticlopidine/Clopidogrel?

Back 30

-Prolonged bleeding time
-Delayed clot retraction

Front 31

How are Ticlopidine/Clopidogrel administered?

Back 31

Orally as prodrugs that are metabolized to active compounds.

Front 32

Which drug is associated with major toxicity?

Back 32

Ticlopidine

Front 33

What is the major toxicity associated with Ticlopidine?

Back 33

-Blood dyscrasias
-Neutropenia

Front 34

What are the 2 main therapeutic indications of Clopidogrel?

Back 34

-MI prophylaxis
-Stroke prophylaxis

Front 35

What are 6 therapeutic indications of Ticlopidine?

Back 35

-2ndry prevention of cerebrovascular disease
-2ndry prevention of MI
-Unstable angina
-Coronary artery stenting
-Periph vascular disease
-TIA's, complicated strokes

Front 36

What is Abciximab?

Back 36

A GP 2b/3a receptor blocker

Front 37

What is GP2b/3a?

Back 37

The plt membrane integrin that binds fibrinogen and is the major plt surface receptor involved in platelet aggregation

Front 38

What is Abciximab's mechanism of action?

Back 38

Binds GP2b/3a on platelets and prevents aggregation by preventing binding fibrinogen.

Front 39

What 2 types of binding are thought to be involved in the mechanism of action of Abciximab?

Back 39

-Steric hindrance
-Conformational changes block access of fibrinogen to its receptor.

Front 40

What is NOT likely the mechanism of Abciximab?

Back 40

Not direct interaction with the RGD binding site of GP2b/3a

Front 41

How is Abciximab administered?

Back 41

IV as a bolus injection, then continuous infusion for up to 72 hrs

Front 42

What are 2 adverse effects of Abciximab?

Back 42

-Bleeding
-Thrombocytopenia is relatively common

Front 43

What increases the risk of recurrent thrombocytopenia due to Abciximab?

Back 43

Re-exposure to the drug.

Front 44

What therapeutic use is Abciximab indicated for?

Back 44

As an adjunct to prevent cardiac ischemia in patients undergoing angioplasty.

Front 45

How is Abciximab always given?

Back 45

WITH aspirin and Heparin - only in that setting.