Antiplatelets

Question 1

When are haemostasis promotion drugs used?

Answer 1

If a patient has:
Haemophilia
Extensive anticoagulation therapy
Haemorrhage after surgery
Menorrhagia (v.heavy period)

Question 2

What do platelets do?

Answer 2

Maintain integrity of circulation and make thrombois and thrombi
-Essential for haemostasis, healing of vessels and inflammation

Question 3

What properties do platelets have?

Answer 3

-Adhesion following vascular damage
-Shape change
-Secretion of granule contents
-Biosynthesis of PAF and prostaglandins
-Aggregation**
-Exposure of acidic phospholipid on surface to promote aggregation

Question 4

What are the mechanism’s of platelet adhesion, activation and secretion?

Answer 4

1) Only activated in blood when damage occurs.
2) The endothelial dies, matrix is then exposed, platelet binds to collagen receptors
3) Soluble Thromboxane A2, stimulates platelets
4) Aggregation activates fibrin,
5) Change of shape and the cytoskeleton changes the platelet

Question 5

What causes bleeding to stop by blocking the blood vessel?

Answer 5

Platelet plug, when contracting this further blocks the blood vessel.

Question 6

What can we inhibit to influence platelet aggregation?

Answer 6

INHIBITING - Thromboxane A2 and ADP, this stops the cells from aggregating, limiting NO + p.
-Removing ADP means less activation of platelets

Question 7

What can we stimulate to influence platelet aggregation?

Answer 7

STIMULATING - Prostacyclin and Nitric oxide
-NO production is short lived, increasing prostacyclin formation inhibits platelets

Question 8

What activates platelets?

Answer 8

ADP
TXA2
Collagen
Fibrinogen

Question 9

What is the aim of antiplatelet drugs?

Answer 9

To decrease platelet aggregation and inhibit thrombus formation in arterial circulation.

Question 10

What are some examples of antiplatelets?

Answer 10

Aspirin
Thienopyridines - Clopidogrel (prasugrel/ticlopidine)
Ticagrelor
Glycoprotein IIb/IIIa inhibitors - Eptifibatide/Tirofiban/Abciximab
Dipyridamole

Question 11

What is Aspirin used for?

Answer 11

NSAID
Antiplatelet
Colonic and rectal cancer
Alzheimer’s disease
Radiation induced diarrhoea

Question 12

What is the MOA of aspirin?

Answer 12

*Irreversibly inactivates COX 1 & 2

Question 13

Where is COX 1 located?

Answer 13

In platelets

Question 14

Where is COX 2 located?

Answer 14

Endothelial cells

Question 15

What is the function of COX 2?

Answer 15

Make prostacyclin, inhibit platelet activation and aggregation

Question 16

What is the function of COX 1?

Answer 16

Synthesises of A2 –> Platelet stimulation

Question 17

What does aspirin do to COX 1?

Answer 17

Irreversibly inactivates cox 1 in platelets
-reducing thromboxane A2
-reducing platelet aggregation

Question 18

What does aspirin do to cox 2?

Answer 18

Irreversible inactivates COX 2 in endothelium
-reduces prostacyclin formation
-Increases platelet aggregation

Question 19

Although aspirin acts on both cox 1 and cox 2 in different ways, this has a net effect zero, so how does it work?

Answer 19

Because, endothelial cells can synthesise new COX-2, as fresh RNA/protein and more COX2/prostacyclin is made. Platelets cannot because they have no nuclei - meaning no thromboxane A2 is made and stores are low.
Meaning: Lower does just inhibit platelets and Higher doses inhibit both

Question 20

What effect does a lower dose of antiplatelets have?

Answer 20

Inhibits platelets only

Question 21

What effect do higher doses of antiplatelet have?

Answer 21

Inhibit platelets and synthesis of new COX 2 is promoted.

Question 22

Can you take a Thienopyridine (clopidogrel/prasugrel) with aspirin?

Answer 22

Yes, they act on a different pathway.

Question 23

What do Thienopyridines work on?

Answer 23

Pro-Drugs
-Inhibit ADP-induced aggregation (ADP receptor antagonists) - block ADP binding to receptors, inhibit platelet activation
-Also antagonise the platelet P2Y12 receptor (Purinergic receptor)

Question 24

What is the role of ADP in platelet aggregation?

Answer 24

Platelet primary and secondary aggregation.
Induces platelet shape, secretion from storage granules, influx and intracellular mobilisation of calcium and inhibition of stimulated adenylyl cyclase activity.

Question 25

What is the role of the P2Y12 receptor?

Answer 25

Plays a central role in platelet function, haemostasis and thrombosis.

Question 26

What type of drug is Ticagrelor?

Answer 26

Nucleoside analogue - like adenosine

Question 27

How does Ticagrelor work?

Answer 27

Blocks P2Y12 ADP receptors on platelets,

Question 28

How is Ticagrelor a allosteric inhibitor?

Answer 28

It has a different binding site than ADP and the blockage is reversible and therefore acts faster and for a shorter period of time.

Question 29

What drug has had a PLATO trial, showing less mortality from all CV causes than another drug?

Answer 29

Ticagrelor causes less mortality than clopidogrel

Question 30

How do Glycoprotein IIB/IIIA receptor antagonists work?

Answer 30

They stop aggregation causing reduced platelets
-These inhibit ALL pathways of platelet activation because they bind to glycoproteins IIb/IIIA receptors, which blocks fibrinogen binding so inhibits aggregation.

Question 31

What is an example of a glycoprotein IIB/IIIA receptor antagonist? - monoclonal antibody

Answer 31

Abciximab - monoclonal antibody
-Only used ONCE - this is £260!
-Used with heparin and aspirin for prevention of complications in pts undergoing percutaneous coronary intervention

Question 32

What cyclic peptides are glycoprotein IIB/IIIA receptor antagonists?

Answer 32

Eptifibatide and Tirofiban
-Adjunct with heparin and aspirin to prevent early MI in pts with unstable angina or NSTEMI