Antiplateletes

Question 1

3 thromboembolic cardiovascular disorders

Answer 1

1. atherosclerosis –> thrombosis –> NSTEMI/STEMI
2. atrial fibrillation –> thromboembolism –> ischaemic stroke/TIA
3. venous thromboembolism –> deep vein thrombosis

Question 2

what triggers platelet activation

Answer 2

endothelial cell damage
exposure of collagen
release of von Willebrand factor

Question 3

how do platelets adhere?

Answer 3

adhere to VWF/collagen matrix and platelet glycoprotein GP1b receptor

Question 4

how do platelets become activated?

Answer 4

shape changes to spiny spheres with protruding pseudopodia

Question 5

in order for platelets to change shape/become activated what is required?

Answer 5

P2Y1/P2Y12 receptors, granular secretion + release platelet activating factor and TXA2

Question 6

how do platelets aggregate?

Answer 6

GP11b/111a receptors are expressed, which bind to fibrinogen

Question 7

what promotes the expression of GP11b/111a receptors

Answer 7

collagen, ADPthrombin, TXA2, 5-HT

Question 8

what else is expressed on the platelet surface?

Answer 8

prothrombin and Factor Xa - thus forming thrombin and fibrin

Question 9

main 4 antiplatelet agents

Answer 9

1. aspirin
2. P2Y12 receptor antagonists
3. glycoprotein 11b/111a receptor inhibitors
4. phosphodiesterase inhibitors

Question 10

what is aspirin

Answer 10

an irreversible COX inhibitor
decrease expression of GP11b/111a receptors
stop platelet aggregation

Question 11

how does aspirin irreversibly inhibit COX

Answer 11

acetylating serine residues

Question 12

what can aspirin be used to treat

Answer 12

stable/unstable angina/ NSTEMI/ STEMI/ angioplasty

Question 13

what promotes platelet aggregation?

Answer 13

ADP

Question 14

through what does ADP promote platelet aggregation?

Answer 14

P2Y receptors

Question 15

2 distinct P2Y receptors

Answer 15

P2Y1 and P2Y12

Question 16

is there a change in shape of the platelet if only P2Y1 is activated?

Answer 16

no, P2Y12 must be activated as well

Question 17

name a P2Y12 receptor antagonist

Answer 17

clopidogrel

Question 18

what can clopidogrel treat?

Answer 18

stable angina/unstable angina/angioplasty

Question 19

do you use glycoprotein 11b/111a receptor inhibitors treat?

Answer 19

angioplasty

Question 20

name a 11b/111a receptor inhibitor

Answer 20

ABCIXIMAB

Question 21

what is ABCIXIMAB?

Answer 21

chimeric monoclonal antibody

Question 22

how do 11b/111a receptors work?

Answer 22

bind to the platelet
blocking the receptor so fibrinogen can’t bind
so the platelets don’t aggregate

Question 23

example of a phosphodiesterase inhibitor

Answer 23

dipyridamole

Question 24

how do phosphodiesterase inhibitors work?

Answer 24

block phosphodiesterase’s and increases cAMP and cGMP and blocks adenosine uptake

Question 25

what effect does an increase of cAMP and cGMP have?

Answer 25

stimulates prostaglandin and inhibits TxA2 synthesis AND VASODILATION

Question 26

2 main effects of dipyridamole

Answer 26

stop platelet aggregation and vasodilation

Question 27

what is a common risk of antiplatelet

Answer 27

bleeding

Question 28

what is thrombotic thrombocytopenic purpura

Answer 28

clot inside a small blood vessel
low blood levels of platelets
purple bruises caused by bleeding underneath the skin

Question 29

therapeutic applications for phosphodiesterase inhibitors

Answer 29

prevention of atherosclerotic event in ischaemic stroke and TIA