Antiplateletes Flashcards
3 thromboembolic cardiovascular disorders
- atherosclerosis –> thrombosis –> NSTEMI/STEMI
- atrial fibrillation –> thromboembolism –> ischaemic stroke/TIA
- venous thromboembolism –> deep vein thrombosis
what triggers platelet activation
endothelial cell damage
exposure of collagen
release of von Willebrand factor
how do platelets adhere?
adhere to VWF/collagen matrix and platelet glycoprotein GP1b receptor
how do platelets become activated?
shape changes to spiny spheres with protruding pseudopodia
in order for platelets to change shape/become activated what is required?
P2Y1/P2Y12 receptors, granular secretion + release platelet activating factor and TXA2
how do platelets aggregate?
GP11b/111a receptors are expressed, which bind to fibrinogen
what promotes the expression of GP11b/111a receptors
collagen, ADPthrombin, TXA2, 5-HT
what else is expressed on the platelet surface?
prothrombin and Factor Xa - thus forming thrombin and fibrin
main 4 antiplatelet agents
- aspirin
- P2Y12 receptor antagonists
- glycoprotein 11b/111a receptor inhibitors
- phosphodiesterase inhibitors
what is aspirin
an irreversible COX inhibitor
decrease expression of GP11b/111a receptors
stop platelet aggregation
how does aspirin irreversibly inhibit COX
acetylating serine residues
what can aspirin be used to treat
stable/unstable angina/ NSTEMI/ STEMI/ angioplasty
what promotes platelet aggregation?
ADP
through what does ADP promote platelet aggregation?
P2Y receptors
2 distinct P2Y receptors
P2Y1 and P2Y12
is there a change in shape of the platelet if only P2Y1 is activated?
no, P2Y12 must be activated as well
name a P2Y12 receptor antagonist
clopidogrel
what can clopidogrel treat?
stable angina/unstable angina/angioplasty
do you use glycoprotein 11b/111a receptor inhibitors treat?
angioplasty
name a 11b/111a receptor inhibitor
ABCIXIMAB
what is ABCIXIMAB?
chimeric monoclonal antibody
how do 11b/111a receptors work?
bind to the platelet
blocking the receptor so fibrinogen can’t bind
so the platelets don’t aggregate
example of a phosphodiesterase inhibitor
dipyridamole
how do phosphodiesterase inhibitors work?
block phosphodiesterase’s and increases cAMP and cGMP and blocks adenosine uptake
what effect does an increase of cAMP and cGMP have?
stimulates prostaglandin and inhibits TxA2 synthesis AND VASODILATION
2 main effects of dipyridamole
stop platelet aggregation and vasodilation
what is a common risk of antiplatelet
bleeding
what is thrombotic thrombocytopenic purpura
clot inside a small blood vessel
low blood levels of platelets
purple bruises caused by bleeding underneath the skin
therapeutic applications for phosphodiesterase inhibitors
prevention of atherosclerotic event in ischaemic stroke and TIA
