Anticoagulants and anti-platelets Flashcards
what are the three things preventing thrombus formation in a normal physiological state.
Prostacyclin - PGI2
Antithrombin proteins
Thrombodulin and protein C and S
how does Prostacyclin naturally inhibit PGI2
this is a prostaglandin that is normally synthesised and secreted by endothelial cells
this PGI2 increases cAMP release in platelets. this decreases the activity of platelet COX therefore meaning that there is a decrease in TXA2 production.
what are our antiplatelet drugs
this is low dose aspirin and clopidogrel.
how does low dose aspirin work
the compound Acetylsalicylate is a non selective COX enzyme inhibitor. so it irreversibly inhibits the COX enzyme in the platelet for the platelets 7-9 day lifespan. thus the platelets wont aggregate as there is no TXA2 being produced
why does low dose aspirin not have the wider effects of a normal NSAID
because of it being such a low dose. it is all broken down in the liver during first pass metabolism. this means it has no wider effect as it doesn’t reach systemic circulation in an activated state, hence it only inhibits the platelets within the hepatic circulations.
hence aspirin has minimal effect on endothelial COX and hence PGI2 release is normal - further aiding anti coagulation
what side effects can NSAID use such as aspirin have
peptic ulceration. as inhibiting COX in stomach means less PGE2 activity hence less protective gastric secretions
can also get reyes syndrome
what does ADP do for normal platelet aggregation
aid platelet aggregation and promotes fibrin binding by producing conformational change in the platelet and also ADP binding to the P2Y receptor induces fibrin receptor expression (GP2b/3a)
pharmacokinetics of clopidogrel
its a prodrug given orally. good when given as monotherapy but also concurrently with aspirin
converted to active metabolite by CYP enzymes
how does clopidogrel function
it non competitively blocks the P2Y receptor on the platelet, meaning that ADP can no longer bind to it. this means ADP can induce a conformational change, but also there is no activation of GP2b/3a receptors. thus reducing platelet activation and their binding to fibrin.
why can clopidogrel be used synergistically with aspirin
they both inhibit platelet aggregation by different mechanisms.
aspirin inhibit COX activity thereby causing less platelet activation due to a lack of TXA2 production .
Clopidogrel inhibits the P2Y receptor reducing platelet activation and also reducing the activation of the GP2b/3a receptor - therefore no binding to fibrin.
what are our anticoagulants and why do we use them
DOAC - dabigatran
Warfarin -
Heparins
use them in stroke risk due to AF, acute MI managment, angioplasty
what is the mechanism of unfractionated heparin
these increase antithrombin activity thereby reducing fibrin formation as it helps antithrombin bind to both factor X and factor 2. inhibiting them
what can we reverse heparins with
protamine sulfate
mechanism of the low molecular weight heparins
these increase antithrombin activities helping it bind to only factor Xa
why use a LMWH over UH
LMWH inhibit the coagulation cascade earlier on at factor X. and only do it at that once place. hence there is less profound effect when using the LMWH
