anticoagulant, antiplatelet and thrombolytic drugs Flashcards
haemostasis
arrest of blood loss from a damaged vessel at the site of injury involves .. in sequence
1) vascular wall damage
2) primary haemostasis
3) activation of blood clotting
what does vascular wall damage incur ?
exposes collagen and tissue factor (TF, thromboplastin)
what does primary haemostasis incur?
> local vasoconstriction
>platelet adhesion, activation and aggregation by fibrinogen
activation of blood clotting …
… and the formation of a stable clot (by fibrin enmeshing platelets)
key events in primary haemostasis
> vessel damage exposes collagen to which platelets bind and become activated
activated platelets extend pseudopodia and synthesise and release thromboxane A2 (TXA2)
thromboxane A2 binds to: platelet GPCR thromboxane receptors TP receptors causing mediator release serotonin (5-hydroxytryptamine) and adenosine diphosphate
:vascular smooth muscle TXA2 receptors causing vasoconstriction that is augmented by mediator 5-HT binding to smooth muscle GPCR 5-HT receptors
ADP binds to platelet GPCR purine receptors that:
act locally to activate further platelets, >aggregate platelets into a ‘soft plug’ act the site of injury - via increased expression of platelet glycoprotein receptors that bind fibrinogen, thromboxane acts similarly
expose acidic phospholipids on the platelet surface that initiate coagulation of blood and solid clot formation