Pharmacology 2.14 Flashcards
(22 cards)
What are the four events which occur in hemostasis?
1) vasoconstriction
2) platele actions: adhesion, activation, release/secretion, aggregation
3) fibrin clot formation/coagulation
4) fibrinolysis
What is hemostasis?
process of normal blood clotting, subsuquent dissolution of the clot, and subsuquent repair of the injured tissue
What are the major components of the hemostatic system?
- vascular endothelium
- platelets
- coagulation system
- fibrinolytic system
What are the functions of the endothelial cell lining as it pertains to hemostasis?
thrombo-resistant by:
1) physical barrier btwn circulating platelets & clotting factors and thrombogenic subendothelial substances (collagen, tissue factor)
2) endothelial production of 2 potent vasodilators and inhibitors of platelet function: prostaglandin I2, PG12; nitric oxide NO)
Which molecule activates fibrinolysis to inhibit thrombosis?
t-PA, a protease; tissue plasminogen activator
Which molecules inhibit platelet aggregation to inhibit thrombosis?
PGI2
NO
What are the events which occur in the Common Pathway of coagulation cascade?
1) prothrombin is converted to thrombin
2) thrombin converts to fibrinogen to fibrin
What are the events which occur in primary hemostasis?
formation of a platelet plug
What are the events which occur in secondary hemostasis?
formation of a fibrin clot
What are the events which occur in platelet adhesion?
Platelet receptors GP1a-IIa and GP VI bind directly to subendothelial collagen
Platelets bind indirectly to collagen via GPIb to von Willebrand factor (vWF) secreted by endothelial cells
What are the events which occur in activation?
- platelet adhesion stimulates their activation!
- releases TXA2
- express Gp IIb/IIIa receptor which will bind to collagen
What are the events which occur in aggregation?
1) vWF binds to collagen
2) platelets bind to vWF
3) platelets release ADP, TXA2
4) fibrin clot mesh forms within platelets
What is the function of vWF
secreted by endothelial cells; platelets bind indirectly to collagen via GPlb to vWF during platelet adhesion
What is the function of ADP
released by platelets and promote platelet aggregation by activating other platelets
What is the function of TXA2?
vasoconstrictor which promotes platelet aggregation and thrombosis + hemostasis; released by platelet
What is the function of thrombin?
blood clotting factor; activated zymogen (enzyme)
What is the function of Gp IIB/IIIA?
platelet receptors (on actual platelet and expressed when platelet is activated) which bind to collagen and allow them to form the clot
What is the function of fibrinogen?
blood clotting factor which allows adjacent platelets to bind to one another during clot formation
What is the funciton of prostacyclin?
vasodilator which inhibits platelet function; released by endothelial cell
What is the function of nitric oxide?
vasodilator which inhibits platelet function
What is the activation of the fibrinolytic system?
1) t-PA (tissue plasminogen activator) is released by endothelial cells and binds to plasminogen and activates it to:
2) plasmin which causes fibrin clot to degrade and release FDP (fibrin degradation products)
What is the inactivation of the fibrinolytic system?
1) PAI (plasminogen activator inhibitor) binds up t-PA so it can not longer promote fibrinolysis
2) Even if plasminogen is converted to its active form (plasmin) there are plasmin inhibitors which will bind to plasmin to keep its degradation activity in check
