Coagulation Pharmacology Flashcards
Hemostasis
Arrest of bleeding from damaged blood vessel
Coagulation
Multi step process to plug the leaking vessel
platelets contain :
organelles, secretory granules
platelets do not contain :
nucleus
progression of microtubules of platelets
- formation of centrosomal microtubule array
- microtubules move to cortex
- pseudopod formation
- formation of protoplatelet elongation, and bending and branching to amplify ends
- protoplatelet release
extrinsic pathway initiating element
tissue factor
intrinsic pathway initiating element
collagen
platelet receptor for collagen
GP 1a
platelet receptor for vWF
GP 1b
release of ____from endothelial cells inhibit thrombogenesis
PGI2, prostacyclin
Platelets secretions following activation
ADP
Thromboxane A2
Serotonin
Function of platelet secretions
> 3 activate and recruit platelets
> TXA2/Serotonin are vasoconstrictors
3 secret platelet secretions induce
> conformation of GPIIb/IIIa receptors to bind fibrinogen
Function of fibrinogen
> cross-linking of platelets
> forms temporary hemostatic plug
Function of fibrin
stabilizes and anchors aggregated platelets
MOA of aspirin
> inhibits platelet COX-1 by acetylation
intereferes with platelet aggregation
prolongs bleeding time
prevents arterial thrombi formation
Key action of aspirin
Inhibition of TXA2 synthesis
Max effective aspirin dose
50-325mg/day
higher doses of aspirin side effect
> blocks PGI2 synthesis
> risks of MI and clotting
Therapeutic reasons for aspirin
> prevent coronary thrombosis in unstable angina
adjunct to thombolytic therapy
reducing recurrence of thrombotic stroke
Clinical consequences of aspirin
> prolongs bleeding time, but no increase in PT time
> hemostasis returns to normal after 36hr after last dose
Two types of ADP receptors
> Coupled to Gq - PLC - IP3 - Ca2+
> Coupled to Gi and inhibition of adenylyl cyclase
Requirement of ADP activation of platelets
> both P2Y12 need to be activated for platelet activation by ADP
Class of drugs that contain ADP activation of platelets
> thienopyridine class of ADP receptor inhibitors > pro-drug
Two drugs within the thienopyridine class
> ticlopidine
> clopidogrel
Thienopyridine MOA
irreversibly block ADP receptor on platelet and subsequent activation of GPIIb/IIIa
