Session 7 Antiplatelet And Fibrinolytic Drugs Flashcards
What is a thrombus?
A clot adhered to vessel wall
What is an embolus?
Intravascular clot distal to site of origin
Compare venous thrombosis and arterial thrombosis
What they are associated with
Fibrin content
Platelet content
Cells etc
VENOUS =
- associated with stasis of blood and/or damage to the veins (less likely to see endothelial damage!)
- HIGH RBC
- HIGH fibrin content
- LOW platelet content
ARTERIAL =
- usually forms at side of atherosclerosis following plaque rupture
- LOWER fibrin content
- HIGH (much higher!) platelet content
What substance that is released and produced by endothelial cells inhibits platelet aggregation?
Prostacyclin
How does prostacyclin (PGI2) inhibit platelet aggregation?
It binds to platelet receptors which increases the concentration of cAMP in platelets
This is coupled with a decrease in platelet aggregatory agents
Stabilise (keeps inactive) GPIIb/IIIa receptors :)
NB: this occurs in healthy endothelium
What do antiplatelet and fibrinolytic drugs target?
Platelet rich “white” arterial thrombi
What do parenteral anticoagulants and heparins/warfarin etc target?
lower platelet content “red” venous thrombi
Give a name of a drug that is an example of a cyclo-oxygenase inhibitor
Aspirin
How is TXA2 formed and what is it? (Thromboxane A2 = TXA2)
TXA2 is a potent platelet aggregating agent
It is formed from arachidonic acid by COX-1
Aspirin inhibits this!
How does aspirin work?
It inhibits the COX-1 mediated production of TXA2 (and so reduces platelet aggregation = IRREVERSIBLE!) - acetylation of CO
TXA2 is formed by COX1 and is a potent platelet aggregating agent
What are
Low doses of aspirin used for?
Low dosing = antiplatelet effects (75mg)
What do higher doses of aspirin do?
Higher doses inhibit endothelial prostacyclin (PGI2)
- imbalance!
how is aspirin absorbed?
Passive diffusion
Hepatic hydrolysis to salicylic acid
What are the warnings / side effects of Aspirin?
- Bleeding time prolonged - Haemorrhagic stroke, GI bleeding (peptic ulcer)
- Reye’s syndrome (avoid if under 16 y.o) - can occur after a viral infection - can be fatal
- Hypersensitivity
- 3rd trimester of pregnancy - aspirin can lead to early closure of the ductus arteriosus!
Need to take these things into account and weight up benefit vs risk
Contradictions of Aspirin?
Other antiplatelet and anticoagulants (additive/synergistic actions)