Week 7 Flashcards
What is the coagulation cascade?
- Damaged blood vessel triggers release of clotting factors.
- Converting Prothrombin to thrombin
- Converting Fibrinogen to fibrin
- Vasoconstriction limits blood flow, platelets for a plug
- Fibrin strand adhere to the plug to form an insoluble clot.
Platelets have the ability to stick together what would this be called?
Thrombocytes
Platelets contain dense granules, what are they?
Contain phospholipids, triglycerides, cholesterol, ATP, ADP, Serotonin (5HT-which they obtain while passing through GIT) Drive the simulation of coagulation
Platlets contain alpha granules, what are they?
Contain secreted proteins as clotting factors, & PDGF
Thrombopoiesis
Hemocytoblast, Megakaryoblast, Promegakaryocyte, Megakaryocyte then form platelets
Takes place in bone marrow,
What is a platelets life span?
8-12 days - destroyed by tissue macrophage system in spleen. someone without a spleen would struggle to get rid of old platelets, this increases the chances of clotting.
Thromocytosis
Increase in platelet count more than 450,000/mm3
Thrombocytopenia
Decrease in platelet count less than 150,000/mm3
What is ITP (idiopathic thrombocytopenia purpura?
Recognises platelets as non-self, the immune system struggles to destroy them..
What happens when something binds to the platelet?
Surface receptors on the platelets
- Transient tethering
- Then they would roll, then
- Activation when the GPVI binds to exposed collagen
- Release alpha and dense granules
- Attracting further platelets
- Aggregate using the fibrinogen
What are some of the G protein coupled receptors on a platelet?
There are some G protein coupled receptor - respond to Thrombin(TP), thromboxaneA2 (PAR4-PAR1) and ADP(P2Y1-P2Y12)
Why are integrins important in platelets?
Because they are the adhesion molecules
What does clopidogrel inhibit?
Activated in Liver
- Interaction between ADP and the P2Y12 G-protein coupled receptor,
- Causing increase of cAMP
- Inhibiting the formation of the clot.
What is Clopidogrel?
Potent oral antiplatelet agent used in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease.
What is clopidogrel used for?
Reducing the risk of heart attack or stroke for the second time. Or have circulatory problems due to narrowing and hardening of the arteries.
How much Clopidogrel turns into its active metabolite?
15% of the drug through oxidation and 85% of the drug is degraded by esterase’s.
What are the limitations of clopidogrel?
- Low efficiency hepatic transformation causes reduced activity and necessity of using high doses.
- Reliance on hepatic processes causes individual variability
- Patients can become resistant after having earlier treatment
- Complexities in therapeutic dosage, slow onset interaction with other drugs and diseases.
Prasugrel vs Clopidogrel
Prasugrel has less genes which can affect treatment response,
Prasugrel was made in what year
2009 - simpler conversion/ less resistance
Tricagrelor was made in what year
2010 - no conversion / less resistance
Cangrelor was made in what year
2015 -no conversion/less resistance
