Pharmacology-Hemostasis, Anti-Coagulants, Thrombolytics Flashcards
What molecules contribute to the normal anti-thrombotic state of the vasculature?
Antithrombin, protein C, protein S and PGI2.
What happens after endothelial injury that leads to development of a clot?
Endothelin release by endothelia -> vasoconstriction -> platelets adhere to vWF and collagen -> platelet gets sticky and degranulate -> ADP and TXA2 release -> platelet recruitment and white plug formation -> Tissue factor release -> thrombin activated -> fibrinogen clipped -> red clot formation.
Coagulation cascade
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How does our body prevent formation of really large clots and break down large clots?
t-PA (fibrinolysis) or thrombomodulin (blocks coagulation cascade)
Where do platelets come from and where are they stored?
They break off of megakaryocytes and are stored in the spleen. They have a life span of about 10 days.
Why is the stain shown in this image significant in combating coagulation disorders?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/077/823/212/q_image_thumb.jpg?1659456535)
It is the GPIIb/IIIa fibrinogen receptor on platelets. This receptor is what allows platelets to bind fibrinogen and form the meshwork of the clot.
What molecules released from the platelets result in the “feed forward loop” causing mass platelet aggregation and thrombus formation?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/077/823/213/q_image_thumb.jpg?1659456535)
ADP, 5-HT and TXA2
![](https://s3.amazonaws.com/brainscape-prod/system/cm/077/823/213/a_image_thumb.jpg?1659418057)
What are the four classes of drugs we use for anti-platelet drug therapies (targeting primary hemostasis)?
COX inhibitors, ADP antagonists, PDE inhibitors and GP IIb/IIIa inhibitors
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In what part of this platelet’s metabolism does aspirin work?
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In a normal cell, binding of vWF causes activation of PLC/PL-A2 which cleaves arachidonic acid. COX-1 then converts it to TxA2 which propels the feed forward loop of platelet aggregation. Aspirin prevent COX-1 and decreases platelet aggregation and degranulation.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/077/823/215/a_image_thumb.jpg?1659418057)
Why must patients be off of aspirin for 7-10 days prior to an operation?
It is an irreversible inhibitor of COX1 and COX2. Since platelets do not have nuclei, it inhibits COX for the life of the platelet, which is 7-10 days.
Why do you only need low dose aspirin to inhibit thrombosis? What happens at high doses of aspirin?
Aspirin is rapidly absorbed into the blood and platelets reside in the blood. At high doses, you also inhibit endothelial COX-1 receptors that make PG12 and normally inhibit platelet aggregation via vasodilation. You want to keep it at low doses so you have both anti-platelet effects.
Why aren’t NSAIDs as effective for platelet aggregation as aspirin is?
They competitively inhibit COX.
What side effects must you be aware of with aspirin?
GI bleeding, allergies, and Reye’s syndrome in children.
Why is eating fish preferential to eating corn if you are hypercoaguable? Is it worth eating fish if you are on prophylactic aspirin therapy?
Fish has omega-3 fatty acids which lead to production of TXA3 which is an anti-inflammatory and vasodilator. Corn has omega-6 fatty acids that product TXA2 and PGE2 which induce platelet aggregation and vasoconstriction. Aspirin blocks COX-1 so it will block all effects by these omega fatty acids.
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A patient just had an acute MI and a stent put in after angioplasty. What anti-platelet drugs could you prescribe to minimize clot formation while he recovers?
Thienopyridines (clopidogrel or prasugrel), you permanently block the P2Y12 (ADP receptor). This leads to long-lasting increases in cAMP and a decrease in surface expression of GPIIb/IIIa.
Why might a patient taking clopidogrel or ticlopidine have little to no anti-coagulant effects and increased side effects? What drug might you want to try with these patients?
These drugs are prodrugs and must be metabolized by CYP450. Administration of omeprazole will impair CYP450 and block prodrug conversion, increasing side-effects. Patients may also have polymorphisms in CYP450 that inhibit prodrug conversion. You could try ticagrelor, which is not a prodrug.