Pharmacology - Antiplatelet, Anticoagulant and Thrombus Drugs Flashcards
What do activated platelets do and release?
Extend pseudopodia and release thromboxane A2 (TXA2). Slide 5
What does thromboxane do?
It binds to platelet TP receptors which stimulates the release of 5-HT serotonin and ADP.
The vascular smooth muscle cells also have TXA2 receptors and when stimulates cause vasoconstriction. Slide 5
What is P2Y12 and what does it allow?
A platelet GPCR purine receptor which ADP binds to.
It allows the signalling of other platelets to bind together by fibrinogen binding to G proteins whcih cross link the platelets. Slide 6
What is thrombin?
Factor IIa.
It is a protease than cleaves fibrinogen to fibrin causing a solid clot to form. Slide 7
What are the two main factors involved in the coagulation cascade and how are they activated?
Factor X and factor II
Factor X is activated into factor Xa by tenase.
Factor II is prothrombin, to prothrombinase and then to thrombin (active factor IIa). Slide 7
What is the difference between an arterial thrombus and a nevous thrombus?
An arterial thrombus is platelet dominated and is white in colour
A venous thrombus is erythrocyte dominated. and red in colour. Slide 8
How do you treat an arterial thrombus and a venous thrombus?
Arterial - antiplatelet drugs
Venous - anticoagulant drugs
Slide 8
What are 4 examples of anticoagulant drugs and where do each target in the coagulation cascade?
Warfarin - blocks modification of factor X and II
Rivaroxiban - Directly inhibits Factor Xa Heparin and LMWHs -
Inactivate factor Xa via anti-thrombin II
Dibigatran - directly inhibits factor IIa.
Slide 9
How are the precursors modified to produce the active factors?
Vitamin K allows the carboxylase enzyme to to actiave the factors. Slide 10
What is the half life of warfarin and what do you have to be careful of before a surgery if someone is on warfarin?
The half life of warfarin is 40hrs.
It takes 2-3 days for inactive factors to be replaced with active factors so you have to wait 4-5 days before performing surgery. Slide 11
What can you do if a patient is overdosed on warfarin?
Administer Vitamin K1 (phytomenadione) or concentrate of plasma clotting factors. Slide 12
What are factors that could potentiate warfarin action?
Liver disease (decreased clotting factors) High metabolic rate Drug interactions. Slide 13
What are factors could lessen warfarin action?
Physiological state - pregnancy (increased factor synthesis), hypothyroidism (decreased degradation of factors)
Vitamin K consumption
Slide 13
What does anti-thrombin III do?
It inhibits all the protease factors whcih reduces the coagulation cascade. Slide 14
How does heparin work and inhibit factors?
It binds to anti-thrombin III and increases the affinity for the serine protease factors.
It simultaneously binds to AT III and Factor IIa to inhibit.
It only needs to bind to AT III to inhibit Xa. Slide 14
