Antiplatelet Drugs Flashcards
What are the 3 parts of virchows triad?
Abnormalities in blood flow
Abnormalities in blood constituents
Abnormalities in the vessel wall
What can cause an abnormality in blood constituents?
Smoking
Surgery- increased clotting factors
Pregnancy
What can cause abnormalities in blood flow?
Stasis- either a cardiac abnormality or immobility
Cardiac cause- AF, mitral valve disease, post MI
Immobility- ill health, post op, economy class flying
What can cause abnormalities in the vessel wall?
Endothelial damage-
atheroma- MI
Hypertension
Toxins- cigarettes, homocysteine.
Which clotting factors are dependent on vitamin K and therefore inhibited by warfarin?
2, 7, 9 and 10
Which clotting factor does LMWH inhibit?
Factor Xa.
Which clotting factors does the heparin AT complex inhibit?
12,11,10,9 and 2(thrombin)
What happens when an atherosclerotic plaque ruptures?
Adhesion, activation and aggregation of platelets via Von Willebrand factor
Activation of clotting factors- fibrinogen—> fibrin—> thrombus formation
How do warfarin and similar anti coagulants work?
What consequence does this have for how quickly it has its effects?
Inhibit production of vitamin K dependent clotting factors by stopping conversion of vit K into active reduced form.
Because of this warfarin takes 2-3 days to have effect because there will still be clotting factors in the blood
What is the pharmacokinetics of warfarin?
Why is it so important to titrate the dose of warfarin slowly?
Good GI absorption, long half life so needs a loading dose. Heavily protein bound. Hepatic metabolism via CYP450s- is different in all of us so warfarin dose needs to be steadily increased.
Which factors are involved in the intrinsic pathway?
12, 11, 9
From what kind of injury does the intrinsic pathway arise?
Eg thrombus clot in the vessels.
From what kind of injury does the extrinsic pathway arise?
From external tissue injury.
What test do we use to measure the intrinsic pathway?
APTT
What test do we use to measure the extrinsic pathway?
PT- commonly converted to INR in most labs.
On which clotting factor do both the extrinsic and intrinsic pathways converge?
What does this do?
Factor X—> Xa
Xa causes conversion of prothrombin to thrombin and from that fibrinogen to fibrin and with help of factor VIII helps to form a stable clot.
What does plasmin do?
Breaks down fibrin clot
How can fibrin degradation products be detected in the blood?
D dimer test
Which clotting factors does Protein C inhibit?
Why do we need to cover the first 2-3 days of warfarin treatment with LMWH?
VIII and V.
Protein C is also Vit K dependent so protein C levels decrease with warfarin treatment so patient becomes slightly more hypercoaguable.
What INR do we aim for in DVT, PE or AF?
2-3
What INR do we aim for in mechanical heart valves, recurrent thromboses or thrombophilia?
2.5-4.5
What drugs inhibit warfarin by inducing its CYP450 enzyme?
Antiepileptics
Rifampicin
St johns wort
Which drugs potentiate warfarin by inhibiting its enzyme?
Amiodarone, quinolone, metronidazole, cimetidine, alcohol.
Cephalosporin reduces vit K from gut bacteria
Aspirin inhibits platelet function so exaggerates effect of warfarin.
How is warfarin overdose reversed?
Stop warfarin Then either: Fresh frozen plasma Prothrombin complex concentrate IV vit K
