308 Antiplatelet and antithrombotic drugs Flashcards
What is the intrinsic coagulation cascade?
XII - XI - IX - VIII
then converges at factor X
What is the extrinsic coagulation cascade?
III - VII
then converges at factor X
Name some DOAC’s that work on factor IIa
Riveroxaban
Apixaban
Name a DOAC that works on factor IIa
Dabigatran
How does Warfarin work?
It’s a vitamin K antagonist that prevents the gamma-carboxylation of factors II,VII,IX,X
What is the prothrombin time?
Tells you about the extrinsic pathway
It’s monitored using the international normalised ratio (INR)
What is the usual target INR?
2.5 for DVT/PE or AF
3.5 for VTE or metal heart valves
What is VTE?
Venous thromboembolism
Where is warfarin metabolised?
In the liver
How long does warfarin take to achieve therapeutic effects?
At least 3 days
Which drug inhibits protein S and C?
Warfarin
What is protein S?
It’s the normal substance in the body that prevents clotting
Protein S deficiency causes blood to clot too easily
What is protein C?
It provides important control of blood coagulation by regulating the activities of factor VIIIa (FVIIIa) and factor Va (FVa), cofactors in the activation of factor X and prothrombin
Deficiency causes blood to clot too easily
How is Warfarin prescribed?
The patient should be given LMW heparin until the INR is 2
What are the interactions of Warfarin?
-Anything to so with CYP450
Enzyme inhibitors will potentiate warfarin and enzyme inhibitors will inhibit warfarin
-Alcohol
Chronic alcoholism inhibits warfarin
-Warfarin binding control due to albumin, absorption of vitamin K in GI tract, synthesis of vitamin K factors by the liver, hereditary resistance
What are the side effects of Warfarin?
-Teratogenic (LMW heparin is used in pregnancy)
-Significant haemorrhage risk
-Minor bleeds
-Skin necrosis
-Alopecia
How is Warfarin reversed?
Give activated prothrombin complex
Eg. Octaplex or Beriplex
It contains vitamin K dependent factors II, VI, IX, X
Fresh frozen plasma (FFP) can be used but is not optimal
How does Heparin work?
It’s a mucopolysaccharide that potentiates anti-thrombin and irreversibly inactivates factor IIa and Xa
What are the 2 different formulations of heparin?
Unfractionated heparin given by IV infusion
Low molecular weight heparin given as an injection
It’s safe in pregnancy
Why is unfractionated heparin rarely given?
Because of inconvenience of administration (IV)
Where is unfractionaed heparin metabolised?
In the liver
What drug partially reverses heparin?
Protamine sulphate
What is Heparin-induced thrombocytopaenia (HIT)?
A rare complication of heparin
Suspect if platelet count falls on heparin
It’s a paradoxical prothrombotic condition that can cause a VTE
How is HIT diagnosed?
Using the HIT screen
Then alternative anticoagulation is used
Heparin is prescribed according to the patient what?
Weight
Name some LMW heparin formulations
Tinzaparin (Innohep)
Enoxaparin (Clexane)
Dalteparin (Fragmin)
Where is LMW heparin metabolised?
In the kidney
Creatinine clearance must be at least 30ml/min
What is the drug Argatroban for?
A direct thrombin inhibitor
Used in place of heparin in patients with HIT
What is the drug Danaparoid for?
A type of anticoagulant
A heparin-like compound
What is the drug Arixtra?
It potentiates anti-thrombin by inhibiting factor Xa
What are DOAC’s?
Direct oral anti-coagulants
Developed as an oral alternative to warfarin, no monitoring is required
What are the 2 classes of DOAC’s?
Direct thrombin (IIa) inhibitor
Direct factor Xa inhibitor
How does Rivaroxaban compare to Apixaban?
Rivaroxaban: direct factor Xa inhibitor dosed OD
Apixaban: anti-Xa inhibitor dosed BD. It’s less affected by renal function and can be used at a reduced dose if renal function in impaired
What are the indications for Rivaroxiban or Apixaban?
VTE prophylaxis
treatment for DVT and PE
Stroke prevention in AF
What is the drug Dabigatran used for?
VTE prophylaxis
treatment for DVT and PE
Stroke prevention in AF
Which drug is Praxbind (Idarucizumab)used to reverse?
Dabigatran
It bind to Dabigatran and blocks its activity
Name some anti-platelet drugs
Aspirin – cyclo-oxygenase inhibitor
Clopidogrel – ADP receptor blocker
Dipyridamole – inhibits phosphodiesterase
Prostacyclin – stimulates adenylate cyclase
Glycoprotein IIb/IIIa inhibitors:
Abciximab – monoclonal antibody
Eptifibatide – snake venom derivative
Tirofiban – blocks platelet aggregation
When are fibrinolytic drugs used?
Work by by converting plasminogen to plasmin
Administered systemically in acute MI, recent thrombotic stroke, major PE, or massive iliofemoral thrombosis
Give examples of fibrinolytic agents
Tissue Plasminogen Activator (tPA, Alteplase)
Also streptokinase and urokinase
