Antithrombotic agents Flashcards
What are the different types of antithrombotic agents
- Anticoagulants (inhibit 1+ components of coag cascade),
- Fibrinolytic agents (enhance lysis of clot),
- Anti-platelet agents (inhibit platelet activation or aggregation via platelet receptor inhibition or platelet signalling pathway inhibition)
Name the different types of anticoagulants and their main mechanism of action
- Heparin and fondaparinux. Act via antithombin and antagonising factor Xa.
- Oral warfarin - Vitamin K antagonist so lowers factors II, VII, IX and X,
- Direct oral anticoagulants which mainly act as Xa inhibitors except dabigatran which is a IIa inhibitor
In more detail describe the mechanism of action of heparins
- Augment activity of endogenous antithrombin (particularly anti IIa and Xa activity).
- Does not cross placenta so can be used in pregnancy
Describe the differences between unfractionated heparin and low molecular weight heparin
LMWH has a safer side effect profile, requires 1 injection a day, higher bioavailabilty, requires no monitoring and can be used in out-patients
What are the indications for hepatin
- Provides immediate short acting anticoagulant effect. so can be used in:
- Acute DVT/PE,
- During cardiac bypass surgery (UFH),
- Acute coronary syndromes,
- Post VTE in cancer patients,
- Prophylaxis of VTE in post op patients and in obstetrics
Explain the mechanism of warfarin and some of its main features
- Inhibits the vitamin K oxide reductase. Important because the process of oxidisation of vitamin K is used in the production of prothrombin.
- It has a narrow theraputic window so require regular INR monitoring. It also has many drug and food interactions
- Long onset and off-set so not good for short term use
What are the indications for use of warfarin?
- Atrial fibrillation (it can reduce the risk of stroke)
- In acute DVT or PE as it reduces risk of recurrent/fatal PEs
- Prosthetic heart valve
What are the benefits of DOACs as apposed to warfarin?
- Rapid onset and offser
- Only requires an annual review,
- Few drug/food interactions,
- Minor side effects whereas warfarin may increase risk of bleed, lower risk of IC haemorrhage.
- Reversal agents are being developed however it is easy to reverse warfarin by vitamin K
Name some examples of DOACs
Factor IIa inhibitor - Dabigatran
Factor Xa inhibitors - Rivaroxaban, apixaban, edoxaban
What is the reversal agent for dabigatran?
Idarucizumab
What are the major fibrinolytic drug classes and some examples and their uses
- Kinases (streptokinase and urokinase) Older drugs
- Tissue plasminogen activators (alteplase, tenecteplase, reteplase)
- Used to breakdown a pathological thrombus
Describe the mechanism of action of kinases and their limitations
- Bind to plasminogen to release plasmin and enhance the breakdown of fibrin.
- However they work on free plasminogen in the blood as well as clot bound. So can cause systemic fibrinolysis and increase risk of bleeds.
- Streptokinase is derived from streptococci bacteria so if previous strep infection/use of streptokinase then immune response can render drug ineffective.
- Urokinase is a cellular derivative
Describe the mechanism of action of clopidogrel and ticlopidine
They irreversibly block the ADP receptor of platelets which decreases the expression of GPIIb/IIIa and reduced binding of fibrin
Name and describe the mechanism of action of GPIIb/IIIa antagonists
Abciximab and tirofiban. They are monoclonal antibodies that antagonise the glycoprotein IIb and IIIa receptors which reduce platelet aggregation and reduce binding of fibrinogen
What is the mechanism of action of aspirin
- Irreversible inhibition of cyclooxygenase which blocks the conversion of arachidonic acid into thromboxane A2, reducing platelet activation
