Lecture 9 Prevention of Thrombosis Flashcards
(40 cards)
What happens when arthrosclerotic plaque forms in an artery?
Blood coagulation:
thrombin, fibrinogen and fibrin form
Platelet reactions:
adhesion , activation and aggregation of platelets
Leads to further aggregation of platelets
What does the rupture of an atherosclerotic plaque in an artery lead to?
A thrombus
What are the three classes of drugs that have been developed to prevent and/or reverse thrombus formation?
Anticoagulant
Antiplatelet agents
Fibrinolytic agents
What is an example of antiplatelet agents?
Aspirin - inhibits COX-1 activity to inhibit platelet aggregation
What is an example of a fibrinolytic agent?
Alteplase - breaks fibrin down
What are the classes of anticoagulant drugs?
Selective factor Xa inhibitors
Direct thrombin inhibitors
Heparin and Low molecular weight heparins
vitamin K antagonists
What are the targets of anticoagulants?
They target various factors in the coagulation cascade preventing stable fibrin framework
What are direct acting oral anticoagulants?
Reversible inhibitors of thrombin (factor X)
Prevents thrombin generation
What are the first line treatments for venous thromboembolisms?
Apixaban or rivaroxaban - Confirmed proximal DVT or PE
which drugs are given if first line treatment of Venous thromboembolism is contraindicated?
Low molecular weight heparin - followed by etexilate or edoxaban
OR
LMWH given with a vitamin K antagonist (at least 5 days) - followed by a vitamin K antagonist on its own
What type of patients would need treatment for venous thromboembolisms?
Patients undergoing surgery
Which drugs are direct acting oral anticoagulant?
Apixaban, dabigatran, etexilate, edoxaban and rivaroxaban
What are the uses of apixaban, dabigatran, etexilate, edoxaban, rivaroxaban?
Prevention of stroke
Secondary prevention of DVT and/or PE
What are the uses of Apixaban, dabigatran, etexilate, rivaroxaban?
Prevention of venous thromboembolism following surgery
What are the uses of rivaroxaban?
Prevention of atherothrombotic events in patients with coronary or peripheral artery disease following an acute myocardial infarction
What are the contraindications of Apixaban?
Avoid in conditions with significant risk of bleeding:
Gastrointestinal ulceration
Malignant neoplasms with high risk of bleeding (erosion of blood vessels)
Oesophageal varices (veins - dilated and distended)
What are the side-effects of Apixaban?
Anaemia
haemorrhage
What are the pharmacodynamics of heparins?
They are a family of sulfated monosaccharides found in the secretory granules of mast cells
Molecular weight 3,000-30,000
Inhibit coagulation by activating antithrombin III
What is the action of antithrombin III in the presence of heparin?
It is a naturally occurring inhibitor of thrombin and clotting factors IX, Xa, XI and XII
In the presence of heparin it becomes 1000 times more active and inhibition of clotting factors is instantaneous
What are the differences between heparin and low molecular weight heparins?
They have more consistent activity
What are examples of low molecular weight heparins?
Daltrparin sodium, enoxaparin sodium and tinzaparin sodium
What are the advantages of heparins?
They are more synthetic so have more consistent effects
They are predictable so easier to figure the dose
What are the pharmacokinetics of heparin and LMWH pharmacokinetics?
Administered via IV or subcutaneously
Heparin has a short half life
LMWH have longer duration of action
Eliminated by renal excretion
Side effects include bleeding and hypersensitivity (thrombocytopenia - too little platelets)
Overdose treated by IV protamine
What is the mechanism of action of vitamin K antagonists?
Inhibition of the activation of vitamin K1 dependent clotting factors: II, VII, IX AND X
48 to 72 hours for the anticoagulant effect to develop
