Anticoagulants, anti-thrombotics and thrombolytics Flashcards
How are haemorrhages prevented and how?
Vasospasm - restricts blood flow and facilitates platelet aggregation
What is the difference between primary and secondary homeostasis?
Primary - formation of a platelet plug via aggregation restricting blood loss
Secondary - Formation of a fibrin clot - reinforces plug
What does a low and high platelet count cause?
Low - excessive bleeding
High - increased risk of thrombosis
What are the five steps in the platelet aggregation mechanism?
- Endothelial Injury
- Exposure
- Adhesion
- Activation
- Aggregation (Primary haemostasis)
What is haemostasis?
A process to prevent bleeding/haemorrhage
What does healthy endothelial cells generate to maintain platelets in inactive state?
Nitric oxide, prostacyclin (PGI2), Expression of CD39
What are the two pathways of secondary haemostasis (coagulation cascade)?
Intrinsic and Extrinsic pathways (both can be activated independently)
What four components regulate the coagulation cascade?
Protein C, Anti-thrombin 3, Tissue factor pathway inhibitor, Plasmin
What commonly causes arterial and venous thrombi and how are they treated?
Arterial - rupture of atherosclerotic plaque - antiplatelets and anticoagulants
Venous - adhesion of blood cells on endothelium - anticoagulants
What three classes of drugs target blood coagulation?
Antiplatelets, anticoagulants and thrombolytic agents
What does aspirin inhibit and how does it prevent and treat arterial thromboembolic disorders?
COX (Irreversibly), inhibiting synthesis of prostaglandins from arachidonic acid (mainly thromboxane A2), inhibiting platelet activation and aggregation
What is the main side effect of aspirin?
It can cause an increased bleeding risk
What other class of drugs are COX Inhibitors?
NSAIDS
What are examples of ADP receptor inhibitors, how do they work and what is their main side effect?
Clopidogrel, prasugrel, ticagrelor
Block ADP binding to platelet P2Y12 receptors -> prevents thrombus formation and increases bleeding time
They increase risk of bleeding
What is an example of a vitamin K antagonist and how does it work?
Warfarin, it’s structurally similar and it inhibits Vitamin K-dependent synthesis of coagulation factors (Factors 2,7,9,10)
How would you reverse warfarins effects and what are its side effects?
Supplementation with vitamin K
Excessive bleeding risk, contraindicated in pregnancy, interacts with CYP450 drugs
What are examples of antithrombin 3 potentiators and what do they inhibit?
- Heparin - thrombin and active factor X
- Enoxaparin (LMWH) - active factor X
- Fondaparinux
How are heparin, enoxaparin and fondaparinux administered?
Parenterally,
Heparin - IV
Enoxaparin/Fondaparinux - SC
What is an example of a direct thrombin inhibitor?
Dabigatran etexilate
What is an example of an active factor X inhibitor?
Apixaban and Rivaroxaban
What thrombolytic agents are derived from tPA, how are they administered and what do they bind to?
Alteplase, Reteplase, Tenecteplase.
Administered by IV
Bind to fibrin proteins in a clot
What are examples of bacterial-derived thrombolytics and what is their main side effect on repeated administration?
Streptokinase and Anistreplase.
There’s a risk of severe allergic reaction as it is a bacterial immunogen
(Note: tPAs used preferentially)
What are thrombolytic drugs used for?
Short Term emergency treatment of pathological thrombosis
What are two examples of anti-fibrinolytics, how do they work and what are they used for?
Animocaproic and Tranexamic acid
Promote clotting by slowing down or preventing fibrinolysis
Haemophilia and in surgery to prevent blood loss
