Antiplatelet, anticoagulant and thrombolytic drugs Flashcards
What is haemostasis?
The human body’s response to blood vessel injury and bleeding.
It involves local vasoconstriction, adhesion and activation of platelets at the site of injury and formation of fibrin.
What is thrombosis?
Pathological haemostasis
It is a haematological plug in the absence of bleeding (haemostasis in the wrong place)
What are the predisposing factors to thrombosis?
Virchow’s triad:
Injury to vessel wall
Abnormal blood flow
Increased coagulability of the blood
Describe arterial thrombus
White thrombus
Mainly platelets in a fribrin mesh
Embolus often lodges in an artery in the brain (stoke) or other organ
Describe venous thrombus
Red thrombus
White head, jelly-like red tail, firbin rich
Embolus usually lodges int the lung (PE)
What are the two pathways that take place after endothelial damage to form a fibrin clot?
Platelet reactions
Blood coagulation
What are the two blood coagulation pathways?
In vivo pathway and contact pathway
What is the role of vitamin K in clot formation?
Vitamin K is needed to carboxylate the clotting factors to convert them into their active form
What is the link between warfarin and vitamin K?
Warfarin prevents the formation of the reduced form of vitamin K that we need to drive gama carboxylation (and activate the clotting factors)
When would you prescribe an anticoagulant?
VENOUS THROMBOSIS Deep vein thrombosis (DVT) Prevention of post-operative thrombosis Patients with artificial heart valves Atrial fibrillation
Give an example of an anticoagulant
Warfarin
Describe the mechanisms of Warfarin action
Renders factors II, VII, IX and X inactive.
Blocks coagulation in vivo.
Is warfarin fast or slow acting?
Slow onset of action (2-3 days)
Has a long and variable half-life (usually about 40hours)
What other anticoagulant could be administered if rapid anticoagulation was needed?
Heparin
Why are patients on warfarin monitored?
Warfarin has a low therapeutic ratio and it can be difficult to stroke the balance between the desired anticoagulant effect and haemorrhage
What factors potentiate warfarin action and increase the risk of haemorrhage?
Liver disease (decrease in clotting factors as they are produced by the liver) High metabolic rate (increased clearance of clotting factors) Drug interactions (effect enzyme action)
What factors lessen warfarin action and result in the risk of thrombus being increased?
Physiological state (pregnancy increases clotting factor synthesis)
Hypothyrodism (decreased degradation of clotting factors)
Vitamin K consumption
Drug interactions
How do you treat an overdose of warfarin?
Administration of vitamin K or concentrate of plasma clotting factors
What is the role of antithrombin III?
Endogenous inhibitor of coagulation
Explain the mechanisms of heparin action
Heparin binds to antithrombin III increasing its affinity for clotting factors. This greatly increases their rate of inactivation.
Give two examples of low molecular weight heparins (LMWHs)
Enoxaparin and dalteparin
LMWHs are now preferred except in what condition?
Renal failure
LMWH is eliminated via renal excretion
Why are LMWHs preferred to heprain?
Heparin is less predictable due to zero order elimination
How does endothelium damage promote thrombus formation?
Vascular damage reveals subendothelial molecules which the platelets adhere to
