Antiplatelets, anticoagulants and fibrinolytics. Flashcards
What 3 intrinsic mechanisms stop the formation of a blood clot in the endothelium?
Thromboxane A2 causes the activation of more platelets.
Step 1) What is the platelet adhesion sequence (when endothelium is damaged)?
Step 2) What causes the platelets to change shape?
Thrombin causes the platelets to change shape
Step 3) Explain the process of platelt aggregation and consolidation?
Step 4) Explain how fibrin stabilises platelts?
Fibrinogen to fibrin causes stabilised platelet aggregate.
Explain the thrombin and ADP receptor activation and how it leads to platelet activation?
ADP inhibits cAMP which stops PKA production therefore increases platelet activation.
Thrombin and ADP causes an increase in PLC activity which results in increased platelet activation.
This will lead to fibrinogen receptor activation.
What are the antiplatelets, anticoagulants and fibrinolytics that we need to know?
Antiplatelets: Aspirin and clopidogrel.
Anticoagulants: LMWHs such as Enoxaparin; oral VKAs (vitamin K antagonist) such as warfarin.
Fibrinolytics: rtPAs (recombinant tissue plasminogen activators) such as alteplase.
What is the mechanism of action of aspirin and why does it need to be at a low dose?
Explain how aspirin inhibits COX in the systemic circulation vs the mesenteric system?
COX1 cannot be regenerated in the platelet as aspirin inhibits it for the lifetime of the platelet.
However COX2 exists on endothelial cells and therefore can have its impact on prostacyclins which are vasodilators and inhibit platelet aggregation.
Which patients would you give low dose aspirin?
Someone who already has occlusive vascular disease.
What are the main risks of using low dose aspirin?
GI ulceration and bleeding.
Clopidogrel is a useful drug if….
How does clopidogrel work?
the patient cannot tolerate aspirin.
Clopidogrel inhibits the P2Y receptor, therefore, inhibits ADPs interaction with platelets and therefore no platelet activation.
ADP causes a change in platelet shape and induces fibrinogen receptor presentation.
How does unfractionated heparin work?
What is the main risk of using heparin?
Increases the action of antithrombin 3 by binding with both prothrombotic factor Xa and thrombin (IIa).
Main risk is haemorrhage and heparin induced thrombocytopenia (causing gangrene as there is catastrophic intravascular coagulation).
How does low molecular weight heparins work?
What is the name of this drug and its trade name?
What are its benefits over unfractionated heparin?
What are the indications for unfractionated heparin?
The risks?
How is unfractionated heparin excreted?
What is the mechanism of action of warfarin?
Warfarin inhibits which factors?
What are the important pharmacokinetic things to remember about warfarin?
- Important to measure the INR not the warfarin levels in the blood.
- Metabolised by the CYP2C9 enzyme, however the S isomer and R isomer are metabolised by different enzymes. This means that just about any drug interacts with it.
What are the main adverse effects of warfarin to know?
What happens if the INR when treating with warfarin goes above 4?
What is the optimal range?
What would you do in a bleeding crisis?
Optimal range from 2-3.
Over 4 you must treat with IV vitamin K.
Bleeding crisis: Give IV freeze dried prothrombin or IV fresh frozen plasma.
how do fibrinolytics work?
Would you give it to someone post MI?
Works by promoting fibrinolysis by converting plasminogen to plasmin to degrade fibrin.
Would only give acutely post MI.
Indications of alteplase/tenecteplase, contraindications and adverse effects?
PCC: prothrombin complex concentrates (given when INR is too high with warfarin treatment).
