14 Antiplatelets and Fibrinolytics Flashcards
Differentiate between likely mechanisms of action for venous thrombosis and arterial thrombosis.
Explain how prostacyclin (PGI2) inhibits platelet aggregation.
PGI2:
Released by endothelial cells
Binds to platelet receptors
Increases [cAMP], decrease calcium
This prevents platelet aggregation
- Decrease in platelet aggregatory agents
- Stabilises GPIIb/IIIa receptors
Outline the process of platelet activation and aggregation.
- What’s released?
- What do the released substances act on?
How does aspirin work as an antiplatelet?
(aspirin works as antiplatelet at low doses, works as analgesic at higher doses)
Aspirin= cyclo-oxygenase inhibitor (COX-1)
COX-1 = an enzyme
COX-1 converts arachidonic acid to thromboxane A2 (TXA)
Why does aspirin not completely inhibit platelet aggregation?
Other pathways for platelet aggregation
How does aspirin get converted to salicylic acid in the body?
Aspirin= absorbed by passive diffusion and then hepatic hydrolysis
What are the contraindications for aspirin? (4)
+ be careful with other antiplatelets/anticoagulants
- Why does inhibition of COX-1 last the lifespan of a platelet?
- Why does aspirin lack efficacy in some people?
- Platelet has no nucleus so can’t change production of COX-1
- COX-1 polymorphisms in people- aspirin will lack efficacy
What are the indications for aspirin? (4) What might a patient need to be given if they are using aspirin long term?
Patient may need gastric protection eg PPIs if using aspirin long term
Give 3 examples of ADP receptor antagonists (antiplatelets).
(Inhibit binding of ADP to P2Y12 receptors–> inhibit activation of GPIIb/IIIa receptors)
- Clopidogrel
- Prasugrel
- Ticagrelor
Give some of the side effects of ADP receptor antagonists.
- Bleeding
- GI upset- dyspepsia, diarrhoea
- Thrombocytopenia
- (Caution: renal and hepatic impairment)
What are some important drug interactions we need to be aware of when prescribing ADP receptor antagonists?
Clopidogrel requires CYPs for activation
CYPs also required for:
- Omeprazole (PPI)
- Ciprofloxacin
- Erythromycin
Also be careful with
- SSRIs
- Other antiplatelets/anticoagulants
- NSAIDs
How many days prior to surgery should clopidogrel be stopped? How many days prior to surgery should ticagrelor be stopped?
Clopidogrel= 7 days prior to surgery
Ticagrelor= 5 days prior to surgery
Give some indications for the ADP receptor antagonists (antiplatelets) clopidogrel and prasugrel.
Clopidogrel
- Monotherapy- if aspririn contraindicated
- NSTEMI- up to 12 months
- STEMI with stent- up to 12 months
- Secondary prevention:
- TIA long term
- Ischaemic stroke
Prasugrel
- ACS patients- adjunct to aspirin
How does abciximab work as an antiplatelet? What is it used for? How is it administered?
- Blocks binding of fibrinogen and von Willebrand factor
- –> blocks GPIIb/IIIa receptors
Use:
Specialist use- high risk percutaneous transluminal coronary angioplasty
Administration:
I.V.I with bolus
How does dipyridamole work as an antiplatelet?
- Inhibits cellular reuptake of adenosine within platelet
- Increase plasma adenosine
- Inhibits platelet aggregation via A2 receptors
- Also prevents cAMP degradation- inhibits expression of GPIIb/IIIa
What are the side effects (3) and inmportant interactions (3) to remember for dipyridamole?
How do streptokinase and alteplase work?
BE CAREFUL- potential for haemorrhagic bleeding
How does tranexamic acid work as an antifibrinolytic? What are some of its indications?
Inhibiton of activation of plasminogen from plasmin
Indications:
- Menorrhagia
- Hereditary angioedema
- Epistaxis
- Haemorrhage following trauma
