6.2.1 Aspirin Flashcards
What is a thrombus?
A clot adhered to a vessel wall
What is an embolus?
Intravascular clot distal to site of origin
What is a venous thrombosis associated with?
Stasis of blood or damage to veins
Describe the characteristics of a venous thrombosis
High red blood cell and fibrin content
Low platelet content evenly distributed
What is an arterial thrombosis caused by?
Forms at site of atherosclerosis following a plaque rupture
Describe the characteristics of an arterial thrombosis
Lower fibrin content
Higher platelet content
What causes thrombosis?
Virchow’s Triad
Way to remember
Triad=3
Skip 3 letters
Vessel wall damage
i
r
c
Hypercoaguability
o
w
‘
Stasis
What happens in healthy endothelium?
Prostacyclin (PGI2) produced and released by endothelial cells
Inhibits platelet aggregation
How does prostacyclin inhibit platelet aggregation?
PGI2 binds to platelet receptors
Increased concentration of cAMP in platelets, this leads to a decrease in calcium
Reduced calcium prevents platelet aggregation
Decrease in platelet aggregatory agents
Stabilises inactive GPIIb/ IIIa receptors
What is the lifespan of a platelet?
8-10 days
10% replaced each day
What is the process of a thrombus formation?
Adhesion
Platelets adhere to exposed collagen fibres on damaged vessel endothelium
Activation
Chemical mediators released by platelets attract more platelets
Aggregation
Platelets are recruited by mediators forming the plateleg plug
What happens in atherosclerosis which causes the formation of a thrombus?
Fibrous cap formation
Plaque ruptures
Thrombus forms over ruptured plaque
What platelet granules are released in platelet activation?
ADP
Thromboxane A2
Serotonin
Platelet activation factor
Thrombin
What happens in platelets after chemical mediators are released?
Increased calcium and decreased cAMP in platelets
This leads to cascade and amplification from platelet to platelet
What drugs are used to treat arterial thrombi?
Antiplatelet and fibrinolytic drugs
Arterial thrombi are platelet rich
What drugs are used for venous thrombi?
Parenteral and oral anticoagulants
What is an example of a parenteral anticoagulant drug?
Heparin
Give an example of an oral anticoagulant
Warfarin
When are both antiplatelet and anticoagulants used?
Secondary prevention
Targeting multiple sites and mechanisms
What does thromboxane A2 form from?
Arachidonic acid by COX-1 (cyclooxygenase)
Give an example of a Cyclo-oxygenase inhibitor
Aspirin
How does aspirin work?
Inhibits cyclooxygenase-1 mediated production of thromboxane A2
Reduces platelet aggregation
Irreversible
Why does aspirin not completely inhibit platelet aggregation?
Other chemical mediators
COX1 not inhibited on all platelets
What are the different dosing regiments of aspirin?
75 mg
Baby aspirin, used long-term to inhibit platelets
Just inhibits COX1
300 mg
Used in acute coronary syndromes
What does aspirin do at higher doses?
Inhibits endothelial prostacyclin PGI2
Causing a decrease in cAMP, increased in Ca2, increase in platelet mediators released and aggregation by activating GPIIb/IIIa
How is aspirin absorbed?
Passive diffusion
Hepatic hydrloysis converts aspirin to salicylic acid
What are the adverse effects of aspirin?
GI irritation
GI bleeding (peptic ulcer)
Haemorrhage (stroke)
Hypersensitivity
When should you not use aspirin?
Reye’s syndrome, avoid in under 16s
Hypersensitivity
3rd trimester of pregnancy - can cause premature closure of ductus arteriosus
What are some important drug to drug interactions with aspirin?
Other anti-platelet and anti-coagulant drugs
(additive/synergistic action)
Why does aspirin not work that well in some people?
COX-1 polymorphisms result in lack of efficacy
Why does anti-platelet effect last lifespan of platelet?
Platelets have no nuclei
Cannot make more COX-1
Inhibition lasts lifespan of the platelet
When do we use aspirin?
- AF patients post stroke
- Secondary prevention of stroke/ TIA and ACS
- Post PCI and stent to reduce ischaemic complications
- Co-prescribed with other anti-platelet agents
- NSTEMI/STEMI- inital once 300mg loading dose, chewable is best
- Acute ischamic stroke 300mg daily 2 weeks
What is required with long-term use of aspirin?
Proton pump inhibitors
