Arterial Thrombosis & Anti-Platelet Drugs Flashcards
What are causes for arterial thrombosis?
High pressure system
Atherosclerosis
Platelet rich thrombus
What is treatment for arterial thrombosis?
Aspirin and other anti-platelet drugs
Modify risk factors for atherosclerosis
What is atherosclerosis?
Damage to endothelium
Recruitment of foamy macrophages rich in cholesterol -> form plaques rich in cholesterol
What conditions occur secondary to stable atherosclerotic plaques and what is the histology?
Hyalinised and calcified
Stable plaques - stable angina (coronary artery); intermittent claudication (leg artery)
Describe unstable atherosclerotic plaques and what conditions they can cause
Plaques rupture - platelets recruited and cause acute thrombosis
Unstable angina or MI (coronary arteries)
Stroke (cerebral arteries)
How does platelet adhesion in atherosclerosis cause arterial thrombosis?
Plaque ruptures - more likely in high pressure environment of arteries
Platelet adheres to it - exposed endothelium and release of Von Willebrand factor
Platelets become activated - release granules that activate coagulation and recruit other platelets to developing platelet plug
Platelet aggregation via membrane glycoproteins
What are risk factors for arterial thrombosis?
Factors that cause damage to endothelium, increase in foamy macrophages and platelet activation:
- Hypertension (damage to endothelium, platelet activation)
- Smoking (endothelium, platelets)
- High cholesterol (accumulated in plaques)
- Diabetes mellitus (endothelium, platelets, cholesterol)
How do we prevent arterial thrombosis?
Stop smoking
Treat hypertension
Treat diabetes
Lower cholesterol
Anti-platelet drugs
Describe how platelet adhesion and accumulation occurs
Endothelial damage exposes collage, VWF and other proteins to which platelets have receptors - platelet adhesion at site of injury
There is then secretion of various chemicals from platelets (e.g. ADP, thromboxane A2) which leads to aggregation of platelets at site of injury
Describe platelet adhesion
Describe platelet aggregation
Describe how platelet activation occurs
How does aspirin work?
Inhibits cyclo-oxygenase which is necessary to produce thromboxane A2 (a platelet agonist released from granules on activation)
What are side effects of aspirin?
Bleeding
Blocks production of prostaglandins: GI ulceration, bronchospasm
How do clopidogrel and prasugrel work?
ADP receptor antagonists
How does dipyridamole work?
Phosphodiesterase inhibitor - increases production of cAMP which inhibits platelet aggregation
Give examples of GP IIb/IIIA inhibitors and how they work
