Arterial Thrombosis Flashcards
What can arterial thrombosis cause?
Ischemic necrosis of tissue supplied by the artery
What is the first phase of arterial thrombosis development?
LDL enters the sub-endothelial space
What is artherosclerosis?
- A disease of the arteries
- Often asymptomatic
- Artherosclerotic plaque pushing aginst arterial wall
- LDL is the main player
- Ischemia or infarction can occur if they rupture
What happens when the arthersclerotic plaque ruptures?
Platlets –> Circulating cells that aggregate on damaged blood vessel walls
- If the platlet response is big enough, can block the artery completly
What happens if platlets block an artery to the heart?
- Oxygen cannot perfuse out of arteries
- Cardiac cells still being told to contract –> creating a demand for oxygen and energy supply is gone
Cardiac cells suffocate
Define Ischemia
- inadequate blood flow to a tissue
What occurs if ischemia is complete? What areas of the body does this occur?
- Myocardial Infarction –> Coronary artery –> coronary artery disease
- Stroke –> cerebrovascular event –> cerebra arteries –> cerebrovascular disease
- Arteries of the limbs –> Peripheral arterial disease
Platlets
- Fragments of larger, multinucleated cells (megakaryocytes)
- No nucleus
Contain granules in cytoplasm
Contain COX-1 enzyme
What is the role of platlets?
Adhere to damaged wall
Aggregate to form a platlet plug
Activate coagulation cascade and other platlets
How do platlets adhere to injured areas?
- Glycoprotein Ib receptors
- Expressed on platlet surface
- Affinity for subendothelial substrates (Collagen and Von Willebrand Factor)
- cause platlets to adhere to injured area
How are platelets activated?
1) Exposure to subendothelial surfaces (adherence/ GP Ib binding)
2) Exposure to activators such as:
Thromboxane
ADP
Thrombin
Serotonin
Platlet Activating factor (PAF)
How does activation of platlets promote aggregation?
- Emergence of GP IIb/IIIA receptor
- receptor that promotes platlet agggregation
FIBRINOGEN CONNECTS THE GP IIB/IIIA RECEPTORS OF TWO PLATLETS TOGETHER
What is fibrinogen?
- the precursor of fibrin - final product of coagulation cascade
- links platlets to ensure aggregation
- localizes substrate for clot formation at site of damage
Once platlets are activated they release?
- Release stored granules of:
Adenosine Diphosphate (ADP)
Thromboxane A2
- Results in the activation of resting platlets and initiates the coagulation cascade
What is prostacyclin (PGI2)?
- produced by endothelial cells
- Promotes vasodilation and decrease platlet aggregation
- Synthesized from arachadonic acid
- Same precursor as thromboxane A2
- Produced by the enzyme familiy –> CYCLOOXYGENASE-2
Cyclooxygenase types:
- COX-1 –> Converets arachdonic acid to thromboxane A2
- COX-2 –> Converts aracdonic acid to prostacyclin (PGI2)
Thromboxane A2 is a….
Platlet Activator
Prostacylin is a…
platlet inhibitor
ASA inhibits….
- COX 1 AND COX 2
- 50-100 x more potent for COX-1
What amount of ASA will inhibit only COX-1?
- 81 mg
How does ASA work?
- Irreversible inhibitor of COX (mainly COX-1) –> Prevents formation of thromboxane A2
- Platelets cannot regenerate COX as no nucleus
- Allows for OD dosing despite short half life
Why is ASA used over NSAIDS?
- NSAIDS are reversible and only inhibit COX-2
- NSAIDS not indicated for anti-platelet action
- NSAIDS reduce inflammation (and pain) by reducing Pg’s in damaged tissue
Two examples of ADP antagonists
How long they are used for?
Clopidogrel
Ticagrelor
Typically 1 year
Clopidogrel
- ADP antagonist
- Prodrug that requires liver metabolism for activation
- Inhibits ADP receptor
- Irreversible inhibitor
Ticagrelor
- Reversible inhibitor of ADP receptor
- Not a prodrug
- Common in Post-Mi setting
How do ADP antagonists work?
- Prevent the consequences following artherosclerotic rupture. Prevents coagulation cascade. Does not reduce the risk of plaque rupture.
What is the role of ADP antagonists?
- Used in people at high risk for MI or stroke primarily as secondary prevention
Glycoprotein IIb/IIIa Inhibitors MOA
- Hopsital use only
- Receptor that prmotes platlet aggregation
- Fibrinogen is the principle target
What other drug is commonly used in coronary artery disease?
Nitroglycerin
- Used to manage or prevent angina
- Angina is pain or discomfort resulting from inadequate blood supply to cardiac muscle
- Can occur in heart attack or when cardiac workload increases
What is the difference between unstable angina and stable angina?
- Unstable angina is due to an unstable plaque and pertains to an ischemic part of the heart.
- Stable angina is a fixed obstruction angina where at rest no angina, but increase cardiac output, angina develops as need for more oxygen and energy. Ischemic pain will go away if decrease workload
How is nitroglycerin used for stable angina?
- Works on veins more than arteries
- By dilating veins, reduce pre-load on heart (filling pressure) by allowing blood to pool in veins
- Decrease preload, decrease workload and decrease pain from angina.
Drugs that can be used to manage/prevent angina?
- Nitroglycerin spray (prn use)
- Nitroglycerin patch
- Beta-blockers and Non-DHP CCB
- DHP CCB
