Arterial Thrombosis

Question 1

What can arterial thrombosis cause?

Answer 1

Ischemic necrosis of tissue supplied by the artery

Question 2

What is the first phase of arterial thrombosis development?

Answer 2

LDL enters the sub-endothelial space

Question 3

What is artherosclerosis?

Answer 3

• 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

Question 4

What happens when the arthersclerotic plaque ruptures?

Answer 4

Platlets –> Circulating cells that aggregate on damaged blood vessel walls
- If the platlet response is big enough, can block the artery completly

Question 5

What happens if platlets block an artery to the heart?

Answer 5

• 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

Question 6

Define Ischemia

Answer 6

• inadequate blood flow to a tissue

Question 7

What occurs if ischemia is complete? What areas of the body does this occur?

Answer 7

• Myocardial Infarction –> Coronary artery –> coronary artery disease
• Stroke –> cerebrovascular event –> cerebra arteries –> cerebrovascular disease
• Arteries of the limbs –> Peripheral arterial disease

Question 8

Platlets

Answer 8

• Fragments of larger, multinucleated cells (megakaryocytes)
• No nucleus
  Contain granules in cytoplasm
  Contain COX-1 enzyme

Question 9

What is the role of platlets?

Answer 9

Adhere to damaged wall
Aggregate to form a platlet plug
Activate coagulation cascade and other platlets

Question 10

How do platlets adhere to injured areas?

Answer 10

• Glycoprotein Ib receptors
• Expressed on platlet surface
• Affinity for subendothelial substrates (Collagen and Von Willebrand Factor)
• cause platlets to adhere to injured area

Question 11

How are platelets activated?

Answer 11

1) Exposure to subendothelial surfaces (adherence/ GP Ib binding)
2) Exposure to activators such as:

Thromboxane
ADP
Thrombin
Serotonin
Platlet Activating factor (PAF)

Question 12

How does activation of platlets promote aggregation?

Answer 12

• Emergence of GP IIb/IIIA receptor
• receptor that promotes platlet agggregation
  FIBRINOGEN CONNECTS THE GP IIB/IIIA RECEPTORS OF TWO PLATLETS TOGETHER

Question 13

What is fibrinogen?

Answer 13

• the precursor of fibrin - final product of coagulation cascade
• links platlets to ensure aggregation
• localizes substrate for clot formation at site of damage

Question 14

Once platlets are activated they release?

Answer 14

• Release stored granules of:

Adenosine Diphosphate (ADP)
Thromboxane A2

• Results in the activation of resting platlets and initiates the coagulation cascade

Question 15

What is prostacyclin (PGI2)?

Answer 15

• 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

Question 16

Cyclooxygenase types:

Answer 16

• COX-1 –> Converets arachdonic acid to thromboxane A2
• COX-2 –> Converts aracdonic acid to prostacyclin (PGI2)

Question 17

Thromboxane A2 is a….

Answer 17

Platlet Activator

Question 18

Prostacylin is a…

Answer 18

platlet inhibitor

Question 19

ASA inhibits….

Answer 19

• COX 1 AND COX 2
• 50-100 x more potent for COX-1

Question 20

What amount of ASA will inhibit only COX-1?

Answer 20

• 81 mg

Question 21

How does ASA work?

Answer 21

• 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

Question 22

Why is ASA used over NSAIDS?

Answer 22

• 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

Question 23

Two examples of ADP antagonists
How long they are used for?

Answer 23

Clopidogrel
Ticagrelor

Typically 1 year

Question 24

Clopidogrel

Answer 24

• ADP antagonist
• Prodrug that requires liver metabolism for activation
• Inhibits ADP receptor
• Irreversible inhibitor

Question 25

Ticagrelor

Answer 25

- Reversible inhibitor of ADP receptor - Not a prodrug - Common in Post-Mi setting

Question 26

How do ADP antagonists work?

Answer 26

- Prevent the consequences following artherosclerotic rupture. Prevents coagulation cascade. Does not reduce the risk of plaque rupture.

Question 27

What is the role of ADP antagonists?

Answer 27

- Used in people at high risk for MI or stroke primarily as secondary prevention

Question 28

Glycoprotein IIb/IIIa Inhibitors MOA

Answer 28

- Hopsital use only - Receptor that prmotes platlet aggregation - Fibrinogen is the principle target

Question 29

What other drug is commonly used in coronary artery disease?

Answer 29

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

Question 30

What is the difference between unstable angina and stable angina?

Answer 30

- 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

Question 31

How is nitroglycerin used for stable angina?

Answer 31

- 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.

Question 32

Drugs that can be used to manage/prevent angina?

Answer 32

- Nitroglycerin spray (prn use) - Nitroglycerin patch - Beta-blockers and Non-DHP CCB - DHP CCB