Anti-platelet agents

Question 1

symptoms of venous thromboembolism

Answer 1

[in leg]

swelling

pain

reddening

Question 2

what are blood clots made from?

Answer 2

activated platelets

RBCs

fibrin

Question 3

what mediates the clotting process?

Answer 3

clotting factors (proteins)

Question 4

coagulation process

Answer 4

1. Vascular injury exposes collagen + Von Willebrand factor (VWF)
2. Platelets adhere to proteins = partially activated
3. Release signalling molecules that recruit more platelets
4. Tissue factor (protein) initiates coagulation cascade
5. VIIa + Xa bond to tissue factor = thrombin production (fully activates platelets)
6. Thrombin converts soluble fibrinogen to insoluble fibrin + activates factor XIII to cross-link fibres - aggregate via surface expression of GPIIb/IIIa receptors

Question 5

main role of VWF?

Answer 5

bridges subendothelila collagen and platelet glycoprotein GPIb receptors

Question 6

platelet activation

Answer 6

Shape changes - requires activation of P2Y1 and P2Y12 receptors by ADP

Granular secretion

Synthesis and release - platelet-activating factor and thromboxane A2 (TXA2)

Question 7

what happens when you inhibit TXA2?

Answer 7

bleeding

Question 8

what happens when you inhibit PGI2?

Answer 8

gastrointestinal ulcers

Question 9

what happens when you inhibit pro inflammatory prostaglandins?

Answer 9

reduction in pain, fever and inflammation

Question 10

what happens when you inhibit prostacyclin-2?

Answer 10

decreases vasodilation and increases production of TxA2

Question 11

normal role of P2Y12 receptors in platelets

Answer 11

stabilisation of activated receptors on platelets

Question 12

Glycoprotein IIb/IIIa receptor inhibitors - mechanism of action

Answer 12

prevent platelet aggregation by blocking glycoprotein IIb/IIIa receptors on their platelet’s plasma membrane + inhibiting fibrinogen binding

Question 13

Phosphodiesterase inhibitors - mechanism of action

Answer 13

inhibits hydrolysis of cAMP + cGMP

stimulation of PGI2 and inhibits TxA2 synthesis

Question 14

which drug combination to use for stable angina and prevention of ACS?

Answer 14

Aspirin + clopidogrel

Question 15

which drug combination to use for unstable angina (NSTEMI + MI)?

Answer 15

High doses of aspirin + P2Y12 antagonist + tirofiban + heparin

Question 16

which drug combination to use for secondary prevention of MI?

Answer 16

Low doses of aspirin + P2Y12 antagonist

Question 17

which drug combination to use for PCI / Angioplasty?

Answer 17

Aspirin + IIb/IIIa inhibitor + heparin

Question 18

what is TTP?

Answer 18

[Thombotic thrombocytopenic purpura]

blood disorder when blood clots form in small blood vessels throughout your body

Question 19

how is TTP inherited?

Answer 19

mutations in ADAMTS13 gene or immunodeficiency in ADAMTS13 enzyme that breaks down VWF

Question 20

how is TTP acquired not by genetics?

Answer 20

drug induced (ticopidine, clopidogrel, prasugrel + chemotherapy)

diseases/conditions (pregnancy, virus, HIV, hepatitis)

Question 21

how is a clot broken down?

Answer 21

Endothelial cells secrete tissue plasminogen activator

activates protease plasmin to degrade fibrin