14. Anti-Platelet Drugs

Question 1

Give the development of a platelet

Answer 1

CD34+ stem cell
Megakaryoblast
Promegakaryocyte
Megakaryocyte

Question 2

What are the mediators which cause the fragmentation of megakaryocytes to platelets?

Answer 2

Thrombopoietin

IL-3, 6

Question 3

What are the 2 types of granules present in platelets?

Answer 3

Alpha and dense

Question 4

What substances are present in alpha granules?

Answer 4

von Willebrand Factor
Fibrinogen
Factor 5
Platelet factor 4

Question 5

What substances are present in dense granules?

Answer 5

ADP
Ca++
Serotonin

Question 6

What is the life span of a platelet?

Answer 6

10 days

Question 7

What is primary haemostasis?

Answer 7

Formation of a platelet plug

Question 8

What is secondary haemostasis?

Answer 8

Clotting cascade

Fibrin traps RBCs

Question 9

What is the difference between an arterial and venous clot?

Answer 9

Arterial due to endothelial damage or rupture of atheroma and venous due to stasis near valves
Arterial more platelet rich and venous more fibrin rich

Question 10

What are the surface glycoprotein receptors on platelets?

Answer 10

GP VI
GPIb-IX-V complex
GPIIIb-IIa complex

Question 11

What does GP VI bind to?

Answer 11

Collagen

Question 12

What does the GPIb-IX-V complex bind to?

Answer 12

von Willebrand factor

Question 13

What does the GPIIb-IIIa complex bind to?

Answer 13

Other platelets

Question 14

What GPCRs are found on the surface of platelets?

Answer 14

PARs

ADP receptors

Question 15

Name 2 ADP receptors found on the surface of platelets?

Answer 15

P2Y1

P2Y12

Question 16

Why is GPIb-IX-V particularly important in high blood pressure?

Answer 16

Holds platelets still at endothelium in fast rushing blood

Question 17

What integrin works alongside GPVI to allow stable adhesion to collagen?

Answer 17

a2B1

Question 18

What happens when platelets release dense granules?

Answer 18

Platelet activation and aggregation

Question 19

How do platelets change shape?

Answer 19

Reorder of actin and tubulin polymers

Question 20

What method of signalling does thromboxane use?

Answer 20

Autocrine

Question 21

What happens when ADP binds to P2Y12, 1?

Answer 21

Induce thromboxane synthesis

Activation of GPIIb/IIIa

Question 22

What kind of signalling is done by GPIIb/IIIa?

Answer 22

Inside out signalling

Question 23

What enzyme converts prostaglandin to thromboxane A2?

Answer 23

Thromboxane synthase

Question 24

What cells produce prostacyclin?

Answer 24

Endothelial cells

Question 25

What are the actions of prostacyclin?

Answer 25

Inhibit platelets | Promote vasodilation

Question 26

What are the functions of thromboxane?

Answer 26

Activation of platelets Change shape Release granules Aggregation

Question 27

What are the pathways of platelet activation?

Answer 27

ADP-P2Y12 (thrombin production) COX-1 (thromboxane production) PAR-1 (thrombin receptor)

Question 28

What is the MOA of aspirin?

Answer 28

Irreversibly inhibits COX-1 producing thromboxane | Reduced capacity of platelets to aggregate

Question 29

What are the uses of aspirin?

Answer 29

Prophylaxis for thrombosis in MI, TIA | Prevent ischaemic events in unstable angina

Question 30

What drug is aspirin usually used with?

Answer 30

Clopidogrel

Question 31

What are the contraindications to using aspirin?

Answer 31

Allergy to ibuprofen Asthma (increase in leucotrienes) Kidney disease, peptic ulcers, gout, gastritis Bleeding risks

Question 32

What is the MOA of dipyridamole?

Answer 32

Reduce uptake of adenosine causing vasodilation

Question 33

What are the uses of dipyridamole?

Answer 33

With warfarin/ aspirin for stroke/TIA

Question 34

What are the uses of ADP receptor antagonists?

Answer 34

Secondary prevention of stroke, TIA, MI Unstable angina PCI, CABG

Question 35

Name 3 ADP receptor antagonists

Answer 35

Clopidogrel Prasugrel Ticagrelor

Question 36

Which enzyme metabolises clopidogrel and prasugrel?

Answer 36

CYP2C19

Question 37

What is the difference between ADP receptor antagonists?

Answer 37

Clopidogrel has a 2 step oxidation process Prasugrel has a 1 step oxidation and is broken down faster Ticagrelor is metabolically active

Question 38

What does clopidogrel bind to?

Answer 38

Cysteine sulphydryl on P2Y12

Question 39

What are the contraindications for prasugrel?

Answer 39

Stroke/TIA because of high risk of bleeding

Question 40

What is the half life of ticagrelor?

Answer 40

7 hours: requires BD dosing

Question 41

Why is there a resistance problem with some ADP receptor inhibitors and how can it be overcome?

Answer 41

Use of the CYP450 enzyme | Using ticagrelor because it's metabolically active

Question 42

Name 3 GPIIb/IIIa inhibitors

Answer 42

Abciximab Tirofiban Eptifibatide

Question 43

What is the composition of abciximab?

Answer 43

7E3 Fab fragments

Question 44

What is the MOA of abciximab?

Answer 44

Binds to RGD site on GPIIb/IIIa | Prevents interaction with fibrinogen

Question 45

What route are GPIIb/IIIa inhibitors given through?

Answer 45

IV

Question 46

What are the uses of abciximab?

Answer 46

Unstable angina | PCI

Question 47

What is the MOA of tirofiban and eptifibatide?

Answer 47

Mimics RGD segment of fibrinogen

Question 48

What is the use of tirofiban?

Answer 48

PCI

Question 49

What are the uses of eptifibatide?

Answer 49

Angina or MI

Question 50

What are the side effects of eptifibatide?

Answer 50

Hypotension CV failure Arrhythmias