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CVD > 14. Anti-Platelet Drugs > Flashcards

14. Anti-Platelet Drugs Flashcards

1
Q

Give the development of a platelet

A

CD34+ stem cell
Megakaryoblast
Promegakaryocyte
Megakaryocyte

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2
Q

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

A

Thrombopoietin

IL-3, 6

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3
Q

What are the 2 types of granules present in platelets?

A

Alpha and dense

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4
Q

What substances are present in alpha granules?

A

von Willebrand Factor
Fibrinogen
Factor 5
Platelet factor 4

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5
Q

What substances are present in dense granules?

A

ADP
Ca++
Serotonin

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6
Q

What is the life span of a platelet?

A

10 days

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7
Q

What is primary haemostasis?

A

Formation of a platelet plug

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8
Q

What is secondary haemostasis?

A

Clotting cascade

Fibrin traps RBCs

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9
Q

What is the difference between an arterial and venous clot?

A

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

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10
Q

What are the surface glycoprotein receptors on platelets?

A

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

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11
Q

What does GP VI bind to?

A

Collagen

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12
Q

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

A

von Willebrand factor

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13
Q

What does the GPIIb-IIIa complex bind to?

A

Other platelets

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14
Q

What GPCRs are found on the surface of platelets?

A

PARs

ADP receptors

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15
Q

Name 2 ADP receptors found on the surface of platelets?

A

P2Y1

P2Y12

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16
Q

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

A

Holds platelets still at endothelium in fast rushing blood

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17
Q

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

A

a2B1

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18
Q

What happens when platelets release dense granules?

A

Platelet activation and aggregation

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19
Q

How do platelets change shape?

A

Reorder of actin and tubulin polymers

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20
Q

What method of signalling does thromboxane use?

A

Autocrine

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21
Q

What happens when ADP binds to P2Y12, 1?

A

Induce thromboxane synthesis

Activation of GPIIb/IIIa

22
Q

What kind of signalling is done by GPIIb/IIIa?

A

Inside out signalling

23
Q

What enzyme converts prostaglandin to thromboxane A2?

A

Thromboxane synthase

24
Q

What cells produce prostacyclin?

A

Endothelial cells

25
Q

What are the actions of prostacyclin?

A

Inhibit platelets

Promote vasodilation

26
Q

What are the functions of thromboxane?

A

Activation of platelets
Change shape
Release granules
Aggregation

27
Q

What are the pathways of platelet activation?

A

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

28
Q

What is the MOA of aspirin?

A

Irreversibly inhibits COX-1 producing thromboxane

Reduced capacity of platelets to aggregate

29
Q

What are the uses of aspirin?

A

Prophylaxis for thrombosis in MI, TIA

Prevent ischaemic events in unstable angina

30
Q

What drug is aspirin usually used with?

A

Clopidogrel

31
Q

What are the contraindications to using aspirin?

A

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

32
Q

What is the MOA of dipyridamole?

A

Reduce uptake of adenosine causing vasodilation

33
Q

What are the uses of dipyridamole?

A

With warfarin/ aspirin for stroke/TIA

34
Q

What are the uses of ADP receptor antagonists?

A

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

35
Q

Name 3 ADP receptor antagonists

A

Clopidogrel
Prasugrel
Ticagrelor

36
Q

Which enzyme metabolises clopidogrel and prasugrel?

A

CYP2C19

37
Q

What is the difference between ADP receptor antagonists?

A

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

38
Q

What does clopidogrel bind to?

A

Cysteine sulphydryl on P2Y12

39
Q

What are the contraindications for prasugrel?

A

Stroke/TIA because of high risk of bleeding

40
Q

What is the half life of ticagrelor?

A

7 hours: requires BD dosing

41
Q

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

A

Use of the CYP450 enzyme

Using ticagrelor because it’s metabolically active

42
Q

Name 3 GPIIb/IIIa inhibitors

A

Abciximab
Tirofiban
Eptifibatide

43
Q

What is the composition of abciximab?

A

7E3 Fab fragments

44
Q

What is the MOA of abciximab?

A

Binds to RGD site on GPIIb/IIIa

Prevents interaction with fibrinogen

45
Q

What route are GPIIb/IIIa inhibitors given through?

A

IV

46
Q

What are the uses of abciximab?

A

Unstable angina

PCI

47
Q

What is the MOA of tirofiban and eptifibatide?

A

Mimics RGD segment of fibrinogen

48
Q

What is the use of tirofiban?

A

PCI

49
Q

What are the uses of eptifibatide?

A

Angina or MI

50
Q

What are the side effects of eptifibatide?

A

Hypotension
CV failure
Arrhythmias

CVD (22 decks)

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