Anti-Platelets

Question 1

How does healthy endothelium prevent platelet aggregation?

Answer 1

1. Prostacyclin is released from healthy endothelium.
2. This increased cAMP production.
3. cAMP prevents Ca+ release, preventing platelet aggregation.
4. GP11B/GP11A receptors are also stabilised.

Question 2

How does unhealthy endothelium promote platelet aggregation?

Answer 2

1. Collagen fibres from exposed subendothelial surface activate platelets
2. Activated platelets release chemical mediators - Thomboxane A2, ADP, serotonin, PAF
3. More platelets are recruited to the platelet plug
4. Chemical mediators cause Ca2+ release and less cAMP production.
5. Elevated Ca2+ causes - release of platelet granules, activated thromboxane A2, activated GPIIB/GPIIA receptors.
6. Cascade amplification and recruitment of other platelets.

Question 3

How does aspirin work?

Answer 3

• Inhibits COX-1 mediated production of thomboxane A2
• Reduced platelet aggregation irreversibly
• Used at low non analgesic doses (75mg)
• Higher doses inhibit endothelial prostacyclin

Question 4

What are some contraindications for aspirin?

Answer 4

• Bleeding time prolonged - haemorrhagic stroke, GI bleeding
• Reye’s syndrome - avoid <16yo
• Hypersensitivity
• 3rd trimester - premature closing ductus arteriosus

Question 5

What should you give to a patient if giving aspirin long term?

Answer 5

A ppi

Question 6

Name 3 ADP receptor antagonists

Answer 6

Clopidogrel
Prasugrel
Ticagrelor

Question 7

How do ADP receptor antagonists work?

Answer 7

Inhibit binding of ADP to P2Y12 receptor, inhibiting activation of GP11B/GP11A receptors.
- Independent of COX pathway

Question 8

Are clopidogrel/prasugrel irreversible?

Answer 8

Yes

Question 9

Which ADP receptor antagonists have a faster onset?

Answer 9

Ticagrelor and prasugrel

Question 10

What are some contraindications and side effects for ADP receptor antagonists?

Answer 10

• Bleeding
• GI upset - Dyspepsia and diarrhea
• Thrombocytopenia
• Caution in renal and hepatic impairment

Question 11

What is important about clopidogrel and CYP enzymes?

Answer 11

• Clopidogrel requires CYP’s for activation

- Caution with CYP inhibitors (esp omeprazole use other gastric protection)

Question 12

What is abciximab?

Answer 12

A glycoprotein 11B/111A inhibitor.

Question 13

How do glycoprotein IIB/IIIA inhibits work?

Answer 13

• An antibody which blocks the GPIIIB/GPIIA receptors.

- This blocks binding of fibrinogen and von Willebrand factor, targeting the final common pathway.

Question 14

What are some side effects of abciximab?

Answer 14

• Bleeding, adjust dose for body weight
• Thrombocytopenia
• Hypotension
• Bradycardia

Question 15

Name a phosphodiesterase inhibitor?

Answer 15

Dipyridamole

Question 16

How do phosphodiesterase inhibitors work?

Answer 16

• Inhibits cellular reuptake of adenosine, increasing plasma adenosine
• This inhibits platelet aggregation via A2 receptors
• Also inhibits phosphodiesterase which prevents cAMP degradation and inhibits expression of GPIIA/GPIIIB

Question 17

What are some side effects of dipyridamole?

Answer 17

Flushing, headaches, hypersensitivity

Question 18

Name three thombolytic agents

Answer 18

Streptokinase - can only be used once
Alteplase
Tranexamic acid

Question 19

What needs ruling out before you give a thombolytic agent?

Answer 19

Intracranial haemmorhage

Question 20

Name an antifibrinolytic - how does it work?

Answer 20

Tranexamic acid

Inhibits activation of plasminogen from plasmin

Question 21

What drug activates plasminogen to plasmin?

Answer 21

Streptokinase/Alteplase