Antiplatlet and fibrinolytic

Question 1

Cyclo-oxygenase inhibitor
Aspirin

Answer 1

Potent platelet aggregating agent thromboxane A2 (TXA2) formed from arachidonic acid by COX-1
Aspiring inhibits COX-1 mediated production of TXA2 and reduces platelet aggregation - irreversible
Higher doses inhibit endothelial prostacyclin (PGI2)
Absorbed by passive diffusion - hepatic hydrolysis to salicylic acid

Aspirin does not completely inhibit platelet aggregation as other aggregating agents not inhibited
Action at low non-analgesic doses (75mg) used to inhibit platlets
Loading doses of 300mg used in acute coronary syndromes as can act on more arachidoin

Question 2

Cyclo-oxygenase inhibitor
Aspirin contraindications

Answer 2

Question 3

ADP receptor antagonists
- Clopidogrel
- Prasugrel
- Ticagrelor

Answer 3

Inhibit binding of ADP to P2Y12 receptor -> inhibit activation of GPIIb/IIa receptors
- independant of COX pathway
Clopidogrel and prasugrel are irreversible inhibitors of P2Y12
- prodrugs - have active hepatic metabolites
- slow onset of action without loading dose - some inter-individual variability in antiplatelet action
Ticagrelor and prasugrel have more rapid onset of action
- act reversibly at diffferent site to clipidogrel and has active metabolites

Question 4

ADP receptor antagonists contraindications
- Clopidogrel
- Prasugrel
- Ticagrelor

Answer 4

Question 5

Phosphodiesterase inhibitors
Dipyridamole (viagra)

Answer 5

Dipyridamole inhibits cellular reuptake of adenosine -> increased adenosine -> inhibits platelet aggregation via adenosine (A2) receptors
Acts as phosphodiesterase inhibitor which prevents cAMP degradation -> inhibit expression of GPIIb/IIIa

Secondary prevention of ischaemic stroke and TIAs
Adjunct for prophylaxis of thromboebolism following valve replacement
Stroke

Question 6

Phosphodiesterase inhibitors
Dipyridamole (viagra) contraindications

Answer 6

Question 7

Glycoprotein IIb/IIIa inhibitors
Abciximab

Answer 7

Blocks binding of fibrinogen and von Willebrand factor (vWF)
Target final common pathway - more complete platelet aggregation
Abciximab - antibody - blocks GPIIb/IIIa receptors >80% reduction in aggregation - bleeding risk
- more than aspirin

Administered i.v.

Question 8

Glycoprotein IIb/IIIa inhibitors
Abciximab contraindications

Answer 8

Question 9

Fibrinolytic (thrombolytic) “clot buster” agents
- Streptokinase
- Alteplase

Answer 9

Question 10

Fibrinolytic (thrombolytic) “clot buster” agents contraindications
- Streptokinase
- Alteplase

Answer 10