Briefly outline the mode of action and half life of aspirin, tirofiban and clopidogrel.
a) Tirofiban – 2b3A inhibitor. Binds to this receptor on platelet membrane
Half life approx 2 hrs – Accumulates in renal failure
b) ASA – Prostaglandin and Thromboxane A2 receptor – Irreversible blockade -platelets affected till replaced.
c) Clopidogrel – Blocks ADP receptor of platelet hence reduces fibrinogen binding to platelet.
Irreversible binding – platelets affected till replaced
The college answer is as detailed as one is expected to produce given that there is only about 90 seconds to think about it.
A slightly more detailed summary of antiplatelet agents is available. The following table is borrowed from there.
|
Drug |
Chemical properties |
Mechanism |
Clearance |
Half-life |
Duration of effect |
|
Aspirin |
Salycilate; |
Irreversible COX-1 inhibition, thus decreased production of the prothrombotic thromboxane A2 |
Renal |
1-2 hrs |
7-10 days |
|
Clopidogrel |
Thienopyridine |
Irreversible inhibition of P2Y12 ADP receptor, thus inhibition of cAMP-dependent platelet activation |
50% renal, |
0.5-1 hrs |
7-10 days |
|
Prasugrel |
Thienopyridine |
Irreversible inhibition of P2Y12 ADP receptor, thus inhibition of cAMP-dependent platelet activation |
Renal |
7 hrs |
7-10 days |
|
Ticagrelor |
Nucleoside (adenosine) analogue |
Reversible inhibition of P2Y12 ADP receptor, thus inhibition of cAMP-dependent platelet activation |
Biliary |
7-8 hrs |
3-5 days |
|
Abciximab |
Fab fragment of a human monoclonal antibody |
Glycoprotein IIb/IIIa inhibition, thus inhibition of platelet binding to fibrinogen and von Willebrand factor. |
Reticulo-endothelial system |
0.5 hr |
18-24 hours |
|
Tirofiban |
Small molecule non-peptide |
Glycoprotein IIb/IIIa inhibition, thus inhibition of platelet binding to fibrinogen and von Willebrand factor. |
Renal |
2 hrs |
4-8 hours |
Siller‐Matula, Jolanta M., Julia Krumphuber, and Bernd Jilma. "Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases." British journal of pharmacology 159.3 (2010): 502-517.
Farid, Nagy A., Atsushi Kurihara, and Steven A. Wrighton. "Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans." The Journal of Clinical Pharmacology 50.2 (2010): 126-142.
Levine, Glenn N., et al. "Newer pharmacotherapy in patients undergoing percutaneous coronary interventions: a guide for pharmacists and other health care professionals." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 26.11 (2006): 1537-1556.