Briefly outline the mode of action and half life of aspirin, tirofiban and clopidogrel.

 

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College Answer

 

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

 

 

Discussion

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;
Weak acid

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,
50% biliary

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

 

 

 

 

 

References

References

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.