Clopidogrel Pathway


Clopidogrel, an antiplatelet agent structurally and pharmacologically similar to ticlopidine, is used to reduce atherosclerotic events such as myocardial infarction, stroke, and vascular death in patients who have had a recent stroke, recent MI, or have established peripheral vascular disease.
The active metabolite of clopidogrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of clopidogrel.

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References

  1. Jennings, L.K., & Saucedo, J.F. (2008). Antiplatelet and anticoagulant agents: key differences in mechanisms of action, clinical application, and therapeutic benefit in patients with non-ST-segment-elevation acute coronary syndromes. Current Opinion in Cardiology, 23(4), 302-308. PMID: 18520712
  2. Mega, J.L., Close, S.L., Wiviott, S.D., Shen, L., Hockett, R.D., Brandt, J.T., et al. (2009). Cytochrome p-450 polymorphisms and response to clopidogrel. New England Journal of Medicine, 360(4), 411-413. PMID: 19106084
  3. Plavix. (2009). [Electronic version]. e-CPS. Retrieved June 24, 2009.