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HOT TOPICS IN CARDIOLOGY: Issue 4, 2006
The phenomenon of “resistance” to antiplatelet drugs
The phenomenon of resistance to antiplatelet drugs
Carlo Patrono, Bianca Rocca
Correspondence to:
Carlo Patrono - MD
Professor of Pharmacology
Department of Pharmacology
University of Roma "La Sapienza"
Center of Excellence on Aging
"G.D'Annunzio" University Foundation
Chieti, Italy
E-mail: cpatrono@unich.it
DOI:

Summary

  • THE CONCEPT OF DRUG RESISTENCE AS EXEMPLIFIED BY RESISTANCE TO CHEMOTHERAPY
  • CLASSIFICATION OF ANTIPLATELET DRUGS BASED ON THEIR MECHANISM OF ACTION
  • Biochemical aspects of platelet function related to the mechanism of action of antiplatelet drugs
  • Glycoprotein IIb/IIIa
  • Platelet arachidonic acid metabolism
  • Platelet P2Y receptors
  • Irreversible and reversible inhibitors of platelet COX-1
  • Irreversible inhibitors: Aspirin
  • Reversible COX-1 inhibitors
  • P2Y12 antagonists: thienopyridines and related compounds
  • Thienopyridines
  • Other P2Y12 antagonists
  • Dipyridamole
  • Blockers of GPIIb/IIIa
  • Intravenous blockers: abciximab, eptifibatide, and tiro­fiban
  • Oral GPIIb/IIIa blockers
  • TP antagonists
  • ASSESSMENT OF PLATELET FUNCTION
  • In vitro and ex vivo assays
  • The bleeding time
  • In vitro platelet aggregation in platelet-rich plasma
  • Platelet aggregation in whole blood
  • Other assays in whole blood
  • Membrane markers of platelet activation
  • Soluble indexes of platelet activation: serum TXB2
  • In vivo assays
  • Plasma indexes of platelet activation
  • Urinary indexes of platelet activation
  • ASPIRIN "RESISTANCE"
  • Clinical aspirin resistance
  • Aspirin resistance defined on the basis of functional end-points
  • PFA-based studies
  • LTA-based studies
  • RPFA-based studies
  • Aspirin resistance defined on mechanism-based biochemical end-points
  • CLOPIDOGREL "RESISTANCE"
  • DETERMINANTS OF THE INTERINDIVIDUAL VARIABILITY IN RESPONSE TO ANTIPLETELET DRUG
  • Introduction: therapy as a science
  • Pharmacokinetic variability
  • Pharmacodynamic variability
  • CONCLUSIONS
  • Variability of the response to antiplatelet drugs: implications for the practicing physician
  • Variability of the response to antiplatelet drugs: implications for the clinical investigator
  • REFERENCES
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