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Off-target effects of glycoprotein IIb/IIIa receptor inhibitors
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Abstract
Soon after identification of the platelet membrane glycoprotein (GP) IIb/IIIa, it has become a target of antiplatelet therapy. There are 3 intravenous GP IIb/IIIa receptor inhibitors, namely— eptifibatide, tirofiban and abciximab, used in the contemporary clinical practice, particularly in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). The aim of the current review is to summarize available knowledge concerning off-target effects of GP IIb/IIIa receptor inhibitors. All 3 drugs have similar antithrombotic properties, but differ with respect to pharmacodynamics, pharmacokinetics and off-target effects. Eptifibatide and tirofiban are highly specific GP IIb/IIIa receptor inhibitors, while abciximab is unselectiveand cross-reacts with integrin avb3 — a vitronectin receptor and leukocyte-associatedi ntegrin Mac-1. As a result of these interactions, abciximab seems to reduce the development of clinical restenosis, decrease infarct size, inhibit adhesion of monocytes to medical steel and modulate the inflammatory response. Intracoronary administration of abciximab provides higher drug concentration in the target area, increasing dose-dependent interactions with other integrins. Off-target effects of small molecule GP IIb/IIIa receptor inhibitors (i.e. eptifibatide and tirofiban) are predominantly connected with their suppressive influence on the inflammatory response. All in all, although GP IIb/IIIa receptor inhibitors are not recommended as a routine therapy during PCI, their antiplatelet properties and potential off-target effects may bebeneficial in certain subsets of patients.
Abstract
Soon after identification of the platelet membrane glycoprotein (GP) IIb/IIIa, it has become a target of antiplatelet therapy. There are 3 intravenous GP IIb/IIIa receptor inhibitors, namely— eptifibatide, tirofiban and abciximab, used in the contemporary clinical practice, particularly in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). The aim of the current review is to summarize available knowledge concerning off-target effects of GP IIb/IIIa receptor inhibitors. All 3 drugs have similar antithrombotic properties, but differ with respect to pharmacodynamics, pharmacokinetics and off-target effects. Eptifibatide and tirofiban are highly specific GP IIb/IIIa receptor inhibitors, while abciximab is unselectiveand cross-reacts with integrin avb3 — a vitronectin receptor and leukocyte-associatedi ntegrin Mac-1. As a result of these interactions, abciximab seems to reduce the development of clinical restenosis, decrease infarct size, inhibit adhesion of monocytes to medical steel and modulate the inflammatory response. Intracoronary administration of abciximab provides higher drug concentration in the target area, increasing dose-dependent interactions with other integrins. Off-target effects of small molecule GP IIb/IIIa receptor inhibitors (i.e. eptifibatide and tirofiban) are predominantly connected with their suppressive influence on the inflammatory response. All in all, although GP IIb/IIIa receptor inhibitors are not recommended as a routine therapy during PCI, their antiplatelet properties and potential off-target effects may bebeneficial in certain subsets of patients.
Keywords
abciximab, eptifibatide, tirofiban, GP IIb/IIIa receptor inhibitor, off-target effects, pleiotropic effects
About this articleTitle
Off-target effects of glycoprotein IIb/IIIa receptor inhibitors
Journal
Issue
Article type
Review Article
Pages
458-464
Published online
2014-10-29
Page views
2380
Article views/downloads
2329
DOI
10.5603/CJ.a2014.0020
Bibliographic record
Cardiol J 2014;21(5):458-464.
Keywords
abciximab
eptifibatide
tirofiban
GP IIb/IIIa receptor inhibitor
off-target effects
pleiotropic effects
Authors
Małgorzata Ostrowska
Piotr Adamski
Marek Koziński
Eliano Pio Navarese
Tomasz Fabiszak
Grzegorz Grześk
Przemysław Paciorek
Jacek Kubica
