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NUEVAS NOCIONES ACERCA DE LOS ANTAGONISTAS DE LOS RECEPTORES GPIIB/GPIIIA

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Los inhibidores de la GPIIb/IIIa ejercen cierto agonismo parcial que limita su efecto terapéutico y favorece la aparición de efectos colaterales cuando son administrados por vía oral. Existen polimorfismos genéticos del receptor que reducen su afinidad por la droga.
cox.jpg Autor:
Dermot Cox
Columnista Experto de SIIC
Artículos publicados por Dermot Cox
Recepción del artículo
27 de Mayo, 2003 		Primera edición
19 de Septiembre, 2003 		Segunda edición, ampliada y corregida
7 de Junio, 2021

NUEVAS NOCIONES ACERCA DE LOS ANTAGONISTAS DE LOS RECEPTORES GPIIB/GPIIIA

Resumen
La unión del fibrinógeno a su receptor en las plaquetas, la glucoproteína (GP) IIb/IIIa, es un requisito indispensable para la agregación plaquetaria. Este hecho fue confirmado por el éxito del tratamiento con antagonistas de estos mediadores en los síndromes agudos coronarios y la angioplastia. Sin embargo, a la inversa de lo que sucede con los compuestos de administración endovenosa, los de incorporación por vía oral no mostraron beneficio y aun incrementaron la mortalidad. Hay varias explicaciones posibles para el escaso rendimiento de los fármacos administrados por esta vía: fueron empleados para tratar un cuadro crónico y no agudo; tuvieron escasa biodisponibilidad, y como consecuencia niveles plasmáticos de la droga relativamente bajos; fueron agonistas parciales y generaron señales pro agregación plaquetaria; su afinidad por la GPIIb/IIIa se vio afectada por polimorfismos en el receptor. El fracaso obedeció, probablemente, a una combinación de todos estos factores. No obstante, al identificar tales problemas debería ser posible desarrollar antagonistas GPIIb/IIIa eficaces por vía oral.

Palabras clave
Plaquetas, antagonistas, glucoproteína IIb/IIIa, trombosis, agregación plaquetaria, síndromes agudos coronarios, fibrinógeno, vía oral, angor inestable


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Oral GPIIb/IIIa antagonists, Lessons learned

Abstract
The binding of fibrinogen to its receptor on platelets, glycoprotein (GP) IIb/IIIa, is an absolute requirement for platelet aggregation. This was confirmed by the success of GPIIb/IIIa antagonists in the treatment of acute coronary syndromes and angioplasty. However, in sharp contrast to the iv compounds, the oral compounds showed no benefit and even increased mortality. There are a number of possible explanations for the poor performance of the oral compounds: they were used to treat a chronic condition rather than an acute condition; they had low bioavailability resulting in relatively low plasma levels of the drug; they were partial agonists and could generate pro-aggregatory signals; their affinity for GPIIb/IIIa was affected by polymorphisms in the receptor. Their failure was probably a combination of all these factors. However, by addressing these issues it should be possible to develop successful oral GPIIb/IIIa antagonists

Key words
Plaquetas, antagonistas, glucoproteína IIb/IIIa, trombosis, agregación plaquetaria, síndromes agudos coronarios, fibrinógeno, vía oral, angor inestable


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Especialidades
Principal: Farmacología
Relacionadas: Cardiología, Medicina Farmacéutica, Medicina Interna



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