Mecanismos de acción y resistencia a glucocorticoides en asma y enfermedad pulmonar obstructiva crónica

Autores/as

  • Alcibey Alvarado González Caja Costarricense del Seguro Social, Hospital San Juan de Dios
  • Isabel Arce Jiménez Universidad de Costa Rica

DOI:

https://doi.org/10.51481/amc.v55i4.811

Palabras clave:

asma, enfermedad pulmonar obstructiva crónica, resistencia a medicamentos, glucocorticoides, inflamación

Resumen

El asma bronquial y la enfermedad pulmonar obstructiva crónica son dos problemas mayores de salud: su incidencia se encuentra en aumento y representan, indiscutiblemente, una causa importante de morbilidad y mortalidad a nivel mundial. Los glucocorticoides se han posicionado como la droga de elección en el tratamiento de padecimientos inmunológicos e inflamatorios crónicos, como el asma bronquial y la enfermedad obstructiva crónica. Estas drogas suprimen la inflamación en múltiples vías moleculares, característica que les confiere destacada eficacia. Su principal acción en dosis terapéuticas se produce por la transrepresión de genes inflamatorios activos, mediante el reclutamiento y actividad de la enzima histona-desacetilasa-2 y la remodelación de la cromatina. En dosis altas, funcionan más bien como transactivadores, acetilando las histonas y estimulando la transcripción de genes antinflamatorios, y potencialmente, también de varios genes relacionados con efectos secundarios. Además, se les reconoce acciones postranscripcionales, que modifican la estabilidad de secuencias de ARN mensajero. A pesar de esto, una respuesta disminuida a los glucocorticoides se presenta en pacientes con asma severa, en asmáticos que fuman y en quienes tienen enfermedad pulmonar obstructiva crónica. Varios mecanismos moleculares de resistencia a glucocorticoides han sido identificados. Se están investigando otros tratamientos antinflamatorios que permitan controlar los síntomas de estos pacientes, así como drogas que puedan revertir los mecanismos moleculares de la resistencia. Problemáticamente, estas terapias podrían ser demasiado específicas para resultar eficaces, como es el caso de los esteroides disociados, en el que es difícil separar efectos antinflamatorios y secundarios.

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Publicado

2013-10-21 — Actualizado el 2013-10-21

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Cómo citar

González, A. A., & Jiménez, I. A. (2013). Mecanismos de acción y resistencia a glucocorticoides en asma y enfermedad pulmonar obstructiva crónica. Acta Médica Costarricense, 55(4), 162–168. https://doi.org/10.51481/amc.v55i4.811