Optimised glucocorticoid therapy: the sharpening of an old spear
Frank Buttgereit a, Gerd-Rüdiger Burmester a and Brian J Lipworth.
The Lancet 2005; 365:801-803.
Context: Glucocorticoids are frequently and successfully used drugs that mediate important immunosuppressive and anti-inflammatory effects. These drugs are also relatively inexpensive, but it is their broad range of adverse reactions that continuously stimulate efforts to optimise glucocorticoid treatment.
Starting point: Last year, Mary Leonard and colleagues studied 60 children and adolescents with nephrotic syndrome intermittently treated with high-dose glucocorticoids (N Engl J Med 2004; 351: 868-75). The patients received an average of 23 g glucocorticoids and were significantly shorter, had a significantly greater body-mass index, and the prevalence of obesity was significantly higher than in controls. The expected deficits in the bone-mineral content of the spine or whole body were not seen, although this finding could be attributed to the highly increased body-mass index of many of the patients.
Where next: Glucocorticoids are urgently needed to treat a wide range of diseases in children and adults. Therefore strategies such as preferred local application or fine-tuned dose regimens have been developed over the past five decades to improve the benefit-risk ratio. However, these efforts with conventional glucocorticoid drugs seem to have almost reached their limits. A further improvement needs qualitatively new drugs, which are currently in the development pipeline, with the most promising being the nitrosoglucocorticoids (nitrosteroids) and selective glucocorticoid-receptor agonists.
COMENTARIO:
Desde su introducción en 1948, los corticoides se han convertido en uno de lo grupos farmacológicos más útiles en la práctica clínica rutinaria. Se utilizan en múltiples patologías de distintas especialidades médicas con muy buenos resultados; en Neumología se administran habitualmente para tratar pacientes asmáticos, con EPOC, con algunas enfermedades intersticiales, etc. Su principal problema son sus conocidos efectos secundarios (diabetes, osteoporosis, aumento de peso, …).
En esta revisión se repasan algunas de las estrategias utilizadas hasta ahora para minimizar estos efectos secundarios:
– Nuevos fármacos con menor actividad mineralocorticoide: prednisona/prednisolona, metilprednisolona.
– Administración local del fármaco: inhalado, tópico, ocular.
– Optimización de la dosis administrando la cantidad mínima imprescindible del fármaco.
Se considera que, con las moléculas actuales, se ha alcanzado un ratio riesgo/beneficio que ya no es superable, y por ello se están desarrollando nuevas estrategias:
– Administrar el corticoide contenido en liposomas para alcanzar una mayor concentración en la zona donde se precisa.
– Formulaciones de liberación retardada.
– Fármacos que inhiben la degradación de los esteroides endógenos (ácido glicerretínico).
– Nuevos fármacos:
Nitroesteroides que combinan el óxido nítrico y la prednisolona consiguiendo efectos sinérgicos.
Agonistas selectivos del receptor del glucocorticoide (ZK 216348) que actúan reduciendo la transactivación (principal causante de los efectos secundarios) y aumentando la transrepresión (implicada en su actividad antiinflamatoria).