AIMS. The aim of this study was to conduct a critical evaluation of the contribution made by the latest antiepileptic drugs (AED) and to describe the pharmacological therapeutic strategies, which do not contemplate the use of traditional AED, employed to treat pharmacoresistant patients. DEVELOPMENT. After comparing the mechanisms of action, as well as the pharmacokinetic and pharmacodynamic characteristics of the classical and new AED, and examining the advantages and disadvantages of each of them, it still turns out to be impossible to achieve a total control of seizures in 20-25% of cases. This is due to the polymorphisms of the enzymes and of their inducers, to the over-expression of the carrier proteins (PGP, MRP) and to polymorphisms undergone by the receptors.

CONCLUSIONS Although there is a need for new AED to be synthesized which can be used to attempt to reduce the rate of pharmacoresistant patients, other strategies must also be developed in the field of pharmacogenomics, and more specifically with regard to AED that are not carried by PGP or MRP. Another important area is that of substances that antagonize these carriers and, thus, allow AED to reach the site where they are to act.

Objetivo Valorar críticamente lo que han aportado los nuevos fármacos antiepilépticos (FAE) y describir las estrategias terapéuticas farmacológicas en los pacientes farmacorresistentes, ajenas a los FAE tradicionales.

Desarrollo Tras comparar los mecanismos de acción, las características farmacocinéticas y farmacodinámicas de los FAE clásicos y nuevos, y referir las ventajas e inconvenientes de cada uno de ellos, resulta que todavía es imposible conseguir el control total de las crisis en 20-25% de casos, debido a los polimorfismos de los enzimas y de sus inductores, a sobreexpresión de proteínas transportadoras (PGP, MRP) y a polimorfismos de los receptores.

Conclusiones Aunque deben sintetizarse nuevos FAE, con los que se intente reducir la tasa de pacientes farmacorresistentes, deben desarrollarse otras estrategias en torno a la farmacogenómica, concretamente la de FAE que no se transporten por PGP o MRP, o la de sustancias que antagonicen a estos transportadores y, con ello, permitan que los FAE lleguen a sus lugares de acción.