Información de la revista
Vol. 58. Núm. 2.
Páginas 136-145 (febrero 2003)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 58. Núm. 2.
Páginas 136-145 (febrero 2003)
Acceso a texto completo
Fármacos antiepilépticos utilizados en la infancia. Nuevos productos y nuevos conceptos
Antiepileptic drugs used in childhood. new products and new concepts
Visitas
14637
C. Garaizar Axpe
Autor para correspondencia
cgaraizar@hcru.osakidetza.net

Correspondencia: Dra. C. Garaizar Axpe.Unidad de Neuropediatría. Hospital de Cruces.48903 Baracaldo. Vizcaya. España
, A. Villaverde Bello, T. Pérez Concha, M. Â Herrera Isasi, A. Álvarez Ruiz de Larrinaga
Unidad de Neuropediatría. Hospital de Cruces. Baracaldo. Vizcaya. España
Este artículo ha recibido
Información del artículo
Introducción

Desde 1990 se han comercializado en nuestro país ocho nuevos fármacos antiepilépticos (FAE), y otros más lo seránen un futuro próximo

Objetivo

Revisar los conceptos que guían el desarrollo de los nuevos fármacos, indicaciones, mecanismo de acción, eficacia y tolerabilidad.

Desarrollo

La intervención farmacológica antiepiléptica no es ya puramente anticonvulsionante, sino que se dirige hoy en día a la prevención de la epileptogénesis, a la modificación del pronóstico de la enfermedad y a revertir la farmacorresistencia. El desarrollo de nuevos fármacos pasó desdela experimentación animal con diferentes productos, hacia el “diseño racional“ de fármacos basado en los mecanismos conocidos de excitación/inhibición neuronal durante la segunda mitad de siglo, para encaminarse actualmente hacia la denominada farmacogenética. Los nuevos FAE estaban indicados inicialmente para las epilepsias focales, aunque algunos han demostrado poseer unespectro de acción más amplio. La farmacocinética de muchos de ellos posee las características ideales, eludiendo el metabolismo hepático y la unión a proteínas. Las interacciones medicamentosas y los efectos secundarios son menores, sobre todo en lo referido a reacciones idiosincrásicasgraves, existiendo alguna excepción que conviene reseñar. La eficacia terapéutica, sin embargo, no es mayor que la de los fármacos clásicos en la mayoría de los casos. Las características específicas de la epilepsia y de la farmacocinética durante la infancia, además de las normas oficiales para el desarrollo de los ensayos clínicos, condicionan una utilización precavida de los nuevos FAE en la infancia, lo que simultáneamente retrasa la accesibilidadde los niños al posible beneficio terapéutico

Palabras clave:
Fármacos antiepilépticos
Gabapentina
Levetiracetam
Lamotrigina
Oxcarbacepina
Tiagabina
Topiramato
Vi-gabatrina
Introduction

Eight new antiepileptic drugs (AED) have been marketed in Spain since 1990 and others will soon follow

Objective

To review the concepts underlying the development of the new drugs, as well as their indications, efficacy and safety

Development

Pharmacologic antiepileptic intervention is no longer solely directed towards an anticonvulsant effect, but also to epileptogenic prevention, disease modification and reversal of pharmacoresistance. The development of new AED, initially based on the screening of putative products in animal models, changed during the last half of the century to a rational design based on known facts about excitatory/inhibitory neuronal mechanisms. More recently, attention has focussed on pharmacogenetics. The new AED were initially indicated for partial epilepsies, but some have been shown to have a broader clinical spectrum. Some show the ideal pharmacokinetic mechanisms, avoiding hepatic metabolism and protein binding. Drug interactions and adverse effects, especially severe idiosyncratic adverse effects, are rare, although there are some exceptions. In most cases, however, seizure control does not seem to be better than with the classic AED. Because of the specific characteristics of childhood epilepsy and pharmacokinetics, as well as the regulations governing the development of clinical trials, the use of new products in children is circumspect, which in turn delays the access of such patients to a possible therapeutic benefit

Key words:
Antiepileptic drugs
Gabapentin
Levetiracetam
Lamotrigine
Oxcarbazepine
Tiagabine
Topiramate
Vigabatrin
El Texto completo está disponible en PDF
Bibliografía
[1.]
M.C. Walker, H.S. White, J.W. Sander.
Disease modification in partial epilepsy.
Brain, 125 (2002), pp. 1937-1950
[2.]
N.R. Temkin, A.D. Jarell, G.D. Anderson.
Antiepileptic agents: How close are weα.
Drugs, 61 (2001), pp. 1045-1055
[3.]
J.J. Cereghino, K. Penry.
Introduction.
Antiepileptic drugs, 4th ed,
[4.]
W. Loscher.
Current status and future directions in the pharmacotherapy of epilepsy.
Trends Pharmacol Sci, 23 (2001), pp. 113-118
[5.]
Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for a revised clinical and electroencephalographic classification of epileptic seizures.
Epilepsia, 22 (1981), pp. 489-501
[6.]
Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for a revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489-501.
[7.]
J. Engel.
A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology.
Epilepsia, 42 (2001), pp. 796-803
[8.]
R. Guerrini, A. Arzimanoglou, O. Brouwer.
Rationale for treating epilepsy in children.
Epileptic Disorders, 4 (2002), pp. 9-21
[9.]
T.A. Glauser, C.E. Pippenger.
Controversies in blood-level monitoring: Reexamining its role in the treatment of epilepsy.
Epilepsia, 41 (2000), pp. 6-15
[10.]
E. Perucca, A. Richens.
General Principles Biotransformation.
Antiepileptic drugs, 4th ed,
[11.]
T.R. Browne.
Pharmacokinetics of antiepileptic drugs.
[12.]
M.A. Dichter.
Mechanisms of action of new antiepileptic drugs.
Adv Neurol, 76 (1998), pp. 1-9
[13.]
J.A. French, B.E. Gidal.
Antiepileptic drugs interactions.
Epilepsia, 41 (2000), pp. 30-36
[14.]
G.T. McInnes, M.J. Brodie.
Drug interactions that matter A critical reappraisal.
Drugs, 36 (1998), pp. 83-110
[15.]
P.N. Patsalos, J.S. Duncan.
Antiepileptic drugs. A review of clinical significant drug interactions.
Drug Safety, 9 (1993), pp. 156-184
[16.]
R.S. Greenwood.
Adverse effects of antiepileptic drugs.
Epilepsia, 41 (2000), pp. 42-52
[17.]
B. Bourgeois.
New dosages and formulations of AEDs for use in pediatric epilepsy.
Neurology, 58 (2002), pp. 2-5
[18.]
T.A. Glausser.
Idiosyncratic reactions: New methods of identifying high-risk patients.
Epilepsia, 41 (2000), pp. 16-29
[19.]
L.J. Wilmore, W.J. Triggs, J.M. Pellock.
Valproate toxicity: Risk screening strategies.
J Child Neurol, 6 (1991), pp. 3-6
[20.]
B.B. Spear.
Pharmacogenetics and antiepileptic drugs.
Epilepsia, 42 (2001), pp. 31-34
[21.]
S.M. Sisodiya, W.R. Lin, B.N. Harding, M.L. Squier, M. Thom.
Drug resistance in epilepsy: Expression of drug resistance proteins in common causes of refractory epilepsy.
Brain, 125 (2002), pp. 22-31
[22.]
M.J. Brodie, P. Kwan.
Staged approach to epilepsy management.
Neurology, 58 (2002), pp. 2-8
[23.]
A.G. Marson, Z.A. Kadir, D.W. Chadwick.
New antiepileptic drugs: A systematic review of their efficacy and tolerability.
Bmj, 313 (1996), pp. 1169-1174
[24.]
M.D. Privitera.
Evidence-based medicine and antiepileptic drugs.
Epilepsia, 40 (1999), pp. 47-56
[25.]
M.J. Brodie.
Management strategies for refractory localizationrelated seizures.
Epilepsia, 42 (2001), pp. 27-30
[26.]
Guidelines for antiepileptic drug trials in children. Commission on Antiepileptic Drugs of the International League Against Epilepsy.
Epilepsia, 35 (1994), pp. 94-100
[27.]
J.M. Pellock.
Pediatric Trials: Practical issues. Special populations and trial design.
Adv Neurol, 76 (1998), pp. 167-171
[28.]
Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations.
Pediatrics, 95 (1995), pp. 286-294
[29.]
T.A. Glauser.
Integrating clinical trial data into clinical practice.
Neurology, 58 (2002), pp. 6-12
Copyright © 2003. Asociación Española de Pediatría
Descargar PDF
Idiomas
Anales de Pediatría
Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?