{"id":1458,"date":"2020-06-30T11:41:08","date_gmt":"2020-06-30T09:41:08","guid":{"rendered":"https:\/\/epilepsiarussi.com\/blog\/?p=1458"},"modified":"2020-06-22T11:43:05","modified_gmt":"2020-06-22T09:43:05","slug":"sinergia-terapeutica-del-clobazam-cbd-combinado-con-cannabidiol-cbd-en-el-tratamiento-del-sindrome-de-dravet-y-lennox-gastaut","status":"publish","type":"post","link":"https:\/\/www.epilepsiarussi.com\/blog\/sinergia-terapeutica-del-clobazam-cbd-combinado-con-cannabidiol-cbd-en-el-tratamiento-del-sindrome-de-dravet-y-lennox-gastaut\/","title":{"rendered":"Sinergia terap\u00e9utica del Clobazam (CBD) combinado con cannabidiol (CBD) en el tratamiento del s\u00edndrome de Dravet y Lennox-Gastaut."},"content":{"rendered":"

\"Clobazam\"<\/a><\/h1>\n

<\/h1>\n

Sinergia terap\u00e9utica del Clobazam (CBD) combinado con cannabidiol (CBD) en el tratamiento del s\u00edndrome de Dravet y Lennox-Gastaut.<\/strong><\/h1>\n

Importante antes de su administraci\u00f3n disponer de un an\u00e1lisis farmacogen\u00e9tico de cada paciente <\/strong><\/h2>\n

S\u00edndrome de Dravet y S\u00cdndrome Lennox-Gastaut<\/strong><\/h2>\n

El s\u00edndrome de Dravet es una forma severa de epilepsia, de origen gen\u00e9tico, que se inicia generalmente antes del primer a\u00f1o de edad. Su principal caracter\u00edstica son diversos tipos de crisis convulsivas originadas a menudo por episodios de fiebre en el ni\u00f1o. Ello puede conllevar a partir de los dos a\u00f1os de edad retrasos en el desarrollo cognitivo, motriz, retrasos en el proceso de aprendizaje y en consecuencia en la conducta.<\/p>\n

Tanto el denominado S\u00edndrome de Dravet como el Lennox-Gastaut se inscriben en las denominadas Epilepsias Raras.<\/a><\/p>\n

Clobazam (CLB) + Cannabidiol (CLB)<\/strong><\/h2>\n

Los \u00faltimos estudios publicados muestran que existe una sinergia terap\u00e9utica positiva para el tratamiento de ambos s\u00edndromes combinando el Clobazam (CLB) con el cannabidiol (CLB). Al final del post se hallan las referencias bibliogr\u00e1ficas que as\u00ed lo avalan.<\/p>\n

Clobazam (CLB) y su principal derivado N-Desmetilclobazam (N-CLB) tienen afinidad por los receptores GABA,(acr\u00f3nimo de Gamma Amino Butyric Acid)<\/em>, que forman el principal sistema inhibidor del proceso generador de epilepsia (epileptog\u00e9nesis) y son eficaces en la pr\u00e1ctica cl\u00ednica para el tratamiento de las crisis epil\u00e9pticas de los pacientes con s\u00edndrome de Dravet y Lennox-Gastaut.<\/p>\n

Clobazam (CLB) Y N-Desmetilclobazam (N-CLB) se eliminan por las enzimas CYP3A4 y CYPP2C19 respectivamente del h\u00edgado y del intestino delgado. La enzima CYP3A4 est\u00e1 modulada por el gen de su mismo nombre en el cromosoma 7 (banda 7q22)<\/em> y la enzima CYPP2C19 tambi\u00e9n por el gen de su mismo nombre del cromosoma 10 (banda 10q23).<\/p>\n

Cannabidiol (CBD) ha demostrado eficacia y seguridad por ensayos cl\u00ednicos en fase III para s\u00edndrome de Dravet y Lennox-Gastaut (1-4) con aprobaci\u00f3n para su prescripci\u00f3n por parte de la FDA (US Food and Drug Administration), agencia estatal americana responsable de la regulaci\u00f3n de medicamentos, alimentos, productos biol\u00f3gicos y otros.<\/p>\n

Se conoce que CBD tiene un mecanismo de acci\u00f3n positivo para los receptores GABAa como el Clobazam (5). Tambi\u00e9n se sabe que CBD aumenta la concentraci\u00f3n plasm\u00e1tica (6,7) de Clobazam (CLB) y su metabolito N-CLB) en la sangre. Por consiguiente, hay una sinergia terap\u00e9utica positiva para el tratamiento combinado de cannabidiol (CBD) y Clobazam (CLB).<\/p>\n

Como existen en los individuos variantes gen\u00e9ticas para los genes CYP3A4 del Clobazam (CLB) y CYPPP2C19 del N-Desmetilclobazam (N-CLB), es muy \u00fatil hacer un an\u00e1lisis farmacogen\u00e9tico en cada paciente para seleccionar muy bien la dosificaci\u00f3n de Clobazam cuando se utiliza conjuntamente con cannabidiol (CBD)en el s\u00edndrome de Dravet o Lennox-Gastaut para conocer la existencia de variaciones de eliminaci\u00f3n del f\u00e1rmaco, pues una variante de eliminaci\u00f3n lenta implica una acumulaci\u00f3n del f\u00e1rmaco y una variante de eliminaci\u00f3n r\u00e1pida una disminuci\u00f3n del f\u00e1rmaco en el organismo. Tambi\u00e9n el nivel plasm\u00e1tico en la sangre de Clobazam puede determinarse de forma rutinaria.<\/p>\n

 <\/p>\n

Referencias<\/strong><\/h3>\n
    \n
  1. Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et\u00a0al. Trial of cannabidiol for drug resistant seizure in the Dravet Syndrome. N Engl J Med. 2017; 376:2011\u201320.<\/li>\n
  2. Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90: e1204\u2013e1211.<\/li>\n
  3. Thiele EA, Marsh ED, French JA, Mazurkiewicz?Beldzinska M, Benbadis SR, Joshi C, et\u00a0al. Cannabidiol in patients with seizures associated with Lennox?Gastaut syndrome (GWPCARE4): a randomized, double?blind, placebo?controlled phase 3 trial. Lancet. 2018; 391:1085\u201396.<\/li>\n
  4. Greenwood SM, VanLandingham KE, Cross JH, Villanueva V, Wirrell EC, Privitera M, et\u00a0al. Effect of cannabidiol on drop seizures in the Lennox\u2013Gastaut Syndrome. N Engl J Med. 2018; 378:1888\u201397.<\/li>\n
  5. Bakas T, van Nieuwenhuijzen PS, Devenish SO, McGregor IS, Arnold JC, Chebib M. The direct actions of cannabidiol and 2arachidonoyl glycerol at GABAA receptors. Pharmacol Res. 2017; 119:358\u201370.<\/li>\n
  6. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug?drug interaction between clobazam and cannabidiol in children. Epilepsia. 2015; 56:1246\u201351<\/li>\n
  7. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP, UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017; 58:1586\u201392<\/li>\n<\/ol>\n

    <\/h1>\n","protected":false},"excerpt":{"rendered":"

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