Hyponatremia by oxcarbacepin in multiple sclerosis, a case to take account / Hiponatremia por oxcarbacepina en esclerosis múltiple, un caso para tener en cuenta

Abstract Hyponatremia is one of the adverse effects in patients treated with oxcarbazepine. This can be seen masked by multiple symptoms which are simply attributable to other diseases, but we must always keep it in mind in a patient with a history of taking that medication. Many of patients are asymptomatic; Doses lower than 120 mmol/L show symptoms of severity which presented a patient with multiple sclerosis, which we will show below, so that diagnostic ability of clinicians plays a fundamental role. This is why the case is exposed in which a woman treated with oxcarbazepine for one of the clinical forms of multiple sclerosis, arrives at emergency departament with manifestations of this electrolytic disorder. For this reason, the clinical case served by the authors is chosen directly. It is concluded that this adverse reaction is not uncommon and that it must be taken into account in the differential diagnosis.

Resumen La hiponatremia es uno de los efectos adversos en los pacientes tratados con oxcarbazepina. Se puede ver enmascarada por múltiples síntomas, atribuibles a otras enfermedades, pero siempre debemos tenerla en mente en un paciente con antecedente de ingesta de dicho medicamento. Muchos de los pacientes son asintomáticos; cifras inferiores a 120 mmol/L ponen de manifiesto síntomas de severidad, como los presentados en el paciente con esclerosis múltiple que mostraremos a continuación. La habilidad diagnóstica del clínico, por tanto, juega un rol fundamental. Debido a esto, se expone un caso en el que una mujer tratada con oxcarbacepina, para una de las formas clínicas de esclerosis múltiple, llega a urgencias con manifestaciones de este trastorno electrolítico. Por esto se escoge el caso clínico atendido por los autores directamente. Se concluye que no es infrecuente esta reacción adversa y que hay que tenerla en cuenta a la hora de los diagnósticos diferenciales.

Bipolaridad: monitoreo terapéutico de drogas antiepilépticas / Bipolarity: Therapeutic monitoring of antiepileptic drugs

Objetivo: Revisión bibliográfica del monitoreo de los fármacos utilizados en el tratamiento de la bipolaridad y las recomendaciones que de allí se derivan para su aplicación en el ámbito de la asistencia clínica de pacientes con patología bipolar. Método: Búsqueda en medline y medscape desde 1998 hasta mayo 2011 de los siguientes términos: monitoreo, valproato, lamotrigina, carbamacepina, gabapentina, topiramato, antiepilépticos, trastornos bipolares, interacciones farmacológicas y eventos adversos. Fueron consultadas las guías de tratamiento (CANMAT: Canadian Network for Mood and Anxiety Treatments, update 2009), aprobaciones de la FDA (Food and Drug Administation, EEUU) y recomendaciones de la Asociación Americana de Psiquiatría (APA). Resultados: Los fármacos para los cuales se halló evidencia documentada en bipolaridad, hasta el momento son: valproato, lamotrigina y carbamacepina; no habiendo evidencia que avale el uso de gabapentina o topiramato. Los principales eventos adversos de los antiepilépticos son los del sistema nervioso; requieren evaluación clínica, ya que carecen de un laboratorio específico. Constituye una excepción la hiperamoniemia producida por valproato que puede medirse en el laboratorio y ser causa de encefalopatía o asociarse, con más frecuencia, a trastornos cognitivos. El monitoreo de valproato está recomendado, así como el de amonio. El monitoreo de lamotrigina podría ser útil. La titulación debe ser lenta, para disminuir riesgo de rash potencialmente fatal. Considerar el inicio del tratamiento con monodroga. Se recomienda el monitoreo de carbamacepina y en caso de polifarmacia: el monitoreo del epóxido de carbamacepina. En los tres fármacos considerar interacciones y la posibilidad de toxicidad aún dentro del rango terapéutico

Objective: Literature review of monitoring of AEDs used in the treatment of bipolarity and the recommendations arising from there for use in the field of clinical care of patients with bipolar disease. Method: Search Medscape and medline from 1998 to May 2011 of the following terms: monitoring, valproate, lamotrigine, carbamazepine, gabapentin, topiramate, antiepileptics, bipolar disorders, drug interactions and adverse events. having consulted in addition to treatment guidelines Canadian Network for Mood and Anxiety Treatments, update 2009 (CANMAT), approvals of the Food and Drug Administration, USA (FDA) and recommendations of the American Psychiatric Association (APA). Results: Drugs with documented evidence for use in bipolar disorder are: valproate, lamotrigine and carbamazepine, there being no evidence to support the use of gabapentin or topiramate. It is important to consider that the main adverse effects of antiepileptic drugs (AEDs) develop in the Nervous System. These symptoms require clinical evaluation, since they lack a specific laboratory, except hyperammonemia: a parameter measurable in the laboratory, produced by valproate that is associated with encephalopathy and cognitive disorders. Valproate monitoring is recommended, as well as ammonium. Monitoring of lamotrigine may be useful. The titration should be slow always, to avoid risk of potentially fatal rash. Consider, where possible, the beginning of treatment with single drug. Carbamazepine monitoring is recommended and in case of polypharmacey: the monitoring of carbamazepine epoxide becomes useful. In all cases should be evaluated possible interactions and their mechanisms to have in mind the possibility of toxicity symptoms even with plasma dosages within the therapeutic range

Therapeutic carbamazepine (CBZ) and valproic acid (VPA) monitoring in children using saliva as a biologic fluid / Monitoramento terapêutico de carbamazepina e ácido valproico em saliva de crianças

OBJECTIVE: The aim of the study was to analyze retrospectively carbamazepine (CBZ) and valproic acid (VPA) salivary data collected from epileptic children during a 3-year period. METHODS: Saliva samples stimulated by citric acid were assayed by FPIA method. One hundred and three patients (aged 1-14 years) were in CBZ or VPA monotherapy or in CBZ-VPA combined therapy. RESULTS: VPA salivary levels were linearly related with daily dose, but a non-linear relationship was found for CBZ, in patients under monotherapy. VPA did not alter saliva CBZ concentration. Conversely, CBZ reduced VPA salivary levels. Non-responsive children displayed higher VPA concentrations. CBZ levels in uncontrolled patients showed non-significant difference in relation with controlled subjects even though their daily doses were higher. CONCLUSION: Citric acid stimulated saliva is reliable enough to perform therapeutic drug monitoring. Saliva drug levels in non-responsive patients would be explained according to the generalized efflux transporter overexpression hypothesis.

OBJETIVO: O objetivo deste estudo foi avaliar retrospectivamente por 3 anos a partir de dados salivares, as terapias com carbamacepina (CBZ) e ácido valproico (VPA) em pacientes pediátricos. MÉTODOS: Foram avaliadas amostras de saliva estimuladas com ácido cítrico por método FPIA em 103 pacientes (idades 1-14 anos) em monoterapia com CBZ ou VPA ou terapia combinada CBZ-VPA. RESULTADOS: Níveis salivares de VPA se relacionaram linearmente com a dose diária, e a relação não linear foi encontrada em pacientes com CBZ. VPA não alterou as concentrações salivares de CBZ, porém a CBZ reduziu os níveis salivares de VPA em pacientes com terapia combinada. Pacientes refratários apresentaram altas concentrações de VPA. Os níveis de CBZ em pacientes não controlados não apresentaram diferenças significativas em relação aos pacientes controlados quando as doses diárias foram mais elevadas. CONCLUSÃO: Saliva estimulada com ácido cítrico é adequada para o monitoramento terapêutico. Níveis da droga na saliva em pacientes que não responderam ao tratamento pode ser explicado pelo transporte de efluxo generalizado.

Farmacocinética poblacional de carbamacepina en pacientes epilépticos adultos / Population pharmacokinetics of carbamazepine in adults with epilepsy

The aim of the present study was to determinate the factors affecting carbamazepine (CBZ) clearance (CL) in adults with epilepsy using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 104 adults receiving CBZ. A total of 161 CBZ steady state serum concentration samples were analyzed. Population CL was calculated by using NONMEM with a one compartment model with first-order absorption and elimination. The following covariates were tested for their influence on clearance (CL): total body weight, age, dose/day, sex, surface area (SA) and comedication with primidone (PRIM), valproic acid or phenytoin (DFH). The final regression model for carbamazepine clearance found best to describe the data was: CL = (0.614 SA + 0.0016 dose/day)(1 + 0.278 DFH)(1 + 0.326 PRIM).

El objetivo de este trabajo es determinar los factores que influyen en el aclaramiento (CL) de carbamacepina (CBZ) en pacientes epilépticos adultos usando un modelo de efectos mixtos y datos de concentraciones séricas de CBZ generados del cuidado rutinario de los pacientes. El número de pacientes incluidos en el estudio fue de 104. Se analizaron un total de 161 concentraciones séricas de CBZ en el estado estacionario. El aclaramiento poblacional se determinó con el programa NONMEM aplicando un modelo monocompartimental con absorción y eliminación de primer orden. Se analizó la influencia de las siguientes covariables sobre el CL: peso corporal total, edad, dosis/día, sexo, superficie corporal (SC) y la comedicación con primidona (PRIM), ácido valproico o difenilhidantoína (DFH). El modelo final de regresión obtenido es el siguiente: CL = (0.614 SC + 0.0016 dosis/día)( 1+ 0.278 DFH)(1 + 0.326 PRIM).