Ácido valproico y ganancia de peso en pacientes con tratamiento antiepiléptico: una revisión sistemática

Introducción: El ácido valproico es un fármaco que se utiliza en el tratamiento de varias enfermedades, entre ellas la epilepsia. Aunque se lo considera un fármaco seguro presenta distintos efectos adversos entre ellos el más común es el aumento considerable de peso corporal. Objetivo: Identificar la relación entre el uso de ácido valproico en pacientes con tratamiento antiepiléptico y la ganancia de peso. Método: Revisión sistemática realizada en la Universidad Abierta Interamericana, en la que se realizó una búsqueda exhaustiva de estudios en la base de datos PubMed con términos MesH sobre Valproic acid AND weight gain. Una vez seleccionados los artículos tras la aplicación de criterios de inclusión y exclusión quedaron 17, los que fueron útiles para llevar a cabo esta investigación. Resultados: La información de los artículos hallados revela que los mecanismos a través del cual el ácido valproico puede generar este incremento de peso corporal aún no están del todo esclarecidos. Se han propuesto varias hipótesis; las más frecuentes en la literatura son: la hiperinsulinemia y resistencia a la insulina, así como también la hiperleptinemia y la resistencia a la leptina, entre otros. Los pacientes que presentan ganancia de peso tienen importantes consecuencias para la salud, en particular, el desarrollo de obesidad y la asociación con dislipidemia, hipertensión arterial, diabetes mellitus tipo 2 y aterosclerosis. Además, al generar cambios en la imagen corporal puede traer aparejada depresión, disminución de la autoestima y confianza en sí mismo, lo que provoca el incumplimiento y abandono del tratamiento. Conclusiones: Se observa la relación de causalidad del ácido valproico sobre la ganancia de peso en pacientes que padecen epilepsia.

Introduction: Valproic acid is a drug used in the treatment of various diseases, including epilepsy. Although it is considered a safe drug, it presents different adverse effects, among them the most common is the considerable increase in body weight. Objective: To identify the relationship between the use of valproic acid in patients with antiepileptic treatment and weight gain. Method: Systematic review carried out at the Universidad Abierta Interamericana, Argentina, in which an exhaustive search of studies was carried out in the PubMed database with MeSH terms on Valproic acid AND weight gain. Once the articles were selected after applying the inclusion and exclusion criteria, 17 remained, which were useful to carry out this research. Results: The information from the articles found reveals that the mechanisms through which valproic acid can generate this increase in body weight are still not fully clarified. Several hypotheses have been proposed; the most frequent in the literature are: hyperinsulinemia and insulin resistance, as well as hyperleptinemia and leptin resistance, among others. Patients who present weight gain have important health consequences, particularly the development of obesity and the association with dyslipidemia, arterial hypertension, type 2 diabetes mellitus, and atherosclerosis. In addition, by generating changes in body image, it can bring depression, decreased self-esteem and self-confidence, which causes non-compliance and abandonment of treatment. Conclusions: The causal relationship of valproic acid on weight gain in patients with epilepsy is observed.

Introdução: O ácido valpróico é um fármaco utilizado no tratamento de diversas doenças, entre elas a epilepsia. Apesar de ser considerado um medicamento seguro, apresenta diversos efeitos adversos, dentre eles o mais comum é o aumento considerável do peso corporal. Objetivo: Identificar a relação entre o uso de ácido valpróico em pacientes em tratamento antiepiléptico e o ganho de peso. Método: Revisão sistemática realizada na Universidad Abierta Interamericana, na qual foi realizada uma busca exaustiva de estudos na base de dados PubMed com termos MeSH sobre ácido valpróico AND ganho de peso. Uma vez selecionados os artigos após a aplicação dos critérios de inclusão e exclusão, restaram 17, que foram úteis para a realização desta pesquisa. Resultados: As informações dos artigos encontrados revelam que os mecanismos pelos quais o ácido valpróico pode gerar esse aumento de peso corporal ainda não estão totalmente esclarecidos. Várias hipóteses foram propostas; os mais frequentes na literatura são: hiperinsulinemia e resistência à insulina, assim como hiperleptinemia e resistência à leptina, entre outros. Pacientes que apresentam ganho de peso trazem importantes consequências para a saúde, principalmente o desenvolvimento de obesidade e associação com dislipidemia, hipertensão arterial, diabetes mellitus tipo 2 e aterosclerose. Além disso, por gerar alterações na imagem corporal, pode trazer depressão, diminuição da autoestima e da autoconfiança, o que ocasiona a não adesão e abandono do tratamento. Conclusões: Observa-se a relação causal do ácido valpróico com o ganho de peso em pacientes com epilepsia.

Hipovitaminosis D en niños y adultos en un prestador de salud del Uruguay y su relación con el uso de antiepilépticos / The effect of antiepileptic drugs in adult and child hypovitaminosis D in a Uruguayan health institution / Hipovitaminose D em crianças e adultos em um provedor de saúde uruguaio e sua relação com o uso de medicamentos antiepilépticos

Resumen: Introducción: la hipovitaminosis D se encuentra ampliamente extendida a nivel mundial, con consecuencias clínicas a nivel óseo y extraóseo. Entre los factores que la causan se encuentran los antiepilépticos (AE). En Uruguay no se conoce su prevalencia en niños ni en pacientes que reciben AE. Objetivos: conocer la prevalencia de hipovitaminosis D de niños y adultos en un prestador de salud y compararla con la prevalencia en pacientes bajo tratamiento con AE. Método: estudio descriptivo, transversal, realizado entre marzo y diciembre de 2017. Las variables analizadas fueron: niveles de vitamina D, calcio, fósforo, fosfatasa alcalina y parathormona intacta. Se consideró insuficiencia de vitamina D niveles menores de 30 ng/ml y déficit niveles menores de 20 ng/ml. Resultados: se incluyeron 113 pacientes, 60 niños y 53 adultos. La prevalencia global de insuficiencia de vitamina D fue de 89% y déficit de 60%. En niños expuestos a AE, la media de vitamina D fue 17,5 ng/ml, y en niños no expuestos 19,6 ng/ml. En adultos la media de vitamina D fue de 18,1 en expuestos a AE y 16,9 en no expuestos. La diferencia de medias no fue estadísticamente significativa en niños ni en adultos. Se observaron niveles de calcemia significativamente descendidos en niños y adultos con AE. Conclusiones: la insuficiencia de vitamina D fue cercana a 90% y el déficit superó el 50%. No se encontraron diferencias significativas entre grupos en hipovitaminosis D, pero se observaron niveles de calcemia reducidos en los expuestos a AE. Es necesario continuar analizando los factores que la causan y sus consecuencias clínicas.

Summary: Introduction: hypovitaminosis D is a highly spread condition worldwide, with clinical consequences that affect bone directly, among other manifestations. Antiepileptic drugs are among factors that cause this deficiency. In Uruguay, there is no information about hypovitaminosis D in children or patients who receive antiepileptic drugs. Objectives: to learn about the prevalence of hypovitaminosis D in children and adults in a health institution and to compare it with the prevalence in patients receiving antiepileptic drugs. Method: descriptive, transversal study conducted from March through December, 2017. The following variables were analysed: vitamin D, calcium, phosphorous, alkaline phosphatase and intact parathyroid hormone. Vitamin D insufficiency was defined as vitamin D levels of less than 30 ng per mL and deficiency as D levels of less than 20 ng per mL. Results: 113 patients were included in the study, 60 of which were children and 53 adults. Global prevalence of vitamin D insufficiency was 89% and deficiency was 60%. In children taking antiepileptic drugs, the average vitamin D value was 17.5 ng/ml and it was 19.6 ng/ml for those not exposed to those drugs. In adults, the average vitamin D value was 18.1 in the population taking antiepileptic drugs and 16.9 in patients not taking that medication. The difference between average values was not statistically significant in children or adults. Calcemia levels observed were significantly lower in both children and adults taking antiepileptic drugs. Conclusions: vitamin D insufficiency was close to 90% and deficiency was over 50%. No significant differences were found between hypovitaminosis D groups, although reduced calcemia was observed in patients exposed to antiepileptic drugs. Further studies are necessary to analyse factors that cause this condition and its clinical consequences.

Resumo: Introdução: a hipovitaminose D está amplamente difundida em todo o mundo, com consequências clínicas a nível ósseo e extraósseo. Entre os fatores que a causam estão os medicamentos antiepilépticos (AE). No Uruguai, sua prevalência em crianças ou em pacientes adultos recebendo AE não é conhecida. Objetivos: conhecer a prevalência de hipovitaminose D em crianças e adultos em um prestador de serviços de saúde e compará-la com a prevalência em pacientes em tratamento com AE. Método: estudo transversal descritivo realizado entre março e dezembro de 2017. As variáveis analisadas foram: níveis de vitamina D, cálcio, fósforo, fosfatase alcalina e paratormona intacta. Níveis menores que 30 ng / ml e níveis de déficit menores que 20 ng / ml foram considerados como insuficiência de vitamina D. Resultados: foram incluídos 113 pacientes, 60 crianças e 53 adultos. A prevalência global de insuficiência de vitamina D foi de 89% e déficit de 60%. Em crianças expostas à AE, a média de vitamina D foi de 17,5 ng / ml e em crianças não expostas de 19,6 ng / ml. Em adultos, a média de vitamina D foi de 18,1 nos expostos ao AE e de 16,9 nos não expostos. A diferença nas médias não foi estatisticamente significativa nas crianças nem nos adultos. Níveis de cálcio significativamente diminuídos foram observados em crianças e adultos com EA. Conclusões: a insuficiência de vitamina D foi próxima a 90% e o déficit ultrapassou 50%. Não foram encontradas diferenças significativas entre os grupos na hipovitaminose D, mas níveis reduzidos de cálcio foram observados naqueles expostos a EA. É necessário continuar analisando os fatores que o causam e suas consequências clínicas.

Assessment of quality of life in patients on antiepileptic drugs: a hospital based cross sectional study

Background: Quality of life (QOL) is a broad, multidimensional concept that usually includes subjective evaluations of both positive and negative aspects of life. Very few studies have been carried out on QOLIE 31 in India and research in this area will identify factors affecting QOL. study was therefore conducted to determine the level of health related QOL of patients of epilepsy in a tertiary care teaching hospital. To evaluate patterns of the use of anti-epileptic drugs (AEDs) and their impact on the Quality of Life (QOL) in patients with epilepsy.Methods: The study was a hospital based cross sectional study conducted by the Department of Pharmacology in association with the Department of Medicine, Government Medical College, Srinagar. A total number of 134 patients, aged >18 years were studied for a period of one and a half years, January 2015-July 2016. QOLIE?31 questionnaire was used for collecting data on health?related QOL.Results: The mean overall QOLIE-31 score was 53 corresponding to a t-score of 44. Amongst the QOLIE-31 subscales, the highest mean score was the cognitive subscale (73.6) followed by medication effects (55.5) and social functions (52).Conclusions: It is evident from our study that there are many factors that influence QOL of people with epilepsy. Among them, type of drug therapy plays an important role. Adding clinical counselling and other interventions to address the physical, mental, psychological, social, and emotional aspects of health wellbeing is likely to achieve better health outcomes for epilepsy patients.

Tratamiento de los síntomas vasomotores en pacientes con cáncer demama: Revisión narrativa

Las mujeres con antecedentes de cáncer de mama suelen experimentar síntomas vasomotores más severos y frecuentes que la población general. Numerosos trabajos han demostrado que los síntomas vasomotores (SVM) son los efectos adversos más frecuentes de la terapia adyuvante, y que hasta 20% de las pacientes con cáncer de mama considera discontinuar el tratamiento debido a estos síntomas, a pesar de su beneficio en la reducción de la recurrencia. Mientras que la terapia sustitutiva hormonal (THM) es usada regularmente en mujeres sanas para tratamiento de los SVM, está contraindicada en pacientes con antecedente de cáncer de mama. Existen muy pocos datos clínicos sobre las intervenciones no farmacológicas, y el papel de las terapias alternativas y complementarias sigue siendo controvertido. La revisión de la literatura da cuenta de que estos agentes farmacológicos, los inhibidores de la recaptación de serotonina-norepinefrina (IRNSs), los inhibidores selectivos de la recaptación de serotonina (IRSs), los antihipertensivos y los anticonvulsivos, disminuyen la intensidad y frecuencia de los SVM, demostrando una mejoría clínicamente significativa. Sin embargo, algunos IRSSs e IRSNs son potentes inhibidores del citocromo P450 2D6 (CYP 2D6), lo que impacta en la concentración de endoxifeno, debiendo ser evitados en pacientes tratadas con tamoxifeno. Son una opción el citalopram y la venlafaxina, si bien su consecuencia sobre la recurrencia y supervivencia del cáncer de mama es controvertida. La eficacia en el tratamiento de los SVM con antidepresivos es menor que con estrógenos y hay pocas publicaciones comparando ambos tratamientos. Faltan datos sobre el lapso de la indicación. Dos fármacos antiepilépticos también han demostrado efectividad, la gabapentina y la pregabalina. Algunas investigaciones comparativas están en curso, y habrá que esperar sus resultados para individualizar cuál es el óptimo en el manejo de los síntomas menopáusicos en mujeres que han padecido cáncer de mama.

Women with a history of breast cancer tend to have more severe and frequent vasomotor symptoms than the general population. Numerous studies have shown that vasomotor symptoms (VMS) are the most frequent adverse event of adjuvant therapy, and that up to 20% of breast cancer patients consider discontinuing treatment because of these symptoms, despite their benefit in the reduction of recurrence. While hormone replacement therapy (HRT) is regularly used in healthy women to treat VMS, it is contraindicated in patients with history of breast cancer. There are few clinical data on non-pharmacological interventions, and the role of alternative and complementary therapies remains controversial. The review of the literature reveals that these pharmacological agents, serotonin-norepinephrine reuptake inhibitors (SSRIs), selective serotonin reuptake inhibitors (IRSs), antihypertensives and anticonvulsants, decrease the intensity and frequency of VMS, demonstrating a clinically significant improvement. However, some IRSSs and SSRIs are potent inhibitors of cytochrome P450 2D6 (CYP 2D6), which impacts on the concentration of endoxifen and should be avoided in patients treated with tamoxifen. In this case, citalopram and venlafaxine are a better therapeutic option, although there is some controversy regarding its consequences on recurrence and survival of breast cancer. The efficacy in the treatment of VMS with antidepressants is lower than that achieved with estrogens and there are few publications comparing both treatments. Neither is clear the optimal treatment duration. Two antiepileptic drugs have also shown to be effective, gabapentin and pregabalin. Some comparative studies are in progress and it is probably necessary to wait for their results to identify the optimal option in the management of menopausal symptoms in women who have had breast cancer.

Manejo de primera crisis afebril: Importancia del enfoque clínico / Management of first nonfebrile seizure: Importance of clinical approach

Una crisis epiléptica es un evento traumático físico como psicológico que plantea dificultades en el diagnóstico y muchas interrogantes para el tratamiento agudo y en el largo plazo. La recurrencia de una crisis epiléptica origina aún más serios y costosos problemas en la vida personal, familiar y laboral del individuo afectado. En estas circunstancias, un correcto abordaje del manejo de individuos con una primera crisis afebril debe ser una prioridad de los sistemas de salud con el objetivo fundamental de prevención de recurrencias. La elección de un fármaco antiepiléptico va a depender de una detallada anamnesis del evento clínico y de la información proveniente de estudios o tests neurofisiológicos y por exámenes de imágenes cerebrales.

Seizures or an epileptic crisis is a traumatic event, both of physical and psychological nature that poses difficulties in the diagnostic process and many questions for its immediate and long-term management. The recurrence of an epileptic crisis causes even more serious and costly problems in the personal, family and work life of the affected individual. Due to this, a correct approach to the management of patients with a first afebrile crisis must be a priority of the health systems, with the primary purpose of preventing recurrences. The choice of an anti-epileptic drug will depend on a detailed anamnesis of the clinical event and onthe information from neurophysiological tests and brain imaging studies.

A Comparative Study between Intranasal Midazolam and Intravenous Midazolam In Control Of Seizure In Children

Introduction: Seizures are one of the important reasons for children visiting the hospital. Febrile seizures are the most common type of seizures found in childhood. Earlier Diazepam was widely used for treating all types of seizures but due to short duration of action, newer drugs were tried and found better than diazepam. Aims: To compare midazolam given intranasally with midazolam given intravenously for the treatment of febrile seizures in children. Methods: This prospective study was conducted in children suffering from seizures at the Paediatric Emergency Department of Teerthanker Mahaveer Medical over a period of 12 months. 84 children between the ages of one months to fourteen years with febrile seizures lasting for at least 10 minutes were eligible for inclusion in our study.  Treatment was considered successful if the seizure ceased within one hundred twenty seconds Results: In group A out of 44 patients, 20(45.5%) patients were responded to Intranasal Midazolam, whereas   in group B 40 patients who were treated with IV Midazolam as first line treatment, 36 patients (90%) had responded to it.  Time recorded for the commencement was more in IV Midazolam group (1.598 min) than IN Midazolam group (0.379 min), but average response time was lesser in group B (1.009 min) than group A (3.001 min). Conclusion: Midazolam given intranasally is a safe and effective treatment for prolonged febrile seizures in children and may be used in general practice and, with appropriate instructions, by the parents of children with recurrent febrile seizures at home.

The impact of different antiepileptic drugs on the sedation of children during magnetic resonance imaging / Impacto de diferentes medicamentos antiepilépticos na sedação de crianças durante a ressonância magnética / Impacto de diferentes medicamentos antiepilépticos en la sedación de niños durante la resonancia magnética

Background and objectives: The induction and inhibition of cytochrome P450 isoenzymes by antiepileptic drugs lead to changes in the clearance of anesthetic drugs eliminated via hepatic metabolism. We investigated the duration of the sedation and additional anesthetic needs during magnetic resonance imaging in epileptic children receiving antiepileptic drugs that cause either enzyme induction or inhibition. Methods: In American Society of Anesthesiology I–II, 120 children aged 3–10 years were included. Group 1: children using antiepileptic drugs that cause cytochrome P450 enzyme induction; Group 2: those using antiepileptic drugs that cause inhibition; and Group 3: those that did not use antiepileptic drugs. Sedation was induced with the use of 0.05 mg kg−1 midazolam and 1 mg kg−1 propofol. An additional 0.05 mg kg−1 of midazolam and rescue propofol (0.5 mg kg−1) were administered and repeated to maintain sedation. The duration of sedation and the additional sedation needed were compared. Results: The duration of the initial dose was significantly shorter in Group I compared with groups II and III (p = 0.001, p = 0.003, respectively). It was significantly longer in Group II compared with groups I and III (p = 0.001, p = 0.029, respectively). The additional midazolam needed for adequate sedation was increased in Group I when compared with groups II and III (p = 0.010, p = 0.001, respectively). In addition, the rescue propofol dose was significantly higher only in Group I when compared with Group III (p = 0.002). Conclusion: In epileptic children, the response variability to the initial sedative agents during the magnetic resonance imaging procedure resulting from the inhibition or induction of the cytochrome P450 isoenzymes by the antiepileptic drugs mandated the titration of anesthetic agents. .

Justificativa e objetivos: A indução e a inibição das isoenzimas do citocromo P450 pelos medicamentos antiepilépticos levam a alterações na depuração de medicamentos anestésicos eliminados pelo metabolismo hepático. Investigamos a duração da sedação e a necessidade adicional de anestésicos durante a ressonância magnética em crianças epilépticas que receberam antiepilépticos que causam a indução ou a inibição de enzimas. Métodos: Foram incluídas no estudo 120 crianças, estado físico ASA I-II, entre 3-10 anos. Grupo 1: em uso de antiepilépticos que causam a indução de enzimas do citocromo P450; Grupo 2: em uso de antiepilépticos que causam a inibição de enzimas do citocromo P450; e Grupo 3: que não usavam antiepilépticos. A sedação foi induzida com midazolam (0,05 mg kg−1) e propofol (1 mg kg−1). Um adicional de 0,05 mg kg−1 de midazolam e resgate com 0,5 mg kg−1 de propofol foram administrados e repetidos para manter a sedação. A duração da sedação e a sedação adicional necessária foram comparadas. Resultados: A duração da dose inicial foi significativamente menor no Grupo I em comparação com os grupos II e III (p = 0,001, p = 0,003, respectivamente) e significativamente maior no Grupo II em comparação com os grupos I e III (p = 0,001, p = 0,029, respectivamente). A necessidade de midazolam adicional para sedação adequada foi maior no Grupo I em comparação com os grupos II e III (p = 0,010, p = 0,001, respectivamente). Além disso, a dose de resgate de propofol foi significativamente maior apenas no Grupo I em comparação com o Grupo III (p = 0,002). Conclusão: Em crianças epilépticas, a variabilidade ...

Justificación y objetivos: La inducción e inhibición de las isoenzimas del citocromo P450 por los medicamentos antiepilépticos conllevan alteraciones en la depuración de medicamentos anestésicos eliminados por el metabolismo hepático. Investigamos la duración de la sedación y la necesidad adicional de anestésicos durante la resonancia magnética en niños epilépticos que reciben antiepilépticos que causan la inducción o inhibición de enzimas. Métodos: Ciento veinte niños, estado físico ASA I-II, con edades entre los 3 y los 10 años, fueron incluidos en el estudio. Grupo i: niños en tratamiento con antiepilépticos que causan la inducción de enzimas del citocromo P450; grupo ii: niños en tratamiento con antiepilépticos que causan la inhibición; y grupo iii: niños que no estaban bajo en tratamiento con antiepilépticos. La sedación fue inducida con midazolam (0,05 mg/kg−1) y propofol (1 mg/kg−1). Se administró una dosis adicional de 0,05 mg/kg−1 de midazolam y una de rescate con 0,5 mg/kg−1 de propofol y fueron repetidas para mantener la sedación. Se compararon la duración de la sedación y la sedación adicional necesaria. Resultados: La duración de la dosis inicial fue significativamente menor en el grupo i en comparación con los grupos ii y iii (p = 0,001; p = 0,003, respectivamente) y significativamente mayor en el grupo iii en comparación con los grupos i y iii (p = 0,001; p = 0,029 respectivamente). La necesidad de midazolam adicional para la sedación adecuada fue mayor en el grupo i en comparación con los grupos ii y iii (p = 0,010; p = 0,001 respectivamente). Además, la dosis de rescate de propofol fue significativamente mayor solamente en el grupo i en comparación con el grupo iii (p = 0,002). Conclusión: ...

Study of effects of antiepileptic therapy on various biochemical and hematological parameters patients suffering of epilepsy.

Background: Low therapeutic index of established antiepileptic drugs (AEDs) coupled with better understanding of the pathophysiology of seizure has encouraged the development of several novel AEDs. The conventional antiepileptics like phenytoin, phenobarbitone, valproate and carbamazepine and newer antiepileptics like levetiracetam, lamotrigine and topiramate etc. are used for epilepsy. AEDs induce potentially toxic effects over a period of time which remains undetermined over very long time. Earlier studies in this regard, states uneven results about biochemical (i.e. blood sugar level, lipid profile) and hematological (Hb%, blood cell count etc.) toxicity of AEDs. Aims: To unveil the toxic effects of AEDs when given singly or as combinations. Methods: Adult epileptics of either sex taking antiepileptic monotherapy or combination therapy for ≥ six months were enrolled. Biochemical and hematological parameters studied were compared with their age and sex matched controls, baseline and amongst groups. Statistical Analysis Used: Student’s ‘t’-test & One way ANOVA followed by posthoc Tukey HSD test for pair wise comparison; p<0.05 was considered significant. Results: Conventional antiepileptic combination therapy was found more toxic; p<0.01 for lipid profile. Combination groups showed significant reduction in Hb% (p<0.05) with no significant difference among them (p>0.05). Monotherapy and conventional combination therapy caused significant reduction in platelet count (p<0.01), but conventional combination therapy was found more toxic in this regard (p<0.05). Conclusions: Monotherapy found less toxic with no significant effects on lipid profile, Hb%, RBC count and O2 carrying capacity and less impact on platelets while combination therapy did not show any advantage over monotherapy and its use must be reserved only for refractory cases.

Phenobarbitone induced drug reaction with eosinophilia and systemic symptoms (DRESS): a case report.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life threatening cutaneous drug reaction with visceral involvement and hematological abnormalities. Being a rare side effect, it is often under-reported and misdiagnosed. The fatal adverse drug reaction is associated most commonly with aromatic anti-epileptics phenytoin, carbamazepine and less frequently with phenobarbitone. Here, we report a case of phenobarbitone induced DRESS in a 1 year old male child. He succumbed to fulminant hepatic failure inspite of being put on steroids, hepatoprotectives, antibiotics and ventilatory support.

Severe Hyponatraemia under Carbamazepine for Secondary Prophylaxis of Post-Traumatic Epilepsy.

Aims: Among the antiepileptic drugs (AEDs) applied for secondary prophylaxis of posttraumatic epilepsy (PTE), carbamazepine (CBZ) may cause severe side effects and worsen traumatic brain injury (TBI). Presentation of Case: Two days after a bicycle accident causing severe TBI, a 23yo female developed a questionable seizure and received CBZ. Since then she required substitution of sodium. Six days after the accident she was extubated. Serum sodium was 123mmol/l. One day after transfer to the general ward, she was found comatose with a serum sodium of 114mmol/l. Cerebral CT showed diffuse cerebral edema. Electroencephalography did not record paroxysmal activity. After replacement of CBZ by levetiracetam, her condition markedly improved with a favourable outcome. Discussion and Conclusion: CBZ was made responsible for severe hyponatraemia in the presented case after exclusion of all other possible causes. Hyponatraemia may trigger the recurrence of cerebral edema after TBI. Hyponatraemia from CBZ may favourably respond to slow substitution of sodium with physiologic saline. CBZ for secondary prophylaxis of PTE may cause hyponatraemia, cerebral edema, and deterioration of pre-existing TBI. Replacement of CBZ by levetiracetame may resolve the condition. CBZ should be used with caution for secondary prophylaxis of PTE in TBI.

Role of clinical pharmacist in rational therapy of pediatric seizures.

Seizures are more common in children than in any other age group, except the elderly. In fact, there are several kinds of seizures that affect only children. Sometimes children outgrow their seizures but many need to be treated for their seizures for their entire life. The main objectives of this study are to study the physician prescribing pattern in pediatric seizures and to educate the patient care taker about the disease and the use of drugs in order to control seizures and improve the quality of life. A non invasive prospective observational study was done with 86 pediatric patients from 01.11.2010 to 30.04.2011. Females were found to be more prone to seizures; prevalence of seizure was more in children aged 1-5 years old. Febrile seizures (46.5%) are the most commonly observed type of seizure in children followed by tonic – clonic seizures (21%) and complex partial seizures (14%). The other types of seizures observed are simple partial seizures (7%), status epilepticus (2.3%) and others (9.3%). We observed that Clobazam is the most commonly prescribed drug for prophylaxis of febrile seizures. Phenytoin, Clobazam and Sodium valproate were commonly used drug in children. We infer that monotherapy for seizure is effective choice of treatment.

Role of clinical pharmacist in rational therapy of pediatric seizures.

Seizures are more common in children than in any other age group, except the elderly. In fact, there are several kinds of seizures that affect only children. Sometimes children outgrow their seizures but many need to be treated for their seizures for their entire life. The main objectives of this study are to study the physician prescribing pattern in pediatric seizures and to educate the patient care taker about the disease and the use of drugs in order to control seizures and improve the quality of life. A non invasive prospective observational study was done with 86 pediatric patients from 01.11.2010 to 30.04.2011. Females were found to be more prone to seizures; prevalence of seizure was more in children aged 1-5 years old. Febrile seizures (46.5%) are the most commonly observed type of seizure in children followed by tonic – clonic seizures (21%) and complex partial seizures (14%). The other types of seizures observed are simple partial seizures (7%), status epilepticus (2.3%) and others (9.3%). We observed that Clobazam is the most commonly prescribed drug for prophylaxis of febrile seizures. Phenytoin, Clobazam and Sodium valproate were commonly used drug in children. We infer that monotherapy for seizure is effective choice of treatment.

Add-on Lamotrigine in Pediatric Epilepsy in India.

Lamotrigine is a newer antiepileptic drug useful as oral adjunctive therapy in refractory epilepsy. Indian data on use of lamotrigine is limited. This study was conducted to evaluate add-on lamotrigine in Indian children with epilepsy. Twenty children (median age 90 months) receiving lamotrigine as add-on therapy for mean 26.7 (19.1) months, were followed for a median period of 7.9 (6-10) months. Follow-up was done every two weeks. The most common seizures types were either generalized tonic-clonic (6, 30%) or myoclonic (8, 40%). The average dose used was 3.86 mg/kg/day (with concomitant valproate). Good response (>50% reduction) or complete seizure control was seen in 72% patients. Side effects were seen in 27.5% patients and were ‘mild’ in more than half of these. Lamotrigine was stopped in two patients due to adverse reactions, which resolved on stopping the drug. Lamotrigine was observed to be an effective, add-on, broad-spectrum antiepileptic with ‘mild’ side effects in Indian children.

Clobazam in refractory childhood epilepsy.

Objective. To evaluate the efficacy of clobazam in childhood refractory epilepsy and to characterize the adverse drug reaction profile in the Indian population. Methods. A cohort of 88 children with ‘refractory’ epilepsy was started on clobazam as add-on therapy. Diagnosis was established and seizure type recorded. Therapeutic response was recorded as ‘complete’, ‘good’, and ‘no response’. Observed side effects were classified as ‘mild’, ‘moderate’ and ‘severe’. Results. Most children were on at least two antiepileptics. Seizures most identified were either partial (36.3%) or generalized tonic-clonic (15.9%). The dose ranged from 0.3-2 mg/kg/day (average 1+0.2 mg/kg/day). Clobazam was effective against all seizure types with complete seizure control seen in 60.2% patients. Tolerance was seen in 5 (5.6%) patients. Side effects were seen in 23 (26%) patients and were ‘mild’ in 20 (86.9%) of them. Clobazam was stopped in three patients who developed ataxia, which resolved on stopping the drug. Conclusion. Clobazam was observed to be an effective broad-spectrum antiepileptic with ‘mild’ side effects in Indian children.

A Case of Pediatric Nephrolithiasis Associated with Topiramate Treatment / 대한소아신경학회지

Topiramate is an antiepileptic drug widely used to treat various seizures, mood disorders and migraine based on its various pharmacological mechanisms. Even though nephrolithiasis is listed as one of its side effects, there have been no cases reporting nephrolithiasis caused by use of topiramate on Korean pediatric patients. Since the use of topiramate is increasing in many patients, the possibility of nephrolithiasis after the treatment needs to be considered. Here, we report our experience in correcting neprholithiasis by simply discontinuing topiramate without administering any additional treatments.

Efeitos endócrinos e metabólicos das drogas antiepilépticas / Endocrine and metabolic effects of antiepileptic drugs

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - tanto no tratamento das epilepsias como para outros fins - frequentemente por um longo tempo. Por essas razões, torna-se fundamental o conhecimento sobre os potenciais efeitos adversos desses medicamentos, muitos deles envolvendo vários aspectos hormonais e metabólicos que devem ser do conhecimento do endocrinologista. Nesta revisão, foi abordada a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, eixo gonadal e função tireoideana, além de ter sido revisado o papel terapêutico dessas medicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AED) have been widely used for a great deal of people - in the treatment of epilepsy and other diseases - throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy.

A Case of Carbamazepine-Induced Peripheral Neuropathy / 대한간질학회지

Peripheral neuropathy is rarely caused by antiepileptic drugs andmost cases were reported about phenytoin. Here we report carbamazepine- induced peripheral neuropathy, which is a very rare condition and the pathogenesis is not well understood. A 19-year-old man presented with a several-year history of bilateral foot pain and pes planus. He had craniopharyngioma and underwent neurosurgery in 1997 and 2007. He had been prescribed by the general dose (600 mg/day) of carbamazepine since 1998 for the treatment of postoperative epilepsy. His muscle power was normal in all limbs and there were no abnormal sensory symptom and sign. Findings of electrodiagnostic studies were compatible with sensorimotor polyneuropathy with mixed axonotmesis and demyelination. His family history and genetic diagnosis excluded the possibility of hereditary neuropathy. After dose reduction of carbamazepine, his bilateral foot pain has been improved slowly. We report a case of carbamazepine-induced peripheral neuropathy.

Farmacogenética e antiepilépticos (farmacologia das drogas antiepilépticas: da teoria à prática) / Pharmacogenetic and antiepileptics

A otimização do uso de antiepilépticos para o tratamento da epilepsia freqüentemente é comprometido pela falta de resposta terapêutica, efeitos colaterais inesperado ou variações inexplicadas dos níveis séricos dos antiepilépticos. A presença de polimorfismo do DNA destes indivíduos está implicada em alterações no transporte de drogas, receptores cerebrais, metabolização de drogas e efeitos colaterais idiossincrásicos graves, que podem explicar partes dos problemas. A maioria dos antiepilépticos são metabolizados pela via do Citocromo P450 ou da UDP-glucoronil-transferase. As enzimas do Citocromo P450 com maior significado clínico são CYP1A2, CYP2D6, CYP2C9, CYP2C19 e CYP3A4. A fenitoina é metabolizados pelo CYP2C9 e CYP2C19, cujos polimorfismos reduzem a atividade metabólica em até 27-54%, ocorrendo em 20-30% da população, variando conforme a origem étnica do indivíduo. A utilização da farmacogenética no tratamento de pessoas com epilepsia é bastante promissora, porém mais estudos são necessários.

The optimized use of antiepileptic drugs to treatment of epilepsy is usually compromised by lack of therapeutic response, unexpected side effects and unexplained variations of antiepileptics plasma levels. The presence of DNA polymorphism in these persons is associated to alterations on drug transportation, cerebral drug receptors, drug metabolization or severe idiosyncratic side-effects, which could explain some of these problems. Most of antiepileptics are metabolized by cytochrome P450 or UDP-glucoronosyl-transferase. The cytochrome P450 enzymes more clinically significant are CYP1A2, CYP2D6, CYP2C9, CYP2C19 and CYP3A4. Phenytoin is metabolized by CYP2C9 e CYP2C19, and polymorphism reduce metabolic activity to 27-54%, occurring at 20-30% of population, according to the person ethnic origin. The use of pharmacogenetics in the treatment of person with epilepsy has a large potential, but more studies are necessary.

Efeitos endócrinos e metabólicos dos antiepilépticos / Endocrine and metabolic effects of antiepileptics drugs

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - seja no tratamento das epilepsias como para outros fins - freqüentemente por longo tempo. Por estas razões, os médicos que utilizam DAE no seu arsenal terapêutico, devem estar atentos para os potenciais efeitos adversos do uso prolongado destes medicamentos. O objetivo desta revisão é analisar a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, função gonadal e tireoideana e suas aplicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AEDs) have been widely used for treatment of epilepsy and other diseases. Continuous and prolonged use of AEDs might be associated with potential adverse effects in different systems, including endocrine and metabolic abnormalities. The purpose of this review was to examine the relationship of AEDs with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism, as well as their implications in the treatment of diabetic neuropathy.

Changes of Body Weight and Lipid Profiles According to Apolipoprotein E Polymorphism in Children with Antiepileptics

PURPOSE: Weight changes, especially weight gain, is a side effect of antiepileptics(especially valproate and carbamazepine). This may be sufficiently severe to cause noncompliance or to require the withdrawal of effective treatment. Unfortunately, the exact mechanism of weight change is not illustrated. Several reports and our experiment suggested that weight gain highly correlated with a familial tendency of obesity. The genetic makeup is a possible factor among those of the factors that influence the impact of obesity on lipid metabolism. The purpose of this prospective, random trial clinical study was to evaluate the coherence between the changes of weight and lipid profiles and apolipoprotein E polymorphism in children with antiepileptics. METHODS: We studied 60 epileptic children treated with antiepileptics. We measured the body mass index and lipid profiles:total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol. Changes of appetite and family histories of obesity were examined. The apolipoprotein E gene polymorphisms of the patients were analyzed by the amplification refractory mutation system method. RESULTS: The body mass indexes of patient were significantly increased in all patient groups. The epileptic children who had E4 genotype showed higher frequencies of hypertriglyceridemia, hypercholesterolemia, and decreased level of HDL-cholesterol than other types. There was no significant difference between Apo E subtype with family histories of obesity and body mass index. CONCLUSION: An association with Apo E4 genotype and changes of serum lipid were demonstrated significantly in children on antiepileptics. But there was no significant difference between Apo E subtype and body mass index.