Alucinaciones como efecto adverso del topiramato / Hallucinations as an adverse effect of topiramate

El topiramato es un fármaco antiepiléptico que bloquea los canales de sodio voltaje-dependientes y potencia la actividad gabaérgica. Entre sus posibles efectos adversos se han descrito algunos muy infrecuentes como las alucinaciones visuales o auditivas. Presentamos un caso de una niña de 7 años con antecedentes de migraña sin aura sin otros antecedentes personales ni familiares de interés que, tras 15 días de tratamiento preventivo con topiramato, desarrolló alucinaciones, cambios de humor bruscos, negativismo e ideas de muerte. Dada la clínica no explicable por otra circunstancia o fármaco se retiró el topiramato con desaparición completa de los síntomas a los 20 días, sin reaparición de estos. Las alucinaciones son un efecto adverso muy inusual del topiramato. El mecanismo fisiopatológico podría estar relacionado con su efecto sobre la actividad GABA. Existen muy pocos casos de este efecto adverso descritos. En pacientes pediátricos solo se han descrito dos casos, siendo este el primer caso descrito en el contexto de tratamiento profiláctico de la migraña (AU)

Topiramate is an antiepileptic drug which blocks voltage-gated sodium channels and enhances GABAergic activity. We report the case of a 7-year-old girl with a medical history of migraine without aura who, after fifteen days of preventive treatment with topiramate developed visual and tactile hallucinations. She also presented sudden mood swings, negativism and even death ideation. She had no other personal or family medical or psychiatric history. Due to the symptomatology, Topiramate was stopped, with a complete disappearance of symptoms twenty days after its suspension, and without the recurrence of them.Hallucinations are a very unusual side effect of Topiramate. There are very few cases of this adverse effect described in the literature. In pediatric patients, there were only two cases, this being the first case described in the context of prophylactic treatment of migraine. (AU)

Comparación de la tiaprida y el topiramato en el tratamiento profiláctico de la migraña crónica: estudio piloto, aleatorizado y doble ciego / Comparison of tiapride and topiramate in the prophylactic treatment of chronic migraine: a randomised, double-blind, pilot study

Objetivo: Evaluar la eficacia y la seguridad de la tiaprida en comparación con el topiramato en la profilaxis de la migraña crónica. Pacientes y métodos: Es un estudio aleatorizado y doble ciego. Un total de 56 pacientes de 18 a 65 años con migraña crónica fueron asignados a dos brazos de tratamiento: tiaprida, 100 mg dos veces al día, o topiramato, 25 mg dos veces al día, durante 12 semanas. El criterio de valoración principal fue el cambio en el promedio mensual de días de migraña. Además, se midió el cambio en el número mensual de días de cefalea, el porcentaje de sujetos con disminución > 50% y > 75% de sus días de migraña mensual, y el cambio del impacto de la cefalea medido por el Headache Impact Test-6. Resultados: La población por intención de tratar incluyó a 39 sujetos (tiaprida = 21; topiramato = 18) y completaron el ensayo 35 participantes (tiaprida = 18; topiramato = 16). El grupo con tiaprida tuvo una reducción media de 7,2 ± 7,5 días con migrañas por mes en comparación con 7,6 ± 5,8 para el grupo con topiramato (p = 0,86). Al igual que en las otras variables de eficacia medidas, no hubo diferencias significativas entre ambos grupos. Los efectos adversos fueron leves en ambos grupos. Conclusión: En pacientes con migraña crónica, la tiaprida demostró ser un tratamiento profiláctico eficaz, seguro y bien tolerado, al compararla con el topiramato.(AU)

Aim: The aim of this study was to evaluate the efficacy and safety of tiapride compared to topiramate as a prophylactic in chronic migraine. Patients and methods: The study was conducted under randomised and double blind conditions. A total of 56 patients aged 18-65 years with chronic migraine were assigned to two treatment arms: tiapride, 100 mg twice daily, or topiramate, 25 mg twice daily, for 12 weeks. The primary endpoint was the change in the monthly average number of migraine days. In addition, measurements were performed to determine the change in the monthly number of headache days, the percentage of subjects with >50% and >75% decrease in their monthly migraine days, and the change in headache impact as measured by the Headache Impact Test-6. Results: The intention-to-treat population included 39 subjects (tiapride = 21; topiramate = 18), 35 of whom (tiapride = 18; topiramate = 16) completed the trial. The tiapride group had a mean reduction of 7.2 ± 7.5 migraine days per month compared to 7.6 ± 5.8 for the topiramate group (p = 0.86). As with the other efficacy variables measured, no differences were found between the two groups. Adverse side effects were mild in both groups. Conclusion. In patients with chronic migraine, tiapride was found to be an effective, safe and well-tolerated prophylactic treatment when compared to topiramate.(AU)

Eficácia do topiramato como terapia adicional em pacientes com estado epiléptico refratário: uma breve revisão sistemática / Efficacy of topiramate as an add-on therapy in patients with refractory status epilepticus: a short systematic review

RESUMO Objetivo: Identificar evidências atuais sobre topiramato para o estado de mal epiléptico refratário. Métodos: Foi revisada a literatura para investigar a eficácia do topiramato no tratamento de estado de mal epiléptico refratário. Os termos de busca utilizados foram: "status epilepticus", "refractory", "treatment" e "topiramate". Não se empregaram restrições. Resultados: A busca identificou 487 artigos que descreviam o uso de topiramato para tratamento de estado de mal epiléptico refratário e seus resultados. Relatos de caso, revisões e experimentos em animais foram excluídos. Após exclusão de duplicatas e aplicação dos critérios de inclusão e exclusão, restaram nove estudos. Realizaram-se análises descritivas e qualitativas, com os seguintes resultados: as taxas de resposta, definidas como término de crises até 72 horas após administração de topiramato, variaram entre 27% e 100%. A mortalidade variou de 5,9% a 68%. Desfechos funcionais positivos, definidos como alta hospitalar, volta à funcionalidade basal ou reabilitação, foram documentados por sete estudos, e as taxas variaram entre 4% e 55%. A maioria dos estudos reportou apenas efeitos colaterais leves ou ausentes. Conclusão: Topiramato foi efetivo em abortar estado de mal epiléptico refratário, apresentando baixa mortalidade e boa tolerabilidade. Portanto, topiramato poderia ser uma boa opção como terceira linha para estado de mal epiléptico refratário, porém mais estudos são necessários.

ABSTRACT Objective: To identify current evidence on the use of topiramate for refractory status epilepticus. Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were "status epilepticus", "refractory", "treatment" and "topiramate". No restrictions were used. Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects. Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.

Macular neurosensory retinal detachment associated with topiramate use. / Desprendimiento de retina neurosensorial macular asociado al uso de topiramato.

A 36 year-old woman with idiopathic intracranial hypertension was treated with topiramate and acetazolamide. The patient was followed-up for 2 years, with a relationship between neurosensory detachments and topiramate being established, with recurrences after the introduction of topiramato and improvement after its withdrawal. These findings point topiramate as a possible cause of the clinical picture. Topiramate may cause retinal and macular neurosensory detachments. Although the ciliochoroidal effusion cases caused by this drug are well-known, its retinal side effects are less common. As it is a widely used drug, neurologists and ophthalmologists should be aware of its possible ocular side effects.

Preventive effects of Topiramate on methylphenidate induced behavioral disorders / Efectos preventivos de topiramato en los trastornos del comportamiento inducidos por metilfenidato

Neuronal cell damage is often caused by prolonged misuse of Methylphenidate (MPH). Topiramate (TPM) carries neuroprotective properties but its assumed mechanism remains unclear. The present study evaluates in vivo role of various doses of TPM and its mechanism against MPH-induced motor activity and related behavior disorder. Thus, we used domoic acid (DOM), bicuculline (BIC), Ketamine (KET), Yohimibine (YOH) and Haloperidole (HAL) as AMPA/kainite, GABAA, NMDA, ɑ2 adrenergic and D2 of dopamine receptor antagonists respectively. Open Field Test (OFT), Elevated Plus Maze (EPM) and Forced Swim Test (FST) were used to study motor activity, anxiety and depression level. TPM (100 and 120 mg/kg) reduced MPH-induced rise and inhibited MPH-induced promotion in motor activity disturbance, anxiety and depression. Pretreatment of animals with KET, HAL, YOH and BIC inhibited TPM- improves anxiety and depression through the interacting with Dopaminergic, GABAA, NMDA and ɑ2-adrenergic receptors.

El daño a las células neuronales a menudo es causado por el uso prolongado de metilfenidato (MPH). El topiramato (TPM) tiene propiedades neuroprotectoras, pero su mecanismo de acción no es claro. El presente estudio evalúa el papel in vivo de varias dosis de TPM y su mecanismo contra la actividad motora inducida por MPH y el trastorno de comportamiento relacionado. Utilizamos ácido domoico (DOM), bicuculina (BIC), ketamina (KET), yohimbina (YOH) y haloperidol (HAL), así como antagonistas AMPA/kainato, GABAA, NMDA, ɑ2-adrenérgico y D2 dopaminérgicos, respectivamente. Se utilizaron las pruebas de campo abierto (OFT), elevación de laberinto (EPM) y natación forzada (FST) para estudiar la actividad motora, la ansiedad y el nivel de depresión. El TPM (100 y 120 mg/kg) redujo el aumento inducido por MPH e inhibió la promoción inducida por MPH en la alteración de la actividad motora, la ansiedad y la depresión. El tratamiento previo de animales con KET, HAL, YOH y BIC inhibió el TPM, mejora la ansiedad y la depresión a través de la interacción con los receptores dopaminérgicos, GABAA, NMDA y ɑ2-adrenérgico.

Glaucoma y miopía agudos inducidos por el uso de topiramato / Acute glaucoma and myopia induced by the use of topiramate

El topiramato es una droga utilizada en varias enfermedades, como las neurológicas y las psiquiátricas. Entre sus efectos adversos se encuentra la producción de miopía aguda y glaucoma por cierre angular secundario en ojos previamente sanos. A pesar de que se trata de efectos adversos relativamente infrecuentes, los mismos deben tomarse en consideración puesto que su expresión clínica (cefalea y dolor periocular, entre otros) puede ser muchas veces confundida con la patología de base para la cual se estaba utilizando el topiramato (por ejemplo, para el tratamiento de la migraña). Lo anterior es importante puesto que dichos efectos adversos solo cesarán con la interrupción del uso de la droga. En este breve artículo de revisión se presentan conceptos básicos acerca de la fisiopatología y del tratamiento de la miopía y del glaucoma por cierre angular inducidos por el uso de topiramato.

Topiramate is a drug used in several diseases, such as neurological and psychiatric ones. Among its adverse effects are the production of acute myopia and glaucoma by secondary angular closure in previously healthy eyes. Although these are relatively infrequent adverse effects, they must be taken into consideration since their clinical expression (headache and periocular pain, among others) can often be confused with the pathology for which topiramate was being used (for example, for the treatment of migraine). The foregoing is important since such adverse effects will only cease with the interruption of the use of the drug. In this brief review article, we present basic concepts about the physiopathology and treatment of myopia and glaucoma by angular closure induced by the use of topiramate.

Contribution of the Visante® OCT and B-scan ultrasound in the diagnosis and follow up of a topiramate-induced bilateral ciliochoroidal effusion syndrome. / Aportes de la tomografía de coherencia óptica Visante® y la ecografía ocular en el diagnóstico y seguimiento del síndrome de efusión ciliocoroideo bilateral secundario a topiramato.

A 45 year-old man with bilateral acute angle-closure and myopia after starting treatment with topiramate, secondary to alcohol and heroin dependence. Using Visante® OCT (Optical Coherence Tomography) and B-scan Ultrasound he was diagnosed with bilateral ciliochoroidal effusion as the pathophysiological mechanism. Topiramate was stopped and ocular hypotensive therapy with a topical cycloplegic and corticosteroids were started, resolving ciliochoroidal effusion syndrome. Visante® OCT and B-scan Ultrasound are useful tools for the diagnosis and follow-up of patients with acute angle-closure and myopia due to topiramate. As a result of broad spectrum of indications for topiramate, physicians and ophthalmologists should be aware of the possible ophthalmological manifestations attributable to this drug.

Acute narrow-angle glaucoma induced by topiramate with acute myopia and macular striae: A case report. / Glaucoma agudo de ángulo cerrado inducido por topiramato con miopización aguda y estrías maculares: a propósito de un caso.

We report the case of a 29-year-old epileptic woman who had been on treatment with topiramate 25mg/day for 9 days. She was referred to the Emergency Department due to reduction in far visual acuity (VA) after increasing the dose to 50mg/day two days before. The ocular examination showed bilateral acute angle closure glaucoma (AACG) and macular striae in both eyes (AO) observed by Retinography and Optical Coherence Tomography (OCT). The AACG is a well-known side effect of topiramate, but the macular striae rarely accompanies it. Although macular striae have been previously described in other cases, very few document those using retinography and OCT images. Therefore, it is important to differentiate a case of AACG induced by topiramate from a case of primary AACG, since they differ in their clinical presentation, mechanism of action, and treatment. Mismanagement can have potentially serious consequences.

Uso del topiramato en pacientes con síndrome de dolor lumbar crónico con síntomas ansiosos y depresivos secundarios a sensibilización central con y sin compromiso neuropático resistente a tratamiento convencional / Use of topiramato in patients with chronic lumbar pain syndrome with ansiosius symptoms and secondary depression to central sensitization with and without neuro-pathic commitment resistant to conventional treatment

INTRODUCCIÓN: El dolor lumbar crónico genera alta disfuncionalidad, su tratamiento es complejo y en algunos casos se presenta refractariedad a tratamientos convencionales. El síndrome de sensibilización central por dolor lumbar involucra presencia de síntomas ansiosos, depresivos, trastorno del sueño, fatiga, alteraciones del apetito y disfuncionalidad en actividades de la vida diaria. El manejo del dolor lumbar crónico con síndrome de sensibilización central es dificultoso, requiere de intervenciones multidimensionales y esquemas farmacológicos atípicos. OBJETIVO: Se describe el uso de topiramato como fármaco coadyuvante en el manejo de pacientes con dolor lumbar crónico resistente a tratamiento standard en 25 pacientes. MATERIALES Y MÉTODO: Seguimiento a 12 semanas y evaluación de funcionalidad, sintomatología ansiosa-depresiva, control del dolor y fatiga a través de múltiples escalas. Resultados: La dosis mediana fue de 300mg. El 72 por ciento (18 pacientes) presenta mejoría estadística en síntomas angustiosos, depresivos, sueño, EVA de dolor y fatiga y funcionalidad. Solo el 16 por ciento (4 pac) presentan reacciones adversas que obligan a suspensión del fármaco. El 12 por ciento (3 pacientes) no presentaron respuesta terapéutica. DISCUSIÓN: El topiramato podría ser una opción coadyuvante para el manejo del síndrome de dolor lumbar crónico con síndrome de sensibilización central.

INTRODUCTION: The chronic low back pain causes severe dysfunction, treatment is complex and in some cases it can be refractory to usual treatment. Central Sensitivity syndrome secondary to chronic low back pain is characterized by anxious, depressive, sleep disorders, fatigue, eating disorders and damage in daily activities life. Management of this syndrome must be integrative and multidimensional. OBJECTIVES: Describe the use of topiramate in 25 patients with chronic low back pain for pain relief in refractory patients to standard treatment, during 12 weeks. MATERIALS AND METHODS: Following during 12 weeks, multiples Assessments about anxiety, depression, functionality, sleep quality, VAS pain and fatigue. Results: Median doses 300mg. 72 percent got pain relief, and decrease in anxious depressive symptoms, improve sleep quality, daily function. 16 percent didn't get pain relief and suffered adverse effects forcing suspension of the drug. 12 percent didn't get pain relief without adverse effects. DISCUSSION: Topiramate might be a treatment option for pain relief in these patients.

Hipertensión endocraneana idiopática: respuesta al tratamiento Topiramato vs Acetazolamida / Endocranial idiopathic hypertension: response to treatment Topiramate vs. Acetazolamide

INTRODUCCIÓN: El término pseudotumorcerebri se reserva para denominar aquellas hipertensiones endocraneanas (HE) que clínicamente asemejan la existencia de un tumor cerebral, debido a la alteración de la circulación del líquido cefalorraquídeo (LCR). Para su diagnóstico se describen los criterios de Dandy-Smith. OBJETIVOS: Objetivo Primario: Determinar el beneficio del uso de Azetazolamida (ACZ) o Topiramato (TPM) en el tratamiento de la hipertensión endocraneana idiopática. Objetivos Secundarios: Uso de Presión de apertura como parámetro indicador para uso de ACZ o TPM. MATERIALES Y MÉTODOS: Tipo de estudio: Descriptivo Retrospectivo Observacional. RESULTADOS: La media de seguimiento fue de 11 meses, con un rango entre 6-12 meses Se estudiaron 5 pacientes con diagnóstico de Hipertensión Endocraneana Idiopática. Del total de los pacientes 5 (100%) tenían F.O patológico y como síntoma cardinal cefalea, 2 (40%) además vómitos. 3 (60%) fue tratado con Topiramato (TPM) mientras que 2 (40%) recibió acetazolamida (ACZ), ambos sin complicaciones (p= 0,07) Del total de los pacientes 3(60%) presento presión de apertura menor de 40 mmHg mientras que en los restantes 2 (40%) fue mayor a 40 mmHg. De estos últimos el 1 paciente recibió TPM y 1 paciente ACZ. Dos pacientes (40%) presentaron en el seguimiento una recaída sintomática, al intentar descender la medicación. No se pudo definir como parámetro de decisión la presión de apertura en del uso de uno u otro medicamento ya que al evaluar el uso de TPM y ACZ en pacientes con presión de apertura mayor a 41 mmHg solo se detallaron 2 pacientes cada uno tratado con un medicamento de los anteriormente descriptos. (Chi cuadrado p= 0.44). Ninguno de los pacientes tratados requirió otro tratamiento complementario como PL seriadas o válvula de derivación ventrículo peritoneal. CONCLUSION: No se logró determinar beneficio en el uso de un medicamento sobre otro en el tratamiento de la hipertensión endocraneana idiopática (p=0,07), pese al tamaño muestral, el cual podría ser un limitante. Coincidentemente con la literatura sigue sin haber evidencia suficiente. No existe un algoritmo de consenso en cuanto al correcto manejo terapéutico y farmacológico de esta entidad. El uso de TPM o ACZ no condiciona la posterior aparición de complicaciones (p= 0.45) El estudio oftalmológico es esencial para diagnóstico y seguimiento. No se pudo establecer correlación entre el valor obtenido en la medición de la presión de apertura y el tratamiento instaurado. (AU)

INTRODUCTION: The term Pseudotumor cerebri is reserved for those endocranial hypertensio (EH) that resemble clinically the existence of a brain tumor, due to alteration of the circulation of the cerebrospinal fluid (CSF). Classically, the Dandy-Smith criteria for diagnosis are described. TYPE OF STUDY: Descriptive observational. OBJECTIVE: Primary Objective: To determine the benefit of the use of Azetazolamide (ACZ) or Topiramate (TPM) in the treatment of idiopathic endocranial hypertension Secondary Objectives: Use of Opening Pressure as indicator parameter for use of ACZ or TPM. MATERIALS AND METHODS: Observed patients(N:5) per clinic with diagnosis of EIH by criteria of Dandy-Smith in the period 2013-2017. I was performed in all patients: RMNC s/contrast Fundus oculi Lumbar puncture + opening pressure. RESULTS: Of the total of patients (5) 100% had F.O pathological and as cardinal symptom headache, and 40% also vomiting. The mean follow-up was 11 months 60% of the patients was treated with topiramate (TPM) while 40% received acetazolamide (ACZ), both without complications. Of the total of patients 60% presented less than 40 opening pressure mmHg, while that in the remaining 40% was greater than 40 mmHg, of which 50% received TPM and 50% ACZ. 40% presented in tracking a symptomatic relapse, trying to get off the medication. None of the treated patients required other adjunctive therapy such as serial PL or ventricleperitoneal shunt. CONCLUSIONS: It was not possible to determine benefit in the use of one drug over another in the treatment of idiopathic intracranial hypertension (p = 0.07), despite the sample size, which could be a limitation. Coincidentally with the literature there is still not enough evidence. There is no consensus algorithm regarding the correct therapeutic and pharmacological management of this entity. The use of TPM or ACZ does not condition the subsequent appearance of complications (p = 0.45) The ophthalmological study is essential for diagnosis and follow-up. No correlation could be established between the value obtained in the measurement of the opening ression and the treatment established. (AU)

Normal anion gap metabolic acidosis secondary to topiramate intake: case report

ABSTRACT Introduction: Topiramate is a drug used to treat various types of epilepsy and as prophylaxis in cases of migrainous headache. One of its mechanisms of action is the inhibition of carbonic anhydrase in the kidney that triggers the excretion of alkaline urine resulting in metabolic acidosis. Case presentation: 17-year-old female patient from Mexico City who regularly uses topiramate, quetiapine and sertraline for the management of depressive disorder. She developed normal anion gap metabolic acidosis secondary to topiramate intake. As a result, she required invasive ventilatory support due to reduced consciousness and respiratory distress. Adequate response to management with laxatives and bicarbonate was achieved, with full renal and neurological recovery. Discussion: Metabolic acidosis is the most common acid-base disorder observed in clinical practice. The difference between measurable cations and anions, known as anion gap, helps to classify the severity of acidosis. Bicarbonate losses or renal tubular disorders generate normal anion gap acidosis as opposed to acidosis resulting from an overproduction of endogenous acid or renal failure, which causes high anion gap. Topiramate is a little known cause of normal anion gap metabolic acidosis; by inhibiting carbonic anhydrase, it causes mixed renal tubular acidosis or type 3 acidosis, as a consequence of the inability to secrete hydrogen ions in the collecting tubule, and a limitation of bicarbonate reabsorption in the proximal tubule. Conclusion: Topiramate, either in therapeutic doses or in overdose, can lead to normal anion gap metabolic acidosis due to the inhibition of carbonic anhydrase in the kidneys. It is usually reversible after starting bicarbonate.

RESUMEN Introducción. El topiramato es un medicamento que se usa en el tratamiento de varios tipos de epilepsia y como profilaxis en casos de cefalea migrañosa. Entre sus mecanismos de acción, la inhibición de la anhidrasa carbónica en el riñón desencadena la excreción de orina alcalina ocasionando acidosis metabólica. Presentación del caso. Paciente femenino de 17 años procedente de la Ciudad de México con antecedente de consumo de topiramato, quetiapina y sertralina para manejo de síndrome depresivo, quien desarrolla acidosis metabólica de anión restante normal secundaria a ingesta de topiramato. La joven requiere soporte ventilatorio invasivo por deterioro del estado de conciencia y síndrome de dificultad respiratoria y presenta adecuada respuesta a manejo con catártico y bicarbonato sin compromiso renal y sin secuelas neurológicas. Discusión. La acidosis metabólica es la alteración ácido base más frecuente en la práctica clínica. La diferencia entre cationes y aniones medibles, conocida como anión restante o brecha aniónica, permite clasificar este tipo de acidosis. Las pérdidas de bicarbonato o trastornos de la función tubular renal generan acidosis de anión restante normal; por el contrario, la acidosis causada por sobreproducción de ácido endógeno o por insuficiencia renal genera anión restante elevado. El topiramato es una causa poco conocida de acidosis metabólica con anión restante normal; al inhibir la anhidrasa carbónica, se ocasiona una acidosis tubular renal mixta o tipo 3 debido a una in capacidad de secreción de hidrogeniones en el túbulo colector y una limitación en la reabsorción del bicarbonato en el túbulo proximal. Conclusión. El topiramato en dosis terapéutica o en sobredosis puede generar acidosis metabólica de anión restante normal debido a la inhibición de la anhidrasa carbónica a nivel renal. Se trata de un cuadro reversible en el cual el manejo con bicarbonato ha mostrado buenos resultados clínicos.

Relevance of weight in the management of patients with type 2 diabetes mellitus: towards an adipocentric approach to diabetes. / Importancia del peso en el control del paciente con diabetes mellitus tipo 2: hacia una visión adipocéntrica del abordaje de la diabetes.

In recent decades, there has been a worldwide parallel increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), which is not surprising, given that increased visceral fat is the main risk factor for the development of T2DM in genetically predisposed individuals. An intervention focused on intensive blood glucose control in T2DM with classic drugs increases the risk of weight gain and the rate of hypoglycaemia. In contrast, weight loss through lifestyle changes, drugs and/or surgery simultaneously improves most cardiovascular (CV) risk factors, including hyperglycemia. Intensive intervention on lifestyle induces an overall benefit in patients with T2DM, but long-term weight loss is modest and has not been shown to reduce CV morbidity and mortality. The emergence of new therapeutic classes for T2DM and obesity, which simultaneously improve HbA1c, weight and other CV risk factors without inducing hypoglycaemia, represents a major change in the management of patients with diabesity. A sodium-glucose cotransporter-2 inhibitor and a GLP-1 receptor agonist have recently been shown to decrease CV and total mortality in type 2 diabetic patients with CV disease. Furthermore, bariatric surgery rapidly induces remission or improvement of T2DM in a large percentage of patients and reduces diabetes-related mortality. The emergence of new therapies raises the possibility of changing the current glucose-centred therapeutic strategy for a weight-centred approach.

Topiramate as concomitant antiepileptic treatment; an isolated perioperative hypofibrinogenaemia.

A description of a case is presented of an isolated hypofibrinogenaemia acquired in relation to taking topiramate used as concomitant treatment of a drug resistant epilepsy. The hypofibrinogenaemia developed in the course of a month after the introduction of the drug, and was diagnosed in the perioperative period.

Topiramato en el tratamiento preventivo de la migraña: experiencia en una policlínica neuropediátrica / Topiramate for the prevention of migraine: Experience at a Child Neurology Clinic

La migraña es la cefalea primaria más frecuente en la infancia y su incidencia aumenta con la edad. Su tratamiento incluye conocer los factores desencadenantes, ajustes en el estilo de vida, manejo de los episodios de cefalea y en algunos casos medicación preventiva. El Topiramato ha mostrado ser eficaz como tratamiento preventivo. El objetivo de este trabajo fue evaluar la respuesta y la seguridad al tratamiento preventivo con Topiramato en pacientes pediátricos. Estudio prospectivo, realizado entre el 01/04/2008 y el 31/10/2013. Se confeccionó un protocolo de estudio, diagnóstico y seguimiento. Se utilizó Topiramato en pacientes con más de 3 episodios de migraña al mes, considerando buena respuesta la reducción mayor al 50% de los mismos. 190 pacientes consultaron por cefaleas. Un 63.9% presentaban migraña. Un 48% fue tratado con Topiramato, siendo eficaz en un 89.6%. En 2 pacientes no hubo respuesta y en 4 se discontinuó por empeoramiento o efectos secundarios que desaparecieron al discontinuarlo. En conclusión el Topiramato es eficaz y seguro en el tratamiento de la migraña en pediatría.

Migraine is the most frequent primary headache in pediatric population, and incidence increases with age. Treatment includes know precipitating factors, changes in life style, acute headaches treatment and in some cases preventive medications. Topiramate has proven efficacy in preventive treatment. The objective of this work was to assess response and safety of Topiramate for migraine in a pediatric population. We made a prospective study, between 04/01/2008 to 10/31/2013. Topiramate was started in patients with 3 or more headache episodes per month and effectiveness was considered when a 50% or more reduction in episodes occurred. 190 patients consulted in this period. 63.9% had migraine. 48% were treated with Topiramate, being effective in 89.6% of patients. In 2 patients there was no response to treatment and in 4 patients treatment was discontinued due to worsening of headaches or secondary effects that disappeared after treatment discontinuation. In conclusion Topiramate is effective and secure for migraine preventive treatment in pediatric population.

Estudo de bioequivalência entre duas formulações de topiramato comprimidos revestidos de 100 mg, em voluntários sadios após administração de dose única / Study of bioequivalence between two formulations of topiramate 100 mg coated tablets, in healthy volunteers after a single dose administration

O estudo foi realizado para comparar a biodisponibilidade/bioequivalência de duas formulações de topiramato 100 mg comprimidos revestidos (Aché Laboratórios Farmacêuticos S/A - formulação teste e Topamax® por Janssen Cilag Farmacêutica Ltda.) em 28 voluntários de ambos os sexos. O estudo foi realizado através de um desenho aberto, randomizado, cruzado em dois períodos com tempo de washout de 14 dias. As amostras de plasma de 23 dos 28 voluntários inicialmente incluídos foram obtidas ao longo de um intervalo de 120 horas. As concentrações de topiramato foram determinadas através de um equipamento LC-MS-MS, utilizando prednisona como padrão interno. A partir dos dados obtidos se calcularam os seguintes parâmetros farmacocinéticos: ASC0-t, ASC0-¥ e Cmax. A razão das médias geométricas de Topiramato/Topamax® 100 mg foi de 100,97% para ASC0-t, 101,38% para ASC0-¥ e 96,94% para Cmax; os intervalos de confiança de 90% foram de 107,02% - 107,40%, 104,45% - 110,42% e 90,98% - 103,29%, respectivamente. Uma vez que os intervalos de confiança de 90% para Cmax e ASC0-t estiveram dentro da faixa de 80% a 125% proposta pelo FDA e pela ANVISA (Agência Nacional de Vigilância Sanitária do Brasil), conclui-se que comprimido revestido de topiramato 100 mg foi bioequivalente ao comprimido de Topamax® de 100 mg e, desta forma, o produto teste pode ser considerado intercambiável na prática médica...

Miopia aguda e hipertensão intraocular após uso de topiramato / Acute miopia and intraocular hypertension after topiramate use

A migrânea acomete cerca de 6% a 7% dos homens e 18% a 20% das mulheres, principalmente entre 25 e 55 anos de idade, e é responsável por enorme impacto na atividade produtiva. O topirama-to é um das drogas antiepilépticas aprovadas pela Food and Drug Administration (FDA), sendo usado para a prevenção da migrânea. É uma droga segura, mas não isenta de efeitos adversos. Embora alterações oftalmológicas causadas pelo uso dessa medicação não sejam comuns, aqui é relatado um caso de uma paciente que, ao procurar profilaxia para as crises de migrânea, apresentou efeito adverso ocular, o qual, se não fosse reconhecido em tempo hábil, causaria efeitos maiores e mais danosos à paciente.

Migraine affects approximately 6% and 7% of men and 18% and 20% of women mainly between 25 and 55 years old, responsible for its enormous impact on productive activity. Topiramate is one of the Food and Drug Administration (FDA) approved antiepileptic drugs used for migraine prevention. It is a safe drug but not without side effects. Although ophthalmologic changes caused by this medication are not common, here is reported a case of a patient looking for pro-phylaxis of migraine attacks exhibited an ocular adverse effect, and if not recognized in due time, larger and more harmful effects could be inflicted to the patient.

[Heat stroke related to the use of topiramate. The importance of prevention]. / Golpe de calor relacionado con el uso de topiramato. La importancia de la prevención.

Heat stroke is the most severe pathology related to heat. It is defined as an increase in core body temperature accompanied by signs of neurological dysfunction. In the absence of an early treatment, it has a very high mortality rate. Topiramate is a well known drug widely used in epilepsy treatment and migraine prevention. Oligohydrosis has been described amongst topiramate side effects, favouring the risk of hyperthermia and heatstroke. We present the case of a patient who developed heat stroke due to physical exercise while under topiramate treatment.

O uso do topiramato na enxaqueca / The use of topiramate of migraine

Apesar da enxaqueca ter significativa prevalência, ter critérios diagnósticos bem definidos, levar a importante impacto na qualidade de vida, ela tem sido sub-reconhecida, subdiagnosticada e subtratada. Destaca-se a utilidade de acompanhamento com diário e a prescrição de tratamento embasado na fisiopatologia e resultantes de protocolos clínicos com boa classe de evidência. Apresenta-se propostas não farmacológicas, bem como propostas medicamentosas, para alívio da crise da enxaqueca e para a prevenção delas, enfatizando-se os mecanismos de ação do topiramato e as evidências do seu benefício e tolerabilidade no tratamento preventivo...

Nuevas drogas en el tratamiento de la obesidad y el sobrepeso / New drugs for the treatment of obesity and overweight / Novas drogas no tratamento da Obesidade e Sobrepeso

a obesidad y el sobrepeso se asocian con un mayor riesgo de mortalidad global y de padecer numerosas patologías crónicas, y son muy difíciles de tratar. Es por esto que la implementación de medidas farmacológicas seguras y eficaces reviste una suprema importancia. La lorcaserina y la combinación fentermina/topiramato son nuevas opciones farmacológicas aprobadas en el año 2012 por la FDA (Food and Drugs Administration de los Estados Unidos), a pesar de su compleja forma de administración, y los requerimientos de un programa de entrenamiento y de monitoreo de postmarketing. En el artículo se describen las nuevas drogas aprobadas, sus mecanismos de acción, efectos adversos, características farmacocinéticas su uso en situaciones especiales, y los inconvenientes con las drogas previamente aprobadas y que fueron retiradas del mercado.Palabras clave: obesidad, sobrepeso, topiramato, fentermina, lorcaserin

besity and overweight are associated with an increased risk of overall mortality and the development of many chronic diseases, and they are very difficult to treat. That is why the implementation of safe and effective pharmacological measures is of paramount importance. Lorcaserin and the combination of phentermine/topiramate are two new pharmacological therapies for chronic weight management. They were approved in 2012 by the U.S. Food and Drug Administration, despite concerns over its complex form of administration and the requirement of a training and post-marketing surveillance program.This article describes newly approved drugs, their mechanisms of action, side effects, pharmacokinetics, and their use in special situations, along with the drawbacks of previously approved drugs that were withdrawn from the market.

A obesidade e o sobrepeso são associados a um maiorrisco de mortalidade global e ao padecimento de numerosaspatologias crônicas, e são muito difícies de tratar. É poristo que a implementação de medidas farmaco lógicasseguras e eficazes possui uma suprema importância.A lorcaserina e a combinação fentemina/topiramato sãonovas opções farmacológicas aprovadas no ano 2012pela FDA (Food and Drugs Administration de los EstadosUnidos), apesar da sua complexa forma de administração, eos requerimentos de um programa de treinamento e demonitoramento de postmarketing. No artigo estão descritas as novas drogas aprova das,seus mecanismos de ação, efeitos adversos, característicasfarmacocinéticas, seu uso em situações especiais, e osinconvenientes com as drogas previamente aprovadas eque foram retiradas do mercado.

Topiramato, efectos en el estado ácido base y consecuencias clínicas / Topiramate: Effects on the Acid-Base Status and Clinical Consequences

En la presente revisión se analiza cómo el topiramato afecta a corto y largo plazo el estado ácido base mediante la inhibición de la anhidrasa carbónica tipo II, generando una acidosis tubular renal mixta que provoca consecuencias clínicas de importancia como nefrolitiasis, osteoporosis y retraso en el crecimiento. Dado que los tratamientos con este fármaco son crónicos, pueden prevenirse estos sucesos de diversas maneras. Se ofrecen pautas para el manejo de las distintas situaciones clínicas

This review provides an analysis of the short-and long-term impact of Topiramate on the acid-base status through the inhibition of carbonic anhydrase II, which leads to a mixed renal tubular acidosis that causes significant clinical consequences such as nephrolithiasis, osteoporosis and growth delay. Because treatments with this drug are chronic, these events may be prevented in different ways. The author offers guidelines for the management of different clinical situations