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Baclofeno , Síndrome de Abstinencia a Sustancias , Humanos , Baclofeno/administración & dosificación , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Fenobarbital/uso terapéutico , Fenobarbital/administración & dosificación , Agonistas de Receptores GABA-B/uso terapéutico , Ácido gamma-Aminobutírico/análogos & derivadosRESUMEN
BACKGROUND: Lacosamide (LCM) is a third-generation antiseizure medication (ASM) currently approved for the treatment of focal seizures in children aged greater than one month. There are limited data on its efficacy in the neonatal age group. We describe our experience with LCM as an adjunct ASM for the treatment of neonatal seizures. METHODS: A retrospective chart review over a five-year period (2018 to 2022) was conducted at Le Bonheur Children's Hospital to identify neonates with electroencephalography (EEG)-proven seizures who were treated with LCM. Data were collected on electroclinical seizure characteristics, underlying etiology, ASMs, treatment response, and any adverse effects. RESULTS: A total of 15 neonates with EEG-confirmed seizures who were treated with LCM were included. Ten neonates achieved seizure cessation after LCM was added to their ASM regimen consisting of phenobarbital, levetiracetam, or both. No new treatment-related adverse effects were noted. CONCLUSIONS: LCM is effective as an adjunct treatment for neonatal seizures. Randomized controlled studies are needed to establish its effectiveness and adequate dosing regimen in this population.
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Anticonvulsivantes , Electroencefalografía , Lacosamida , Convulsiones , Humanos , Lacosamida/administración & dosificación , Lacosamida/farmacología , Estudios Retrospectivos , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacología , Recién Nacido , Masculino , Convulsiones/tratamiento farmacológico , Femenino , Quimioterapia Combinada , Fenobarbital/administración & dosificación , Fenobarbital/uso terapéutico , Levetiracetam/administración & dosificación , Levetiracetam/farmacologíaRESUMEN
OBJECTIVE: The study aims to describe our experience with the implementation of phenobarbital as a primary sedation strategy during neonatal extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Retrospective chart review in a level IV neonatal intensive care unit between 2011 and 2021 comparing neonatal ECMO patients before and after the implementation of a sedation-analgesia (SA) protocol using scheduled phenobarbital as the primary sedative. Groups were compared for neonatal and ECMO characteristics, cumulative SA doses, and in-hospital outcomes. Comparison between groups was performed using Mann-Whitney test on continuous variables and chi-square on nominal variables. RESULTS: Forty-two patients were included, 23 preprotocol and 19 postprotocol. Birth, pre-ECMO, and ECMO clinical characteristics were similar between groups except for a lower birth weight in the postprotocol group (p = 0.024). After standardization of phenobarbital SA protocol, there was a statistically significant reduction in median total morphine dose (31.38-17.65 mg/kg, p = 0.006) and median total midazolam dose (36.21-6.36 mg/kg, p < 0.001). There was also a reduction in median total days on morphine by 7.5 days (p = 0.026) and midazolam by 6.6 days (p = 0.003). There were no differences in ECMO duration or in-hospital outcomes between groups. CONCLUSION: In this cohort, short-term use of phenobarbital as primary sedation strategy during neonatal ECMO was associated with reduced opioid and midazolam burden. Such reduction, however, did not affect in-hospital outcomes. KEY POINTS: · Prolonged sedation on ECMO puts infants at risk for iatrogenic withdrawal.. · Phenobarbital is a feasible sedation strategy for ECMO.. · Phenobarbital sedation strategy may mitigate risk by decreasing opioid and midazolam burden..
Asunto(s)
Analgésicos Opioides , Oxigenación por Membrana Extracorpórea , Hipnóticos y Sedantes , Unidades de Cuidado Intensivo Neonatal , Midazolam , Fenobarbital , Humanos , Fenobarbital/administración & dosificación , Fenobarbital/uso terapéutico , Recién Nacido , Estudios Retrospectivos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Femenino , Masculino , Analgésicos Opioides/administración & dosificación , Midazolam/administración & dosificación , Morfina/administración & dosificación , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversosRESUMEN
BACKGROUND: Phenobarbital may offer advantages over benzodiazepines for severe alcohol withdrawal syndrome (SAWS), but its impact on clinical outcomes has not been fully elucidated. OBJECTIVE: The purpose of this study was to determine the clinical impact of phenobarbital versus benzodiazepines for SAWS. METHODS: This retrospective cohort study compared phenobarbital to benzodiazepines for the management of SAWS for patients admitted to progressive or intensive care units (ICUs) between July 2018 and July 2022. Patients included had a history of delirium tremens (DT) or seizures, Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar) >15, or Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score ≥4. The primary outcome was hospital length of stay (LOS). Secondary outcomes included progressive or ICU LOS, incidence of adjunctive pharmacotherapy, and incidence/duration of mechanical ventilation. RESULTS: The final analysis included 126 phenobarbital and 98 benzodiazepine encounters. Patients treated with phenobarbital had shorter median hospital LOS versus those treated with benzodiazepines (2.8 vs 4.7 days; P < 0.0001); a finding corroborated by multivariable analysis. The phenobarbital group also had shorter median progressive/ICU LOS (0.7 vs 1.3 days; P < 0.0001), and lower incidence of dexmedetomidine (P < 0.0001) and antipsychotic initiation (P < 0.0001). Fewer patients in the phenobarbital group compared to the benzodiazepine group received new mechanical ventilation (P = 0.045), but median duration was similar (1.2 vs 1.6 days; P = 1.00). CONCLUSION AND RELEVANCE: Scheduled phenobarbital was associated with decreased hospital LOS compared to benzodiazepines for SAWS. This was the first study to compare outcomes of fixed-dose, nonoverlapping phenobarbital to benzodiazepines in patients with clearly defined SAWS and details a readily implementable protocol.
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Benzodiazepinas , Tiempo de Internación , Fenobarbital , Fenobarbital/uso terapéutico , Fenobarbital/administración & dosificación , Humanos , Benzodiazepinas/uso terapéutico , Benzodiazepinas/administración & dosificación , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Adulto , Delirio por Abstinencia Alcohólica/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Anciano , Unidades de Cuidados Intensivos/estadística & datos numéricos , Hipnóticos y Sedantes/uso terapéutico , Hipnóticos y Sedantes/administración & dosificación , Índice de Severidad de la Enfermedad , Estudios de CohortesRESUMEN
BACKGROUND: Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication. OBJECTIVE: To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations. METHODS: Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures. RESULTS: Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures. CONCLUSION AND RELEVANCE: This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation.
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Tiempo de Internación , Lorazepam , Fenobarbital , Humanos , Fenobarbital/administración & dosificación , Fenobarbital/uso terapéutico , Lorazepam/administración & dosificación , Lorazepam/uso terapéutico , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Adulto , Anciano , Hospitalización/estadística & datos numéricos , Unidades de Cuidados Intensivos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/uso terapéutico , Delirio por Abstinencia Alcohólica/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Respiración ArtificialRESUMEN
BACKGROUND: Hepatocellular carcinoma is a particularly dangerous and severe kind of liver cancer. Many anticancer drugs fail to complete the treatment of hepatocellular carcinoma without any side effects. There should be appropriate and without side effective treatments for hepatocellular carcinoma. OBJECTIVE: The objective of the current study was to evaluate how quercetin and silymarin in a niosomal formulation affected hepatocyte carcinoma caused by diethylnitrosamine. METHODS: Five groups were created from the thirty male rats. Normal control (untreated group), tumor group (administered dimethylnitrosoamine 200 mg/kg), treatment group I (administered 50 mg/kg of niosomal encapsulated quercetin), treatment group II (administered 50 mg/kg of niosomal encapsulated silymarin), and treatment group III (administered 50 mg/kg of niosomal encapsulated quercetin + silymarin). Then, biochemical estimation, serum analysis, and histopathological examination were carried out. RESULTS: Treatment group III, treated with niosomal encapsulation of a combination of quercetin + silymarin 50 mg/kg, demonstrated the significant restoration of alpha-fetoprotein and carcinoembryonic antigen and also antioxidants like superoxide dismutase and nitric oxide. The histopathological examination showed improved liver architecture in this group compared to other treatment groups. CONCLUSION: Our findings revealed that a potent anticancer effect was observed in treatment group III as niosomal formulation increased the bioavailability of the drug within the body. In order to completely understand the underlying processes and evaluate the therapeutic effectiveness of these chemicals in the therapy of hepatocellular carcinoma, further investigation and clinical trials are required.
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Carcinoma Hepatocelular , Dimetilnitrosamina , Liposomas , Fenobarbital , Quercetina , Silimarina , Animales , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/administración & dosificación , Silimarina/farmacología , Silimarina/administración & dosificación , Silimarina/uso terapéutico , Masculino , Fenobarbital/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Ratas , Dimetilnitrosamina/toxicidad , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/inducido químicamente , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Ratas Wistar , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patologíaRESUMEN
Patients with cerebral malaria with polymorphic Cytochrome P450 2C19 (CYP2C19) genotypes who receive concurrent treatment with quinine are at risk of inadequate or toxic therapeutic drug concentrations due to metabolic drug interactions. The study aimed to predict the potential dose regimens of quinine when coadministered with phenobarbital in adult patients with cerebral malaria and complications (e.g., lactic acidosis and acute renal failure) and concurrent with seizures and acute renal failure who carry wild-type and polymorphic CYP2C19. The whole-body physiologically based pharmacokinetic (PBPK) models for quinine, phenobarbital, and quinine-phenobarbital coadministration were constructed based on the previously published information using Simbiology®. Four published articles were used for model validation. A total of 100 virtual patients were simulated based on the 14-day and 3-day courses of treatment. using the drug-drug interaction approach. The predicted results were within 15% of the observed values. Standard phenobarbital dose, when administered with quinine, is suitable for all groups with single or continuous seizures regardless of CYP2C19 genotype, renal failure, and lactic acidosis. Dose adjustment based on area under the curve ratio provided inappropriate quinine concentrations. The recommended dose of quinine when coadministered with phenobarbital based on the PBPK model for all groups is a loading dose of 2000 mg intravenous (i.v.) infusion rate 250 mg/h followed by 1200 mg i.v. rate 150 mg/h. The developed PBPK models are credible for further simulations. Because the predicted quinine doses in all groups were similar regardless of the CYP2C19 genotype, genotyping may not be required.
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Anticonvulsivantes/administración & dosificación , Antimaláricos/administración & dosificación , Malaria Cerebral/tratamiento farmacológico , Fenobarbital/administración & dosificación , Quinina/administración & dosificación , Convulsiones/tratamiento farmacológico , Acidosis Láctica/epidemiología , Acidosis Láctica/patología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/patología , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Antimaláricos/uso terapéutico , Área Bajo la Curva , Simulación por Computador , Citocromo P-450 CYP2C19/genética , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Genotipo , Humanos , Malaria Cerebral/complicaciones , Malaria Cerebral/epidemiología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Fenobarbital/uso terapéutico , Quinina/uso terapéutico , Convulsiones/etiología , Adulto JovenRESUMEN
INTRODUCTION: Cannabidiol (CBD) is one of the main components of the cannabis plant that has demonstrated anti-epileptic seizure effect. Following its clinical development, in September 2019 the European Medicines Agency approved its indication for the adjunctive therapy of epileptic seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), combined with clobazam (CLB), in patients of 2 years of age and older. AIM: To establish recommendations on the use of plant-derived highly purified CBD on which Spanish experts have reached consensus for the treatment of epilepsy in patients with DS and LGS based on their clinical experience and the scientific evidence. DEVELOPMENT: Consensus meeting with the participation of four Spanish neurologists and neuropediatric who are experts in epilepsy secondary to DS and LGS and with clinical experience in the use and management of CBD. They discussed on several topics, including posology (starting dose, dose escalation schema), efficacy (assessment of outcomes and indications for treatment withdrawal), and safety (evaluation, drug-drug interactions, adverse events management). CONCLUSIONS: In order to optimise CBD treatment, a slow dose escalation (= 4 weeks) is recommended until the maximum recommended dose or the desire effect is reached. It is also recommended that the concomitant antiseizure medications (ASMs) be reduced in case of adverse events due to interactions, and that the treatment continues for at least 6 months if it is well tolerated. The efficacy and safety of CBD must be assessed individually, considering the benefits and risks for individual patients.
TITLE: Cannabidiol para el tratamiento del síndrome de Lennox-Gastaut y del síndrome de Dravet: recomendaciones de expertos sobre su uso en la práctica clínica en España.Introducción. El cannabidiol (CBD) es uno de los componentes principales de la planta del cannabis que ha demostrado efecto ante las crisis epilépticas. Tras su desarrollo clínico, obtuvo su aprobación por la Agencia Europea del Medicamento en septiembre de 2019 para el tratamiento de las crisis epilépticas asociadas con el síndrome de Lennox-Gastaut (SLG) y el síndrome de Dravet (SD), en combinación con el clobazam (CLB), en pacientes a partir de los dos años. Objetivo. Establecer unas recomendaciones de manejo del CBD derivado de la planta altamente purificado consensuadas por expertos españoles en el tratamiento de la epilepsia para su uso en pacientes con SD y SLG, basándose en su experiencia clínica y en la evidencia científica. Desarrollo. Reunión de consenso de un grupo de cuatro neurólogos y neuropediatras españoles expertos en el manejo de la epilepsia asociada al SD y el SLG y con experiencia clínica en el uso de CBD. Se debatió sobre diferentes áreas, incluyendo la posología (dosis de inicio, pauta de escalada), la eficacia (valoración de resultados e indicaciones para la suspensión del tratamiento) y la seguridad (evaluación, interacciones entre fármacos, manejo de efectos adversos). Conclusiones. Para optimizar el tratamiento con CBD, se recomienda una pauta lenta de escalada de dosis (de cuatro semanas o más) hasta alcanzar la dosis máxima recomendada o el efecto deseado, reducir los fármacos anticrisis epilépticas concomitantes si aparecen efectos adversos por interacciones y mantener el tratamiento al menos seis meses si se tolera. La eficacia y la seguridad del CBD deben evaluarse de forma individual, considerando el beneficio y el riesgo para cada paciente.
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Anticonvulsivantes/uso terapéutico , Cannabidiol/uso terapéutico , Epilepsias Mioclónicas/tratamiento farmacológico , Síndrome de Lennox-Gastaut/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Cannabidiol/administración & dosificación , Cannabidiol/efectos adversos , Clobazam/administración & dosificación , Clobazam/uso terapéutico , Clonazepam/administración & dosificación , Clonazepam/uso terapéutico , Diazepam/administración & dosificación , Diazepam/uso terapéutico , Dioxolanos/administración & dosificación , Dioxolanos/uso terapéutico , Esquema de Medicación , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Fenobarbital/administración & dosificación , Fenobarbital/uso terapéutico , Pirrolidinonas/administración & dosificación , Pirrolidinonas/uso terapéutico , España , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Ácido Valproico/administración & dosificación , Ácido Valproico/uso terapéuticoRESUMEN
ABSTRACT: The aim of this study was to explore the compliance of epilepsy patients in the Phenobarbital Epilepsy Management Project in a rural area of China and its influencing factors, so as to provide the basis for further strategies.A retrospective study researching on the compliance of epilepsy patients in the Phenobarbital Epilepsy Management Project of Rural China was conducted. The Nan County, Hunan Province as a typical rural China was selected as the study site. We collected the compliance and other relative factors from 2017 to 2019 though the Phenobarbital Epilepsy Management Project data system.The good compliance patients in the Phenobarbital Epilepsy Management Project in a rural area of China were 98.99% (393/397); only 4 cases had poor compliance. The factors affecting the compliance of epilepsy patients were "adverse reactions of digestive tract symptoms," "how the patient felt physically, mentally, or working and learning ability during this period," and "the ratio of the attack to the previous one."The rate of good compliance among the epilepsy patients in the Phenobarbital Epilepsy Management Project in a rural area of China was high. More attention to education, patients' psychology, and the curative effect of family members may improve the compliance of patients with epilepsy further.
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Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Cooperación del Paciente/estadística & datos numéricos , Fenobarbital/uso terapéutico , Adolescente , Adulto , Anticonvulsivantes/administración & dosificación , Niño , Preescolar , China , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Fenobarbital/administración & dosificación , Estudios Retrospectivos , Población Rural , Adulto JovenRESUMEN
PURPOSE: The concomitant use of direct oral anticoagulants (DOAC) and strong P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) inducers may lead to reduced DOAC levels and therapeutic failure. This study aimed to describe DOAC concentrations in patients receiving strong P-gp and CYP3A4 inducers, in relation to individual risk factors for high or low DOAC levels. METHODS: We retrospectively identified hospitalized patients simultaneously receiving a DOAC and carbamazepine, phenobarbital, phenytoin, or rifampicin between 2016 and 2021. Among them, patients who underwent DOAC measurement at steady state were included. DOAC peak or trough levels were compared with on-therapy ranges observed in pivotal trials. Individual risk factors for high or low DOAC levels were identified. RESULTS: We included 17 patients (median age 75 years), mainly receiving apixaban and carbamazepine. For 5 patients (29%), DOAC trough or peak level was below the expected range. Among the remaining 12 patients, 8 had at least one measurement in the lower quartile of the range. The median number of risk factors for drug accumulation was 0 (range 0-1) in patients with ≥1 measurement below the range and 2 (range 0-3) in other patients. DOAC measurement led to treatment adjustments in 9 patients (DOAC dose increase or switch). CONCLUSION: Our data suggest a significant risk of reduced DOAC levels in patients taking strong P-gp and CYP3A4 inducers, especially those without risk factors for drug accumulation. DOAC measurement could help manage this relevant drug-drug interaction.
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Anticoagulantes/administración & dosificación , Inductores de las Enzimas del Citocromo P-450/administración & dosificación , Administración Oral , Anciano , Carbamazepina/administración & dosificación , Interacciones Farmacológicas , Monitoreo de Drogas , Femenino , Humanos , Masculino , Fenobarbital/administración & dosificación , Fenitoína/administración & dosificación , Estudios Retrospectivos , Rifampin/administración & dosificaciónRESUMEN
BACKGROUND: Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities. This is an updated version of the Cochrane Review previously published in 2018. OBJECTIVES: To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease). SEARCH METHODS: For the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and proportion of participants experiencing adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to there being limited available data. MAIN RESULTS: We included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low. AUTHORS' CONCLUSIONS: This review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine. Large RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.
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Enfermedad de Alzheimer/complicaciones , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Lamotrigina/uso terapéutico , Levetiracetam/uso terapéutico , Fenobarbital/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticonvulsivantes/administración & dosificación , Cognición/efectos de los fármacos , Depresión/complicaciones , Depresión/tratamiento farmacológico , Femenino , Humanos , Lamotrigina/administración & dosificación , Levetiracetam/administración & dosificación , Masculino , Fenobarbital/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención SecundariaRESUMEN
The sodium-potassium-chloride (Na-K-Cl) cotransporter NKCC1 is found in the plasma membrane of a wide variety of cell types, including neurons, glia and endothelial cells in the brain. Increased expression of neuronal NKCC1 has been implicated in several brain disorders, including neonatal seizures and epilepsy. The loop diuretic and NKCC inhibitor bumetanide has been evaluated as an antiseizure agent alone or together with approved antiseizure drugs such as phenobarbital (PB) in pre-clinical and clinical studies with varying results. The equivocal efficacy of bumetanide may be a result of its poor brain penetration. We recently reported that the loop diuretic azosemide is more potent to inhibit NKCC1 than bumetanide. In contrast to bumetanide, azosemide is not acidic, which should favor its brain penetration. Thus, azosemide may be a promising alternative to bumetanide for treatment of brain disorders such as epilepsy. In the present study, we determined the effect of azosemide and bumetanide on seizure threshold in adult epileptic mice. A structurally related non-acidic loop diuretic, torasemide, which also blocks NKCC1, was included in the experiments. The drug effects were assessed by determing the maximal electroshock seizure threshold (MEST) in epileptic vs. nonepileptic mice. Epilepsy was induced by pilocarpine, which was shown to produce long-lasting increases in NKCC1 in the hippocampus, whereas MEST did not alter NKCC1 mRNA in this region. None of the three loop diuretics increased MEST or the effect of PB on MEST in nonepileptic mice. In epileptic mice, all three diuretics significantly increased PB's seizure threshold increasing efficacy, but the effect was variable upon repeated MEST determinations and not correlated with the drugs' diuretic potency. These data may indicate that inhibition of NKCC1 by loop diuretics is not an effective means of increasing seizure threshold in adult epilepsy.
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Bumetanida/administración & dosificación , Fenobarbital/administración & dosificación , Convulsiones/tratamiento farmacológico , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/administración & dosificación , Miembro 2 de la Familia de Transportadores de Soluto 12 , Sulfanilamidas/administración & dosificación , Torasemida/administración & dosificación , Animales , Anticonvulsivantes/administración & dosificación , Quimioterapia Combinada , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Epilepsia/metabolismo , Femenino , Ratones , Pilocarpina/toxicidad , Convulsiones/inducido químicamente , Convulsiones/genética , Convulsiones/metabolismo , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: The safety of combining buprenorphine with a benzodiazepine or barbiturate in the treatment of concurrent alcohol and opioid withdrawal has not been well established. In this study we examine a cohort of patients treated with buprenorphine and phenobarbital or benzodiazepines for co-occurring opioid and alcohol withdrawal. METHODS: This is a retrospective cohort study of ED patients treated for opioid and alcohol withdrawal from January through December 2018. The primary outcome was unexpected airway intervention, or the administration of naloxone for respiratory depression. RESULTS: There were 16 patients treated for opioid and alcohol withdrawal. The mean age was 44.3 (standard deviation [SD] 13.1), 12 (75.0%) were male, and 8 (50.0%) of the patients were admitted to the hospital. For opioid withdrawal, six patients received intravenous buprenorphine, with doses between 0.3 mg to 1.8 mg; 12 patients received sublingual buprenorphine, with doses between 4 mg to 32 mg. For alcohol withdrawal, 10 patients received lorazepam with doses between 1 mg and 8 mg; 10 patients received phenobarbital with doses between 260 mg to 1040 mg. There were no unexpected airway interventions related to medications used for opioid or alcohol withdrawal. One patient with severe pneumonia was an expected intubation for respiratory failure. CONCLUSIONS: We describe a cohort of patients treated for opioid and alcohol withdrawal in the ED. There were no serious adverse events related to the medications used to treat opioid or alcohol withdrawal. Further work should assess optimal use of medical therapy for opioid and alcohol withdrawal and the transition to maintenance treatment for substance use disorders.
Asunto(s)
Trastornos Relacionados con Alcohol/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Adulto , Anciano , Buprenorfina/administración & dosificación , Servicio de Urgencia en Hospital , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Lorazepam/administración & dosificación , Masculino , Persona de Mediana Edad , Antagonistas de Narcóticos/administración & dosificación , Fenobarbital/administración & dosificación , Estudios RetrospectivosRESUMEN
BACKGROUND: Epilepsy with myoclonic absences (EMA) is a rare childhood-onset syndrome characterized by absences of responsiveness accompanied by bilateral rhythmic clonic-like myoclonic jerks. Herein, we describe the case of a child with EMA, resistant to multiple commonly used antiepileptic drugs, in whom low-dose phenobarbital unexpectedly achieved complete remission of epilepsy. CASE REPORT: A 10-year-old boy was referred to our hospital because of pharmaco-resistant frequent myoclonic absence seizures (MASs) and occasional generalized tonic-clonic seizures (GTCSs) that had commenced at the age of 7 years. Antiepileptic drugs including valproate sodium (VPA), levetiracetam, ethosuximide (ESM), clobazam, zonisamide, topiramate, clonazepam and lamotrigine were tested without significant effects. At the age of 8 years, phenobarbital was added to the VPA and ESM and increased to 1.2 mg/kg/day (blood concentration 8.6 µg/mL), which suppressed MASs completely within 1 month, and epileptic discharges on electroencephalography (EEG) within 5 months. To date, the boy has been seizure-free with normal EEG for 2 years. CONCLUSION: Phenobarbital is a potential therapeutic option for pharmaco-resistant EMA.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsia Tipo Ausencia/tratamiento farmacológico , Fenobarbital/administración & dosificación , Niño , Humanos , MasculinoRESUMEN
BACKGROUND: Due to enhancing serotonergic and noradrenergic neurotransmission, moclobemide may influence seizure phenomena. In this study, we examined the effect of both acute and chronic treatment with moclobemide on seizures and the action of first-generation antiepileptic drugs: valproate, carbamazepine, phenobarbital and phenytoin. METHODS: The effect of moclobemide on seizures was assessed in the electroconvulsive threshold test, while its influence on antiepileptic drugs was estimated in the maximal electroshock test in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay. RESULTS: Given acutely, moclobemide at 62.5 and 75 mg/kg increased the electroconvulsive threshold. In contrast, chronic treatment with moclobemide up to 75 mg/kg did not influence this parameter. Acute moclobemide applied at subthreshold doses (up to 50 mg/kg) enhanced the antielectroshock effects of carbamazepine, valproate and phenobarbital. Chronic moclobemide (37.5-75 mg/kg) increased the action of all four antiepileptic drugs. All revealed interactions, except these between moclobemide and phenobarbital, seem to have pharmacokinetic nature, because the antidepressant drug, either in acute or in chronic treatment, increased the brain concentrations of respective antiepileptic drugs. In terms of undesired neurotoxic effects, acute and chronic moclobemide, antiepileptic drugs, and their combinations did not produce significant motor or long-term memory impairment. CONCLUSIONS: Acute and chronic therapy with moclobemide can increase the effectiveness of some antiepileptic drugs against the maximal electroshock test. In mice, this effect was, at least partially, due to pharmacokinetic interactions. So far as the results of experimental studies can be transferred to clinical conditions, moclobemide seems safe for the application in patients with epilepsy and depression. Possibly, in the case of certain antiepileptic drugs combined with moclobemide, their doses should be adjusted downwards.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Carbamazepina/administración & dosificación , Electrochoque , Moclobemida/administración & dosificación , Inhibidores de la Monoaminooxidasa/administración & dosificación , Fenobarbital/administración & dosificación , Fenitoína/administración & dosificación , Convulsiones/tratamiento farmacológico , Ácido Valproico/administración & dosificación , Animales , Encéfalo/metabolismo , Carbamazepina/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Epilepsia/tratamiento farmacológico , Femenino , Masculino , Memoria a Largo Plazo/efectos de los fármacos , Ratones , Moclobemida/efectos adversos , Inhibidores de la Monoaminooxidasa/efectos adversos , Actividad Motora/efectos de los fármacos , Fenobarbital/metabolismo , Fenitoína/metabolismo , Ácido Valproico/metabolismoRESUMEN
The objective of this study was to describe the pharmacokinetics (PK) of intravenous phenobarbital in neonates and infants on extracorporeal membrane oxygenation (ECMO) and to provide dosing recommendations in this population. We performed a retrospective single-center PK study of phenobarbital in neonates and infants on ECMO between January 1, 2014, and December 31, 2018. We developed a population PK model using nonlinear mixed-effects modeling, performed simulations using the final PK parameters, and determined optimal dosing based on attainment of peak and trough concentrations between 20 and 40 mg/L. We included 35 subjects with a median (range) age and weight of 14 days (1-154 days) and 3.4 kg (1.6-8.1 kg), respectively. A total of 194 samples were included in the analysis. Five children (14%) contributing 30 samples (16%) were supported by continuous venovenous hemodiafiltration (CVVHDF). A 1-compartment model best described the data. Typical clearance and volume of distribution for a 3.4-kg infant were 0.038 L/h and 3.83 L, respectively. Clearance increased with age and CVVHDF. Although on ECMO, phenobarbital clearance in children on CVVHDF was 6-fold higher than clearance in children without CVVHDF. In typical subjects, a loading dose of 30 mg/kg/dose followed by maintenance doses of 6-7 mg/kg/day administered as divided doses every 12 hours reached goal concentrations. Age did not impact dosing recommendations. However, higher doses were needed in children on CVVHDF. We strongly recommend therapeutic drug monitoring in children on renal replacement therapy (excluding slow continuous ultrafiltration) while on ECMO.
Asunto(s)
Terapia de Reemplazo Renal Continuo/métodos , Oxigenación por Membrana Extracorpórea , Modelos Biológicos , Fenobarbital/farmacocinética , Administración Intravenosa , Factores de Edad , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Simulación por Computador , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Dinámicas no Lineales , Fenobarbital/administración & dosificación , Estudios Retrospectivos , Distribución TisularRESUMEN
OBJECTIVE: To assess the effect of an acidic beverage (Orange juice) on the change in serum Phenobarbital concentrations in children with seizure who take Phenobarbital as the main treatment. METHODS: We did a parallel design and placebo controlled randomized clinical trial. Patients attending Heshmatiyeh Hospital (Iran) were recruited from October 2016 to December 2017. Forty patients randomly assigned to either experimental group or control group. Firstly, 5 mL blood sample was taken from both groups to measure serum Phenobarbital concentration before experiment. Then, one oral dose of Phenobarbital (2.5 mg/kg) with 100 mL of corporate Orange juice (pH = 3.5) (experiment group) or 100 mL of mineral water (neutral pH) (control group) was given to each group, respectively. After 2 h of administration, another blood sample was taken. The high-performance liquid chromatographic system was used for measurement of serum Phenobarbital concentration. RESULTS: There was significant increase in serum Phenobarbital concentrations after taking Phenobarbital in experiment group in comparison to control group. Statistical analysis revealed a significant increase in change of serum Phenobarbital concentrations in experiment group versus control group. CONCLUSION: The results of the current trial indicate that the level of serum Phenobarbital in the experiment group was higher than that of control group.
Asunto(s)
Anticonvulsivantes/sangre , Citrus sinensis , Jugos de Frutas y Vegetales , Aguas Minerales/administración & dosificación , Fenobarbital/sangre , Convulsiones/tratamiento farmacológico , Adolescente , Anticonvulsivantes/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Fenobarbital/administración & dosificación , Método Simple CiegoRESUMEN
Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Benzodiazepinas/administración & dosificación , Servicios Médicos de Urgencia , Levetiracetam/administración & dosificación , Fenobarbital/administración & dosificación , Guías de Práctica Clínica como Asunto , Estado Epiléptico/tratamiento farmacológico , Administración Intranasal , Administración Rectal , Adulto , Anticonvulsivantes/uso terapéutico , Benzodiazepinas/uso terapéutico , Niño , Estudios Transversales , Diazepam/administración & dosificación , Diazepam/uso terapéutico , Humanos , Inyecciones Intramusculares , Inyecciones Intravenosas , Levetiracetam/uso terapéutico , Lorazepam/administración & dosificación , Lorazepam/uso terapéutico , Midazolam/administración & dosificación , Midazolam/uso terapéutico , Fenobarbital/uso terapéutico , Estado Epiléptico/diagnóstico , Estados UnidosRESUMEN
Cysticercosis is a neglected tropical disease set as health priority by WHO. Most of the reported cases included isolated types of cysticercosis affecting the skin, the eyes or the brain . Disseminated types, however, are rare. We here report a case of disseminated cysticercosis affecting the brain, the eyes and the skin in a Senegalese female patient aged 66 years admitted with headaches and chronic seizures. Clinical examination showed cerebellar syndrome associated with generalized and painless nodular subcutaneous lesions. Diagnosis was confirmed based on histopathological examination of skin biopsy which showed cysticerci. Patient's outcome was good under albendazole therapy.
Asunto(s)
Encéfalo/parasitología , Cisticercosis/diagnóstico , Ojo/parasitología , Piel/parasitología , Anciano , Albendazol/administración & dosificación , Encéfalo/patología , Cisticercosis/tratamiento farmacológico , Cisticercosis/patología , Diagnóstico Diferencial , Ojo/patología , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/tratamiento farmacológico , Infecciones Parasitarias del Ojo/patología , Femenino , Cefalea/diagnóstico , Cefalea/tratamiento farmacológico , Cefalea/parasitología , Humanos , Neurocisticercosis/diagnóstico , Neurocisticercosis/tratamiento farmacológico , Neurocisticercosis/patología , Fenobarbital/administración & dosificación , Prednisolona/administración & dosificación , Convulsiones/diagnóstico , Convulsiones/tratamiento farmacológico , Convulsiones/parasitología , Senegal , Piel/patología , Enfermedades Cutáneas Parasitarias/diagnóstico , Enfermedades Cutáneas Parasitarias/tratamiento farmacológicoRESUMEN
Organophosphate (OP) exposure induces status epilepticus (SE), a medical emergency with high morbidity and mortality. Current standard medical countermeasures lose efficacy with time so that treatment delays, in the range of tens of minutes, result in increasingly poor outcomes. As part of the Countermeasures Against Chemical Threats Neurotherapeutics Screening Program, we previously developed a realistic model of delayed treatment of OP-induced SE using the OP diisopropyl fluorophosphate (DFP) to screen compounds for efficacy in the termination of SE and elimination of neuronal death. Male rats were implanted for electroencephalogram (EEG) recordings 7 days prior to experimentation. Rats were then exposed to DFP, and SE was induced for 60 minutes and then treated with midazolam (MDZ) plus one of three antiseizure drugs (ASDs)-phenobarbital (PHB), memantine (MEM), or dexmedetomidine (DMT)-in conjunction with antidotes. EEG was recorded for 24 hours, and brains were stained with Fluoro-Jade B for quantification of degenerating neurons. We found that PHB + MDZ induced a prolonged suppression of SE and reduced neuronal death. MEM + MDZ treatment exacerbated SE and increased mortality; however, surviving rats had fewer degenerating neurons. DMT + MDZ significantly suppressed SE with only a minimal reduction in neuronal death. These data demonstrate that delayed treatment of OP-induced SE with other ASDs, when added to MDZ, can achieve greater seizure suppression with additional reduction in degenerating neurons throughout the brain compared with MDZ alone. The effect of a drug on the severity of seizure activity did not necessarily determine the drug's effect on neuronal death under these conditions. SIGNIFICANCE STATEMENT: This study assesses the relative effectiveness of three different delayed-treatment regimens for the control of organophosphate-induced status epilepticus and reduction of subsequent neuronal death. The data demonstrate the potential for highly effective therapies despite significant treatment delay and a potential disconnect between seizure severity and neuronal death.