Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.184
Filtrar
1.
Rev Fac Cien Med Univ Nac Cordoba ; 77(3): 211-213, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32991111

RESUMO

INTRODUCTION: The anticonvulsant hypersensitivity syndrome is a rare adverse reaction in which the skin, lymph nodes and internal organs are affected. It is usually caused by classic anticonvulsants such as phenytoin, carbamazepine or phenobarbital. CASE REPORT: Here we present the case of a 25-year-old woman from Córdoba, Argentina, who suffered a severe reaction to oxcarbazepine with a rash, lymphadenopathy, hepatitis and an unusual analytic. Clinical abnormalities were reversed after oxcarbazepine was terminated and treatment with diphenhydramine and dexamethasone was initiated. DISCUSSION: DRESS syndrome is a hypersensitivity reaction that takes weeks to manifest, and is characterized by rash, leukocytosis with eosinophilia, adenopathies, liver involvement, and reactivation of the herpes virus 6, being more frequent in carbamazepine or phenytoin, and in rare cases to oxcarbazepine. CONCLUSIONS: In general, this strong medicine is not taken into account as a cause of hypersensitivity, reports suggest that it could be related to cases similar to this one, and studies that are more targeted are required, due to the morbidity and mortality of the syndrome.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Adulto , Anticonvulsivantes/efeitos adversos , Argentina , Carbamazepina/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Feminino , Humanos , Fenitoína/efeitos adversos
4.
Lancet ; 395(10231): 1217-1224, 2020 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-32203691

RESUMO

BACKGROUND: Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. METHODS: In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18-65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075. FINDINGS: Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18-65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41-62) of children, 44% (33-55) of adults, and 37% (19-59) of older adults; with fosphenytoin in 49% (38-61) of children, 46% (34-59) of adults, and 35% (17-59) of older adults; and with valproate in 52% (41-63) of children, 46% (34-58) of adults, and 47% (25-70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. INTERPRETATION: Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. FUNDING: National Institute of Neurological Disorders and Stroke, National Institutes of Health.


Assuntos
Anticonvulsivantes/administração & dosagem , Levetiracetam/administração & dosagem , Fenitoína/análogos & derivados , Estado Epiléptico/tratamento farmacológico , Ácido Valproico/administração & dosagem , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Lactente , Levetiracetam/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fenitoína/administração & dosagem , Fenitoína/efeitos adversos , Ácido Valproico/efeitos adversos , Adulto Jovem
5.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
6.
Am J Case Rep ; 21: e919828, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31996666

RESUMO

BACKGROUND Phenytoin is an antiepileptic drug that is usually prescribed as a prevention treatment for tonic-clonic seizures or partial seizures, and as a prophylaxis for the neurosurgical related seizures. Phenytoin administration has several drawbacks; one drawback phenytoin-induced thrombocytopenia, which is a rare and significant adverse event. We report a rare adverse event after phenytoin prophylaxis therapy after a brain tumor debulking surgery, which resulted in severe unpredicted thrombocytopenia. CASE REPORT A 40-year-old male with no known health problems started to have an on/off headaches and loss of memory. Clinical investigations revealed a right frontal brain lesion. On the first day of admission, the patient was managed on neurosurgical seizure prophylaxis therapy of 100 mg intravenous phenytoin every 8 hours and 4 mg oral dexamethasone every 6 hours. On the fifth day of hospital admission, the patient underwent tumor debulking surgery. Twenty-four hours post-surgery, the patient's platelet level dropped to 26×109/L. Severe thrombocytopenia was managed first by transfusion of 17 units of platelets and by cessation of intravenous phenytoin plus the starting of 500 mg levetiracetam orally twice daily. Further management included infusion of 34 grams (0.4 g/kg) intravenous immunoglobulin (IVIG) over 5 days. Five days later, the patient gradually recovered with a platelet count of 239×109/L. CONCLUSIONS Phenytoin-induced thrombocytopenia is considered a rare event, but it has life-threatening consequences. The first and cornerstone management of this event is the cessation of phenytoin, followed by consideration of appropriate management based on the level of thrombocytopenia severity, and avoiding concomitant therapy of phenytoin and the use of dexamethasone as neurosurgical-related seizure prophylaxis.


Assuntos
Anticonvulsivantes/efeitos adversos , Neoplasias Encefálicas/cirurgia , Procedimentos Cirúrgicos de Citorredução , Fenitoína/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Trombocitopenia/induzido quimicamente , Adulto , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Levetiracetam/uso terapêutico , Masculino
7.
PLoS One ; 15(1): e0227359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31899779

RESUMO

OBJECTIVE: Epilepsy management especially in developing country is challenging. Seizures recurrence can be caused by both drug and non-drug related problems such as inadequate antiepileptic regimens, adverse drug reaction and poor adherence. Patient treatment satisfaction also affects the treatment out comes by improving medication adherence. This study aimed to assess drug therapy problems (DTPs) and treatment satisfaction among ambulatory epileptic patients at Tikur Anbessa Specialized Hospital. METHODS: A prospective cross-sectional study was conducted on 291 epileptic patients. Data was collected through patient interview and medical charts review. DTPs were identified based on the standard treatment guidelines and Micromedex® was used as drug interaction checker. Cipolle DTPs classification was used to classify the DTPs and Treatment Satisfaction with Medicine Questionnaire (SATMED-Q) was used to assess treatment satisfaction. Binary logistic regressions were utilized to identify the associated factors. RESULTS: Phenobarbital 195 (67%) and phenytoin 97 (33.3%) were the most frequently prescribed antiepileptic medications as monotherapy or combination therapy. Only 54 (18.6%) of the study participants had controlled seizure. DTP was found in 205(70.4%) of the study participants. From 352 DTPs identified, adverse drug reaction 146 (41.5%) was the leading DTPs followed by ineffective drugs 98 (27.8%) drug interaction 45 (12.8%) and inappropriate dose 42(11.9%). Headache, depression and epigastric pain were frequently reported adverse drug reaction. Among the study participants 167 (57.3%) were adherent to their medications. The number of medications taken by the patients had significant association with occurrence of DTPs, whereas source of medication and seizure free periods were found to have significant association with poor adherence. The global patient satisfaction was (67.4%) and lower satisfaction rate was found with regard to impact on daily activities (62.0%), treatment effectiveness (64.7%) and medical care (65.9%). CONCLUSION: Prevalence of DTPs among ambulatory epileptic patients was high and about half of the patients were nona-dherent for their medication. The overall treatment satisfaction of the patients was suboptimal.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Adesão à Medicação , Satisfação Pessoal , Fenobarbital/efeitos adversos , Fenitoína/efeitos adversos , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Estudos Transversais , Interações Medicamentosas , Etiópia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
9.
Pharm. care Esp ; 22(2): 95-105, 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-196963

RESUMO

INTRODUCCIÓN: Se evaluaron las interacciones medicamentosas (IM) y el monitoreo terapéutico de fármacos (MTF) inadecuado como causa de problemas de efectividad y/o seguridad a la terapia antiepiléptica en un grupo de pacientes colombianos. MÉTODOS: Todos los casos de RAM y/o de fallo terapéutico (FT) fueron detectados por un médico farmacólogo mediante farmacovigilancia activa y validados con un farmacéutico. También se evaluaron las IM con la herramienta Lexicomp®, y los niveles plasmáticos de los antiepilépticos. RESULTADOS: 11 de los 77 sujetos (14,3%; IC95% 7,4 -24,1) tenía un problema de efectividad; 30 (39,0% IC95% 28,0 - 50,8) un problema de seguridad; y 30 pacientes (39,0% IC95% 28,0 - 50,8) un problema mixto de efectividad y seguridad. CONCLUSIÓN: En el 70% de los pacientes con RAM y en el 37% de los pacientes con FT el problema pudo deberse a una IM y/o a un MTF inadecuado o insuficiente. Se recomienda el acompañamiento de farmacia clínica para el manejo de pacientes con epilepsia


INTRODUCTION: Drug interactions (DI) and inappropriate therapeutic drug monitoring (TDM) were evaluated as cause of therapeutic failures (TF) and/or adverse reactions to antiepileptic therapy (ADR) in a group of Colombian patients. METHODS: All cases of ADR and/or therapeutic failure (TF) were detected by a pharmacologist through active pharmacovigilance and validated with a pharmacist. DI were also evaluated with the Lexicomp® tool and plasma levels of antiepileptics were assessed. RESULTS: 11 of the 77 subjects (14.3%) had TF; 30 of them (39%) had at least one ADR. inally, 30 patients (39%) had TF and ADR at the same time. CONCLUSION: In 70% of patients with ADR and in 37% of patients with TF, the problem could be related to a drug interaction or inadequate therapeutic drug monitoring. The involvement of Clinical Pharmacy service is recommended for the management of patients with epilepsy


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Epilepsia/tratamento farmacológico , Interações Medicamentosas , Monitoramento de Medicamentos , Anticonvulsivantes/efeitos adversos , Farmacovigilância , Fenitoína/efeitos adversos , Resultado do Tratamento , Anticonvulsivantes/sangue , Colômbia
10.
BMJ Case Rep ; 12(12)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31811093

RESUMO

Hepatic cytochrome P450 enzyme induction is associated with certain antiepileptic drugs (AEDs) and may result in hypocalcaemia secondary to vitamin D deficiency. We report a case of a 44-year-old man with a history of epilepsy, who presented with breakthrough seizures after having previously been seizure-free for 11 years. Investigations revealed severe hypocalcaemia with a corrected calcium of 1.7 mmol/L. His phenytoin dose was increased, and he was started on calcium supplementation. He was discharged with a corrected calcium level of 2.05 mmol/L but was readmitted 1 week later with further seizures and a corrected calcium of 1.89 mmol/L. 25-hydroxyvitamin D was low. AED-induced hypocalcaemia was suspected, which had been made paradoxically worse by the increase in phenytoin dose. Alfacalcidol was prescribed and he was switched from phenytoin to levetiracetam with resolution of hypocalcaemia and no further seizures. The authors recommend screening for calcium and vitamin D deficiency in patients on enzyme-inducing AEDs.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Hipocalcemia/diagnóstico , Fenitoína/efeitos adversos , Convulsões/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Hipocalcemia/sangue , Hipocalcemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade
11.
N Engl J Med ; 381(22): 2103-2113, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31774955

RESUMO

BACKGROUND: The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied. METHODS: In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death. RESULTS: A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant. CONCLUSIONS: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).


Assuntos
Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Fenitoína/análogos & derivados , Estado Epiléptico/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Benzodiazepinas/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Humanos , Hipotensão/induzido quimicamente , Infusões Intravenosas , Injeções Intramusculares , Levetiracetam/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fenitoína/efeitos adversos , Fenitoína/uso terapêutico , Ácido Valproico/efeitos adversos , Adulto Jovem
13.
Am J Case Rep ; 20: 1572-1575, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31653824

RESUMO

BACKGROUND Stress cardiomyopathy (SCM) is a transient dysfunction of the left ventricle due to physical or emotional triggers that produces a range of electrocardiogram (ECG) changes. While ST-segment elevation or depression often leads to more urgent investigation and diagnosis, T-wave inversions can result in delayed diagnosis. CASE REPORT A 44-year-old woman with a prior left middle cerebral artery septic embolic stroke from endocarditis resulting in residual dense right sided hemiparesis and aphasia was admitted to the hospital for treatment of Staphylococcus aureus bacteremia. While hospitalized, she experienced a generalized seizure that was aborted with lorazepam and then loaded with phenytoin. Her ECG following the seizure showed a prolonged QT interval, for which her methadone that she was stabilized on during hospitalization was held. Her ECG to follow-up on her QT interval 25 h following the seizure showed new diffuse symmetric deep T-wave inversions. While initially believed to be due to the either the discontinuation of methadone or initiation of phenytoin, retrospective analysis revealed that these changes were more suggestive of a missed SCM. CONCLUSIONS We report a patient who experienced a generalized seizure resulting in diffuse, symmetric, deep T-wave inversions that were incorrectly attributed to medication effects before identifying the likely diagnosis of SCM. Fortunately for this patient, there were no consequences of the delayed diagnosis, but this case emphasises the importance of considering SCM following a generalized seizure in any patient with ECG abnormalities.


Assuntos
Eletrocardiografia , Convulsões/etiologia , Cardiomiopatia de Takotsubo/diagnóstico , Adulto , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Humanos , Metadona/uso terapêutico , Fenitoína/efeitos adversos
14.
Int J Immunopathol Pharmacol ; 33: 2058738419828259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31663446

RESUMO

Several distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers, caused gingival overgrowth. One of the main drugs associated with the gingival overgrowth is the anti-epileptic such as phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. In our study, we evaluate the effect of phenytoin, a drug whose active substance is phenytoin, on gingival fibroblasts of healthy volunteers. Gene expression of 29 genes was investigated in gingival fibroblasts' cell culture treated with phenytoin compared with untreated cells. Among the studied genes, only 13 genes (CXCL5, CXCL10, CCR1, CCR3, CCR5, CCR6, IL-1A, IL-1B, IL-5, IL-7, IL-6R, BMP-2, and TNFSF-10) were statistically significant. All but one gene resulted downregulated after 24 h of treatment with phenytoin. BPM2 was the only, although weakly, up-expressed gene. Probably, we have not highlighted overexpression of the other inflammatory molecules because the study was performed on healthy people. Many studies show that phenytoin induces the overexpression of these cytokines but, probably, in our study, the drug does not have the same effect because we used gingival fibroblasts of healthy people.


Assuntos
Anticonvulsivantes/efeitos adversos , Gengiva/efeitos dos fármacos , Crescimento Excessivo da Gengiva/induzido quimicamente , Fenitoína/efeitos adversos , Adulto , Idoso , Células Cultivadas , Criança , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Expressão Gênica/efeitos dos fármacos , Gengiva/metabolismo , Crescimento Excessivo da Gengiva/metabolismo , Voluntários Saudáveis , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Masculino , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
15.
J Med Case Rep ; 13(1): 250, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31401974

RESUMO

BACKGROUND: Various antiepileptic drugs can potentially cause psychiatric side effects in patients with epilepsy, but the precise mechanism of these actions remains unknown. In recent years, the common polymorphism C677T in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has attracted attention for its role in the onset of psychiatric diseases. MTHFR and several vitamins (as cofactors) are crucial for remethylation of homocysteine via folate and homocysteine metabolism. We report a case of a Japanese patient who presented with reversible schizophrenia-like symptoms during antiepileptic drug therapy. CASE PRESENTATION: Our patient had frontal lobe epilepsy and had been treated with several antiepileptic drugs since the age of 13 years. He developed auditory hallucinations and multiple personalities at 17 years of age, several months after the initiation of phenytoin and phenobarbital, despite these antiepileptic drugs being used within the therapeutic ranges. Genetic analysis revealed that he was homozygous for the C677T polymorphism of MTHFR. Hyperhomocysteinemia, hypomethionemia, and multiple vitamin deficiencies, including folate, riboflavin, and pyridoxal, were identified at the age of 23 years. Vitamin supplementation and alteration of the antiepileptic drugs improved his psychotic symptoms. Multiple vitamin deficiencies with homozygous MTHFR C677T should be considered in patients presenting with schizophrenia-like symptoms during antiepileptic drug therapy. CONCLUSIONS: To the best of our knowledge, this is the first report of antiepileptic drug-induced psychosis associated with homozygous C677T and multiple vitamin deficiencies. Our findings will contribute to the elucidation of the pathogenesis of the psychiatric side effects of antiepileptic drugs and lead to improved medical management for patients with epilepsy.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Fenobarbital/efeitos adversos , Fenitoína/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Adolescente , Deficiência de Vitaminas/complicações , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Polimorfismo Genético , Psicoses Induzidas por Substâncias/diagnóstico , Psicoses Induzidas por Substâncias/genética , Adulto Jovem
16.
Cochrane Database Syst Rev ; 7: CD001911, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31318037

RESUMO

BACKGROUND: This is an update of a Cochrane Review first published in 2002 and last updated in 2017. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, carbamazepine and phenytoin are commonly-used broad spectrum antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is a current first-line treatment for focal onset seizures in the USA and Europe. Phenytoin is no longer considered a first-line treatment, due to concerns over adverse events associated with its use, but the drug is still commonly used in low- to middle-income countries because of its low cost. No consistent differences in efficacy have been found between carbamazepine and phenytoin in individual trials; however, the confidence intervals generated by these trials are wide, and therefore, synthesising the data of the individual trials may show differences in efficacy. OBJECTIVES: To review the time to treatment failure, remission and first seizure with carbamazepine compared with phenytoin when used as monotherapy in people with focal onset seizures (simple or complex focal and secondarily generalised), or generalised onset tonic-clonic seizures (with or without other generalised seizure types). SEARCH METHODS: For the latest update, we searched the following databases on 13 August 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy's Specialised Register and CENTRAL; MEDLINE; the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov); and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing monotherapy with either carbamazepine or phenytoin in children or adults with focal onset seizures or generalised onset (tonic-clonic) seizures. DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD) review. Our primary outcome was time to treatment failure. Our secondary outcomes were time to first seizure post-randomisation, time to six-month remission, time to 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs), with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI. MAIN RESULTS: IPD were available for 595 participants out of 1102 eligible individuals, from four out of 11 trials (i.e. 54% of the potential data). For remission outcomes, a HR greater than 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes, a HR greater than 1 indicates an advantage for carbamazepine. Most participants included in analysis (78%) were classified as experiencing focal onset seizures at baseline and only 22% were classified as experiencing generalised onset seizures; the results of this review are therefore mainly applicable to individuals with focal onset seizures.Results for the primary outcome of the review were: time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type for 546 participants: 0.94, 95% CI 0.70 to 1.26, moderate-certainty evidence); time to treatment failure due to lack of efficacy (pooled HR adjusted for seizure type for 546 participants: 0.99, 95% CI 0.69 to 1.41, moderate-certainty evidence); both showing no clear difference between the drugs and time to treatment failure due to adverse events (pooled HR adjusted for seizure type for 546 participants: 1.27, 95% CI 0.87 to 1.86, moderate-certainty evidence), showing that treatment failure due to adverse events may occur earlier on carbamazepine than phenytoin, but we cannot rule out a slight advantage to carbamazepine or no difference between the drugs.For our secondary outcomes (pooled HRs adjusted for seizure type), we did not find any clear differences between carbamazepine and phenytoin: time to first seizure post-randomisation (582 participants): 1.15, 95% CI 0.94 to 1.40, moderate-certainty evidence); time to 12-month remission (551 participants): 1.00, 95% CI 0.79 to 1.26, moderate-certainty evidence); and time to six-month remission (551 participants): 0.90, 95% CI 0.73 to 1.12, moderate-certainty evidence).For all outcomes, results for individuals with focal onset seizures were similar to overall results (moderate-certainty evidence), and results for the small subgroup of individuals with generalised onset seizures were imprecise, so we cannot rule out an advantage to either drug, or no difference between drugs (low-certainty evidence). There was also evidence that misclassification of seizure type may have confounded the results of this review, particularly for the outcome 'time to treatment failure'. Heterogeneity was present in analysis of 'time to first seizure' for individuals with generalised onset seizures, which could not be explained by subgroup analysis or sensitivity analyses.Limited information was available about adverse events in the trials and we could not compare the rates of adverse events between carbamazepine and phenytoin. Some adverse events reported on both drugs were abdominal pain, nausea, and vomiting, drowsiness, motor and cognitive disturbances, dysmorphic side effects (such as rash). AUTHORS' CONCLUSIONS: Moderate-certainty evidence provided by this systematic review does not show any differences between carbamazepine and phenytoin in terms of effectiveness (retention) or efficacy (seizure recurrence and seizure remission) for individuals with focal onset or generalised onset seizures.However, some of the trials contributing to the analyses had methodological inadequacies and inconsistencies, which may have had an impact on the results of this review. We therefore do not suggest that results of this review alone should form the basis of a treatment choice for a person with newly-onset seizures. We did not find any evidence to support or refute current treatment policies. We implore that future trials be designed to the highest quality possible, with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Fenitoína/uso terapêutico , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Criança , Humanos , Fenitoína/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Convulsões/prevenção & controle , Falha de Tratamento , Resultado do Tratamento
17.
Br J Clin Pharmacol ; 85(9): 2163-2169, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31206740

RESUMO

Phenytoin drug reaction with eosinophilia and systemic symptoms (DRESS) in 3 Aboriginal Australians positive for HLA-B*56:02 has been previously reported. We report the allele frequency of HLA-B*56:02 in 2 South Australian populations, 1 Aboriginal (4.8%, 95% confidence interval 2.4-7.8%) and the other European (0%). We compared the frequency with publicly available information on HLA-B*56:02 status in other Indigenous Australian (n = 4) and European Australian cohorts (n = 1). In the Indigenous Australian cohorts, HLA-B*56:02 allele frequency ranged from 1.3 to 19%. We also describe an additional case of phenytoin DRESS (RegiSCAR DRESS score 7) in an Aboriginal Australian that was associated with HLA-B*56:02 and with CYP2C9*1/*3 genotype. In Aboriginal Australians, phenytoin DRESS appears distinctly linked to HLA-B*56:02 with an allele carriage rate substantially higher than in Europeans, but also with considerable regional variation. Investigations of human leucocyte antigen and other contributing genes and severe adverse drug reactions in understudied non-European populations are required to optimize safe medication use and inform risk mitigation strategies.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/genética , Predisposição Genética para Doença , Antígenos HLA-B/genética , Povos Indígenas/genética , Fenitoína/efeitos adversos , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Variação Biológica da População , Estudos de Coortes , Citocromo P-450 CYP2C9/genética , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Feminino , Frequência do Gene , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Indian J Pharmacol ; 51(2): 120-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31142948

RESUMO

Phenytoin is an anticonvulsant which is also a Class IB antiarrhythmic. Its common adverse drug reactions (ADRs) include gastrointestinal symptoms, psychiatric disorders, gingival hyperplasia, and rash. Bradycardia and hypotension following intravenous (IV) phenytoin are rare ADRs. We report the case of a 62-year-old female with subarachnoid hemorrhage and right bundle branch block, who developed sinus bradycardia and hypotension on administration of IV phenytoin. This case report serves as a note for caution on patient selection for the administration of phenytoin and highlights the need for specific guidelines on the same.


Assuntos
Anticonvulsivantes/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Fenitoína/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
20.
Lancet ; 393(10186): 2135-2145, 2019 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-31005386

RESUMO

BACKGROUND: Phenytoin is the current standard of care for second-line treatment of paediatric convulsive status epilepticus after failure of first-line benzodiazepines, but is only effective in 60% of cases and is associated with considerable adverse effects. A newer anticonvulsant, levetiracetam, can be given more quickly, is potentially more efficacious, and has a more tolerable adverse effect profile. We aimed to determine whether phenytoin or levetiracetam is the superior second-line treatment for paediatric convulsive status epilepticus. METHODS: ConSEPT was an open-label, multicentre, randomised controlled trial conducted in 13 emergency departments in Australia and New Zealand. Children aged between 3 months and 16 years, with convulsive status epilepticus that failed first-line benzodiazepine treatment, were randomly assigned (1:1) using a computer-generated permuted block (block sizes 2 and 4) randomisation sequence, stratified by site and age (≤5 years, >5 years), to receive 20 mg/kg phenytoin (intravenous or intraosseous infusion over 20 min) or 40 mg/kg levetiracetam (intravenous or intraosseous infusion over 5 min). The primary outcome was clinical cessation of seizure activity 5 min after the completion of infusion of the study drug. Analysis was by intention to treat. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12615000129583. FINDINGS: Between March 19, 2015, and Nov 29, 2017, 639 children presented to participating emergency departments with convulsive status epilepticus; 127 were missed, and 278 did not meet eligibility criteria. The parents of one child declined to give consent, leaving 233 children (114 assigned to phenytoin and 119 assigned to levetiracetam) in the intention-to-treat population. Clinical cessation of seizure activity 5 min after completion of infusion of study drug occurred in 68 (60%) patients in the phenytoin group and 60 (50%) patients in the levetiracetam group (risk difference -9·2% [95% CI -21·9 to 3·5]; p=0·16). One participant in the phenytoin group died at 27 days because of haemorrhagic encephalitis; this death was not thought to be due to the study drug. There were no other serious adverse events. INTERPRETATION: Levetiracetam is not superior to phenytoin for second-line management of paediatric convulsive status epilepticus. FUNDING: Health Research Council of New Zealand, A+ Trust, Emergency Medicine Foundation, Townsville Hospital Private Practice Fund, Eric Ormond Baker Charitable Fund, and Princess Margaret Hospital Foundation.


Assuntos
Anticonvulsivantes/administração & dosagem , Levetiracetam/administração & dosagem , Fenitoína/administração & dosagem , Estado Epiléptico/tratamento farmacológico , Adolescente , Idoso , Anticonvulsivantes/efeitos adversos , Austrália , Criança , Pré-Escolar , Esquema de Medicação , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Levetiracetam/efeitos adversos , Masculino , Nova Zelândia , Fenitoína/efeitos adversos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...