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valproate toxicity

Jia Liu, Lu-Ning Wang, Yu-Ping Wang
BACKGROUND: Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME. This is an updated version of the original Cochrane Review published in Issue 12, 2015. OBJECTIVES: To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME...
April 23, 2017: Cochrane Database of Systematic Reviews
T N Shiny, Vikram K Mahajan, Karaninder S Mehta, Pushpinder S Chauhan, Ritu Rawat, Rajni Sharma
AIM: To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. METHODS: Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant...
March 26, 2017: World Journal of Methodology
H Y Chong, Z Mohamed, L L Tan, D B C Wu, F H Shabaruddin, M Dahlui, Y D Apalasamy, S R Snyder, M S Williams, J Hao, L H Cavallari, N Chaiyakunapruk
BACKGROUND: Strong association was documented between human leukocyte antigen (HLA)-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Beyond Asia, the HLA testing is potentially valuable in many countries with increasingly diverse communities of Asian ancestry, to facilitate an early recognition of patient susceptibility to SCARs. OBJECTIVE: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/ toxic epidermal necrolysis in an ethnically-diverse Malaysian population...
March 27, 2017: British Journal of Dermatology
Jose Ramiro Espinoza-Zamora, Juan Labardini-Méndez, Alejandro Sosa-Espinoza, Celia López-González, Magnolia Vieyra-García, Myrna Candelaria, Valentin Lozano-Zavaleta, Diana Vanesa Toledano-Cuevas, Nidia Zapata-Canto, Eduardo Cervera, Alfonso Dueñas-González
OBJECTIVES: To evaluate the activity and safety of hydralazine and valproate (Transkrip) in cutaneous T-cell lymphoma (CTCL). METHODS: Previously untreated and progressive/refractory CTCL patients received hydralazine at 83 mg or 182 mg/day for slow and rapid acetylators respectively plus magnesium valproate at a total dose of 30 mg/Kg t.i.d daily in continuous 28-day cycles in this phase II study. The primary objective was overall response rate (ORR) measured by the modified severity weighted assessment tool (m-SWAT), secondary end-points were time to response (TTR), time to progression (TTP), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety...
April 2017: Expert Opinion on Investigational Drugs
Jerome Niquet, Roger Baldwin, Lucie Suchomelova, Lucille Lumley, Roland Eavey, Claude G Wasterlain
During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAA Rs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAA Rs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAA Rs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE...
April 2017: Epilepsia
Neetu Godhwani, Sami L Bahna
OBJECTIVE: To alert physicians about the peculiar adverse effects of antiepilepsy drugs (AEDs) on the immune system. DATA SOURCES: PubMed literature during the past 25 years. STUDY SELECTIONS: Reports and review articles on the hypersensitivities of AEDs and their effect on immunity. RESULTS: AEDs have significant effects on the immune system in the form of hypersensitivity or immune suppression. IgE-mediated reactions can be urticaria, angioedema, bronchospasm, or anaphylaxis...
December 2016: Annals of Allergy, Asthma & Immunology
Rafael García Carretero, Marta Romero Brugera, Monica Olid-Velilla, Inmaculada Salamanca-Ramirez
Haematological toxicity due to antiepileptic drugs is uncommon, but the increased risk of aplastic anaemia has been reported. Few case reports have been published regarding pancytopenia associated with levetiracetam treatment, and its intrinsic pathogenesis is still unknown. We describe the case of a woman aged 77 years who presented with abdominal pain and loss of appetite. She had been taking valproic acid, due to a previous episode of epileptic seizures, and presented with drowsiness and dizziness. Valproate was discontinued and therapy with levetiracetam was initiated...
December 7, 2016: BMJ Case Reports
Francesco Caponigro, Elena Di Gennaro, Franco Ionna, Francesco Longo, Corrado Aversa, Ettore Pavone, Maria Grazia Maglione, Massimiliano Di Marzo, Paolo Muto, Ernesta Cavalcanti, Antonella Petrillo, Fabio Sandomenico, Piera Maiolino, Roberta D'Aniello, Gerardo Botti, Rossella De Cecio, Nunzia Simona Losito, Stefania Scala, Annamaria Trotta, Andrea Ilaria Zotti, Francesca Bruzzese, Antonio Daponte, Ester Calogero, Massimo Montano, Monica Pontone, Gianfranco De Feo, Francesco Perri, Alfredo Budillon
BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds...
November 25, 2016: BMC Cancer
G Munch, N Godart
INTRODUCTION: Adolescence is a unique phase of the human developmental process. In adolescents, psychotropic medications may have different efficacy and tolerance profiles compared to those at other stages of the lifespan. Mood stabilizers are a complex pharmacological category including lithium, some anticonvulsants, and some second generation antipsychotics. Focusing on this class of pharmacological agents, we aim to answer the following questions: in which indications and according to which modalities should mood stabilizers be prescribed during adolescence? METHODS: Information was sought from the websites of the French Haute Autorité de santé (HAS) and Agence nationale de sécurité du médicament et des produits de santé (ANSM), the American Food and Drug Administration (FDA) and the British National Institute for Health and Clinical Excellence (NICE)...
November 18, 2016: L'Encéphale
M Hamza, S Halayem, R Mrad, S Bourgou, F Charfi, A Belhadj
BACKGROUND: The etiology of autism spectrum disorders (ASD) is complex and multifactorial, and the roles of genetic and environmental factors in its emergence have been well documented. Current research tends to indicate that these two factors act in a synergistic manner. The processes underlying this interaction are still poorly known, but epigenetic modifications could be the mediator in the gene/environment interface. The epigenetic mechanisms have been implicated in susceptibility to stress and also in the pathogenesis of psychiatric disorders including depression and schizophrenia...
September 27, 2016: L'Encéphale
Ajay Gupta, Amit Kumar, Andaleeb Abrari, Rana Patir, Sandeep Vaishya
BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Infants are in the high-risk category. Complete surgical resection is the single most important determinant of prognosis and survival in nonmetastatic disease. Infants with large primaries after incomplete resection/biopsy and poor general condition have bad prognosis. They are considered poor candidates for intensive chemotherapy involving high dose methotrexate/autologous stem cell transplantation as they are often unable to tolerate these aggressive regimens...
September 2016: World Neurosurgery
Rachel G Greenberg, Chiara Melloni, Huali Wu, Daniel Gonzalez, Lawrence Ku, Kevin D Hill, Christoph P Hornik, Michael Cohen-Wolkowiez, Jeffrey T Guptill
OBJECTIVES: Our study aimed to determine whether data obtained from the medical literature can be used to estimate the therapeutic index of 5 antiepileptic drugs (AEDs): carbamazepine, lamotrigine, phenobarbital, phenytoin, and valproate. METHODS: We performed a literature search using PubMed and EMBASE to collect published safety, efficacy, and therapeutic monitoring data for 5 AEDs and extracted all relevant information into a drug- and study-specific drug database...
September 2016: Clinical Neuropharmacology
Daniel Haranaka Funai, Florian Didier, Jaime Giménez, Santiago Esplugas, Pilar Marco, Amilcar Machulek
The abatement of valproic acid sodium salt (VA) via photo-Fenton process was investigated to evaluate the effect of irradiation type. Three different light sources have been used: UVA (black light blue lamps, BLB reactor), UVC (UVC reactor) and simulated sunlight in a Solarbox (SB). Using the highest concentrations of Fe(2+) (10mgL(-1)) and H2O2 (150mgL(-1)), 100% of VA degradation was observed in BLB and UVC devices, and 89.7% in Solarbox. Regarding mineralization, 67.4% and 76.4% of TOC conversion were achieved in BLB and UVC, respectively...
June 19, 2016: Journal of Hazardous Materials
Matthew D Hensley, Vikhyat S Bebarta, Douglas J Borys
OBJECTIVE: Significant adverse effects after acute pediatric methotrexate (MTX) exposures have been limited to parenteral exposures. Treatment recommendations for pediatric MTX exposures do not differentiate between routes of exposure. We report the incidence of significant clinical effects and drug-specific treatments reported in a large series of acute, pediatric MTX ingestions. METHODS: Poison center records of all MTX ingestions by patients younger than 17 years during 2000 to 2005 were collected from 6 poison centers...
October 2016: Pediatric Emergency Care
Nahla S El-Shenawy, Reham Z Hamza
BACKGROUND: This study investigated whether the combination of sodium valproate (SV) with L-cysteine (LC) can decrease the SV toxicity of kidneys. SV caused alternation in oxidative/antioxidant balance. METHODS: Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in kidney tissue, and enzymatic antioxidant activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase as well as total antioxidant capacity were evaluated in renal tissues...
September 1, 2016: Journal of Basic and Clinical Physiology and Pharmacology
Lay Kek Teh, Manikandan Selvaraj, Zakaria Bannur, Mohd Ikhwan Mohd Ismail, Hanip Rafia, Wan Chung Law, Sapiah Sapuan, Santhi Puvanarajah, Pakeer Shaik Syed Ali, Mohd Zaki Salleh
PURPOSE: The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated. METHODS: DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers. RESULTS: Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609...
2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Matthias Nissen, Sebastian M Buehler, Marco Stubbe, Jan Gimsa
We investigated the effects of acute valproate (VPA) on mouse embryonic primary cortex cells (MEPCs). Intracellular ATP concentrations were compared with changes in the mean action potential (AP) frequencies of MEPC networks growing on microelectrode arrays. Our data implies biphasic reactions towards increasing VPA concentrations for both parameters. Intracellular ATP and mean AP frequencies increased around characteristic concentrations of 0.15 and 0.07mM to hormetic plateaus of approx. 120% and 160% of their controls, before fading around 17 and 1...
June 2016: Bio Systems
P Ramey, M R Osborn, K M Lowen, R C Reed, B Abou-Khalil
OBJECTIVES: The objective of this study was to evaluate possible nonlinear lamotrigine (LTG) pharmacokinetics at elevated concentration. LTG is reported to have linear kinetics, so that elimination rate is linearly proportional to blood concentration and a change in dose is accompanied by a proportionate change in serum concentration. We encountered patients in whom LTG serum concentration increased dramatically in response to minor or no change in LTG dose. We studied this phenomenon in patients with LTG toxicity in one clinic...
February 2017: Acta Neurologica Scandinavica
Alberto Grande-Martín, José Manuel Pardal-Fernández, María Carmen Carrascosa-Romero, Carlos De Cabo
Antiepileptic drugs may occasionally increase seizure frequency or eliciting de novo seizure occurrence; the underlying mechanism of these effects is not known. The potential adverse effects of valproic acid in myoclonic astatic epilepsy have been noted by experienced clinicians in various different regions of the world, but this important observation has not been sufficiently reported. We present the case of tonic status epilepticus in an 8-year-old boy with Doose syndrome related to valproic acid. Valproic acid, such as others antiepileptic drugs, is liable to produce paradoxical effects such as the atypical seizures we report...
June 2016: Neuropediatrics
Catherine Chiron
INTRODUCTION: Stiripentol and vigabatrin are the two anticonvulsant drugs currently approved in severe infantile-onset epilepsies, respectively Dravet syndrome and infantile spasms. AREAS COVERED: For both, the indication was discovered by chance thanks to an exploratory study. Both demonstrated indisputable efficacy through randomized-controlled trials. Stiripentol as adjunctive therapy to clobazam and valproate performed better than placebo, and vigabatrin as first-line monotherapy better than the reference steroid therapy in spasms due to tuberous sclerosis...
June 2016: Expert Opinion on Pharmacotherapy
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