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valproate toxicity

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https://www.readbyqxmd.com/read/29159461/severe-hyperammonemic-encephalopathy-requiring-dialysis-aggravated-by-prolonged-fasting-and-intermittent-high-fat-load-in-a-ramadan-fasting-month-in-a-patient-with-cptii-homozygous-mutation
#1
P Phowthongkum, C Ittiwut, V Shotelersuk
BACKGROUND: Carnitine palmitoyltransferase II (CPTII) deficiency is a mitochondrial fatty acid oxidation disorder that can present antenatally as congenital brain malformations, or postnatally with lethal neonatal, severe infantile, or the most common adult myopathic forms. No case of severe hyperammonemia without liver dysfunction has been reported. CASE PRESENTATION: We described a 23-year-old man who presented to the emergency department with seizures and was found to have markedly elevation of serum ammonia...
November 21, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29119932/relevance-of-cyp2c9-function-in-valproate-therapy
#2
Katalin Monostory, Andrea Nagy, Katalin Toth, Tamas Budi, Adam Kiss, Mate Deri, Gabor Csukly
Genetic polymorphisms of drug metabolizing enzymes can substantially modify the pharmacokinetics of a drug and eventually its efficacy or toxicity; however, inferring a patient's drug metabolizing capacity merely from his or her genotype can lead to false prediction. Non-genetic host factors (age, sex, disease states) and environmental factors (nutrition, co-medication) can transiently alter the enzyme expression and activities resulting in genotype-phenotype mismatch. Although valproic acid is a well-tolerated anticonvulsant, pediatric patients are particularly vulnerable to valproate injury that can be partly attributed to the age-related differences in metabolic pathways...
November 9, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29049976/sodium-valproate-enhances-doxorubicin-induced-cognitive-dysfunction-in-wistar-rats
#3
Thaneshwar Verma, Sanchari Basu Mallik, G V Ramalingayya, Pawan G Nayak, Anoop Kishore, K Sreedhara R Pai, Krishnadas Nandakumar
BACKGROUND: Increasing number of scientific reports have highlighted the role of histone acetylation/deacetylation in neurodegenerative conditions, including chemotherapy-induced cognitive dysfunction (also known as chemobrain). Multiple sources state that increased activity of histone deacetylases (HDACs) play a detrimental role in chemobrain. In the present study, sodium valproate, a well-known HDAC inhibitor, was explored for its neuroprotective potential against chemobrain development...
October 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29033486/topiramate-induced-acute-liver-injury-a-rare-adverse-effect
#4
Archish Khivsara, Jeffrey Pradeep Raj, Divya Hegde, Mangala Rao
Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or predictable DILI. Although it is common in first-generation antiepileptic drugs (AEDs), it is rare in newer AEDs such as topiramate. Topiramate commonly causes neurological adverse effects such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare and has been previously reported in combination with other drugs such as valproate and carbamazepine. Here, we report a case of topiramate-induced asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol dependence syndrome and alcohol withdrawal complicated with seizures...
May 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29027197/the-risk-of-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-in-new-users-of-antiepileptic-drugs
#5
Noel Frey, Michael Bodmer, Andreas Bircher, Stephan Rüegg, Susan S Jick, Christoph R Meier, Julia Spoendlin
OBJECTIVE: Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. METHODS: In a matched case-control study of 480 previously validated SJS/TEN cases (1995-2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs...
October 13, 2017: Epilepsia
https://www.readbyqxmd.com/read/28838247/the-auditory-and-vestibular-toxicities-induced-by-antiepileptic-drugs
#6
REVIEW
Sherifa A Hamed
Epilepsy is a chronic medical disease in one third of patients and is associated with comorbid adverse somatic conditions due to epilepsy itself or its long-term treatment with antiepileptic drugs (AEDs). Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the auditory and vestibular systems. These abnormalities may be reversible or irreversible. Areas covered: This article review the evidence that long-term treatment with some antiepileptic drugs (AEDs) [e...
November 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28831600/encouraging-results-with-the-compassionate-use-of-hydralazine-valproate-transkrip%C3%A2-as-epigenetic-treatment-for-myelodysplastic-syndrome-mds
#7
Myrna Candelaria, Sebastian Burgos, Mayra Ponce, Ramiro Espinoza, Alfonso Dueñas-Gonzalez
The hypomethylating agents azacytidine and decitabine are unaffordable for many patients with MDS. The combination of the DNA methyltransferase inhibitor hydralazine and the histone deacetylase inhibitor valproate has shown preliminary efficacy in MDS. The aim of this study is to evaluate the clinical efficacy and safety of hydralazine/valproate in a case series of MDS patients treated in a compassionate manner. Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day...
November 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28767208/lithium-use-but-not-valproate-use-is-associated-with-a-higher-risk-of-chronic-kidney-disease-in-older-adults-with-mental-illness
#8
Soham Rej, Nathan Herrmann, Kenneth Shulman, Hadas D Fischer, Kinwah Fung, Ziv Harel, Andrea Gruneir
OBJECTIVE: Lithium is an essential mood disorder treatment; however, it remains unclear whether lithium increases chronic kidney disease (CKD) risk. There are few data on this in the elderly, even though older adults may be particularly susceptible to CKD. We wished to determine whether lithium is associated with increased CKD risk relative to valproate in older adults. METHODS: This nested case-control study analyzed province-wide administrative health data from mental health service users aged ≥ 66 years in Ontario, Canada, from 2003 to 2014...
August 1, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28748469/protocols-and-applications-of-cellular-metabolomics-in-safety-studies-using-precision-cut-tissue-slices-and-carbon-13-nmr
#9
Gabriel Baverel, Maha El Hage, Guy Martin
Numerous xenobiotics are toxic to human and animal cells by interacting with their metabolism, but the precise metabolic step affected and the biochemical mechanism behind such a toxicity remain often unknown. In an attempt to reduce the ignorance in this field, we have developed a new approach called cellular metabolomics. This approach, developed in vitro, provides a panoramic view not only of the pathways involved in the metabolism of physiological substrates of any normal or pathological human or animal cell but also of the beneficial and adverse effects of xenobiotics on these metabolic pathways...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28686997/management-of-epilepsy-in-merrf-syndrome
#10
REVIEW
Josef Finsterer, Sinda Zarrouk-Mahjoub
Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a rare syndromic mitochondrial disorder (MID) with a broad phenotypic but narrow genotypic heterogeneity. One of the predominant phenotypic features in addition to myopathy is epilepsy. The most frequent seizure type in MERRF is generalised myoclonic seizure but also focal myoclonic, focal atonic, generalised tonic-clonic, generalised atonic, generalised myoclonic-atonic, typical absences, or tonic-clonic seizures of unknown onset have been reported...
August 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28649495/non-hyperammonaemic-valproate-encephalopathy-after-20%C3%A2-years-of-treatment
#11
Elizabeth Caruana Galizia, Jeremy D Isaacs, Hannah R Cock
Sodium valproate is a commonly used antiseizure drug with broad indications for different seizuretypes and epilepsy syndromes. Well-recognised side effects include weight gain, tremor, dizziness, and unsteadiness. Non-hyperammonaemic parkinsonism, with or without cognitive impairment, is a rare adverse effect of sodium valproate. We present the case of a sixty year-old lady with a generalized seizure disorder, treated with phenytoin, valproate, lamotrigine and clonazepam. Following withdrawal of phenytoin she developed an akinetic-rigid syndrome, with ataxia and marked cognitive impairment...
2017: Epilepsy & Behavior Case Reports
https://www.readbyqxmd.com/read/28610743/valproate-and-sodium-butyrate-attenuate-manganese-decreased-locomotor-activity-and-astrocytic-glutamate-transporters-expression-in-mice
#12
James Johnson, Edward Alain B Pajarillo, Equar Taka, Romonia Reams, Deok-Soo Son, Michael Aschner, Eunsook Lee
Manganese (Mn) is an essential trace element, but chronic overexposure to this metal, either environmentally or occupationally may cause manganism, a disease analogous to Parkinson's disease. Inhibitors of histone deacetylases, such as valproic acid (VPA) and sodium butyrate (NaB) exert neuroprotective effects in various animal models of neurological disorders. Thus, the present study investigated whether VPA or NaB prevent Mn-induced neurotoxicity by assessing locomotor activities and expression of astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST), in C57BL/6 mice...
June 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28542253/repurposing-the-anti-epileptic-drug-sodium-valproate-as-an-adjuvant-treatment-for-diffuse-intrinsic-pontine-glioma
#13
Clare L Killick-Cole, William G B Singleton, Alison S Bienemann, Daniel J Asby, Marcella J Wyatt, Lisa J Boulter, Neil U Barua, Steven S Gill
Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines. Furthermore, sodium valproate caused an increase in acetylation of histone H3. Changes in cell viability were consistent with an induction of apoptosis in DIPG cells in vitro, determined by flow cytometric analysis of Annexin V staining and assessment of apoptotic markers by western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28490965/protective-effects-of-fennel-oil-extract-against-sodium-valproate-induced-hepatorenal-damage-in-albino-rats
#14
Wael M Al-Amoudi
Foeniculum vulgare (Apiaceae) is commonly known as fennel. This herb is well-known worldwide and traditionally used as curative herbal therapy for the treatment of epileptic disease, seizurescarminative, digestive, lactogogue, diuretic, treating respiratory and gastrointestinal disorders. The aim of present study is to investigate the possible effect of fennel oil against the toxicity of Sodium-Valproic (SVP) in albino rats. In order to assess the protection of fennel oil on SVP induced hepato- and nephro-toxicity, male albino rats were treated with 1 ml/kg b...
May 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28449218/development-and-pharmacologic-characterization-of-the-rat-6-hz-model-of-partial-seizures
#15
COMPARATIVE STUDY
Cameron S Metcalf, Peter J West, Kyle E Thomson, Sharon F Edwards, Misty D Smith, H Steve White, Karen S Wilcox
OBJECTIVE: The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. METHODS: A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis...
June 2017: Epilepsia
https://www.readbyqxmd.com/read/28434203/topiramate-monotherapy-for-juvenile-myoclonic-epilepsy
#16
REVIEW
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
https://www.readbyqxmd.com/read/28396847/patch-testing-and-cross-sensitivity-study-of-adverse-cutaneous-drug-reactions-due-to-anticonvulsants-a-preliminary-report
#17
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
https://www.readbyqxmd.com/read/28346659/is-universal-hla-b-15-02-screening-a-cost-effective-option-in-an-ethnically-diverse-population-a-case-study-of-malaysia
#18
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: A strong association has been documented between HLA-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs. OBJECTIVES: 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...
October 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28277033/efficacy-of-hydralazine-and-valproate-in-cutaneous-t-cell-lymphoma-a-phase-ii-study
#19
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
https://www.readbyqxmd.com/read/28225161/treatment-of-experimental-status-epilepticus-with-synergistic-drug-combinations
#20
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
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