1,662 results match your criteria Toxicity Phenytoin


Synthesis and Characterization of Biologically Significant 5-[N,N-dialkylamino alkoxy] azaindole 2-one, 3-thiosemicarbazones and 5-[N,N-dialkylamino alkoxy] azaindole 3-hydrazone, 2-ones.

Adv Exp Med Biol 2020 ;1195:189-198

University college of Pharmaceutical Sciences, Kakatiya University, Warangal, India.

In the present work, new indole derivatives, i.e., 5-[N,N-di alkyl amino alkoxy] azaindole 2,3- di-one derivatives, are synthesized and characterized. Read More

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http://dx.doi.org/10.1007/978-3-030-32633-3_27DOI Listing
January 2020

Phenytoin - An anti-seizure drug: Overview of its chemistry, pharmacology and toxicology.

Food Chem Toxicol 2020 May 4;142:111393. Epub 2020 May 4.

Biomedical Research Centre, University Hospital, Hradec Kralove, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address:

Phenytoin is a long-standing, anti-seizure drug widely used in clinical practice. It has also been evaluated in the context of many other illnesses in addition to its original epilepsy indication. The narrow therapeutic index of phenytoin and its ubiquitous daily use pose a high risk of poisoning. Read More

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http://dx.doi.org/10.1016/j.fct.2020.111393DOI Listing

A novel screening test to predict the developmental toxicity of drugs using human induced pluripotent stem cells.

Authors:
Nobuo Aikawa

J Toxicol Sci 2020 ;45(4):187-199

Translational Research Unit, R&D Division, Kyowa Kirin Co., Ltd.

In vitro human induced pluripotent stem (iPS) cells testing (iPST) to assess developmental toxicity, e.g., the induction of malformation or dysfunction, was developed by modifying a mouse embryonic stem cell test (EST), a promising animal-free approach. Read More

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http://dx.doi.org/10.2131/jts.45.187DOI Listing
January 2020

A Novel Correction Equation Avoids High-Magnitude Errors in Interpreting Therapeutic Drug Monitoring of Phenytoin among Critically Ill Patients.

Ther Drug Monit 2020 Feb 10. Epub 2020 Feb 10.

Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Boston, MA.

Background: Phenytoin has a narrow therapeutic index and the potential of under-treatment or toxicity. Available equations are used to correct for the impact of hypoalbuminemia on unbound (free) phenytoin levels. The authors aimed to determine the accuracy of equations used to estimate free phenytoin in hospitalized patients and assess the impact of using additional clinical data. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000739DOI Listing
February 2020

Behavioural, electrocorticographic, and electromyographic alterations induced by Nerium oleander ethanolic extract: Anticonvulsant therapeutics assessment.

Neurotoxicology 2020 May 5;78:21-28. Epub 2020 Feb 5.

Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil.

Nerium oleander Linn. is an Apocynaceae shrub which is among the most toxic ornamental plants. Although seizures are one of the symptoms associated with N. Read More

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http://dx.doi.org/10.1016/j.neuro.2020.02.001DOI Listing

Antiepileptic Overdose.

Authors:
Shakuntala Murty

Indian J Crit Care Med 2019 Dec;23(Suppl 4):S290-S295

Department of Emergency Medicine, St. John's Medical College and Hospital, Bengaluru, Karnataka, India.

Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Read More

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http://dx.doi.org/10.5005/jp-journals-10071-23301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996662PMC
December 2019

Phenytoin Toxicity Treatment with Haemodialysis in Epilepsy due to Glioblastoma Multiforme: Case Report and Review of the Literature.

Case Rep Neurol 2019 Sep-Dec;11(3):344-350. Epub 2019 Dec 10.

Department of Medicine, Faculty of Health Sciences, Aga Khan University (East Africa) Medical College, Nairobi, Kenya.

Phenytoin is one of the most commonly used anticonvulsants in the developing world, but lack of monitoring and concurrent medications can easily lead to toxicity. We report the case of a 35-year-old female on phenytoin for symptomatic epilepsy due to previously treated glioblastoma multiforme, who presented with status epilepticus 1 week after being treated for a urinary tract infection. She was loaded with phenytoin and levetiracetam as per emergency protocol but had a persistently low level of consciousness, and her preloading phenytoin level result came back in the toxic range. Read More

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http://dx.doi.org/10.1159/000504470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940471PMC
December 2019

Cardiac Collapse Secondary to Phenytoin Toxicity in a Neonate Treated with Extracorporeal Membrane Oxygenation Support (ECMO).

J Med Toxicol 2020 Apr 26;16(2):230-235. Epub 2019 Nov 26.

Louisiana State University Health Sciences Center, Department of Pediatrics, Division of Neonatology, Children's Hospital of New Orleans, 200 Henry Clay Avenue, New Orleans, LA, 70118, USA.

Introduction: Although medication toxicity is uncommon in neonates, there are several medications used in this population that pose a risk. Phenytoin has an increased risk of toxicity given its narrow therapeutic window and variations in drug elimination.

Case Report: We describe the case of a 3-day-old male infant who developed cardiovascular collapse secondary to severe phenytoin toxicity (max phenytoin level 86 μg/mL) and was placed on extracorporeal membrane oxygenation support (ECMO). Read More

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http://dx.doi.org/10.1007/s13181-019-00742-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099106PMC

Phencyclidine: A Rare Cause of Saccadic Intrusions.

Ann Indian Acad Neurol 2019 Oct-Dec;22(4):503-505. Epub 2019 Oct 25.

Department of Neurology, National Hospital of Sri Lanka, Colombo, Sri Lanka.

Saccadic intrusions such as opsoclonus and ocular flutter are often due to a paraneoplastic or a parainfectious condition. Toxins/drugs may rarely cause them. Herein, we report a rare case of ocular flutter/opsoclonus due to phencyclidine (PCP) toxicity. Read More

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http://dx.doi.org/10.4103/aian.AIAN_174_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839326PMC
October 2019

Mild foot electrical stimulation is comparable with phenytoin in inhibiting pentylenetetrazol-induced kindling in rats.

J Physiol Sci 2019 Nov 5;69(6):1071-1076. Epub 2019 Nov 5.

Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Khonin Shahr Street, Sardasht, Arak, 38481-7-6941, Iran.

Increasing evidence demonstrates that electric stimulation has anticonvulsant effects. The present study was undertaken to investigate the effects of mild foot electrical stimulation (MFES) on the development of pentylenetetrazol (PTZ) kindling and compare its effectiveness with the more commonly used treatment, phenytoin. Kindling was induced in rats by repeated injections (every 24 h) of PTZ (37. Read More

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http://dx.doi.org/10.1007/s12576-019-00726-0DOI Listing
November 2019

Dl-3-n-butylphthalide inhibits phenytoin-induced neuronal apoptosis in rat hippocampus and cerebellum.

J Integr Neurosci 2019 Sep;18(3):277-283

Department of Neurology, People's Hospital in Shijiazhuang, 36 Fanxi Road, Shijiazhuang 050000, Hebei, P. R. China.

Rats were divided into six groups: sham/control , Dl-3-n-butylphthalide, P1 (low phenytoin, 100 mg/kg), P2 (high phenytoin, 200 mg/kg), NP1 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 100 mg/kg), NP2 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 200 mg/kg). Hematoxylin/eosin and Nissl staining showed that, compared to the sham/control group, the Dl-3-n-butylphthalide group had no obvious hippocampal and cerebellar neuron loss, but there was a significant neuron loss in the P1 and P2 groups (P < 0.05), which was more obvious in the P2 group (P < 0. Read More

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http://dx.doi.org/10.31083/j.jin.2019.03.174DOI Listing
September 2019
1 Read

A case report of phenytoin-induced eosinophilic pneumonia.

Respir Med Case Rep 2019 11;28:100922. Epub 2019 Aug 11.

Department of Pulmonary and Critical Care, University of Texas Southwestern Medical Center, USA.

Eosinophilic pneumonia comprises a rare and potentially serious group of lung diseases characterized by abnormal accumulation of eosinophils in the lungs. Many medications including the anticonvulsant phenytoin, have been implicated in the development of eosinophilic pneumonia. Attributing eosinophilic pneumonia to a medication or toxin can be difficult and may only be achieved by exclusion. Read More

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http://dx.doi.org/10.1016/j.rmcr.2019.100922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710233PMC
August 2019
1 Read

Insights into Molecular Interactions of human Wnt5b and Frizzled proteins for their role in teratogenicity.

Bioinformation 2019 15;15(4):246-254. Epub 2019 Apr 15.

Toxicology and Computational Biology Group, Centre for Bioinformatics, M. D. University, Rohtak, Haryana 124001 India.

Wnt-Fzd signalling plays vital role in different physiological pathways including embryonic development and supposed to be probable target of many teratogens. The present study was done to investigate the role of human Wnt5b interaction with different isoforms of human Fzds and also the molecular interactions of their complexes with selected known teratogens [Carbamazepine (CBZ), Retinoic acid (RA), Valproic acid (VPA), Aminopterin (AMP) and Phenytoin (PHY)] using Niclosamide (NLM) as standard. The models of hWnt5b and hFzd isoforms, whose solved crystal structures were unavailable, were generated using homology modeling and hWnt5b was subjected to protein-protein docking studies against different isoforms of hFzd. Read More

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http://dx.doi.org/10.6026/97320630015246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599440PMC
April 2019
5 Reads

Synthesis and pharmacological evaluation of novel N-Mannich bases derived from 5,5-diphenyl and 5,5-di(propan-2-yl)imidazolidine-2,4-dione core.

Bioorg Med Chem Lett 2019 08 3;29(16):2387-2392. Epub 2019 Jun 3.

Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland.

The aim of this study was to design and synthesize two series of N-Mannich bases with imidazolidine-2,4-dione core as a potential anticonvulsant with reduced toxicity and broad antiseizure activity. Preliminary screening revealed that the majority of synthesized compounds were effective in the maximal electroshock seizure (MES) and/or subcutaneous pentylenetetrazole (scPTZ) test. The most active in vivo compound, 18 (3-((4-methylpiperazin-1-yl)methyl)-5,5-diphenylimidazolidine-2,4-dione), exhibited an ED value comparable to that of phenytoin in the MES test (38. Read More

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http://dx.doi.org/10.1016/j.bmcl.2019.06.001DOI Listing
August 2019
20 Reads

High and variable population prevalence of HLA-B*56:02 in indigenous Australians and relation to phenytoin-associated drug reaction with eosinophilia and systemic symptoms.

Br J Clin Pharmacol 2019 09 19;85(9):2163-2169. Epub 2019 Jul 19.

General Medicine, Royal Adelaide Hospital, Adelaide, Australia.

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. Read More

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http://dx.doi.org/10.1111/bcp.14025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710506PMC
September 2019
27 Reads

Phenytoin Toxicity Manifesting as Acute Psychosis: An Uncommon Side Effect of a Common Drug.

Asian J Neurosurg 2019 Apr-Jun;14(2):532-534

Department of Neurosurgery and Gamma Knife, All India Institute of Medical Sciences and Jai Prakash Narayan Apex Trauma Center, New Delhi, India.

Antiepileptic drug-induced psychotic disorder represents an iatrogenic, adverse drug reaction. Phenytoin has rarely been shown to be a causative agent of acute psychosis in patients. We present such a rare case of short term use of phenytoin causing toxicity manifesting as acute psychosis and complete recovery following phenytoin withdrawal. Read More

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http://dx.doi.org/10.4103/ajns.AJNS_86_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516005PMC
May 2019
6 Reads

Phenytoin toxicity due to drug interaction with doxepin and changes in patient factors.

Nurse Pract 2019 Jun;44(6):13-16

Samarth P. Shah is a clinical pharmacy specialist of internal medicine/acute stroke at Methodist University Hospital, Memphis, Tenn. Aseala Abousaud is a pharmacist at Emory Healthcare, Atlanta, Ga. Reshma R. Nair is a medical student at the American University of Integrative Sciences, School of Medicine, Tucker, Ga. Jaclyn Bergeron is a hospitalist at Methodist University Hospital, Memphis, Tenn., and an assistant professor of internal medicine at the University of Tennessee College of Medicine, Memphis, Tenn. B. Tate Cutshall is a clinical pharmacy specialist of internal medicine at Methodist University Hospital, Memphis, Tenn.

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http://dx.doi.org/10.1097/01.NPR.0000558162.07091.09DOI Listing
June 2019
5 Reads

Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning.

Biol Blood Marrow Transplant 2019 07 11;25(7):1424-1431. Epub 2019 Mar 11.

Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, WA, USA.

High-dose busulfan (BU) followed by high-dose cyclophosphamide (CY) before allogeneic hematopoietic cell transplantation (HCT) has long been used as treatment for hematologic malignancies. Administration of phenytoin or newer alternative antiepileptic medications (AEMs) prevents seizures caused by BU. Phenytoin induces enzymes that increase exposure to active CY metabolites in vivo, whereas alternative AEMs do not have this effect. Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615968PMC
July 2019
53 Reads

Adverse Drug Reactions of Anti-Epileptic Drugs in Children with Epilepsy: A Cross-Sectional Study.

Curr Drug Saf 2019 ;14(3):217-224

Department of Pediatrics, School of Medical Sciences & Research, Sharda University, Greater Noida, UP 201310, India.

Background: Adverse drug reactions (ADRs) due to antiepileptic drugs (AEDs) in children contribute to poorer patient outcomes. However, reliable data ragarding such ADRs is not available.

Objectives: Thus, the aim of the present study was to determine the incidence and patterns of ADRs of antiepileptic drugs in children aged 2-17 years presenting to a tertiary care teaching hospital. Read More

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http://dx.doi.org/10.2174/1574886314666190311112710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875869PMC
February 2020
10 Reads

Treatment of prolonged tacrolimus toxicity using phenytoin in a haemodialysis patient.

J Clin Pharm Ther 2019 Aug 4;44(4):640-643. Epub 2019 Mar 4.

Erie County Medical Center, Buffalo, New York.

What Is Known And Objective: Treatment of tacrolimus toxicity includes holding tacrolimus and supportive care. The objective is to describe considerations for pharmacologic induction of tacrolimus metabolism.

Case Description: A 52-year-old male with a failed renal transplant on chronic haemodialysis developed tacrolimus toxicity due to a drug-drug interaction with darunavir/ritonavir. Read More

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http://dx.doi.org/10.1111/jcpt.12829DOI Listing
August 2019
8 Reads

Aqueous Extract of Wood Ear Mushroom, Auricularia polytricha (Agaricomycetes), Demonstrated Antiepileptic Activity against Seizure Induced by Maximal Electroshock and Isoniazid in Experimental Animals.

Int J Med Mushrooms 2019 ;21(1):29-35

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo NSW 2007, Australia; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Lot 1 Kookaburra Circuit, New Lambton Heights, Newcastle, NSW 2305, Australia.

Auricularia polytricha is a popular mushroom found all over the world. This article describes a study of the antiepileptic effect of A. polytricha, a mushroom that is used traditionally for treating asthma, rheumatism, tumors, cough, fever, and epilepsy, and for its antimicrobial effect. Read More

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http://dx.doi.org/10.1615/IntJMedMushrooms.2018029113DOI Listing
June 2019
9 Reads

Evaluation of a human in vitro skin test for predicting drug hypersensitivity reactions.

Toxicol Appl Pharmacol 2019 04 12;369:39-48. Epub 2019 Feb 12.

Alcyomics Ltd, Bulman House, Regent Centre, Gosforth, Newcastle-upon-Tyne NE3 3LS, United Kingdom; Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne NE2 4HH, United Kingdom. Electronic address:

The occurrence of drug hypersensitivity reactions (DHRs) following administration of low molecular weight (LMW) drugs is an important health concern. However, in vivo animal models which could be used as tools for the prediction of DHRs are lacking. As a result, research has focused on development of in vitro tools for predicting DHRs. Read More

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http://dx.doi.org/10.1016/j.taap.2019.02.005DOI Listing

Phenytoin Toxicity During Neoadjuvant Concurrent Capecitabine and Radiation Therapy for Rectal Adenocarcinoma: Case Report of a Drug Interaction.

Cureus 2018 Nov 23;10(11):e3625. Epub 2018 Nov 23.

Radiation Oncology, The University of Ottawa, Ottawa, CAN.

Phenytoin toxicity occurs when serum levels exceed the therapeutic level, leading to symptoms such as nystagmus, slurred speech, and decreased coordination. This toxicity is sometimes caused by drug interactions. Interactions between phenytoin and capecitabine are not commonly documented. Read More

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http://dx.doi.org/10.7759/cureus.3625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347445PMC
November 2018
9 Reads

Phenytoin-induced hypothermia.

BMJ Case Rep 2019 Jan 22;12(1). Epub 2019 Jan 22.

Department of Rheumatology, Glasgow Royal Infirmary, Glasgow, UK.

A 60-year-old man with cerebral palsy and epilepsy was admitted with acute lethargy and deterioration in coordination. He was noted to be hypothermic at 35°C on admission. Routine work-up revealed toxic levels of phenytoin. Read More

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http://dx.doi.org/10.1136/bcr-2018-227443DOI Listing
January 2019
5 Reads

Teratogenicity of antiepileptic drugs.

Curr Opin Neurol 2019 04;32(2):246-252

Department of Internal Medicine and Therapeutics, University of Pavia, Clinical Trial Center, IRCCS Mondino Foundation, Pavia, Italy.

Purpose Of Review: We review data on the comparative teratogenicity of antiepileptic drugs (AEDs), focusing on major congenital malformations (MCMs), intrauterine growth restriction, impaired cognitive development, and behavioral adverse effects following prenatal exposure.

Recent Findings: Prospective registries and meta-analyses have better defined the risk of MCMs in offspring exposed to individual AEDs at different dose levels. Valproate is the drug with the highest risk, whereas prevalence of MCMs is lowest with lamotrigine, levetiracetam, and oxcarbazepine. Read More

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http://dx.doi.org/10.1097/WCO.0000000000000659DOI Listing
April 2019
64 Reads

A novel oxazolidinone derivative PH192 demonstrates anticonvulsant activity in vivo in rats and mice.

Eur J Pharm Sci 2019 Mar 10;130:21-26. Epub 2019 Jan 10.

Department of Pharmacology & Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait.

The pharmacotherapeutic management of seizure disorders with currently available medications is not optimal due to side effects and failure of some patients to respond to all available medications. As such there is the need to develop new antiseizure drugs by looking at new chemical classes of compounds. We recently screened, in vitro, a new class of compounds, the oxazolidinones, for actions in the brain that may indicate potential for antiseizure activity. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09280987193001
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http://dx.doi.org/10.1016/j.ejps.2019.01.011DOI Listing
March 2019
17 Reads
3.350 Impact Factor

Graph theoretical analysis, in silico modeling, prediction of toxicity, metabolism and synthesis of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl) phenyl) quinazolin-4(3H)-ones as NMDA receptor inhibitor.

Drug Dev Res 2019 05 4;80(3):368-385. Epub 2019 Jan 4.

Department of Pharmacology, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.

Hit, Lead & Candidate Discovery A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d-aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. Read More

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http://doi.wiley.com/10.1002/ddr.21511
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http://dx.doi.org/10.1002/ddr.21511DOI Listing
May 2019
14 Reads

A systematic review of phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets in China.

Medicine (Baltimore) 2018 Dec;97(51):e13689

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Objective: In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets (CPEHTT).

Method: A literature search was performed in the following databases: WANFANG DATA, HowNet, National Library Reference and Consultation Alliance, Full-text Database of Foreign Medical Journals, PubMed and Ovid. The search terms were "Compound Phenytoin Sodium, ephedrine Hydrochloride and Theophylline Tablets," and "poisoning," or "toxicity," in Chinese and in English. Read More

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http://Insights.ovid.com/crossref?an=00005792-201812210-0007
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http://dx.doi.org/10.1097/MD.0000000000013689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320048PMC
December 2018
18 Reads

Unexplained encephalopathy with phenytoin toxicity - hyperammonemia, the underlying cause.

Neurol India 2018 Nov-Dec;66(6):1829-1831

Department of Neurology, King George's Medical University, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.4103/0028-3886.246257DOI Listing
September 2019
9 Reads

Naringin in a combined therapy with phenytoin on pentylenetetrazole-induced kindling in rats.

Epilepsy Behav 2018 12 8;89:159-168. Epub 2018 Nov 8.

UAS Laboratories, LLC, 555 N 72nd Avenue, Wausau, WI 54401, United States of America.

Phenytoin (Dilantin) is an orally active, use-dependent voltage-gated sodium channel inhibitor and is a potent, economical, and widely used anticonvulsant agent. The objective of the present study was to investigate the effect of the combined treatment of naringin (40 mg/kg and 80 mg/kg) and phenytoin on prevention of seizure attacks, development of kindling, oxidative stress, cognitive impairment, and neurochemicals in the frontal cortex, temporal cortex, and hippocampus, and morphological changes in the hippocampus. Treatment with the high dose of naringin (80 mg/kg) along with phenytoin has shown to offer protection against seizures, development of kindling, and cognition enhancement through Y-maze test and improved % conditioned avoidance response (% CAR) through pole climbing test in pentylenetetrazole (PTZ)-induced kindling model. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15255050183053
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http://dx.doi.org/10.1016/j.yebeh.2018.10.006DOI Listing
December 2018
29 Reads

Ameliorative Effects of α-Tocopherol and/or Coenzyme Q10 on Phenytoin-Induced Cognitive Impairment in Rats: Role of VEGF and BDNF-TrkB-CREB Pathway.

Neurotox Res 2019 Feb 29;35(2):451-462. Epub 2018 Oct 29.

Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Phenytoin is one of the most well-known antiepileptic drugs that cause cognitive impairment which is closely related to cAMP response element-binding protein (CREB) brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, vascular endothelial growth factor (VEGF), an endothelial growth factor, has a documented role in neurogenesis and neuronal survival and cognitive impairment. Therefore, this study aimed to investigate the influence of powerful antioxidants: α-Toc and CoQ10 alone or combined in the preservation of brain tissues and the maintenance of memory formation in phenytoin-induced cognitive impairment in rats. Read More

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http://link.springer.com/10.1007/s12640-018-9971-6
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http://dx.doi.org/10.1007/s12640-018-9971-6DOI Listing
February 2019
10 Reads

Evaluation of Cytotoxic Effect and Antioxidant Activity of Grape Seed Extract, Crocin, and Phenytoin.

Arch Razi Inst 2017 09 22;72(3):181-187. Epub 2016 Sep 22.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Antioxidant compounds inhibit formation of free radicals, chelate catalytic metals, and scavenge free radicals in biological systems. In addition, antioxidants play a decisive role in prevention of numerous physiological dysfunctions, cancers, and metabolic disorders. This study sought to evaluate the antioxidant capacity and cytotoxic effect of grape seed extract (GSE), crocin (CRO), and phenytoin (PHEN) on a human breast cancer cell line (MCF-7). Read More

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http://archrazi.areeo.ac.ir/article_111609.html
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http://dx.doi.org/10.22092/ari.2017.111609DOI Listing
September 2017
25 Reads

Recurrent epileptiform discharges in the medial entorhinal cortex of kainate-treated rats are differentially sensitive to antiseizure drugs.

Epilepsia 2018 11 17;59(11):2035-2048. Epub 2018 Oct 17.

Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.

Objective: Approximately 30% of patients with epilepsy are refractory to existing antiseizure drugs (ASDs). Given that the properties of the central nervous systems of these patients are likely to be altered due to their epilepsy, tissues from rodents that have undergone epileptogenesis might provide a therapeutically relevant disease substrate for identifying compounds capable of attenuating pharmacoresistant seizures. To facilitate the development of such a model, this study describes the effects of classical glutamate receptor antagonists and 20 ASDs on recurrent epileptiform discharges (REDs) in brain slices derived from the kainate-induced status epilepticus model of temporal lobe epilepsy (KA-rats). Read More

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http://dx.doi.org/10.1111/epi.14563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215509PMC
November 2018
25 Reads

[Valproic acid toxicity due to misinterpretation of plasma levels: increase in unbound fraction caused by hypoalbuminaemia and renal dysfunction].

Ned Tijdschr Geneeskd 2018 08 16;162. Epub 2018 Aug 16.

VUmc, afd. Ziekenhuispsychiatrie, Amsterdam.

Background: Valproic acid is one of the most widely prescribed drugs for the treatment of epilepsy and bipolar disorder. As only the unbound fraction of a medicinal product is pharmacologically active, in some strong protein-bound psychotropic drugs such as valproic acid and phenytoin, a rise in this fraction can lead to severe toxicity.

Case Description: A 65-year-old male with a type 1 bipolar disorder developed a number of neurological symptoms including sluggishness, muscle weakness, difficulty in walking and disorders of micturition after his mood stabiliser was changed to valproic acid. Read More

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August 2018
11 Reads

Analysis of phenytoin drug concentration for evaluation of clinical response, uncontrolled seizures and toxicity.

Pak J Pharm Sci 2018 Jul;31(4(Special)):1697-1700

Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.

The narrow therapeutic index, non-linear pharmacokinetics and unpredictable absorption require regular therapeutic monitoring of phenytoin. The influence of genetic differences, sex, age and race on the phenytoin plasma levels and its metabolites is well recognized. This study is aimed at evaluating phenytoin plasma drug concentration and its relationship with clinical response, persistent seizures and toxicity in different gender and various age groups of Chinese epileptic patients. Read More

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July 2018
25 Reads

Influence of Inflammation on the Pharmacokinetics of Perampanel.

Ther Drug Monit 2018 12;40(6):725-729

Department of Clinical Research, National Epilepsy Center, NHO, Shizuoka Institute of Epilepsy and Neurological Disorders.

Background: It is well-known that the pharmacokinetics of various drugs are influenced by inflammation. This study evaluated the relationship between C-reactive protein (CRP; an inflammation marker) and the pharmacokinetics of perampanel.

Methods: Among 111 patients who underwent measurement of both CRP and perampanel, 23 patients had a serum CRP level exceeding 1. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000556DOI Listing
December 2018
27 Reads

Phenytoin and Rifampin Do Not Decrease Levels in Acute Tacrolimus Toxicity.

J Investig Med High Impact Case Rep 2018 Jan-Dec;6:2324709618765862. Epub 2018 Mar 24.

Maricopa Integrated Health System, Department of Emergency Medicine, Phoenix, AZ, USA.

Tacrolimus is used in bone marrow transplant patients to prevent graft-versus-host disease. There have been few case reports of tacrolimus toxicity (>30 ng/mL) in solid organ recipients as well as in nontransplant patients. Several case reports suggest phenytoin and rifampin decrease tacrolimus levels in toxicity, but does it actually make a difference? A 60-year-old man with acute myeloblastic leukemia after allogenic stem cell transplant with fever, diarrhea, and abdominal pain was transferred to the intensive care unit for persistent hypotension and acute hypoxic respiratory failure requiring intubation. Read More

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http://dx.doi.org/10.1177/2324709618765862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062773PMC
March 2018
13 Reads

Toxicological evaluation of convulsant and anticonvulsant drugs in human induced pluripotent stem cell-derived cortical neuronal networks using an MEA system.

Sci Rep 2018 Jul 10;8(1):10416. Epub 2018 Jul 10.

Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology, 35-1 Yagiyama Kasumicho, Taihaku-ku, Sendai, Miyagi, 982-8577, Japan.

Functional evaluation assays using human induced pluripotent stem cell (hiPSC)-derived neurons can predict the convulsion toxicity of new drugs and the neurological effects of antiepileptic drugs. However, differences in responsiveness depending on convulsant type and antiepileptic drugs, and an evaluation index capable of comparing in vitro responses with in vivo responses are not well known. We observed the difference in synchronized burst patterns in the epileptiform activities induced by pentylentetrazole (PTZ) and 4-aminopryridine (4-AP) with different action mechanisms using multi-electrode arrays (MEAs); we also observed that 100 µM of the antiepileptic drug phenytoin suppressed epileptiform activities induced by PTZ, but increased those induced by 4-AP. Read More

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http://dx.doi.org/10.1038/s41598-018-28835-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039442PMC
July 2018
34 Reads

Interventions for chronic non-hypovolaemic hypotonic hyponatraemia.

Cochrane Database Syst Rev 2018 06 28;6:CD010965. Epub 2018 Jun 28.

Renal Division, Sector Metabolic and Cardiovascular Conditions, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium, 9000.

Background: Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.

Objectives: This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia. Read More

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http://dx.doi.org/10.1002/14651858.CD010965.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513194PMC
June 2018
34 Reads

The neuropathology of the adult cerebellum.

Authors:
Arnulf H Koeppen

Handb Clin Neurol 2018 ;154:129-149

Research, Neurology, and Pathology Services, Veterans Affairs Medical Center and Departments of Neurology and Pathology, Albany Medical College, Albany, NY, United States. Electronic address:

This chapter summarizes the neuropathologic features of nonneoplastic disorders of the adult cerebellum. Gait ataxia and extremity dysmetria are clinical manifestations of diseases that interrupt the complex cerebellar circuitry between the neurons of the cerebellar cortex, the cerebellar nuclei (especially the dentate nuclei), and the inferior olivary nuclei. The cerebellum is a prominent target of several sporadic and hereditary neurodegenerative diseases, including multiple system atrophy, spinocerebellar ataxia, and Friedreich ataxia. Read More

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http://dx.doi.org/10.1016/B978-0-444-63956-1.00008-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279249PMC
September 2018
16 Reads

Toxic-induced cerebellar syndrome: from the fetal period to the elderly.

Handb Clin Neurol 2018 ;155:333-352

Neurology Service, Hôpital Erasme, Brussels, Belgium.

The cerebellum is a brain region which is particularly susceptible to intoxication. Clinical presentation is heterogeneous. It is often considered that elderly patients and patients presenting pre-existing structural lesions of the posterior fossa are particularly at risk of developing a toxic-induced cerebellar syndrome (TOICS). Read More

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http://dx.doi.org/10.1016/B978-0-444-64189-2.00022-6DOI Listing
October 2018
40 Reads

Consequences of Phenytoin Exposure on Hepatic Cytochrome P450 Expression during Postnatal Liver Maturation in Mice.

Drug Metab Dispos 2018 08 8;46(8):1241-1250. Epub 2018 Jun 8.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.)

The induction of cytochrome P450 (P450) enzymes in response to drug treatment is a significant contributing factor to drug-drug interactions, which may reduce therapeutic efficacy and/or cause toxicity. Since most studies on P450 induction are performed in adults, enzyme induction at neonatal, infant, and adolescent ages is not well understood. Previous work defined the postnatal ontogeny of drug-metabolizing P450s in human and mouse livers; however, there are limited data on the ontogeny of the induction potential of each enzyme in response to drug treatment. Read More

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http://dx.doi.org/10.1124/dmd.118.080861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053591PMC
August 2018
17 Reads

Development and Validation of an LC-MS/MS Method and Comparison with a GC-MS Method to Measure Phenytoin in Human Brain Dialysate, Blood, and Saliva.

J Anal Methods Chem 2018 1;2018:8274131. Epub 2018 Apr 1.

Clinical Pharmacy and Epidemiology, Hospital Pharmacy, University of Basel, Spitalstrasse 26, CH-4031 Basel, Switzerland.

Phenytoin (PHT) is one of the most often used critical dose drugs, where insufficient or excessive dosing can have severe consequences such as seizures or toxicity. Thus, the monitoring and precise measuring of PHT concentrations in patients is crucial. This study develops and validates an LC-MS/MS method for the measurement of phenytoin concentrations in different body compartments (i. Read More

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https://www.hindawi.com/journals/jamc/2018/8274131/
Publisher Site
http://dx.doi.org/10.1155/2018/8274131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901821PMC
April 2018
17 Reads

The novel sodium channel modulator GS-458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy.

Epilepsia 2018 06 21;59(6):1166-1176. Epub 2018 May 21.

Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Objective: De novo mutations of SCN8A, encoding the voltage-gated sodium channel Na 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Read More

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http://doi.wiley.com/10.1111/epi.14196
Publisher Site
http://dx.doi.org/10.1111/epi.14196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142814PMC
June 2018
19 Reads

Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice.

J Appl Toxicol 2018 09 16;38(9):1215-1223. Epub 2018 May 16.

Department of Pharmacology, Laboratory of Physiology and Pharmacology of Reproduction, Universidade Federal de Goiás, Goiânia, GO, Brazil.

Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. Read More

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http://dx.doi.org/10.1002/jat.3631DOI Listing
September 2018
25 Reads

Persistent Bradycardia with the Long-term Use of Phenytoin and Oxycodone: First Case Report.

Cureus 2018 Feb 8;10(2):e2169. Epub 2018 Feb 8.

Assistant Clinical Professor of Internal Medicine, West Virginia University School of Medicine.

Phenytoin is a medication that is used primarily in the treatment of epilepsy as well as generalized tonic-clonic seizures and status epilepticus. Phenytoin is also considered a class IB antiarrhythmic medication by shortening the duration of the action potential and increasing myocardial conduction. The neurologic adverse effects of phenytoin are well-documented and include altered mental status, ataxia, and nystagmus. Read More

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http://dx.doi.org/10.7759/cureus.2169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889162PMC
February 2018
19 Reads

Clinical Characteristics and Etiology of Bilateral Vestibular Loss in a Cohort from Central Illinois.

Authors:
Jorge C Kattah

Front Neurol 2018 1;9:46. Epub 2018 Mar 1.

Illinois Neurologic Institute, University of Illinois College of Medicine, Peoria, IL, United States.

Background: Previous series of bilateral vestibular loss (BVL) identified numerous etiologies, but surprisingly, a cause in a significant number of cases remains unknown. In an effort to understand possible etiology and management strategies, a global effort is currently in progress. Here, I contribute my 10-year experience with both acute and chronic BVL during the 2007-2017 decade. Read More

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http://dx.doi.org/10.3389/fneur.2018.00046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837982PMC
March 2018
9 Reads

[Effect of Environmental Factors on the Ecotoxicity of Pharmaceuticals and Personal Care Products].

Authors:
Kazumi Sugihara

Yakugaku Zasshi 2018 ;138(3):277-280

Faculty of Pharmaceutical Sciences, Hiroshima International University.

 In recent years, pharmaceuticals and personal care products (PPCPs) have emerged as significant pollutants of aquatic environments and have been detected at levels in the range of ng/L to μg/L. The source of PPCPs is humans and livestock that have been administered pharmaceuticals and subsequently excreted them via urine and feces. Unlike agricultural chemicals, the environmental dynamics of PPCPs is not examined and they would undergo structural transformation by environmental factors, e. Read More

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http://dx.doi.org/10.1248/yakushi.17-00177-2DOI Listing
March 2018
11 Reads