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Environmental Toxicology and... Jun 2024Antiepileptic drugs, such as phenytoin, are often leaked into aquatic systems through sewage facilities due to their low metabolic rate. Fish, such as the Japanese...
Antiepileptic drugs, such as phenytoin, are often leaked into aquatic systems through sewage facilities due to their low metabolic rate. Fish, such as the Japanese medaka (Oryzias latipes), demonstrate abnormal swimming behavior such as equilibrium abnormalities, rotational behavior, and vertical swimming, when exposed to phenytoin. Therefore, it is hypothesized that predator avoidance may be hindered. This study aimed to investigate the effects of phenytoin exposure-induced behavioral abnormalities in predator avoidance in Japanese medaka. The results showed that individuals with behavioral abnormalities had a reduced ability to avoid danger. Furthermore, the fish demonstrated a delayed recognition reaction to approaching predators. Additionally, predatory fish, such as silver pike characin (Ctenolucius hujeta), were more likely to prey upon abnormal individuals. In conclusion, the fish exposed to phenytoin demonstrated behavioral changes that increased its predation risk. This study is the first to determine the effects of behavioral abnormalities in Japanese medaka which was induced after phenytoin exposure on predator risk avoidance.
Topics: Animals; Phenytoin; Oryzias; Anticonvulsants; Water Pollutants, Chemical; Behavior, Animal; Predatory Behavior; Avoidance Learning
PubMed: 38763435
DOI: 10.1016/j.etap.2024.104474 -
Scientific Reports May 2024The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the...
The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood-brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.
Topics: Gelatin; Anticonvulsants; Silicon Dioxide; Hydrogen-Ion Concentration; Phenytoin; Drug Delivery Systems; Humans; Ferric Compounds; Drug Liberation; Drug Carriers; Magnetic Iron Oxide Nanoparticles; Magnetite Nanoparticles; Nanoparticles; Particle Size
PubMed: 38762571
DOI: 10.1038/s41598-024-62248-z -
Epilepsy Research Jul 2024Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during...
BACKGROUND
Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior.
METHODS
Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control.
RESULTS
Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286).
CONCLUSIONS
Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.
Topics: Humans; Anticonvulsants; Self-Injurious Behavior; United States; United States Food and Drug Administration; Male; Female; Adverse Drug Reaction Reporting Systems; Adult; Adolescent; Middle Aged; Suicide; Young Adult; Databases, Factual; Pharmacovigilance; Child; Aged
PubMed: 38761467
DOI: 10.1016/j.eplepsyres.2024.107382 -
Pakistan Journal of Pharmaceutical... Jan 2024This research aimed to develop the phenytoin-loaded bionanosuspension by utilising the novel biopolymer from Juglans regia andreduce the long-term treatment cost of...
This research aimed to develop the phenytoin-loaded bionanosuspension by utilising the novel biopolymer from Juglans regia andreduce the long-term treatment cost of epilepsy and increase the efficiency of therapy. A novel biopolymer with remarkable inbuilt properties was isolated and used in the development of a nano capsulated dispersed system. The diverse proportions of phenytoin and biopolymer with different ratios 1:2, 1:3, 1:4, 1:5 and 1:8 were taken for the planning of details PJNC1-PJNC5. The bionanosuspension was assessed for dispersibility, pH, % entrapment efficiency, stability study and in vitro drug discharge. The formulation PJNC2 with 1:3 drug biopolymer proportion showed significant outcomes for various assessments with t50% of 16.51 h and r estimation of 0.9884. PJNC2 showed 92.07%±2.5 drug delivery in 36h and was stable. The bionanosuspension was found to be stable and safe for the delivery of nanosized phenytoin utilising the biopolymer having a remarkable stabiliser cum retardant property.
Topics: Phenytoin; Biopolymers; Drug Compounding; Drug Stability; Juglans; Anticonvulsants; Drug Liberation; Particle Size; Drug Carriers; Nanoparticles
PubMed: 38741404
DOI: No ID Found -
Pediatric Critical Care Medicine : a... May 2024To compare levetiracetam and phenytoin as prophylaxis for the short-term development of status epilepticus (SE) during care of pediatric patients with acute severe...
Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the "Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial" Dataset, 2014-2017.
OBJECTIVES
To compare levetiracetam and phenytoin as prophylaxis for the short-term development of status epilepticus (SE) during care of pediatric patients with acute severe traumatic brain injury (TBI).
DESIGN
Nonprespecified secondary analysis using propensity score matching.
SETTING
We used the Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT NCT04077411) dataset (2014-2017).
SUBJECTS
Patients less than 18 years old with Glasgow Coma Scale Score less than or equal to 8 who received levetiracetam or phenytoin as a prophylactic anticonvulsant therapy.
INTERVENTION
None.
MEASUREMENT AND MAIN RESULTS
Of the 516 total patients who qualified for the case-control study, 372 (72.1%) patients received levetiracetam, and 144 (27.9%) received phenytoin. After propensity score matching, the pair-matched analysis with 133 in each group failed to identify an association between levetiracetam versus phenytoin use and occurrent of SE (3.8% vs. 0.8%, p = 0.22), or mortality (i.e., in-hospital, 30-d and 60-d). However, on closer inspection of the statistical testing, we cannot exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with the following: up to a mean difference of 7.3% greater prevalence of SE; up to a mean difference of 13.9%, 12.1%, and 13.9% greater mortality during the hospital stay, and 30-, and 60-days after hospital arrival, respectively. Last, analysis of 6 months Glasgow Outcome Scale Extended score in those without premorbid comorbidities, there was an association between favorable outcomes and use of phenytoin rather than levetiracetam prophylaxis.
CONCLUSIONS
In ADAPT, the decision to use prophylactic levetiracetam versus phenytoin failed to show an association with occurrence of subsequent SE, or mortality. However, we are unable to exclude the possibility that selecting levetiracetam rather than phenytoin for prophylaxis was associated with greater prevalence of SE and mortality. We are unable to make any recommendation about one prophylactic anticonvulsant medication over the other, but recommend that further larger, contemporary studies in severe pediatric TBI are carried out.
PubMed: 38717237
DOI: 10.1097/PCC.0000000000003526 -
Clinical Genetics Jul 2024FGF12 related epilepsy presents with variable phenotypes. We report another patient with a duplication involving the FGF12 gene who presented similar to other published...
FGF12 related epilepsy presents with variable phenotypes. We report another patient with a duplication involving the FGF12 gene who presented similar to other published cases having normal early development and responded to phenytoin.
Topics: Humans; DNA Copy Number Variations; Fibroblast Growth Factors; Epilepsy; Male; Female; Phenotype
PubMed: 38715525
DOI: 10.1111/cge.14542 -
Epilepsy & Behavior : E&B Jul 2024In lower-middle income countries such as Bhutan, the treatment gap for epilepsy is over 50% as compared to a treatment gap of less than 10% in high-income countries. We... (Observational Study)
Observational Study
BACKGROUND & OBJECTIVE
In lower-middle income countries such as Bhutan, the treatment gap for epilepsy is over 50% as compared to a treatment gap of less than 10% in high-income countries. We aim to analyze the quality of epilepsy care for women of childbearing potential in Bhutan using the Quality Indicators in Epilepsy Treatment (QUIET) tool, and to assess the usefulness of the tool's section for women with active epilepsy (WWE) in the Bhutanese setting.
METHODS
A prospective convenience cohort was enrolled in Thimphu, Paro, Punakha, and Wangdue, Kingdom of Bhutan, in 2022. Bhutanese women of childbearing potential at the time of enrollment (18-44 years old) were evaluated for the diagnosis of active epilepsy and underwent a structured survey-based interview with Bhutanese staff. Participants were surveyed on their epilepsy, pregnancy, and antiseizure medicine (ASM) histories. The clinical history and quality of epilepsy care of adult WWE were assessed using a section of the QUIET tool for women, an instrument originally developed by the U.S. Department of Veterans Affairs to analyze the quality of epilepsy care for American adults.
RESULTS
There were 82 Bhutanese WWE of childbearing potential, with mean age of 30.6 years at enrollment (range 18-44, standard deviation (SD) 6.6) and mean age of 20.3 years at epilepsy diagnosis (range 3-40, SD 8.0)). 39 % (n = 32) had a high school or above level of education, and 42 % (n = 34) were employed. 35 % (n = 29) reported a seizure within the prior week, and 88 % (n = 72) reported a seizure within the prior year. 49 % (n = 40) of participants experienced > 100 lifetime seizures. All but one participant took antiseizure medications (ASMs). At enrollment, participants presently took no (n = 1), one (n = 3), two (n = 37), three (n = 25), four (n = 11), or over five (n = 5) ASMs. The most common ASMs taken were levetiracetam (n = 40), phenytoin (n = 27), carbamazepine (n = 23), phenobarbital (n = 22), and sodium valproate (n = 20). 61 % of all WWE took folic acid. Of the 40 previously pregnant WWE, eight (20 %) took folic acid during any time of their pregnancy. 35 % (n = 29) used betel nut (doma, quid) and 53 % (n = 21) of pregnant WWE used betel nut during pregnancy.
CONCLUSIONS
Based on data about WWE participants' ASM, supplement, and substance use, our study identified the high use of first generation ASMs (including valproate), frequently in polytherapy, and betel nut use as treatment gaps in women of childbearing potential age with active epilepsy in Bhutan. To address these gaps for locations such as Bhutan, we propose modifications to the QUIET tool's "Chronic Epilepsy Care for Women" section.
Topics: Humans; Female; Bhutan; Epilepsy; Adult; Young Adult; Adolescent; Pregnancy; Anticonvulsants; Quality of Health Care; Prospective Studies; Cohort Studies; Pregnancy Complications
PubMed: 38704988
DOI: 10.1016/j.yebeh.2024.109819 -
Schmerz (Berlin, Germany) Apr 2024Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is...
Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.
PubMed: 38689064
DOI: 10.1007/s00482-024-00810-4 -
Journal of the American Veterinary... Apr 2024To provide a video tutorial describing intraperitoneal (IP) and intracoelomic (IC) therapeutics (IP/IC fluid therapy, euthanasia, direct peritoneal resuscitation).
OBJECTIVE
To provide a video tutorial describing intraperitoneal (IP) and intracoelomic (IC) therapeutics (IP/IC fluid therapy, euthanasia, direct peritoneal resuscitation).
ANIMALS
Dogs, cats, and exotic pets.
METHODS
Peritoneal and coelomic centesis allows for delivery of fluids or to perform euthanasia. The peritoneal and coelomic membranes contain a vast network of capillaries and lymphatics that allow absorption of fluids and blood products. Needles are inserted aseptically IP or IC at species-specific locations to avoid iatrogenic damage. In mammals, the needle is inserted in a periumbilical location at a 1- to 2-cm radius from the umbilicus, while the needle is inserted into the ventral inguinal fossa in chelonians and lateroventrally in lizards and snakes. Direct peritoneal resuscitation is a human technique in which a dextrose/electrolyte solution infused IP reduces ischemia-reperfusion injury, edema, and tissue necrosis to improve mortality in patients with diseases like shock and sepsis or who require acute abdominal surgery.
RESULTS
Isotonic crystalloids are given IP/IC at 10- to 20-mL/kg doses (smaller volumes in reptiles) and blood products at standard calculated doses. Sodium pentobarbital without phenytoin (3 mL/4.5 kg) is used for IP/IC euthanasia.
CLINICAL RELEVANCE
Being aware of multiple routes for fluid and blood product administration allows treatment in animals for which intravenous or intraosseous catheterization is undesirable or impossible. While intravenous or intraosseous routes are always preferred, especially for resuscitation, familiarity with locations for IP/IC fluid and euthanasia is useful. Techniques like direct peritoneal resuscitation are not currently used in animals but might be translated to veterinary cases in the future.
PubMed: 38688326
DOI: 10.2460/javma.24.03.0150 -
Journal of Cancer Research and... Apr 2024There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted...
INTRODUCTION
There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome.
MATERIAL AND METHODS
A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors.
RESULTS
There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862).
CONCLUSIONS
Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.
Topics: Humans; Female; Anticonvulsants; Male; Glioblastoma; Middle Aged; Brain Neoplasms; Aged; Chemoradiotherapy, Adjuvant; Adult; Cohort Studies; Phenytoin; Registries; Levetiracetam; Valproic Acid
PubMed: 38687925
DOI: 10.4103/jcrt.jcrt_750_22