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Acta Neurologica Scandinavica Jun 2018Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status... (Review)
Review
Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.
Topics: Administration, Cutaneous; Administration, Intravenous; Anticonvulsants; Exanthema; Humans; Infusions, Intravenous; Levetiracetam; Phenytoin; Piracetam; Status Epilepticus; Treatment Outcome
PubMed: 29624640
DOI: 10.1111/ane.12928 -
Seizure Oct 2021To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a meta-analysis of RCTs.
METHODS
We systematically searched PubMed, Embase, Cochrane, FDA.gov, and ClinicalTrials.gov for RCTs (published before July 31, 2020; no language restrictions). Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO: CRD42020202736. Eleven studies fulfilled the established criteria. We assessed pooled data by using a random-effects model. Quality analysis was performed by using version 2 of the Cochrane risk-of-bias tool (RoB 2). RevMan v.5.3 was used to perform statistical analyses, and publication bias (egger's test) was assessed with Stata MP v.14.0.
RESULTS
Levetiracetam was similar to (fos)phenytoin in seizure termination rate (risk ratio [RR] 0.94; 95% CI 0.87 to 1.01), time of seizure termination (mean difference [MD] 0.44; -0.60 to 1.49), and drug resistance ([RR] 1.12, 0.86 to 1.45). The safety outcome showed a significant statistical difference between fosphenytoin group and levetiracetam group ([RR] 1.44, 1.14 to 1.81), while there was no significant difference observed between phenytoin treatment and levetiracetam treatment ([RR] 1.26, 0.99 to 1.60).
CONCLUSION
Levetiracetam was similar to (fos)phenytoin in cessation rate convulsive status epilepticus, and drug resistance, while it was superior (fos)phenytoin in pooled safety outcome. Further exploration is still needed as to whether it is the first choice for second-line drugs.
Topics: Anticonvulsants; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 34284302
DOI: 10.1016/j.seizure.2021.07.012 -
The Journal of Pediatrics Sep 2017
Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Administration, Oral; Epilepsy; Female; Humans; India; Infant, Newborn; Male; Phenytoin; Pregnancy; Pregnancy Complications; Rare Diseases; Respiratory Distress Syndrome, Newborn; Ultrasonography, Prenatal
PubMed: 28578158
DOI: 10.1016/j.jpeds.2017.05.018 -
Journal of Pharmaceutical and... May 2023Barbiturates which are old pharmaceutical drugs are still widely used in medical treatment of epilepsy and for general anesthesia. To date, more than 2500 different...
Barbiturates which are old pharmaceutical drugs are still widely used in medical treatment of epilepsy and for general anesthesia. To date, more than 2500 different barbituric acid analogs have been synthesized, and 50 of them were introduced into medical use over the last century. Due to their highly addictive properties, pharmaceuticals containing barbiturates are under strict control in many countries. However, by considering the worldwide problem with new psychoactive substances (NPS) the introduction of new designer barbiturate analogs into the dark market might serve a serious public health problem in the near future. For this reason there is an increasing need for application methods for barbiturates monitoring in biological samples. The UHPLC-QqQ-MS/MS method for determination of 15 barbiturates, phenytoin, methyprylon and glutethimide was developed and fully validated. The biological sample volume was reduced to only 50 µL. A simple LLE (pH 3 with ethyl acetate) was successfully applied. The lower LOQ was 10 ng/mL. The method enables differentiation of structural isomers: hexobarbital and cyclobarbital; as well as amobarbital and pentobarbital. Chromatographic separation was achieved with the use of the alkaline mobile phase (pH 9) and Acquity UPLC BEH C18 column. Furthermore, the novel fragmentation mechanism of barbiturates was proposed, which may have a great impact in identification of novel barbiturates analogs introduced to illegal marketplaces. The presented technique has a great potential to be applied in forensic, clinical and veterinary toxicological laboratories, as was evidenced by the positive results of international proficiency tests.
Topics: Chromatography, High Pressure Liquid; Phenytoin; Glutethimide; Tandem Mass Spectrometry; Barbiturates
PubMed: 36868027
DOI: 10.1016/j.jpba.2023.115318 -
Epilepsy Research May 2023Epilepsy is an important cause of morbidity and mortality especially in low- and middle-income countries. People with epilepsy (PWE) face difficulties in access to... (Review)
Review
Epilepsy is an important cause of morbidity and mortality especially in low- and middle-income countries. People with epilepsy (PWE) face difficulties in access to healthcare, appropriate diagnostic tests and anti-seizure medications (ASM). Bhutan is one such country in the Himalayas that has reported doubling of the prevalence of epilepsy from 155.7 per 100,000 population in 2017 to 312.4 in 2021. The country has one centre for electroencephalography and magnetic resonance imaging for a population of 0.7 million and does not have any neurologists as of 2023. There are 16 ASMs registered in the country but only selected medications are available at the primary level hospitals (phenobarbital, phenytoin and diazepam). There are challenges in the availability of these medicines all time round the year in all levels of hospitals. Neurosurgical treatment options are limited by the lack of adequate pre-surgical evaluation facilities and lack of trained human resources. The majority of PWE have reported facing societal stigma with significant impact on the overall quality of life. It is important to screen for psychiatric comorbidities and provide psychological support wherever possible. There is a need for a comprehensive national guideline that will cater to the needs of PWE and their caregivers within the resources available in the country. A special focus on the institutional and human resource capacity development for the study and care of epilepsy is recommended.
Topics: Humans; Bhutan; Quality of Life; Epilepsy; Phenytoin; Social Stigma; Anticonvulsants
PubMed: 36965308
DOI: 10.1016/j.eplepsyres.2023.107126 -
Brain and Behavior May 2018Status epilepticus (SE) is a neurological emergency which can be life-threatening. Several medical regimens are used in order to control it. In this study, we intended... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Status epilepticus (SE) is a neurological emergency which can be life-threatening. Several medical regimens are used in order to control it. In this study, we intended to evaluate the clinical efficacy and tolerability of sodium valproate and intravenous phenytoin (IV PHT) in the control of SE.
METHODS
One hundred and ten consecutive patients suffering from benzodiazepine refractory SE who were referred to the emergency ward from March 2014 to March 2015 were randomly divided into two groups. The first group received intravenous sodium valproate, 30 mg/kg as loading dose and then 4-8 mg/kg every 8 hr as maintenance regimen. The second group received IV PHT 20 mg/kg as loading dose and then 1.5 mg/kg for 8 hr as maintenance therapy. All patients were monitored for vital signs every 2 hr up to 12 hr. The patients were also followed up for 7 days regarding drug response and adverse effects.
RESULTS
The administration of sodium valproate and phenytoin respectively resulted in seizure control in 43 (78.18%) and 39 (70.90%) of the patients within 7 days of drug administration ( = .428). Seven-day mortality rate was similar in both groups (12.73% vs. 12.73%; = .612). There was no significant difference in adverse effects between two groups.
CONCLUSION
Sodium valproate is preferred to IV PHT for treatment and control of SE due to its higher tolerability and lower hemodynamic instability.
Topics: Adult; Aged; Anticonvulsants; Benzodiazepines; Drug Resistance; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Phenytoin; Status Epilepticus; Treatment Outcome; Valproic Acid; Young Adult
PubMed: 29761006
DOI: 10.1002/brb3.951 -
Clinical Transplantation Dec 2022
Topics: Humans; Tacrolimus; Sirolimus; Phenytoin; Immunosuppressive Agents; Kidney Transplantation
PubMed: 36063141
DOI: 10.1111/ctr.14809 -
Journal of Pharmaceutical and... Jan 2023Surface-enhanced Raman spectroscopy (SERS) for quantitative analysis is challenging owing to the unstable enhanced effect. However, it can be improved by combining it...
Surface-enhanced Raman spectroscopy (SERS) for quantitative analysis is challenging owing to the unstable enhanced effect. However, it can be improved by combining it with chemometrics. In this study, we established a quantitative analysis method for phenytoin sodium (PS) based on partial least-squares (PLS) and linear regression (LR) models combined with SERS. Gold nanoparticles (AuNPs) were optimally enhanced substrates for PS. 180 PS samples in the concentration range of 0.98 - 980 μg mL were used to establish a quantitative prediction model by PLS regression, and an accurate and robust prediction was achieved. Furthermore, we found that SERS peak intensity showed a good linear correlation with the concentration of PS in the concentration range of 1 - 80 μg mL . After using P-mercaptobenzoic acid as an internal standard, the accuracy and precision of the LR model were significantly improved compared with that of the model without an internal standard. In general, PLS chemometrics and LR model with internal standard which were combined with SERS in this paper provide new possible analytical methods for analytes to develop a rapid and sensitive quantitative analysis method.
Topics: Least-Squares Analysis; Spectrum Analysis, Raman; Linear Models; Phenytoin; Gold; Metal Nanoparticles
PubMed: 36410132
DOI: 10.1016/j.jpba.2022.115160 -
The Annals of Pharmacotherapy Jun 2016
Topics: Anticonvulsants; Critical Illness; Humans; Phenytoin; Protein Binding; Seizures
PubMed: 27083917
DOI: 10.1177/1060028016644620 -
Molecular Cancer Jan 2015Voltage-gated Na(+) channels (VGSCs) are heteromeric protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are...
BACKGROUND
Voltage-gated Na(+) channels (VGSCs) are heteromeric protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are classically expressed in electrically excitable cells, e.g. neurons. VGSCs are also expressed in tumour cells, including breast cancer (BCa) cells, where they enhance cellular migration and invasion. However, despite extensive work defining in detail the molecular mechanisms underlying the expression of VGSCs and their pro-invasive role in cancer cells, there has been a notable lack of clinically relevant in vivo data exploring their value as potential therapeutic targets.
FINDINGS
We have previously reported that the VGSC-blocking antiepileptic drug phenytoin inhibits the migration and invasion of metastatic MDA-MB-231 cells in vitro. The purpose of the present study was to establish whether VGSCs might be viable therapeutic targets by testing the effect of phenytoin on tumour growth and metastasis in vivo. We found that expression of Nav1.5, previously detected in MDA-MB-231 cells in vitro, was retained on cells in orthotopic xenografts. Treatment with phenytoin, at a dose equivalent to that used to treat epilepsy (60 mg/kg; daily), significantly reduced tumour growth, without affecting animal weight. Phenytoin also reduced cancer cell proliferation in vivo and invasion into surrounding mammary tissue. Finally, phenytoin significantly reduced metastasis to the liver, lungs and spleen.
CONCLUSIONS
This is the first study showing that phenytoin reduces breast tumour growth and metastasis in vivo. We propose that pharmacologically targeting VGSCs, by repurposing antiepileptic or antiarrhythmic drugs, should be further studied as a potentially novel anti-cancer therapy.
Topics: Animals; Anticonvulsants; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Female; Humans; Mice; Neoplasm Metastasis; Neovascularization, Pathologic; Phenytoin; Sodium Channel Blockers; Sodium Channels; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 25623198
DOI: 10.1186/s12943-014-0277-x