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Journal of Pharmacy & Pharmaceutical... 2016The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are...
Coupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02.
PURPOSE
The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated.
METHODS
DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers.
RESULTS
Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine.
Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Female; Genotype; HLA-B Antigens; Heterozygote; Humans; Male; Middle Aged; Molecular Docking Simulation; Stevens-Johnson Syndrome; Young Adult
PubMed: 27096699
DOI: 10.18433/J38G7X -
Neurology Jun 2023A 66-year-old man with seizures that started at 61 years eventually developed drug-resistant epilepsy and was managed with medications and vagal nerve stimulation. The...
A 66-year-old man with seizures that started at 61 years eventually developed drug-resistant epilepsy and was managed with medications and vagal nerve stimulation. The patient had a convulsive event at 61 years, followed by recurrent events of confusion and speech arrest lasting 30-120 seconds. He underwent gadolinium-enhanced brain MRI and angiogram, which revealed pial enhancement in the right occipital, parietal, and posterior temporal regions with subcortical atrophy. CSF findings were unremarkable. Continuous video EEG showed electroclinical correlation for his episodes of confusion and speech arrest with recurrent brief runs of rhythmic delta from the right temporal region with evolution and spread to the entire right hemisphere. The patient tried multiple antiseizure medications including valproic acid, topiramate, phenytoin, carbamazepine, levetiracetam, brivaracetam, and lamotrigine without success. He was eventually put on a combination of lacosamide, zonisamide, clonazepam, and primidone, which helped to a certain extent, but the patient continued to have daily episodes and 10-12 electroclinical seizures noted on a follow-up 24-hour ambulatory EEG. Follow-up brain MRI with contrast confirmed the diagnosis. Phase II intracranial monitoring for surgical management was offered to the patient, which he deferred because of risks. Vagal nerve stimulator (VNS) was also offered as a palliative therapy to which the patient agreed. Gradual titration in VNS settings over 1 year helped to achieve seizure freedom. Presentation of focal seizure with this type of atypical etiology is rare. Typically, surgical management is used to achieve seizure freedom in this condition; successful management with VNS has not been reported so often.
Topics: Male; Humans; Middle Aged; Aged; Drug Resistant Epilepsy; Seizures; Vagus Nerve Stimulation; Brain; Clinical Reasoning; Treatment Outcome
PubMed: 36792377
DOI: 10.1212/WNL.0000000000206890 -
RSC Advances Jun 2019Three sets of functional monomers namely urea-based, 2-ureido-4[1]-primidone (UPy)-based and norbornene based functional monomers were designed and synthesized. These...
Three sets of functional monomers namely urea-based, 2-ureido-4[1]-primidone (UPy)-based and norbornene based functional monomers were designed and synthesized. These functional monomers (FM) were obtained in decent yields using amine and isocyanate/norbornene as starting materials. Methacrylate and styrene isocyanate with 1,4-diaminobutane/tris(2-aminoethyl)amine were chosen for the synthesis of symmetrical, asymmetrical and three-branched urea-functional monomers, respectively. UPy-based FMs were synthesized with isocyanate and 2-amino-4-hydroxy-6-methylpyrimidine. The synthesis of these monomers feature short reaction times, mild reaction conditions and no need for column chromatographic purification. Furthermore, the norbornene based FM was used for preparing molecularly imprinted polymers (MIPs) by Ring-Opening Metathesis Polymerization (ROMP). Results showed that these synthetic routes represent a convenient and useful approach for synthesis of novel functional monomers.
PubMed: 35514692
DOI: 10.1039/c9ra01852b -
Acta Medica Iranica 2015The present study has been directed to investigate Ursodeoxycholic Acid (UDCA) effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs...
The present study has been directed to investigate Ursodeoxycholic Acid (UDCA) effect in children, to reduce the high Liver transaminases induced by Anticonvulsant drugs (drug induced hepatitis). This idea has been driven from Cytoprotective and antioxidant properties of UDCA to be used in drug induced inflammation in Liver. Twenty two epileptic patients aged between 4 mo - 3 yr whom were under anticonvulsant therapy with drugs such as valperoic acid, primidone, levetiracetam, Phenobarbital or any combination of them and had shown Liver transaminases rise , after rule out of Viral-Autoimmune, Metabolic and Anatomic causes, have been prescribed UDCA in dose of 10-15 mg/kg/day, at least for 6 months. Any patient who have shown confusing factors such as genetic disorders with liver involvement or spontaneous decline in enzymes or had not treatment compliance has been excluded from the study. Transaminases range changes as well as Probable side effects of the drug have been monitored. The results indicated that UDCA is effective and well tolerable in the children with drug induced hyper transaminasemia. No side effect has been seen and recorded in this study. Based on this study and its results, we recommend UDCA as a safe and effective choice in drug induced hepatotoxicities.
Topics: Anticonvulsants; Antioxidants; Chemical and Drug Induced Liver Injury; Child, Preschool; Female; Humans; Infant; Liver Function Tests; Male; Pilot Projects; Prospective Studies; Transaminases; Ursodeoxycholic Acid
PubMed: 26069172
DOI: No ID Found -
Scientific Reports Feb 2021Trace organic compounds (TrOCs) enter rivers with discharge of treated wastewater. These effluents can contain high loads of dissolved organic matter (DOM). In a 48 h...
Trace organic compounds (TrOCs) enter rivers with discharge of treated wastewater. These effluents can contain high loads of dissolved organic matter (DOM). In a 48 h field study, we investigated changes in molecular composition of seven DOM compound classes (FTICR-MS) and attenuation of 17 polar TrOCs in a small urban stream receiving treated wastewater. Correlations between TrOCs and DOM were used to identify simultaneous changes in surface water and the hyporheic zone. Changes in TrOC concentrations in surface water ranged between a decrease of 29.2% for methylbenzotriazole and an increase of 152.2% for the transformation product gabapentin-lactam. In the hyporheic zone, only decreasing TrOC concentrations were observed, ranging from 4.9% for primidone to 93.8% for venlafaxine . TrOC attenuation coincided with a decline of molecular diversity of easily biodegradable DOM compound classes while molecular diversity of poorly biodegradable DOM compound classes increased. This concurrence indicates similar or linked attenuation pathways for biodegradable DOM and TrOCs. Strong correlations between TrOCs and DOM compound classes as well as high attenuation of TrOCs primarily occurred in the hyporheic zone. This suggests high potential for DOM turnover and TrOC mitigation in rivers if hyporheic exchange is sufficient.
PubMed: 33603043
DOI: 10.1038/s41598-021-83750-8 -
Cureus Apr 2024Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder that presents with acute to subacute onset of unilateral progressive optic neuropathy, with...
Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder that presents with acute to subacute onset of unilateral progressive optic neuropathy, with sequential involvement of the fellow eye months to years later. The condition may be accompanied by neurological symptoms, including tremors, dystonia, seizures, or psychosis, in which case, it is termed LHON-plus. Here, we present the case of a 53-year-old man who was initially diagnosed with essential tremor but was later found to have LHON-plus after the onset of bilateral visual loss and a genetic panel. His essential tremor was refractory to standard pharmacological therapies, including propranolol, primidone, and topiramate. As a result, he elected to undergo bilateral deep brain stimulation (DBS) of the bilateral ventral intermediate nucleus of the thalamus with a dramatic improvement in symptoms. To our knowledge, this is the first case of essential tremor presenting in the context of LHON-plus to be treated successfully with DBS. While DBS has been applied in LHON-plus presenting with dystonia with limited success, our outcome suggests that there is promise in this approach and that more research is needed to evaluate it.
PubMed: 38756271
DOI: 10.7759/cureus.58255 -
Therapie 2020Pitch perception modifications are among the little-known adverse effects observed with antiepileptics, mainly affecting patients treated with carbamazepine (CBZ). Here,...
Pitch perception modifications are among the little-known adverse effects observed with antiepileptics, mainly affecting patients treated with carbamazepine (CBZ). Here, we describe an original French case of pitch perception modification due to CBZ resulting in perfect pitch loss. We also reviewed the literature as well as French and world health organisation global pharmacovigilance database. The case report concerns a 22-year-old patient with perfect pitch with untreated left temporal partial epilepsy. Following a generalized seizure, the introduction of CBZ prolonged release (200mg twice a day) is decided. As soon as CBZ is introduced, the patient notices a change in pitch perception, about a semitone lower. This adverse effect persisted despite a gradual decrease in doses. The patient reported a total recovery of his perfect pitch when CBZ stopped completely 11 years later. In the French pharmacovigilance database, only one other case of pitch perception modification under CBZ was recorded (no cases were found with oxcarbazepine, lacosamide, sodium valproate, lamotrigine, levetiracetam, phenobarbital, phenytoin, primidone, ethosuximide, vigabatrine, felbamate, gabapentin, tiagabine and topiramate). In the literature, 27 cases of pitch perception modification have been published with CBZ, 1 case with oxcarbazepine and 1 case with lacosamide. Pitch perception modification is a very rare adverse effect of CBZ, oxcarbazepine and lacosamide, identified in the literature mainly in the Japanese population, in experienced musicians. A rapid onset after the introduction of treatment, a complete resolution of symptoms, in most cases upon discontinuation of treatment, is observed, with no sequelae reported. Due to the impact on quality of life, especially in patients whose profession is related to music, knowledge of this adverse event seems important to evoke this diagnosis.
Topics: Adult; Anticonvulsants; Epilepsy; Humans; Pharmacovigilance; Pitch Perception; Quality of Life; Young Adult
PubMed: 32204934
DOI: 10.1016/j.therap.2020.02.017 -
RSC Advances Mar 2018The rejection behaviors of two different charged composite hollow fiber nanofiltration (NF) membranes for six pharmaceutical molecules, primidone, carbamazepine,...
The rejection behaviors of two different charged composite hollow fiber nanofiltration (NF) membranes for six pharmaceutical molecules, primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin, were characterized in this study. The saturation adsorption behaviors of the different pharmaceutical molecules on each membrane surface were studied and found to be related to the molecular weight, charge and hydrophilicity of the pharmaceutical molecules. After the pharmaceutical molecules reached adsorption equilibrium, the rejection rates of different NF membranes were characterized. The rejection rates of primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin by the PEI-NF membrane were 85.6%, 91.8%, 79.9%, 98.1%, 93.3%, and 97.1%, respectively. Meanwhile, the rejection rates of the pharmaceutical molecules by the PIP-NF membrane were 82.2%, 85.4%, 91.5%, 79.1%, 87% and 93.3%, respectively. The influence of feed concentration, operation pressure, temperature, pH and ionic strength on the rejection behaviors of the different charged NF membranes were also studied.
PubMed: 35540449
DOI: 10.1039/c8ra00519b