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1.
J Neurol Sci ; 442: 120387, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36041330

RESUMO

BACKGROUND: There are no prospective, longitudinal studies investigating patterns of medication use among essential tremor (ET) patients. Our goal was to fill this knowledge gap. We also had a unique opportunity to examine medication use patterns primarily among elders with longstanding ET. We hypothesized that by the time ET patients reach advanced ages, medication changes would be uncommon - that is, they may have reached some kind of equipoise. METHODS: A prospective, longitudinal cohort of ET cases was evaluated across three time points. Cases were not ascertained from a treatment setting, thereby removing important selection biases. Each reported current medications and dosages of each. RESULTS: There were 144 cases (mean baseline age = 76.1 ± 9.4 years). The mean observation period = 2.9 ± 0.2 years. Primidone and propranolol were the most commonly used medications, although almost one-half of cases (44.4%) reported using neither during this period. A third of primidone users (33.3%) and a quarter of propranolol users (24.6%) reported changes in use vs. nonuse during the observation period. The majority of our cases made some change in their daily medication dosage during the course of the study - 73.3% of primidone users and 57.9% of propranolol users. CONCLUSION: In this prospective, longitudinal study, use vs. nonuse and daily dosage of both primidone and propranolol fluctuated across time for a sizable proportion of ET cases. Even among elders with chronic, longstanding ET, there is considerable ongoing medication adjustment, underscoring the need to improve the medication situation for ET patients.


Assuntos
Tremor Essencial , Primidona , Humanos , Idoso , Idoso de 80 Anos ou mais , Primidona/uso terapêutico , Tremor Essencial/tratamento farmacológico , Tremor Essencial/epidemiologia , Propranolol/uso terapêutico , Estudos Longitudinais , Tremor/tratamento farmacológico
2.
Brain Nerve ; 74(5): 637-644, 2022 May.
Artigo em Japonês | MEDLINE | ID: mdl-35589658

RESUMO

For essential tremors that are refractory to standard medical treatment, surgical treatment is considered when there is obstruction in activities of daily living. However, there are patients who do not wish to undergo or are contraindicated for surgical treatment. In this paper, we explored what is considered to be the standard medical treatment and when surgery cannot be performed. In Japan, medical treatment is based on the use of arotinolol and primidone, and combination therapy and second-line drugs are extensively discussed. Furthermore, an algorithm of the treatment for essential tremors in Japan has been provided.


Assuntos
Tremor Essencial , Atividades Cotidianas , Tremor Essencial/tratamento farmacológico , Tremor Essencial/cirurgia , Humanos , Japão , Primidona/uso terapêutico
3.
Environ Res ; 212(Pt D): 113531, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35613632

RESUMO

Water polluted by pharmaceutically active compounds (PhACs) and water-borne pathogens urgently need to develop eco-friendly and advanced water treatment techniques. This paper evaluates the potential of using calcium peroxide (CaO2), a safe and biocompatible oxidant both PhACs (thiamphenicol, florfenicol, carbamazepine, phenobarbital, and primidone) and pathogens (Escherichia coli, Staphylococcus aureus) in water. This paper evaluates the potential of using calcium peroxide (CaO2) as a safe and biocompatible oxidant to remove both PhACs (thiamphenicol, florfenicol, carbamazepine, phenobarbital, and primidone) and pathogens (Escherichia coli, Staphylococcus aureus) in water. The increased CaO2 dosage increased efficiencies of PhACs attenuation and pathogens inactivation, and both exhibited pseudo-first-order degradation kinetics (R2 > 0.90). PhACs attenuation were mainly via oxidization (H2O2, •OH/O•-, and O2•-) and alkaline hydrolysis (OH-) from CaO2. Moreover, concentrations of these reactive species and their contributions to PhACs attenuation were quantified, and mechanistic model was established and validated. Besides, possible transformation pathways of target PhACs except primidone were proposed. As for pathogen indicators, the suitable inactivation dosage of CaO2 was 0.1 g L-1. The oxidability (18-64%) and alkalinity (82-36%) generated from CaO2 played vital roles in pathogen inactivation. In addition, CaO2 at 0.01-0.1 g L-1 can be applied in remediation of SW contaminated by PhACs and pathogenic bacteria, which can degrade target PhACs with efficiencies of 21-100% under 0.01 g L-1 CaO2, and inactivate 100% of test bacteria under 0.1 g L-1 CaO2. In short, capability of CaO2 to remove target PhACs and microbial pathogens reveals its potential to be used as a representative technology for the advanced treatment of waters contaminated by organic compounds and microbial pathogens.


Assuntos
Tianfenicol , Poluentes Químicos da Água , Carbamazepina/análise , Escherichia coli , Peróxido de Hidrogênio , Oxidantes , Preparações Farmacêuticas , Primidona , Poluentes Químicos da Água/análise
4.
Pain ; 163(11): 2200-2212, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35413036

RESUMO

ABSTRACT: The transient receptor potential cation channel subfamily M member-3 (TRPM3) channel is a recently recognized noxious heat sensor that is involved in inflammatory thermal hyperalgesia. To examine its involvement in the development of hyperalgesia in interstitial cystitis/painful bladder syndrome (IC/PBS), rats with cyclophosphamide (CYP)-induced chronic cystitis were used as a model of IC/PBS. Mechanical and thermal hyperalgesia in lower abdominal region overlying the bladder in CYP rats were measured using von Frey filaments and radiant heat, respectively. Transient receptor potential cation channel subfamily M member-3 expression at the mRNA, protein, and functional levels in dorsal root ganglion neurons innervating the bladder was detected using RNA in situ hybridization (RNAscope), Western blotting, immunohistochemistry, and Ca 2+ imaging, respectively. Transient receptor potential cation channel subfamily M member-3 channels were expressed on most of the bladder primary afferent nerve terminals containing calcitonin gene-related peptide and their cell bodies in L6-S1 dorsal root ganglion. Activation of TRPM3 in the bladder wall by its specific agonist pregnenolone sulphate or CIM0216 induced spontaneous bladder pain, calcitonin gene-related peptide release, and neurogenic inflammation that was evidenced by edema, plasma extravasation, inflammatory cell accumulation, and mast cell infiltration. In CYP rats, pretreatment with the TRPM3 antagonist primidone (2 mg/kg, i.p.) significantly alleviated the mechanical and thermal hyperalgesia, bladder submucosal edema, mast cell infiltration, and bladder hyperactivity. Cyclophosphamide-induced cystitis was associated with TRPM3 upregulation at the mRNA, protein, and functional levels in bladder afferent neurons. Our results suggest that upregulation of TRPM3 channels is involved in the development of chronic pain in CYP-induced cystitis, and targeting TRPM3 may be a pharmacological strategy for treating bladder pain in IC/PBS.


Assuntos
Dor Crônica , Cistite Intersticial , Cistite , Canais de Cátion TRPM , Canais de Potencial de Receptor Transitório , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dor Crônica/complicações , Ciclofosfamida/toxicidade , Cistite/induzido quimicamente , Cistite/complicações , Cistite/metabolismo , Cistite Intersticial/complicações , Hiperalgesia/tratamento farmacológico , Primidona/uso terapêutico , RNA , RNA Mensageiro/metabolismo , Ratos , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Regulação para Cima , Bexiga Urinária/inervação
5.
Artigo em Inglês | MEDLINE | ID: mdl-35415009

RESUMO

Background: Although first line therapies for essential tremor have been identified from small clinical trials, responses are variable. We conducted a survey of tremor management in a large sample of ET cases. Methods: The Movement Disorders Clinical Case Registry within a US Veterans Health Administration medical center was used to identify 1468 patients with ET. Results: Of 1468 charts reviewed, 1074 (73.19%) met criteria for ET with characterization of temporal course and treatment; 291/1074 subjects (27.1%) did not receive any treatment. Almost half (500/1074; 46.6%) of the patients received monotherapy, 196/1074 (18.2%) two, 66/1074 (6.1%) three, and 21/1074 (2.0%) four or more medications. Of all prescriptions, primidone was the most used (546/1172; 46.6%), followed by propranolol (419; 35.8%), topiramate (122; 10.4%) and gabapentin (35; 3.0%). Medication response was available for a total of 1030 prescriptions, of which 138 (13.4%) were discontinued due to side effects; 180 (17.5%) prescriptions were ineffective. Furthermore, 52/1074 patients (4.8%) were treated with botulinum toxin injections and 41/1074 (3.8%) underwent deep brain stimulation surgery. Discussion: Our data suggest that more widespread recognition of limitations underlying conventional approaches, as well as increased referrals for nonpharmacological therapies, may be necessary to achieve improved outcomes in ET populations.


Assuntos
Tremor Essencial , Tremor Essencial/tratamento farmacológico , Humanos , Primidona/uso terapêutico , Propranolol/uso terapêutico , Estudos Retrospectivos , Topiramato/uso terapêutico
6.
Seizure ; 98: 57-70, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35427849

RESUMO

BACKGROUND: Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the potential adverse effects caused by exposure to antiseizure medications (ASMs). OBJECTIVE: The objectives of this review were: to evaluate concentrations of ASMs in breastmilk of lactating WWE, qualitatively synthesize evidence that can be used to estimate theoretical doses as estimated daily intake (EDI) and relative infant dose (RID) of ASMs, and to evaluate potential risks to infants as a result of exposure to ASMs from breastmilk. METHODS: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020223645. The databases: MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. A qualitative synthesis was adopted in this study. RESULTS: A total of 15 records were included in this systematic review. The included studies reported levels of 8 ASMs in the breastmilk of WWE. The highest RIDs of carbamazepine, lamotrigine, primidone, phenobarbital, gabapentin, valproic acid, ethosuximide, levetiracetam, and topiramate were 3.70%, 36.33%, 4.96%, 3.15%, 4.37%, 1.90%, 31.49%, 12.50%, and 12.18%, respectively. Breastfeeding might be limited or even discontinued when signs of excessive sedation/drowsiness and/or poor weight gain are evident on infants exposed to primidone and phenobarbital, ethosuximide/primidone, or ethosuximide/phenobarbital. CONCLUSIONS: Concentrations of ASMs can be detected in breastmilk of WWE and plasma/serum of infants exposed via breastmilk. Healthcare providers and WWE might use the findings of this study to make informed decisions on the safety of breastfeeding while taking ASMs.


Assuntos
Epilepsia , Leite Humano , Anticonvulsivantes/efeitos adversos , Aleitamento Materno , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Etossuximida/uso terapêutico , Feminino , Humanos , Lactente , Lactação , Fenobarbital/uso terapêutico , Primidona/uso terapêutico , Revisões Sistemáticas como Assunto
7.
Am J Health Syst Pharm ; 79(15): 1250-1254, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35212353

RESUMO

PURPOSE: We report a unique case of transiently elevated liver function test (LFT) values associated with concurrent use of dabigatran and primidone, which has not previously been described in the scientific literature. SUMMARY: Management of drug-drug interactions requires a fundamental understanding of pharmacodynamic and pharmacokinetic parameters. Despite the use of available best predictive models, idiosyncratic drug reactions may still occur when a newly approved medication begins to be used in the general population. We report a case of a possible interaction (Naranjo adverse drug reaction probability score of 3, Roussel Uclaf causality assessment method score of 3) between dabigatran and primidone in a 70-year-old Caucasian male resulting in a transient elevation of LFT values. The patient was transitioned from warfarin to dabigatran in the setting of persistently subtherapeutic international normalized ratio values. During a routine outpatient follow-up appointment approximately 1 month after dabigatran initiation, the patient was discovered to have LFT values greater than 5 times the upper limit of normal. Dabigatran was thus discontinued; the patient was returned to warfarin therapy and their LFT values returned to baseline. CONCLUSION: Studies have indicated a potential for reduced dabigatran efficacy with concurrent use of primidone due to P-glycoprotein induction, thereby potentiating the risk for thrombosis. To date, reports of this interaction resulting in hepatic injury are lacking. The present case suggests that this interaction may be clinically significant with regard to selection of antithrombotic medication therapy in patients on primidone therapy.


Assuntos
Fibrilação Atrial , Dabigatrana , Idoso , Anticoagulantes , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Humanos , Coeficiente Internacional Normatizado , Testes de Função Hepática , Masculino , Primidona/uso terapêutico , Varfarina
9.
Life Sci ; 268: 118967, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417951

RESUMO

AIMS: Sensory nerve activation modulates ureteral contractility by releasing neuropeptides including CGRP and neurokinin A (NKA). TRPM3 is a recently discovered thermosensitive channel expressed in nociceptive sensory neurons, and plays a key role in heat nociception and chronic pain. The aim of this study is to examine the role of TRPM3 activation in human ureter motility. MAIN METHOD: Human proximal ureters were obtained from fourteen patients undergoing nephrectomy. Spontaneous or NKA-evoked contractions of longitudinal ureter strips were recorded in an organ bath. Ureteral TRPM3 expression was examined by immunofluorescence. KEY FINDINGS: Spontaneous contractions were observed in 60% of examined strips. TRPM3 activation using pregnenolone sulphate (PS) or CIM0216 (specific TRPM3 agonists) dose-dependently reduced the frequency of spontaneous and NKA-evoked contractions, with IC50s of 241.7 µM and 4.4 µM, respectively. The inhibitory actions of TRPM3 agonists were mimicked by CGRP (10 to 100 nM) or a cAMP analogue (8-Br-cAMP; 1 mM). The inhibitory actions of TRPM3 agonists (300 µM PS or 30 µM CIM0216) were blocked by pretreatment with primidone (TRPM3 antagonist; 30 µM), tetrodotoxin (sodium channel blocker; 1 µM), olcegepant (CGRP receptor antagonist; 10 µM), or H89 (non-specific PKA inhibitor; 30 µM). TRPM3 was co-expressed with CGRP in nerves in the sub-urothelial and intermuscular regions of the ureter. SIGNIFICANCE: TRPM3 channels expressed on sensory terminals of the human ureter involve in inhibitory sensory neurotransmission and modulate ureter motility via the CGRP-cAMP-PKA signal pathway. Targeting TRPM3 may be a pharmacological strategy for promoting the ureter stone passage.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPM/metabolismo , Ureter/fisiologia , Adulto , Idoso , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Nefrectomia , Neurocinina A/metabolismo , Neurocinina A/farmacologia , Técnicas de Cultura de Órgãos , Pregnenolona/farmacologia , Primidona/farmacologia , Células Receptoras Sensoriais/efeitos dos fármacos , Canais de Cátion TRPM/agonistas , Canais de Cátion TRPM/antagonistas & inibidores , Ureter/efeitos dos fármacos
10.
Eur J Pharmacol ; 896: 173907, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33503462

RESUMO

Niemann-Pick disease type C (NPC) is caused by a loss of function of either NPC1 or NPC2 protein, resulting in the accumulation of unesterified, free-cholesterol (free-C) in cells/tissues and thus leading to cell/tissue damage. In the brain of patients/animals with NPC, as a consequence of the accumulation of free-C in late endosomes/lysosomes (LE/LY) in cells, multiple lipids including complex sphingolipids are accumulated, and almost all patients/animals ultimately develop progressive/fatal neurodegeneration. Several reagents that are considered to act in the brain show beneficial effects on NPC-model animals. In the present study, we investigated the effects of antiepileptic drugs, such as primidone and valproic acid, on the accumulation of free-C in NPC1-null CHO cells and NPC1* fibroblasts, human fibroblasts established from a patient with NPC1 mutation. Like valproic acid, treatment with primidone reduced free-C levels in LE/LY in NPC1-null/mutant cells. Down-regulation of cholesterol ester levels in NPC1-null cells and up-regulation of HMG-CoA reductase and low-density lipoprotein receptor mRNA levels in NPC1* cells were partially recovered by primidone treatment. Thus, primidone was suggested to enhance free-C trafficking from LE/LY to endoplasmic reticulum in NPC1-null/mutant cells. In NPC1-null mice, oral application of primidone (100 mg/kg/day) extended lifespan by approximately 5 days, although the first days showing ataxia, a typical symptom of neuromotor dysfunction, were not affected. Our findings suggest the potential of primidone for the treatment of NPC.


Assuntos
Colesterol/metabolismo , Fibroblastos/efeitos dos fármacos , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Primidona/farmacologia , Animais , Transporte Biológico , Células CHO , Cricetulus , Modelos Animais de Doenças , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Fibroblastos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Longevidade/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/metabolismo , Doença de Niemann-Pick Tipo C/fisiopatologia , Fatores de Tempo , Ácido Valproico/farmacologia
12.
Cell Death Differ ; 28(5): 1610-1626, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33273695

RESUMO

The receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. Recent studies suggest that RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome. Additionally, it could ameliorate or prevent multi-organ failure induced by cytokine release in the context of hyperinflammation, as seen in COVID-19 patients. Therefore, we searched for a RIPK1 inhibitor and present the aromatic antiepileptic and FDA-approved drug primidone (Liskantin®) as a potent inhibitor of RIPK1 activation in vitro and in a murine model of TNFα-induced shock, which mimics the hyperinflammatory state of cytokine release syndrome. Furthermore, we detected for the first time RIPK1 activation in the respiratory tract epithelium of hospitalized patients who tested positive for SARS-CoV-2 infection. Our data provide a strong rationale for evaluating the drug primidone in conditions of hyperinflammation in humans.


Assuntos
COVID-19/enzimologia , Primidona/farmacologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , SARS-CoV-2/metabolismo , Animais , COVID-19/patologia , Morte Celular/efeitos dos fármacos , Células HEK293 , Células HT29 , Humanos , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Inflamação/patologia , Células Jurkat , Camundongos , Células NIH 3T3 , Células U937
13.
Artigo em Inglês | MEDLINE | ID: mdl-35070493

RESUMO

Background: There are few medications for the treatment of essential tremor (ET). One of these, primidone, which is one of only two front-line agents, is associated with considerable adverse drug reactions (ADRs). It is unclear why some primidone-treated ET patients develop ADRs whereas others do not, and why these ADRs seem to be more prevalent in ET patients than primidone-treated patients with epilepsy. Objective: To review several possible explanations underlying the above-referenced differences. Methods: A literature search was conducted in PubMed in October 2021. Studies reporting the ADRs of primidone in different neurological conditions were comprehensively reviewed. Discussion: Although there were no head-to-head data, a review of the previous studies on ET and epilepsy patients indicates that the former is relatively more intolerant to primidone. Moreover, not all ET patients develop ADR of similar nature or severity. We discuss several potential mechanisms for this variability in the intolerance to primidone. These include: (i) older age (ET vs. epilepsy patients), (ii) cross-tolerance to primidone in patients with epilepsy, (iii) neurobiological (GABA-related) abnormalities associated with ET. Conclusion: We speculate that there are several possible explanations for primidone intolerance in ET. These possibilities should be tested in future studies, and we propose the roadmap for designing these studies. It is of value to obtain detailed insight into these complex issues because primidone remains one of the few frontline anti-tremor medications in ET. Answers to issues we have raised in this article could facilitate more customized formulation of primidone in ET patients.


Assuntos
Tremor Essencial , Primidona , Idoso , Tremor Essencial/tratamento farmacológico , Humanos , Primidona/efeitos adversos , Tremor
14.
Braz. dent. sci ; 24(1): 1-9, 2021. tab, ilus
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1141391

RESUMO

Objective: Gingival hyperplasia (GH) is one of the side effects of anticonvulsant drugs. The aim of this study was to verify the prevalence of GH associated with the use of anticonvulsant, through a systematic review. Material and Methods: Systematic search was done at databases Pubmed and Embase between January 1984 and March of 2020 for identification of articles addressing the prevalence of GH associated with the use of anticonvulsant drugs. The methodological index for non-randomized studies (MINORS) was independently assessed for quality in the selected papers. Results: The search identified 4.471 references. Nine articles were selected and evaluated 632 participants. All of the studies included in the systematic review showed a low risk of bias. The anticonvulsants used by patients were carbamazepine, ethosuximide, phenytoin, primidone, phenobarbital, sodium valproate. The studies showed a correlation between different types of anticonvulsants and GH prevalence, with a range from 0% to 73%. Among the anticonvulsants used, phenytoin showed the greatest incidence of GH, varying between 15.61% and 73% in patients. Conclusion: In the analysis of the results obtained in the literature, it is possible to notice that the great majority of studies presented incidence of GH associated with anticonvulsant use. However, further studies are necessary to understand the anticonvulsant action mechanism inducing GH, as well as the prevention forms, given that GH is a significant side effect. (AU)


Objetivo: Hiperplasia gengival (HG) é um dos efeitos colaterais das drogas anticonvulsivantes. O objetivo deste estudo foi verificar a prevalência de HG associada ao uso de anticonvulsivantes, por meio de uma revisão sistemática. Material e Métodos: A busca sistemática foi realizada nas bases de dados Pubmed e Embase entre janeiro de 1984 e março de 2020 para identificação de artigos que abordassem a prevalência de HG associada ao uso de drogas anticonvulsivantes. Foi avaliado independentemente, o risco de viés através do "Methodological index for non-randomized studies" (MINORS), para análise da qualidade dos trabalhos selecionados. Resultados: A pesquisa identificou 4.471 referências. Nove artigos foram selecionados e avaliaram 632 participantes. Todos os estudos incluídos na revisão sistemática mostraram baixo risco de viés. Os anticonvulsivantes utilizados pelos pacientes foram carbamazepina, etossuximida, fenitoína, primidona, fenobarbital e valproato de sódio. Os estudos mostraram correlação entre os diferentes tipos de anticonvulsivantes e a prevalência de HG, com variação entre 0% a 73%. Entre os anticonvulsivantes utilizados, a fenitoína apresentou a maior incidência de HG, variando entre 15,61% e 73% em pacientes. Conclusão: Na análise dos resultados obtidos na literatura, é possível notar que a grande maioria dos estudos apresentou incidência de HG associada ao uso de anticonvulsivantes. No entanto, estudos adicionais são necessários para compreender o mecanismo de ação do anticonvulsivante para a indução da HG, bem como as formas de prevenção, dado que a HG é um efeito colateral significativo (AU)


Assuntos
Humanos , Fenobarbital , Fenitoína , Primidona , Carbamazepina , Prevalência , Ácido Valproico , Etossuximida , Hiperplasia Gengival , Anticonvulsivantes
15.
Clin Chem Lab Med ; 58(5): 828-835, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32045349

RESUMO

Background Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) can serve as a valuable tool in optimising and individualising epilepsy treatment, especially in vulnerable groups such as pregnant women, the elderly and children. Unfortunately, TDM is often performed suboptimally due to limitations in blood collection. Therefore, we investigated volumetric absorptive micro sampling (VAMS) - a new home-sampling technique. We aimed to evaluate VAMS to determine and quantify the different AEDs and concentrations of 16 different AEDs in whole blood collected by VAMS. Methods Patient blood samples (n = 138) were collected via venepunctures at the Academic Centre for Epileptology Kempenhaeghe. AED concentrations were determined, and these concentrations were used to compare the VAMS method (whole blood) with the conventional method (serum). In addition, the recovery was examined as well as the impact of haematocrit. Finally, AED-spiked blood was used to test the stability of the AEDs inside the micro-sampler devices over a period of time and whether temperature had an effect on the stability. Results VAMS allows for an accurate detection of 16 different AEDs within 2 days after sampling. Deviation in recovery was less than 10% and high correlations were found between VAMS and conventional sampling. Moreover, haematocrit does not have an effect with values between 0.3 and 0.5 (L/L). Finally, although storage temperature of VAMS does affect some AEDs, most are unaffected. Conclusions VAMS enables an accurate detection of a wide variety of AEDs within 2 days after sampling.


Assuntos
Anticonvulsivantes/sangue , Teste em Amostras de Sangue Seco/métodos , Monitoramento de Medicamentos/métodos , Carbamazepina/sangue , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Gabapentina/sangue , Hematócrito , Humanos , Primidona/sangue , Espectrometria de Massas em Tandem , Temperatura
16.
Curr Neuropharmacol ; 18(6): 518-537, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31976837

RESUMO

BACKGROUND: Essential Tremor (ET) is likely the most frequent movement disorder. In this review, we have summarized the current pharmacological options for the treatment of this disorder and discussed several future options derived from drugs tested in experimental models of ET or from neuropathological data. METHODS: A literature search was performed on the pharmacology of essential tremors using PubMed Database from 1966 to July 31, 2019. RESULTS: To date, the beta-blocker propranolol and the antiepileptic drug primidone are the drugs that have shown higher efficacy in the treatment of ET. Other drugs tested in ET patients have shown different degrees of efficacy or have not been useful. CONCLUSION: Injections of botulinum toxin A could be useful in the treatment of some patients with ET refractory to pharmacotherapy. According to recent neurochemical data, drugs acting on the extrasynaptic GABAA receptors, the glutamatergic system or LINGO-1 could be interesting therapeutic options in the future.


Assuntos
Tremor Essencial/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Anticonvulsivantes/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Sinapses Elétricas/efeitos dos fármacos , Humanos , Neurofarmacologia , Primidona/uso terapêutico , Propranolol/uso terapêutico
17.
Water Res ; 172: 115463, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31962269

RESUMO

The presence of Dissolved Organic Matter (DOM) can exert a strong influence on the effectiveness of the UV/chlorine process. This study examined the impact of five DOM isolates with different characteristics on the degradation kinetics of model contaminant primidone (PM) during UV/chlorine treatment. The formation of Disinfection By-Products (DBPs) from DOM after 15-min UV/chlorine treatment followed by 24 h chlorination was investigated and compared with chlorination alone. The use of chemical probes and radical scavengers revealed that •OH and ClO• were the main radical species responsible for the loss of PM at acidic and alkaline conditions, respectively. All tested DOM isolates significantly inhibited the decay of PM. A strong negative correlation (>0.93) was observed between the decay rate constants of PM and SUVA of DOM isolates, except for EfOM isolate, which induced the strongest inhibitory effect due to its higher abundance in sulfur-containing functional groups (i.e., sink of •OH/Cl• radicals). Compared with chlorination, the formation of Adsorbable Organic Chlorine (AOCl) and Trichloromethane (TCM) during the UV/Chlorine process was enhanced and hindered for low SUVA isolates and high SUVA DOM, respectively. However, Dichloroacetonitrile (DCAN) formation was generally lower for all isolates except for Ribou Reservoir DOM at pH 8.4 because of its high reactive nitrogenous DBP precursors at caustic conditions. However, when normalized to the chlorine consumed, the UV/Chlorine process always led to a lower DBPs formation compared with chlorination alone.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Cloro , Desinfecção , Halogenação , Cinética , Primidona
18.
Postgrad Med J ; 96(1132): 84-93, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31575730

RESUMO

Essential tremor is the most common cause of tremor involving upper limbs, head and voice. The first line of treatment for limb tremor is pharmacotherapy with propranolol or primidone. However, these two drugs reduce the tremor severity by only half. In medication refractory and functionally disabling tremor, alternative forms of therapy need to be considered. Botulinum toxin injections are likely efficacious for limb, voice and head tremor but are associated with side effects. Surgical interventions include deep brain stimulation; magnetic resonance-guided focused ultrasound and thalamotomy for unilateral and deep brain stimulation for bilateral procedures. Recent consensus classification for essential tremor has included a new subgroup, 'Essential tremor plus', who have associated subtle neurological 'soft signs', such as dystonic posturing of limbs and may require a different treatment approach. In this review, we have addressed the current management of essential tremor with regard to different anatomical locations of tremor as well as different modalities of treatment.


Assuntos
Inibidores da Liberação da Acetilcolina/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Estimulação Encefálica Profunda/métodos , Tremor Essencial/terapia , Moduladores GABAérgicos/uso terapêutico , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Tálamo/cirurgia , Toxinas Botulínicas/uso terapêutico , Tremor Essencial/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Primidona/uso terapêutico , Propranolol/uso terapêutico , Cirurgia Assistida por Computador , Estimulação Magnética Transcraniana
19.
Neurologist ; 24(5): 150-151, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478998

RESUMO

INTRODUCTION: Dupuytren, Ledderhose, and Peyronie diseases are chronic fibrotic conditions related to progressive fibrosis of the palmar fascia, plantar fascia, and tunica albuginea, respectively. These conditions have been associated with antiepileptic drug use, mainly phenobarbital and primidone. CASE REPORT: A 71-year-old man developed simultaneous Dupuytren, Ledderhose, and Peyronie diseases after primidone use for essential tremor. CONCLUSIONS: There are a few reports associating barbiturate use to connective tissue disorders, and some suggest that drug withdrawal may result in a better prognosis. Therefore, physicians must be aware of such adverse events when caring for patients on long-term barbiturate use.


Assuntos
Anticonvulsivantes/efeitos adversos , Contratura de Dupuytren/induzido quimicamente , Tremor Essencial/tratamento farmacológico , Fibromatose Plantar/induzido quimicamente , Induração Peniana/induzido quimicamente , Primidona/efeitos adversos , Idoso , Tremor Essencial/complicações , Humanos , Masculino
20.
Sci Total Environ ; 696: 133826, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450049

RESUMO

Pharmaceutical and personal care products (PPCPs) are a group of emerging contaminants that have frequently been detected in aqueous environments. Phototransformation driven by solar irradiation is one of the most important natural processes for the elimination of PPCPs. In this study, primidone (PMD) was chosen as a model "photorefractory" compound. A series of experiments were conducted to assess if reactive intermediates (RIs), such as hydroxyl radical (HO), singlet oxygen (1O2), and triplet states of dissolved organic matter (3DOM⁎), inhibited or enhanced the photochemical transformation of PMD under simulated solar irradiation. The results indicate that HO plays a key role in the photodegradation of PMD and that dissolved oxygen can affect the degradation rate of PMD by promoting HO formation. Our results demonstrated that PMD can not only react with free HO (HO-free) but also react with lower-energy hydroxylation agents (HO-like). The contributions of HO-free and HO-like to PMD degradation in various dissolved organic matter (DOM) solutions were estimated by a methane-quenching experiment. The results indicated that the HO-like species were important in the photodegradation of "photorefractory" compounds. The bimolecular reaction rate constant of the reaction of free HO with PMD was measured as (5.21 ±â€¯0.02) × 109 M-1 s-1 by using electron pulse radiolysis. Furthermore, PMD was used as a probe to estimate the steady-state concentration of HO-free in various DOM solutions. Using the multivariate statistical strategies of orthogonal projection to latent structures discriminant analysis (OPLS-DA) and hierarchical clustering, 28 photochemical transformation products (TPs) of PMD were successfully identified from the DOM matrix.


Assuntos
Cosméticos/análise , Fotólise , Primidona/análise , Poluentes Químicos da Água/análise , Radical Hidroxila , Oxigênio Singlete
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