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1.
J Water Health ; 21(11): 1703-1715, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38017600

RESUMEN

Illegal mining has overshadowed pharmaceutical pollution even though exposure to pharmaceutical waste is high. Consumption of fish potentially polluted with pharmaceuticals from the rivers continues with little concern or potential threat it poses. In the present study, the residues of one antibiotic (Chloramphenicol), five hormones (progesterone, 17-beta Estradiol, Estrone, 17a-Ethynylestradiol, and one), three environmental contaminants (4-para-nonylphenol, 4-tert-octylphenol, and Bisphenol A), one barbiturate (Primidone) and one analgesic (Diclofenac sodium salt), were investigated from fish samples from the rivers Pra, Narkwa, and the Volta. The results show a high concentration of drugs in River Pra in comparison to those in Rivers Narkwa and Volta. The hazard quotients (HQs) for the environmental contaminants were all above 1, except Bisphenol A. Furthermore, the HQs from this study suggest that consumers of fish from any of the three rivers stand a hazard risk of Chloramphenicol (19), 17a-Ethynylestradiol (4), Estrone (1.366), Diclofenac sodium salt (3.29), Progesterone (4.598), 4-tert-octylphenol (87.2), and 4-para-nonylphenol (7.252), but negligible risk against E2 (0.687), Primidone (0.014), Testosterone (0.16), and Bisphenol A (0.642). Of the fish species studied, the highest concentration of all pharmaceuticals put together is found in Clarias gariepinus, Labeo senegalensis, and Chrysichthys nigrodigitatus in that order.


Asunto(s)
Bagres , Contaminantes Químicos del Agua , Animales , Estrona , Progesterona/análisis , Ghana , Primidona/análisis , Diclofenaco , Preparaciones Farmacéuticas , Medición de Riesgo , Cloranfenicol/análisis , Agua , Contaminantes Químicos del Agua/análisis , Ríos/química , Monitoreo del Ambiente/métodos
2.
Brain Nerve ; 74(5): 637-644, 2022 May.
Artículo en Japonés | MEDLINE | ID: mdl-35589658

RESUMEN

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.


Asunto(s)
Temblor Esencial , Actividades Cotidianas , Temblor Esencial/tratamiento farmacológico , Temblor Esencial/cirugía , Humanos , Japón , Primidona/uso terapéutico
3.
Artículo en Inglés | MEDLINE | ID: mdl-35415009

RESUMEN

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.


Asunto(s)
Temblor Esencial , Temblor Esencial/tratamiento farmacológico , Humanos , Primidona/uso terapéutico , Propranolol/uso terapéutico , Estudios Retrospectivos , Topiramato/uso terapéutico
4.
Pain ; 163(11): 2200-2212, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35413036

RESUMEN

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.


Asunto(s)
Dolor Crónico , Cistitis Intersticial , Cistitis , Canales Catiónicos TRPM , Canales de Potencial de Receptor Transitorio , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Dolor Crónico/complicaciones , Ciclofosfamida/toxicidad , Cistitis/inducido químicamente , Cistitis/complicaciones , Cistitis/metabolismo , Cistitis Intersticial/complicaciones , Hiperalgesia/tratamiento farmacológico , Primidona/uso terapéutico , ARN , ARN Mensajero/metabolismo , Ratas , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo , Regulación hacia Arriba , Vejiga Urinaria/inervación
5.
Braz. dent. sci ; 24(1): 1-9, 2021. tab, ilus
Artículo en Inglés | BBO - Odontología, LILACS | ID: biblio-1141391

RESUMEN

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)


Asunto(s)
Humanos , Fenobarbital , Fenitoína , Primidona , Carbamazepina , Prevalencia , Ácido Valproico , Etosuximida , Hiperplasia Gingival , Anticonvulsivantes
6.
Postgrad Med J ; 96(1132): 84-93, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31575730

RESUMEN

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.


Asunto(s)
Inhibidores de la Liberación de Acetilcolina/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Estimulación Encefálica Profunda/métodos , Temblor Esencial/terapia , Moduladores del GABA/uso terapéutico , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Tálamo/cirugía , Toxinas Botulínicas/uso terapéutico , Temblor Esencial/fisiopatología , Humanos , Imagen por Resonancia Magnética , Primidona/uso terapéutico , Propranolol/uso terapéutico , Cirugía Asistida por Computador , Estimulación Magnética Transcraneal
7.
Neurologist ; 24(5): 150-151, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31478998

RESUMEN

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.


Asunto(s)
Anticonvulsivantes/efectos adversos , Contractura de Dupuytren/inducido químicamente , Temblor Esencial/tratamiento farmacológico , Fibromatosis Plantar/inducido químicamente , Induración Peniana/inducido químicamente , Primidona/efectos adversos , Anciano , Temblor Esencial/complicaciones , Humanos , Masculino
8.
Molecules ; 24(9)2019 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-31058864

RESUMEN

In this work, primidone, a high persistent pharmacological drug typically found in urban wastewaters, was degraded by different ozone combined AOPs using TiO2 P25 and commercial WO3 as photocatalyst. The comparison of processes, kinetics, nature of transformation products, and ecotoxicity of treated water samples, as well as the influence of the water matrix (ultrapure water or a secondary effluent), is presented and discussed. In presence of ozone, primidone is rapidly eliminated, with hydroxyl radicals being the main species involved. TiO2 was the most active catalyst regardless of the water matrix and the type of solar (global or visible) radiation applied. The synergy between ozone and photocatalysis (photocatalytic ozonation) for TOC removal was more evident at low O3 doses. In spite of having a lower band gap than TiO2 P25, WO3 did not bring any beneficial effects compared to TiO2 P25 regarding PRM and TOC removal. Based on the transformation products identified during ozonation and photocatalytic ozonation of primidone (hydroxyprimidone, phenyl-ethyl-malonamide, and 5-ethyldihydropirimidine-4,6(1H,5H)-dione), a degradation pathway is proposed. The application of the different processes resulted in an environmentally safe effluent for Daphnia magna.


Asunto(s)
Óxidos/química , Ozono/química , Primidona/análisis , Titanio/química , Tungsteno/química , Contaminantes Químicos del Agua/análisis , Animales , Catálisis , Daphnia/efectos de los fármacos , Daphnia/crecimiento & desarrollo , Radical Hidroxilo/química , Cinética , Oxidación-Reducción , Procesos Fotoquímicos , Luz Solar , Rayos Ultravioleta , Agua/química , Purificación del Agua
9.
JAMA Otolaryngol Head Neck Surg ; 142(2): 117-21, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26660910

RESUMEN

IMPORTANCE: Essential vocal tremor is difficult to treat. An effective pharmacologic treatment could allow patients to avoid or decrease the frequency or dosage of botulinum neurotoxin injections. OBJECTIVE: To evaluate the efficacy of primidone in the treatment of essential vocal tremor. DESIGN, SETTING, AND PARTICIPANTS: Medical records of all patients with a primary or secondary diagnosis of laryngeal spasm or essential tremor treated with primidone between June 1, 2012, and March 21, 2014, at a tertiary care medical center were reviewed. Data analysis occurred in April 2014. MAIN OUTCOMES AND MEASURES: Duration of therapy, improvement of symptoms, and whether the patient subsequently initiated botulinum neurotoxin therapy. RESULTS: All 30 patients were female (mean [SD] age, 71.9 [11.8] years). Mean (SD) therapy duration was 5.25 (7.22) months. Nine patients (30%) had other vocal conditions (4 had coexisting spasmodic dysphonia, 4 had laryngopharyngeal reflux disease, and 1 had muscle tension dysphonia). Twelve (40%) had previously undergone treatment. Fourteen of 26 patients (54%) reported an improvement in their vocal symptoms, and 16 of 29 (55%) did not discontinue primidone therapy. Twenty-two of 30 patients (73%) experienced adverse effects. Therapy was discontinued by 11 of 21 patients (52%) who experienced adverse effects and 2 of 8 patients (25%) who did not report adverse effects (P = .24) (1 patient who had adverse effects was missing data on discontinuation of therapy). Sixteen patients (53%) subsequently initiated botulinum toxin therapy, including 5 of 14 patients (36%) who reported clinical improvement with primidone therapy and 7 of 12 patients (58%) who did not report improvement (P = .43). CONCLUSIONS AND RELEVANCE: Primidone therapy was an effective pharmacologic treatment for essential vocal tremor in 14 of 26 patients in this case series, providing an alternative to botulinum neurotoxin therapy.


Asunto(s)
Músculos Laríngeos/efectos de los fármacos , Primidona/uso terapéutico , Calidad de la Voz , Anciano , Toxinas Botulínicas Tipo A/uso terapéutico , Femenino , Humanos , Inyecciones Intramusculares , Músculos Laríngeos/fisiopatología , Fármacos Neuromusculares/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Disfunción de los Pliegues Vocales/tratamiento farmacológico , Disfunción de los Pliegues Vocales/fisiopatología
10.
BMC Psychiatry ; 15: 157, 2015 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-26163145

RESUMEN

BACKGROUND: With aging of society the absolute number and the proportion of patients with cognitive deficits increase. Multiple disorders and diseases can foster cognitive impairment, e.g., Alzheimer's disease (AD), depressive disorder, or polypharmacy. CASE PRESENTATION: A 74 year old man presented to the Old Age Psychiatry Service with cognitive deficits while being treated for recurrent depressive episodes and essential tremor with Venlafaxine, Lithium, and Primidone. Neuropsychological testing revealed a medio-temporal pattern of deficits with pronounced impairment of episodic memory, particularly delayed recall. Likewise, cognitive flexibility, semantic fluency, and attention were impaired. Positron emission tomography (PET) with fluorodeoxyglucose was performed and revealed a pattern of glucose utilization deficit resembling AD. On cessation of treatment with Lithium and Primidone, cognitive performance improved, particularly episodic memory performance and cognitive flexibility. Likewise, glucose metabolism normalized. Despite normalization of both, clinical symptoms and glucose utilization, the patient remained worried about possible underlying Alzheimer's disease pathology. To rule this out, an amyloid-PET was performed. No cortical amyloid was observed. CONCLUSION: Pharmacological treatment of older subjects may mimic glucose metabolism and clinical symptoms of Alzheimer's disease. In the present case both, imaging and clinical findings, reversed to normal on change of treatment. Amyloid PET is a helpful tool to additionally rule out underlying Alzheimer's disease in situations of clinical doubt even if clinical or other imaging findings are suggestive of Alzheimer's disease.


Asunto(s)
Antidepresivos/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastornos del Metabolismo de la Glucosa/inducido químicamente , Trastornos de la Memoria/inducido químicamente , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Anticonvulsivantes/efectos adversos , Atención/efectos de los fármacos , Trastornos del Conocimiento/diagnóstico por imagen , Trastorno Depresivo Mayor/diagnóstico por imagen , Diagnóstico Diferencial , Quimioterapia Combinada , Temblor Esencial/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Trastornos del Metabolismo de la Glucosa/diagnóstico por imagen , Humanos , Compuestos de Litio/efectos adversos , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Memoria Episódica , Recuerdo Mental/efectos de los fármacos , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones/métodos , Primidona/efectos adversos , Radiofármacos , Recurrencia , Clorhidrato de Venlafaxina/efectos adversos
12.
Parkinsonism Relat Disord ; 19(2): 171-5, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23062997

RESUMEN

BACKGROUND: Many essential tremor patients continue to require tremor suppressing medications following deep brain stimulation. The true incidence of medication usage in the years following surgery remains unclear, and the use of medications has not been included in the post-operative analyses of tremor severity and also quality of life. METHODS: Among 28 essential tremor patients treated with deep brain stimulation at a single center between January 2002 and April 2010, we analyzed the prevalence and dosage of pre-operative tremor suppressing medications versus post-operative medications at 12 and 36 months following surgery. We also assessed the influence of medication continuation on clinical outcome measures, such as the Fahn-Tolosa-Marin Tremor Rating Scale, and the 36 item short-form health quality of life survey. RESULTS: Both unilateral and bilateral deep brain stimulation resulted in a decrease in primidone use (p = 0.0082, 0.046, respectively), and bilateral deep brain stimulation patients used less tremor suppressing medications 36 months following surgery (p = 0.02). The decision to discontinue primidone after surgery resulted in a non-significant long-term improvement in tremor motor score (23 points versus 15 points, p = 0.19), and did not significantly influence the physical and mental composite quality of life scores (p = 0.81, 0.23, respectively). CONCLUSIONS: Bilateral deep brain stimulation effectively eliminated the need for tremor suppressing medications, while unilateral stimulation was not as effective in reducing medication usage. Clinicians and patients should be aware that discontinuation of primidone after surgery may worsen tremor in unilateral deep brain stimulation cases, but discontinuation will not likely impact quality of life.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Estimulación Encefálica Profunda/métodos , Temblor Esencial/terapia , Primidona/uso terapéutico , Anciano , Terapia Combinada , Femenino , Humanos , Masculino , Resultado del Tratamiento
13.
Cas Lek Cesk ; 150(8): 451-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22026081

RESUMEN

Epilepsy is a serious health disorder affecting both paediatric and adult population worldwide. Due to difficulties in identifying its aetiology, initial management is often guided by empiric therapy measures. Symptomatic control requires the use of antiepileptic drugs (AEDs), many of which have the potential for adverse drug interactions. Children are especially susceptible to drug interactions and frequently exhibit atypical adverse events, which may require special care. Aim. To demonstrate a case of a 15 year old girl suffering from refractory epilepsy with underlying focal cortical dysplasia (FCD), whose seizure deterioration was most probably associated with drug-drug interactions between prescribed common antiepileptic drugs, namely valproic acid, phenobarbital or the prodrug primidon and carbamazepine.


Asunto(s)
Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Adolescente , Encéfalo/anomalías , Carbamazepina/efectos adversos , Interacciones Farmacológicas , Quimioterapia Combinada , Epilepsia/complicaciones , Femenino , Humanos , Fenobarbital/efectos adversos , Primidona/efectos adversos , Ácido Valproico/efectos adversos
14.
Parkinsonism Relat Disord ; 16(9): 604-7, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20691629

RESUMEN

BACKGROUND: Although small treatment trials have examined the efficacy of front-line medications in tremor reduction in essential tremor (ET), an overall survey of pharmacological management has not been undertaken in a large sample of ET cases. OBJECTIVES: To conduct a survey of medication usage among several hundred ET patients. METHODS: A computerized database at the Neurological Institute of New York was used to identify 223 ET patients cared for by movement disorder neurologists and 37 cared for by general neurologists. Each had been seen one or more times within past five years. Lifetime treatment data were abstracted from clinical records. RESULTS: One-hundred-sixty-three (73.1%) of 223 patients cared for by movement disorder neurologists had taken medication for ET during their lifetime; 53/163 (32.5%) had taken ≥4 medications; 31/163 (19.0%) had taken ≥5 medications; and 3 (1.8%), ≥10 medications. Nearly three-quarters (158/223 [70.9%]) had taken primidone or propranolol, yet 89/158 (56.3%) had discontinued both. Among 11 patients who had undergone ET surgery, the mean number of ET medications tried was 6.0 ± 2.8 (range = 3-12). Medication usage by general neurologists was less than by movement disorder specialists (p < 0.001). One-third of general neurologists' patients (14/37 [37.8%]) had taken primidone or propranolol at some point and 6/14 (42.9%) had discontinued both. CONCLUSIONS: In this large survey, a substantial proportion of ET patients failed treatment with both front-line medications. Among patients seeing movement disorder specialists, the number of medications they had had to try was sizable. These data demonstrate the limitations of current pharmacological options for ET.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Temblor Esencial/tratamiento farmacológico , Neurología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Especialización , Adulto , Anciano , Utilización de Medicamentos , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , New York , Primidona/uso terapéutico , Propranolol/uso terapéutico , Adulto Joven
16.
Psychiatr Serv ; 60(11): 1439-45, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19880458

RESUMEN

The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a large-scale practical clinical trial to determine which of several treatments are the most effective "next-steps" for patients with major depressive disorder whose symptoms do not remit or who cannot tolerate an initial treatment and, if needed, ensuing treatments. Entry criteria were broadly defined and inclusive, and patients were enrolled from psychiatric and primary care clinics. All participants began on citalopram and were managed by clinic physicians, who followed an algorithm-guided acute-phase treatment through five visits over 12 weeks. At the end of each sequence, patients whose depression had not fully remitted were eligible for subsequent randomized trials in a sequence of up to three clinical trials. In general, remission rates in the study clinics were lower than expected, suggesting the need for several steps to achieve remission for most patients. There was no clear medication "winner" for patients whose depression did not remit after one or more aggressive medication trials. Both switching and augmenting appeared to be reasonable options when an initial antidepressant treatment failed, although these two strategies could not be directly compared. Further, the likelihood of remission after two vigorous medication trials substantially decreased, and remission would likely require more complicated medication regimens for which the existing evidence base is quite thin. STAR*D demonstrated that inclusion of more real-world patients in clinical trials is both feasible and informative. Policy implications of the findings, as well as the study's limitations, are discussed.


Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Adolescente , Adulto , Anciano , Bupropión/uso terapéutico , Citalopram/uso terapéutico , Terapia Cognitivo-Conductual , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/terapia , Inhibidores de Captación de Dopamina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Primidona/uso terapéutico , Inducción de Remisión , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del Tratamiento , Clorhidrato de Venlafaxina , Adulto Joven
17.
Seizure ; 18(2): 109-18, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18760938

RESUMEN

Phenobarbital and primidone frequently have adverse effects on mental functions. Therefore, an attempt was made to taper barbiturates in 85 patients out of a resident population with epilepsy and intellectual disability who were selected according to clinical criteria. The objectives were to reduce the use of barbiturates, to improve the patients' cognitive and psychological state, and to reduce polypharmacy while avoiding seizure exacerbation. Four months after complete withdrawal changes in seizure frequency were assessed as well as changes in cognitive abilities, psychological state and behaviour (using the clinical global impression scale). In 13 patients the tapering failed due to complications (seizure increase in 11 patients). In 72 patients the barbiturate was completely withdrawn (mean duration of tapering: 393 days). Cognitive improvement was achieved in 17 patients (23.6%), 5 patients (6.9%) deteriorated. Seizure frequency remained unchanged in 33 patients (45.8%), in another 15 patients (20.8%) the seizure frequency decreased. Reduction in polypharmacy was obtained in 61 patients (84.7%). In an overall judgement (clinical global impression scale) of cognitive abilities AND seizure control, 25 patients (34.7%) were improved. 31 patients (43.1%) remained unchanged while 12 patients deteriorated (4 patients: impossible to judge). For statistical analysis three outcome groups were defined: the improved group (N=25), the unchanged group (N=31), and the deteriorated/failed group (N=25) consisting of the 12 deteriorated patients plus the 13 patients in whom tapering failed. Stepwise logistic regression revealed a history of an attempt to withdraw phenobarbital/primidone (p=0.017; OR 3.8), age (p=0.012) and seizure frequency (marginally significant: p=0.097) as outcome predictors. Older age was associated with better outcome. A high seizure frequency before tapering was related to good outcome, while seizure freedom and a history of failed withdrawal were associated with deterioration/failure. Outcome did not depend on duration of barbiturate therapy, dosage or serum concentration, co-medication, reduction rate, degree of intellectual disability, or epilepsy syndrome. In summary, the number of barbiturate medications has been considerably reduced, but the principal aim of the project, to relieve patients from assumed barbiturate side effects, has been achieved only in one out of four patients.


Asunto(s)
Anticonvulsivantes/efectos adversos , Barbitúricos/efectos adversos , Cognición/efectos de los fármacos , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Discapacidad Intelectual/complicaciones , Quimioterapia Combinada , Humanos , Inteligencia/efectos de los fármacos , Fenobarbital/efectos adversos , Primidona/efectos adversos , Convulsiones/etiología , Convulsiones/prevención & control
18.
Epilepsy Res ; 82(1): 1-6, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18644700

RESUMEN

OBJECTIVES: Patients with epilepsy have excess morbidity and mortality due to ischemic cardiovascular disease. Many of these patients have elevated concentrations of plasma total homocysteine (Hcy), which is an acknowledged risk factor for cardiovascular disease, venous thromboembolic disease, foetal malformations and dementia. Hyperhomocysteinemia may have negative effects through mechanisms involving oxidative damage. In the present study, we have investigated the aminothiol redox-status in patients on antiepileptic drugs. Thereafter, in a subset of patients with elevated total Hcy, we evaluated the effect of B-vitamin therapy. METHODS: In the first part of the study, 101 patients on antiepileptic drugs were compared with 101 matched healthy controls. The redox-species of Hcy, cysteine and cysteinylglycine, the major aminothiols in plasma, were analyzed by high-performance liquid chromatography (HPLC). Hyperhomocysteinemia was defined as fasting total Hcy above 12 micromol/L and/or post-methionine load concentrations above 38 micromol/L. In the second part of the study, 33 patients identified with hyperhomocysteinemia were supplemented with three B-vitamins for 30 days; folic acid (B9), pyridoxine (B6) and riboflavin (B2). RESULTS: All redox-species of Hcy were significantly elevated in the patients, except the fasting concentrations of reduced Hcy (p=0.09). The reduced/total ratio of cysteine in fasting plasma was lower in the patients than in the controls: 5.20% vs. 6.19%, respectively (p=0.006). After 30 days of B-vitamin supplementation, the plasma concentrations of reduced, oxidized and protein-bound Hcy species were significantly lowered by 17%, 22% and 28%, respectively. The reduced/total ratio of cysteine rose from 4.9% to 7.9% (p=0.007). CONCLUSIONS: Patients on antiepileptic drugs have abnormal aminothiol redox-status associated with hyperhomocysteinemia. This is similar to findings in patients with cardiovascular disease. B-vitamin supplementation partially corrects the abnormal aminothiol redox-status. Possibly, B-vitamin supplementation may be useful in drug-induced hyperhomocysteinemia.


Asunto(s)
Anticonvulsivantes/efectos adversos , Epilepsia/metabolismo , Ácido Fólico/uso terapéutico , Hiperhomocisteinemia/tratamiento farmacológico , Piridoxina/uso terapéutico , Riboflavina/uso terapéutico , Adulto , Anticonvulsivantes/uso terapéutico , Carbamazepina/efectos adversos , Carbamazepina/uso terapéutico , Estudios de Casos y Controles , Cisteína/sangre , Dipéptidos/sangre , Evaluación de Medicamentos , Epilepsia/tratamiento farmacológico , Femenino , Ácido Fólico/administración & dosificación , Humanos , Hiperhomocisteinemia/inducido químicamente , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Metionina , Oxidación-Reducción , Fenobarbital/efectos adversos , Fenobarbital/uso terapéutico , Fenitoína/efectos adversos , Fenitoína/uso terapéutico , Primidona/efectos adversos , Primidona/uso terapéutico , Piridoxina/administración & dosificación , Riboflavina/administración & dosificación , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéutico , Deficiencia de Vitamina B/sangre , Deficiencia de Vitamina B/inducido químicamente , Deficiencia de Vitamina B/tratamiento farmacológico
19.
Epilepsia ; 49(11): 1965-8, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18513351

RESUMEN

Despite contrary recommendations by expert opinion and international guidelines phenobarbital remains the most widely prescribed anticonvulsant worldwide. Although associated connective tissue disorders were described in a timely way after its introduction, the association between plantar fibromatosis--also called Ledderhose syndrome--and phenobarbital seems not to be well known in general. Our case series uniquely demonstrates that continuous phenobarbital treatment leads to recurrent plantar fibromatosis and may result in long-term disability and numerous unnecessary operations. In general, the association between connective tissue disorders and phenobarbital most prominently appears in adult patients of northern European descent. However, our case series and data from the literature suggest that patient groups less susceptible to connective tissue disorders may as well develop Ledderhose syndrome or other associated syndromes as Dupuytren's contractures, frozen shoulder, Peyronie's disease or complex regional pain syndrome in the course of phenobarbital treatment.


Asunto(s)
Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Fibroma/inducido químicamente , Fibroma/patología , Enfermedades del Pie/inducido químicamente , Enfermedades del Pie/patología , Neoplasias de Tejido Conjuntivo/inducido químicamente , Neoplasias de Tejido Conjuntivo/patología , Fenobarbital/efectos adversos , Adulto , Esquema de Medicación , Quimioterapia Combinada , Femenino , Fibroma/cirugía , Enfermedades del Pie/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Recurrencia Local de Neoplasia , Neoplasias de Tejido Conjuntivo/cirugía , Primidona/uso terapéutico
20.
Med Clin (Barc) ; 129(16): 632-7, 2007 Nov 03.
Artículo en Español | MEDLINE | ID: mdl-18001678

RESUMEN

Essential tremor is the most common adult movement disorder. Traditionally considered as a benign disease, it can cause an important physical and psychosocial disability. Drug treatment remains poor and often unsatisfactory. Current therapeutical strategies are reviewed according to the level of discomfort caused by tremor: mild tremor, non-pharmacological strategies, alcohol, acute pharmacological therapy; moderate tremor, pharmacological therapies (propranolol, gabapentin, primidone, topiramate, alprazolam and other drugs), and severe tremor, the role of functional surgery is emphasized (thalamic deep brain stimulation, thalamotomy). It is also described the more specific treatment of head tremor with the use botulinum toxin. Finally, several points are exposed to guide the immediate research of this disease in near future.


Asunto(s)
Temblor Esencial/tratamiento farmacológico , Adulto , Anciano , Alprazolam/efectos adversos , Alprazolam/uso terapéutico , Aminas/efectos adversos , Aminas/uso terapéutico , Antipsicóticos/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Ácidos Ciclohexanocarboxílicos/efectos adversos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Estimulación Encefálica Profunda , Temblor Esencial/epidemiología , Temblor Esencial/cirugía , Fructosa/efectos adversos , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Gabapentina , Movimientos de la Cabeza , Humanos , Persona de Mediana Edad , Primidona/efectos adversos , Primidona/uso terapéutico , Propranolol/efectos adversos , Propranolol/uso terapéutico , Índice de Severidad de la Enfermedad , Tálamo/fisiopatología , Tálamo/cirugía , Topiramato , Tranquilizantes/uso terapéutico , Trastornos de la Voz/tratamiento farmacológico , Trastornos de la Voz/etiología , Ácido gamma-Aminobutírico/efectos adversos , Ácido gamma-Aminobutírico/uso terapéutico
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