RESUMEN
Misuse of prescription medications has risen to popularity. Reasons for this practice include the self-medication of sleep and psychiatric disorders and attempts to counteract the dysphoric side effects of stimulant drugs. Clonazepam, a commonly prescribed benzodiazepine, has been increasingly used as a countermeasure to cocaine side-effects, including sleep reduction and anxiety. As both substances may impair sleep and aggravate psychiatric conditions, this study aimed to evaluate the long-term effects of the interaction of clonazepam and cocaine on anxiety-like behavior, and the short-term effects of this drug combination on sleep using male Wistar rats. Animals received saline, cocaine (15 mg/kg), clonazepam (1.25 mg/kg) or both drugs for 16 days. Sleep recording was performed on the first day of treatment to evaluate acute treatment effects. One day after the end of the treatment period, the open field and elevated plus-maze tests were used to assess anxiety-like behavior. Blood samples were collected for analysis of corticosterone levels. Rats receiving both drugs presented an increase in impulsivity when moving between arms in the elevated plus-maze and a reduction in exploratory behavior in the open field test. These findings suggest the presence of a withdrawal behavioral syndrome, which can manifest as a paradoxical increase in exploratory activity after a period without receiving the drug and may indicate the development of dependence. Combined treatment reduced paradoxical sleep time and increased its onset latency. There was no significant difference regarding corticosterone levels across any group. Our results contribute to the understanding of the risks of combining cocaine and clonazepam. Association of these drugs may impair sleep architecture and aggravate the dependence symptoms already seen when these substances are used separately. These findings may be useful in helping to counteract the impairments resulting from the combined use of these 2 substances and to raise awareness of these associated risks.
Asunto(s)
Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Clonazepam/efectos adversos , Clonazepam/farmacología , Cocaína/efectos adversos , Cocaína/farmacología , Sueño REM/efectos de los fármacos , Síndrome de Abstinencia a Sustancias/etiología , Animales , Ansiedad/sangre , Clonazepam/administración & dosificación , Cocaína/administración & dosificación , Corticosterona/sangre , Conducta Exploratoria/efectos de los fármacos , Masculino , Prueba de Campo Abierto/efectos de los fármacos , Ratas , Ratas Wistar , Síndrome de Abstinencia a Sustancias/sangreRESUMEN
Clonazepam is a benzodiazepine commonly prescribed to treat panic disorder, epilepsy, anxiety, depression and certain types of seizures. This study aimed to evaluate the bioequivalence between two formulations of clonazepam tablets in order to meet regulatory requirements for marketing in Colombia and other countries in Latin America. An open-label, randomized, single-dose, two-period, two-sequence, two-treatment crossover study was conducted in 36 healthy subjects of both genders. Subjects received a single dose of clonazepam 2 mg test tablet (Sanofi-Aventis de Colombia S.A.) and reference product (Rivotril®, Produtos Roche Químicos e Farmacêuticos S.A.) under fasting conditions according to a randomly assigned order with a 21-day washout period. Serial blood samples were collected up to 96 h post-dose. Plasma concentrations of clonazepam were obtained by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated using non-compartmental methods. A total of 36 healthy subjects were enrolled and 31 of them completed the study. Twenty-nine adverse events were reported (11 events with test product versus 18 events with reference product). There were no serious adverse events during the study. Geometric mean ratios (90% confidence intervals) for Cmax and AUC0-96h were 103.28% (98.10-108.64) and 102.50% (99.87-105.19), respectively. The test formulation of clonazepam 2 mg tablet manufactured by Sanofi-Aventis de Colombia S.A. was considered bioequivalent to reference product Rivotril® (Produtos Roche Químicos e Farmacêuticos S.A.) according to regulatory requirements. Both formulations were safe and well-tolerated during the study.
Asunto(s)
Anticonvulsivantes/farmacocinética , Clonazepam/farmacocinética , Administración Oral , Adolescente , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Área Bajo la Curva , Disponibilidad Biológica , Clonazepam/administración & dosificación , Clonazepam/efectos adversos , Estudios Cruzados , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Comprimidos , Equivalencia Terapéutica , Adulto JovenRESUMEN
This descriptive, ecological study of clonazepam consumption in Rio de Janeiro State (RJ) estimated use prevalence from 2009 to 2013 using data from the National Controlled Product Management System operated by Brazil's health surveillance agency, Anvisa. Consumption was measured by total population and by population over 18 years old, using the standardised Daily Defined Doses of 8 mg (anticonvulsant) and 1 mg (sedative-hypnotic). The municipalities of the Rio de Janeiro Metropolitan Region were grouped by Human Development Index (HDI) and GINI index, subjected to cluster analysis and ranked by clonazepam consumption. From 2009 to 2013, consumption in the state rose from 0.35 to 1.97 DDD/1000 population, but the figures are higher for individuals over 18 years of age. A DDD of 1 mg instead of 8mg returns consumption in 2013 of 21 DDD/1000 population over 18 years of age. Consumption in 2013 was highest - 3.38 and 4.52 DDD, respectively - in Rio de Janeiro and Niterói, which have the highest HDIs. This suggests that up to 2% of the adult population uses clonazepam, possibly as a sedative-hypnotic. This broad use and use outside therapeutic indications deserves attention, given clonazepam's potential for abuse and adverse reactions.
O objetivo do estudo é estimar a prevalência do uso de clonazepam no Estado do Rio de Janeiro (RJ). Estudo ecológico e descritivo do consumo de clonazepam (2009-2013), com dados do Sistema Nacional de Gerenciamento de Produtos Controlados da Anvisa. O consumo foi medido pela Dose Diária Definida, com indicadores por população total e com 18 anos e mais utilizando a DDD padronizada de 8mg (anticonvulsivante) e a de 1mg (hipnosedativo). Os Municípios da Região Metropolitana foram agrupados segundo os Índices de Desenvolvimento Humano (IDH) e de GINI, submetidos à análise de conglomerados e apresentados segundo o consumo de clonazepam. No Estado do RJ, o consumo entre 2009 e 2013 aumentou de 0,35 para 1,97 DDD/1000 habitantes. Os valores são maiores para os indivíduos acima de 18 anos. Empregando-se 1mg ao invés de 8mg, chega-se a 21 DDD/1000 habitantes acima de 18 anos, em 2013. Rio de Janeiro e Niterói, com os maiores IDH, apresentaram em 2013 os maiores consumos, 3,38 e 4,52 DDD, respectivamente. Os dados sugerem que até 2% da população adulta é usuária de clonazepam, possivelmente como hipnosedativo. Deve-se atentar para o uso ampliado e fora de indicações terapêuticas, dados o potencial de abuso e as reações adversas ao clonazepam.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Clonazepam/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Pautas de la Práctica en Medicina/tendencias , Adulto , Brasil , Análisis por Conglomerados , Relación Dosis-Respuesta a Droga , Femenino , Humanos , MasculinoRESUMEN
Resumo O objetivo do estudo é estimar a prevalência do uso de clonazepam no Estado do Rio de Janeiro (RJ). Estudo ecológico e descritivo do consumo de clonazepam (2009-2013), com dados do Sistema Nacional de Gerenciamento de Produtos Controlados da Anvisa. O consumo foi medido pela Dose Diária Definida, com indicadores por população total e com 18 anos e mais utilizando a DDD padronizada de 8mg (anticonvulsivante) e a de 1mg (hipnosedativo). Os Municípios da Região Metropolitana foram agrupados segundo os Índices de Desenvolvimento Humano (IDH) e de GINI, submetidos à análise de conglomerados e apresentados segundo o consumo de clonazepam. No Estado do RJ, o consumo entre 2009 e 2013 aumentou de 0,35 para 1,97 DDD/1000 habitantes. Os valores são maiores para os indivíduos acima de 18 anos. Empregando-se 1mg ao invés de 8mg, chega-se a 21 DDD/1000 habitantes acima de 18 anos, em 2013. Rio de Janeiro e Niterói, com os maiores IDH, apresentaram em 2013 os maiores consumos, 3,38 e 4,52 DDD, respectivamente. Os dados sugerem que até 2% da população adulta é usuária de clonazepam, possivelmente como hipnosedativo. Deve-se atentar para o uso ampliado e fora de indicações terapêuticas, dados o potencial de abuso e as reações adversas ao clonazepam.
Abstract This descriptive, ecological study of clonazepam consumption in Rio de Janeiro State (RJ) estimated use prevalence from 2009 to 2013 using data from the National Controlled Product Management System operated by Brazil's health surveillance agency, Anvisa. Consumption was measured by total population and by population over 18 years old, using the standardised Daily Defined Doses of 8 mg (anticonvulsant) and 1 mg (sedative-hypnotic). The municipalities of the Rio de Janeiro Metropolitan Region were grouped by Human Development Index (HDI) and GINI index, subjected to cluster analysis and ranked by clonazepam consumption. From 2009 to 2013, consumption in the state rose from 0.35 to 1.97 DDD/1000 population, but the figures are higher for individuals over 18 years of age. A DDD of 1 mg instead of 8mg returns consumption in 2013 of 21 DDD/1000 population over 18 years of age. Consumption in 2013 was highest - 3.38 and 4.52 DDD, respectively - in Rio de Janeiro and Niterói, which have the highest HDIs. This suggests that up to 2% of the adult population uses clonazepam, possibly as a sedative-hypnotic. This broad use and use outside therapeutic indications deserves attention, given clonazepam's potential for abuse and adverse reactions.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Pautas de la Práctica en Medicina/tendencias , Clonazepam/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Anticonvulsivantes/administración & dosificación , Brasil , Análisis por Conglomerados , Relación Dosis-Respuesta a DrogaRESUMEN
OBJECTIVE: To assess how pediatric neurologists prescribe home seizure rescue medications to treat acute prolonged seizures and clusters of seizures in children. STUDY DESIGN: A brief, email survey was sent to the members of the Pediatric Epilepsy Research Consortium assessing seizure rescue medication prescribing practices for patients of different age groups, cognitive abilities, and seizure type. Survey responses were anonymous. RESULTS: Thirty-six respondents (of 76 surveyed; 47% response rate) completed the survey. Rectal diazepam was the most commonly chosen rescue medication for a prolonged convulsive seizure in a severely developmentally delayed 16-year-old (44%) and typical and delayed 7-year-old (44% and 61%, respectively), 3-year-old (78% and 86%, respectively), and 9-month-old (83%) patients. Most responders (69%) indicated that developmentally typical 16-year-olds would be prescribed intranasal midazolam. For clusters of seizures, clonazepam orally disintegrating tablets were the most frequent first-line option in all age groups, except developmentally delayed 3-year-old and 9-month-old children, for whom rectal diazepam was chosen more commonly. Medication dosing generally followed standard dosing guidelines with very few exceptions. CONCLUSIONS: Rectal diazepam remains the most frequently used rescue medication for prolonged seizures for nearly all age groups, except in developmentally typical teenagers, for whom intranasal midazolam is used more often. Clonazepam orally disintegrating tablets are the most frequently used medication for treatment of clusters of seizures, except in younger patients. Further work is necessary to establish best practices for type and administration route of seizure rescue medications.
Asunto(s)
Pautas de la Práctica en Medicina , Estado Epiléptico/tratamiento farmacológico , Administración Intranasal , Administración Oral , Administración Rectal , Adolescente , Factores de Edad , Anticonvulsivantes/administración & dosificación , Niño , Preescolar , Clonazepam/administración & dosificación , Discapacidades del Desarrollo/complicaciones , Diazepam/administración & dosificación , Humanos , Lactante , Midazolam/administración & dosificación , Neurología/métodos , Pediatría/métodos , Estado Epiléptico/complicaciones , Encuestas y CuestionariosRESUMEN
El objetivo fue determinar mediante una revisión sistemática, cuáles tratamientos farmacológicos para el Síndrome de Boca Urente (SBU) logran una reducción de síntomas, según Escala Visual Análoga (EVA). Se realizó una búsqueda bibliográfica en la bases de datos PubMed y SciELO, Trip Database, Scopus Database, EBSCO host y LILACS entre el 2005 y 2015. De 72 artículos, se seleccionaron un total de 11. Los tratamientos sistémicos usados fueron, Hipericum perforatum, Catuama, Clonazepam, Ácido alfa lipoico y Lafutidina. Entre los tratamientos tópicos, Aceite de oliva virgen enriquecido con licopeno, Lisozima lactoperoxidasa, Clonazepam y Capsaicina. Los fármacos que obtuvieron mejores resultados para el tratamiento del SBU fueron Lafutidina, Catuama, Clonazepam tópico y sistémico, y en menor grado Capsaicina.
The aim of this study was to determine through a systematic review, which is the best drug treatment for burning mouth syndrome (SBU), measured on a Visual Analogue Scale. A scientific literature search was conducted in PubMed and SciELO, Trip Database, Database Scopus, EBSCO host and LILACS data between 2005 and 2015. Of a total of 72 articles, 11 were included for analysis. Systemic treatments were Lycopene-enriched virgin olive oil, Hypericum perforatum, Catuama, Clonazepam, Alpha lipoic acid; topical treatments were Lysozyme lactoperoxidase, Clonazepam, Capsaicin and Lafutidine. The best results obtained were with Lafutidine, Catuama, topical and systemic Clonazepam, and to a lesser degree Capsaicin.
Asunto(s)
Humanos , Síndrome de Boca Ardiente/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Capsaicina/administración & dosificación , Muramidasa/administración & dosificación , Administración Tópica , Ácido Tióctico/administración & dosificación , Clonazepam/administración & dosificación , Administración Sistémica , Escala Visual AnalógicaAsunto(s)
Síndrome de Boca Ardiente/tratamiento farmacológico , Clonazepam/administración & dosificación , Moduladores del GABA/administración & dosificación , Antisépticos Bucales/uso terapéutico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Proyectos PilotoRESUMEN
La mioclonía poshipoxia crónica o síndrome de Lance Adams es una complicación rara que se produce en pacientes que sobreviven a la hipoxia o la hipotensión prolongada, días o semanas después del daño cerebral. Se presentó un caso con este síndrome, secundario a shock hipovolémico por embarazo ectópico roto. El electroencefalograma con ausencia de paroxismos apoya el origen subcortical de las mioclonías, con respuesta favorable al alonazepán. Se detallaron estudios de neuroimagen y potenciales evocados auditivos de tallo cerebral(AU)
The chronic poshipoxia myoclonus or Lance Adams syndrome is a rare complication that occurs in patients who survive prolonged hypoxia or hypotension, days or weeks after the complication. A case with this syndrome, hypovolemic shock secondary to a ruptured ectopic pregnancy is presented. EEG with no paroxysms supports the origin of myoclonus subcortical with favorable response to alonazepán. Neuroimaging and auditory evoked potentials and brainstem studies were detailed(AU)
Asunto(s)
Humanos , Femenino , Adulto Joven , Síndrome de Adams-Stokes , Mioclonía/tratamiento farmacológico , Clonazepam/administración & dosificación , Choque/tratamiento farmacológicoRESUMEN
CONTEXT: It is known that oxidative stress occurs in peripheral blood in an experimental animal model of diabetes and depression, and acute treatment with insulin and clonazepam (CNZ) has a protective effect on oxidative stress in this model. OBJECTIVE: This study evaluated the effect of insulin plus CNZ on oxidative stress parameters in the liver of diabetic male rats induced with streptozotocin (STZ) and subjected to forced swimming test (FST). MATERIALS AND METHODS: Diabetes was induced by a single intraperitoneal (i.p.) dose of STZ 60 mg/kg in male Wistar rats. Insulin (4 IU/kg) plus CNZ acute i.p. treatment (0.25 mg/kg) was administered 24, 5 and 1 h before the FST. Nondiabetic control rats received i.p. injections of saline (1 mL/kg). Protein oxidative damage was evaluated by carbonyl formation and the antioxidant redox parameters were analyzed by the measurements of enzymatic activities of the superoxide dismutase (SOD), catalase and glyoxalase I (GLO). Glycemia levels also were determined. RESULTS: Our present study has shown an increase in carbonyl content from diabetic rats subjected to FST (2.04 ± 0.55), while the activity of catalase (51.83 ± 19.02) and SOD (2.30 ± 1.23) were significantly decreased in liver from these animals, which were reverted by the treatment. Also, the activity of GLO (0.15 ± 0.02) in the liver of the animals was decreased. DISCUSSION AND CONCLUSION: Our findings showed that insulin plus CNZ acute treatment ameliorate the antioxidant redox parameters and protect against protein oxidative damage in the liver of diabetic rats subjected to FST.
Asunto(s)
Clonazepam/farmacología , Depresión/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Insulina/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Catalasa/metabolismo , Clonazepam/administración & dosificación , Depresión/fisiopatología , Diabetes Mellitus Experimental/fisiopatología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Insulina/administración & dosificación , Lactoilglutatión Liasa/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Oxidación-Reducción/efectos de los fármacos , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Estreptozocina , Superóxido Dismutasa/metabolismo , Factores de TiempoRESUMEN
A consolidated memory recalled by a specific reminder can become unstable (labile) and susceptible to facilitation or impairment for a discrete period of time. This labilization phase is followed by a process of stabilization called reconsolidation. The phenomenon has been shown in diverse types of memory, and different pharmacological agents have been used to disclose its presence. Several studies have revealed the relevance of the GABAergic system to this process. Consequently, our hypothesis is that the system is involved in the reconsolidation of declarative memory in humans. Thus, using our verbal learning task, we analyzed the effect of benzodiazepines on the re-stabilization of the declarative memory. On Day 1, volunteers learned an association between five cue- response-syllables. On Day 2, the verbal memory was labilized by a reminder presentation, and then a placebo capsule or 0.25 mg or 0.03 mg of clonazepam was administered to the subjects. The verbal memory was evaluated on Day 3. The volunteers who had received the 0.25 mg clonazepam along with the specific reminder on Day 2, exhibited memory improvement. In contrast, there was no effect when the drug was given without retrieval, when the memory was simply retrieved instead of being reactivated or when short-term memory testing was performed 4 h after reactivation. We discuss the GABAergic role in reconsolidation, which shows a collateral effect on other memories when the treatment is aimed at treating anxiety disorders. Further studies might elucidate the role of GABA in the reconsolidation process associated with dissimilar scenarios. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
Asunto(s)
Clonazepam/farmacología , Agonistas del GABA/farmacología , Memoria/efectos de los fármacos , Nootrópicos/farmacología , Sustancias para Mejorar el Rendimiento/farmacología , Aprendizaje Verbal/efectos de los fármacos , Adulto , Clonazepam/administración & dosificación , Señales (Psicología) , Relación Dosis-Respuesta a Droga , Femenino , Agonistas del GABA/administración & dosificación , Humanos , Masculino , Memoria a Largo Plazo/efectos de los fármacos , Memoria a Corto Plazo/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Nootrópicos/administración & dosificación , Sustancias para Mejorar el Rendimiento/administración & dosificación , Estudiantes , Adulto JovenRESUMEN
This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Clonazepam/administración & dosificación , Trastorno de Pánico/tratamiento farmacológico , Paroxetina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adolescente , Adulto , Anticonvulsivantes/efectos adversos , Brasil , Clonazepam/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Entrevista Psicológica , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Trastorno de Pánico/diagnóstico , Trastorno de Pánico/psicología , Paroxetina/efectos adversos , Inventario de Personalidad , Estudios Prospectivos , Retratamiento , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Adulto JovenRESUMEN
Numerous countries have witnessed increasing misuse of benzodiazepines. This cross-sectional study assessed the factors associated with prescription of benzodiazepines for users of the Municipal Health Service in Colonel Fabriciano, Minas Gerais State, Brazil. Data were collected from official records on drug prescription (n = 1,866) from September to October 2006. Bivariate and multivariate analyses using Poisson regression were performed. Prolonged benzodiazepine use was independently associated with benzodiazepine type and patient participation in health programs. Concomitant use of other psychoactive drugs was independently associated with age and participation in health programs. Type of benzodiazepine (clonazepam or diazepam) was independently associated with age and gender, as well as with participation in health programs. Factors associated with benzodiazepine prescription show the problem's extent and should be considered in planning interventions to rationalize the use of these drugs in Brazil, particularly through health program planning.
Asunto(s)
Clonazepam/administración & dosificación , Diazepam/administración & dosificación , Factores de Edad , Ansiolíticos/administración & dosificación , Brasil , Estudios Transversales , Interacciones Farmacológicas , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Factores SocioeconómicosRESUMEN
High-potency benzodiazepines, such as clonazepam, are frequently used in the treatment of panic disorder (PD) because of their rapid onset of action and good tolerability. However, there is concern about their potential to cause withdrawal symptoms. We aimed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years. A specific scale for judging withdrawal was also developed, the Composite Benzodiazepine Discontinuation Symptom Scale. We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication. The trial consisted of a 4-month period of tapering and an 8-month follow-up period. The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached, followed by a decrease of 0.25 mg per week. The mean dosage at the start of tapering was 2.7 +/- 1.2 mg/d. In total, 51 (68.9%) of the patients were free of the medication after the 4 months of tapering according to the protocol, and 19 (26.0%) of the patients needed another 3 months to be free of medication. Clonazepam discontinuation symptoms were mostly mild and included mainly: anxiety, shaking/trembling/tremor, nausea/vomiting, insomnia/nightmares, excessive sweating, tachycardia/palpitations, headache, weakness, and muscle aches. The improvement in PD and general well-being was maintained during both the taper and follow-up phases. Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually. We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk.
Asunto(s)
Clonazepam/administración & dosificación , Trastorno de Pánico/tratamiento farmacológico , Trastorno de Pánico/psicología , Síndrome de Abstinencia a Sustancias/prevención & control , Síndrome de Abstinencia a Sustancias/psicología , Adolescente , Adulto , Anciano , Clonazepam/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Escalas de Valoración Psiquiátrica/normas , Síndrome de Abstinencia a Sustancias/etiología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
This study was undertaken to model the relationship between clonazepam plasma concentrations and a central nervous system adverse effect (impairment of the psychomotor performance) following the oral administration of immediate-release tablets of clonazepam in healthy volunteers. Such a (P)pharmacokinetic/(P)pharmacodynamic (PK/PD) study is important to interpret properly the consequences of determined levels of plasma concentrations of psychoactive therapeutic drugs reported to be involved in road-traffic accidents. Twenty-three male subjects received a single oral dose of 4 mg clonazepam. Plasma concentration, determined by on-line solid phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry, and psychomotor performance, quantified through the Digit Symbol Substitution Test, were monitored for 72 hours. A 2-compartment open model with first order absorption and lag-time better fitted the plasma clonazepam concentrations. Clonazepam decreased the psychomotor performance by 72 +/- 3.7% (observed maximum effect), 1.5 to 4 hours (25th-75th percentile) after drug administration. A simultaneous population PK/PD model based on a sigmoid Emax model with time-dependent tolerance described well the time course of effect. Such acute tolerance could minimize the risk of accident as a result of impairment of motor skill after a single dose of clonazepam. However, an individual analysis of the data revealed a great interindividual variation in the relationship between clonazepam effect and plasma concentration, indicating that the phenomenon of acute tolerance can be predicted at a population, but not individual, level.
Asunto(s)
Administración Oral , Sistema Nervioso Central/efectos de los fármacos , Clonazepam/farmacocinética , Cognición/efectos de los fármacos , Trastornos Psicomotores/inducido químicamente , Desempeño Psicomotor/efectos de los fármacos , Adulto , Sistema Nervioso Central/fisiopatología , Clonazepam/administración & dosificación , Clonazepam/efectos adversos , Clonazepam/farmacología , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Umbral del Dolor , Trastornos Psicomotores/metabolismo , Tiempo de Reacción , Valores de Referencia , Espectrometría de Masas en Tándem , Adulto JovenRESUMEN
The antischistosomal activity of clonazepam, when administered alone or in association with oxamniquine and praziquantel, was experimentally evaluated in mice infected with Schistosoma mansoni. The animals were treated 45 days post-infection with a single dose, by oral route, according to three treatment schedules: clonazepam 25 mg/kg and sacrificed 15 min, 1h or 4 h after treatment; clonazepam 1.0, 2.5 or 10.0 mg/kg and sacrificed 15 days post-treatment or with the dose of 10 mg/kg in association with oxamniquine 50 mg/kg or praziquantel 200 mg/kg, single dose, orally, every schedule with a control group. The efficacy of the drugs in vivo was assessed by means of worm counts and their distribution in mesentery and liver, mortality and oogram changes. In the chemotherapeutic schedules used, clonazepam did not present antischistosomal activity and the result of the association of this drug with oxamniquine or praziquantel was not significantly different from the one obtained when these two last drugs were administered alone. In the in vitro experiments, the worms exposed to 0.6 mg/mL clonazepam remained motionless throughout the 8-day-period of observation, without egg-laying, whereas the worms of the control group showed normal movements, egg-laying and hatching of miracidia on the last day of observation. The results obtained in the present study confirm the action of clonazepam on S. mansoni adult worm, in vitro, causing total paralysis of males and females. However, no additive or synergistic effects were observed when clonazepam were used in association with oxamniquine or praziquantel.
Asunto(s)
Animales , Femenino , Masculino , Ratones , Clonazepam/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/farmacología , Clonazepam/administración & dosificación , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Hígado/parasitología , Mesenterio/parasitología , Oxamniquina/administración & dosificación , Oxamniquina/farmacología , Praziquantel/administración & dosificación , Praziquantel/farmacología , Esquistosomicidas/administración & dosificación , Factores de TiempoRESUMEN
Burning mouth syndrome (BMS) is a chronic disease characterized by burning of the oral mucosa associated with a sensation of dry mouth and/or taste alterations. BMS occurs more frequently among postmenopausal women. The pathophysiology of the disease is still unknown, and evidence is conflicting; although some studies suggest a central origin, others point to a peripheral neuropathic origin. The efficacy of some medications in the treatment of BMS suggests that the dopaminergic system may be involved.
Asunto(s)
Síndrome de Boca Ardiente/diagnóstico , Síndrome de Boca Ardiente/terapia , Administración Oral , Síndrome de Boca Ardiente/epidemiología , Clonazepam/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Femenino , Humanos , Masculino , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/patología , Posmenopausia/efectos de los fármacos , Posmenopausia/fisiologíaRESUMEN
The antischistosomal activity of clonazepam, when administered alone or in association with oxamniquine and praziquantel, was experimentally evaluated in mice infected with Schistosoma mansoni. The animals were treated 45 days post-infection with a single dose, by oral route, according to three treatment schedules: clonazepam 25 mg/kg and sacrificed 15 min, 1h or 4 h after treatment; clonazepam 1.0, 2.5 or 10.0 mg/kg and sacrificed 15 days post-treatment or with the dose of 10 mg/kg in association with oxamniquine 50 mg/kg or praziquantel 200 mg/kg, single dose, orally, every schedule with a control group. The efficacy of the drugs in vivo was assessed by means of worm counts and their distribution in mesentery and liver, mortality and oogram changes. In the chemotherapeutic schedules used, clonazepam did not present antischistosomal activity and the result of the association of this drug with oxamniquine or praziquantel was not significantly different from the one obtained when these two last drugs were administered alone. In the in vitro experiments, the worms exposed to 0.6 mg/mL clonazepam remained motionless throughout the 8-day-period of observation, without egg-laying, whereas the worms of the control group showed normal movements, egg-laying and hatching of miracidia on the last day of observation. The results obtained in the present study confirm the action of clonazepam on S. mansoni adult worm, in vitro, causing total paralysis of males and females. However, no additive or synergistic effects were observed when clonazepam were used in association with oxamniquine or praziquantel.
Asunto(s)
Clonazepam/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/farmacología , Animales , Clonazepam/administración & dosificación , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Femenino , Hígado/parasitología , Masculino , Mesenterio/parasitología , Ratones , Oxamniquina/administración & dosificación , Oxamniquina/farmacología , Praziquantel/administración & dosificación , Praziquantel/farmacología , Esquistosomicidas/administración & dosificación , Factores de TiempoRESUMEN
Diabetes-associated depression may occur due to changes in the quality of life imposed by treatment, or may be a consequence of the biochemical changes accompanying the disease. We evaluated the oxidative stress from diabetic animals submitted to an experimental model of depression and the effects of clonazepam. Male Wistar rats were induced to diabetes with streptozotocin and submitted to forced swimming test. Clonazepam was administered 24, 5 and 1 h before test. The animals were sacrificed by decapitation, and plasma and erythrocytes were separated, as well as hippocampus, cortex and striatum. Reactive species of thiobarbituric acid (TBARS) and total antioxidant reactivity (TAR) as well as antioxidant enzyme activities catalase (CAT) and superoxide dismutase (SOD) were evaluated. Results showed a significant increase of TBARS and a significant decrease of TAR in plasma from diabetic animals, which was altered by clonazepam. There were no effects of CAT and SOD activities in erythrocytes from tested animals. The results observed in hippocampus showed a significant increase of TBARS from diabetic rats, altered by clonazepam, and no one alteration was verified in TAR. The significant increase of TBARS and the significant decrease of TAR in cortex from diabetic rats were not altered by clonazepam administration. There were no alterations of TBARS and TAR in striatum from tested animals. Besides, clonazepam reverses the immobility in diabetic rats. Considering the action of clonazepam, it is suggested that it could be an alternative therapeutic for depression to diabetic patients, once it could give a protection against free radicals.