ABSTRACT
OBJECTIVES: To describe haematological adverse effects in adolescents with anorexia nervosa who are taking olanzapine. METHODS: Case series report. CASE REPORT: The reported cases (two female patients and one male) were found to have blood test abnormalities after starting olanzapine and to rapidly recover their platelet and neutrophil values after the drug was discontinued. Low haemoglobin values persisted longer than observed in other series. These abnormalities became more noticeable when the dose of olanzapine was increased to 5â¯mg/day (initial dose 2.5â¯mg/day). It should be noted that two of the patients already had values indicative of mild neutropenia before they started the antipsychotic drug, and that these worsened as they continued taking the drug. In one of the patients there was only a decrease in neutrophil values, as well as mild anaemia. CONCLUSIONS: This first case series of haematological abnormalities in adolescents with anorexia nervosa who are taking olanzapine found values corresponding to pancytopenia in two of the three cases reported. It would be worthwhile to consider heightening haematological surveillance in this population when starting treatment with olanzapine and rethinking our knowledge regarding the frequency of these side effects.
Subject(s)
Anorexia Nervosa , Antipsychotic Agents , Benzodiazepines , Olanzapine , Humans , Olanzapine/adverse effects , Olanzapine/administration & dosage , Female , Adolescent , Antipsychotic Agents/adverse effects , Antipsychotic Agents/administration & dosage , Male , Benzodiazepines/adverse effects , Benzodiazepines/administration & dosage , Pancytopenia/chemically induced , Dose-Response Relationship, DrugABSTRACT
Objective: Olanzapine is widely used throughout the world to treat patients with schizophrenia and bipolar disorder. Olanzapine has numerous side effects, but respiratory depression has not been reported with doses as low as 5 mg. Clinical case: An elderly woman presented with severe hypercarbia, hypoxia, and impaired consciousness possibly due to low doses of oral olanzapine. There is no accepted antidote for the side effects of olanzapine, so we followed the patient with respiratory support and electrolyte correction. Symptoms improved after 2 weeks and did not recur. Results and conclusions: Elderly patients, women, and non-smokers may have elevated olanzapine concentrations and may do better with lower than usual doses. If somnolence is observed in a patient taking olanzapine, a blood gas should be obtained and appropriate respiratory care should be provided. We expect that this case report will add to the existing body of literature on the appropriate use of olanzapine. (AU)
Objetivo: Olanzapina se utiliza de manera amplia a nivel mundial para tratar a los pacientes con esquizofrenia y trastorno bipolar. Tiene numerosos efectos secundarios, pero no se había reportado depresión respiratoria con dosis bajas de 5 mg. Caso clínico: Una mujer mayor acudió con hipercarbia severa, hipoxia y deterioro de la consciencia, debido posiblemente a la administración de dosis bajas de olanzapina oral. No existe antídoto aceptado para los efectos secundarios de olanzapina, por lo que seguimos a la paciente con soporte respiratorio y corrección de electrolitos. Los síntomas mejoraron transcurridas dos semanas, no produciéndose recidiva. Resultados y conclusiones: Los pacientes mayores, mujeres, y no fumadores pueden tener concentraciones elevadas de olanzapina, siendo adecuado utilizar dosis más bajas de lo habitual. De observarse somnolencia en un paciente que toma olanzapina, deberán obtenerse gases sanguíneos, y aportarse cuidados respiratorios adecuados. Esperamos que este informe de caso ayude al cuerpo existente de la literatura con relación al uso adecuado de olanzapina. (AU)
Subject(s)
Humans , Female , Aged , Olanzapine/administration & dosage , Olanzapine/adverse effects , Olanzapine/therapeutic use , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapyABSTRACT
Olanzapina es un antipsicótico atípico comercializado en Europa desde finales de 1996, que continúa siendo uno de los principios activos más ampliamente utilizados en la actualidad en el territorio español. Sin embargo, su elevada tasa de eventos adversos metabólicos y su uso en algunos escenarios clínicos continúan siendo motivo de controversia. El objetivo de este estudio fue explorar los conocimientos, actitudes y prácticas del uso de este medicamento entre psiquiatras españoles. Se diseñó y distribuyó un cuestionario autodiligenciado en el que se exploraron algunos aspectos posológicos en la práctica clínica, la experiencia y las tendencias de uso en distintos contextos y expectativas a futuro. Se tabularon los datos y se realizó un análisis descriptivo. Se obtuvieron respuestas de 129 psiquiatras en ejercicio de todo el territorio español, con una edad promedio de 45,46 años (SD=9,57) y una razón mujer:hombre de 1,04:1. Tras más de 25 años en el mercado, olanzapina continúa siendo un antipsicótico ampliamente usado en distintos escenarios clínicos en la esquizofrenia y otros trastornos mentales (preferiblemente a dosis entre 5 y 10 mg/día). Los psiquiatras españoles están familiarizados con la necesidad de establecer estrategias farmacológicas y no farmacológicas para el control metabólico de quienes usan este medicamento.(AU)
Olanzapine, a second-generation antipsychotic marketed in Europe since late 1996, continues to be one of the most widely used molecules in Spain today. However, its high rate of adverse metabolic events and its use in some clinical settings are still controversial. The objective of this study was to explore the knowledge, attitudes, and practices of use of this medication among Spanish psychiatrists. A self-filled questionnaire was designed and distributed. Dosage, experience, and trends of use in different contexts were explored, as well as future expectations. Data were tabulated and a descriptive analysis was performed. 129 practicing psychiatrists throughout the Spanish territory participated in the study, with an average age of 45.46 years (SD=9.57) and a female: male ratio of 1.04:1. After more than 25 years on the market, Olanzapine continues to be an antipsychotic widely used in different clinical settings, both in Schizophrenia and other mental disorders (preferably at doses between 5 and 10 mg/day). Spanish psychiatrists are familiar with the need to establish pharmacological and non-pharmacological strategies for the metabolic control of patients using this drug.(AU)
Subject(s)
Humans , Male , Female , Middle Aged , Olanzapine/administration & dosage , Olanzapine/adverse effects , Olanzapine/therapeutic use , Antipsychotic Agents , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Surveys and Questionnaires , Psychiatry , Spain , Mental Health , Mental DisordersABSTRACT
Introdução: a olanzapina é um dos fármacos antipsicóticos benzodiazepínicos mais usados no mundo. Apesar da sua eficiência, em concentrações excessivas, ela sói ser tóxica, como quaisquer outros fármacos desta classe. Assim, neste trabalho, se avaliou, pela primeira vez, a possibilidade da detecção eletroquímica do fármaco olanzapina, assistida pelo compósito do oxihidróxido de cobalto (III), emparelhado com o dióxido, com um corante esquaraínico. Método: o modelo matemático trivariante correspondente inclui dois cenários de oxidação do fármaco, possíveis para o caso, incluindo a eletropolimerização indireta da molécula da benzodiazepina condensada, bem como a oxidação do fármaco pelo átomo do enxofre. Este modelo tem sido desenvolvido e analisado mediante a teoria de estabilidade linear e análise de bifurcações. Resultados e discussão: a análise do modelo há mostrado que a hibridez do mecanismo do processo eletroanalítico, aliada à composição e descomposição dos compostos iônicos aquando da sua realização, aumenta a probabilidade da ocorrência do comportamento oscilatório, em relação ao caso mais simples e mais comum. No entretanto, a instabilidade oscilatória se realiza nos valores dos parâmetros, que estão além do limite de detecção. Por sua vez, o estado estacionário se obtém e se mantém facilmente, indicando um processo eletroanalítico eficiente, controlado pela difusão do analito. Conclusões: trata-se de um processo eletroanalítico eficiente, em que o composto de cobalto funciona como substância ativa, e o corante desempenha o papel de mediador
SUMMARY Introduction: olanzapine is one of the most used antipsychotic drugs in the world. Although it is efficient, it may be toxic in excess. Therefore, in this work the possibility of olanzapine electrochemical determination over an electrode, modified by the cobalt (III) oxyhydroxide in pair with its dioxide in a composite with squaraine dye. Methods: the trivariant correspondent mathematical model includes two scenarios of the drug oxidation, possible for the case, including the indirect electropolymerization of the condensed benzodiazepine molecule, like also its oxidation by sulfur atom. This model has been developed and analyzed by means of stability theory and bifurcation analysis. Results and discussion: the analysis of the model has shown that the mechanism hybridity of the electroanalytical process, alongside with the formation and decomposition of ionic compounds during its realization, augments the possibility for the oscillatory behavior realization, relatively to the simplest and commonest case. Nevertheless, the oscillatory instability is realized in parameter values far beyond the detection limit. On the other hand, the stable steady-state is easy to obtain and maintain, indicating an efficient electroanalytical process, controlled by the analyte diffusion. Conclusions: the electroanalytical process is efficient. The cobalt compound is acting as an active substance, and the dye is the mediator.
Introducción: la olanzapina es uno de los fármacos antipsicóticos más utilizados en el mundo. Aunque es eficaz, puede resultar tóxico en exceso. Por tanto, en este trabajo se plantea la posibilidad de la determinación electroquímica de olanzapina sobre un electrodo, modificado por el oxihidróxido de cobalto (III) en pareja con su dióxido en un composito con colorante de escuaraína. Métodos: el modelo matemático correspondiente incluye dos escenarios de oxidación del fármaco, posibles para el caso, que incluyen la electropolimerización indirecta de la molécula de benzodiazepina condensada, así como su oxidación por átomo de azufre. Este modelo ha sido desarrollado y analizado mediante teoría de estabilidad y análisis de bifurcación. Resultados y discusión: el análisis del modelo ha demostrado que el mecanismo de hibridación del proceso electroanalítico, junto con la formación y descomposición de compuestos iónicos durante su realización, aumenta la posibilidad de realización del comportamiento oscilatorio, relativamente al caso más simple y común. Sin embargo, la inestabilidad oscilatoria se realiza en valores de parámetros mucho más allá del límite de detección. Por otro lado, el estado estacionario estable es fácil de obtener y mantener, lo que indica un proceso electroanalítico eficiente, controlado por la difusión del analito. Conclusiones: el proceso electroanalítico es eficiente. El compuesto de cobalto actúa como sustancia activa y el colorante es el mediador.
ABSTRACT
Resumen Se han descrito una serie de reacciones adversas asociadas a antipsicóticos, entre las que destacan las reacciones adversas hematológicas propias de algunos antipsicóticos atípicos. Las más renombradas han sido clásicamente las discrasias sanguíneas asociadas al uso de olanzapina. En este trabajo nos enfocamos en una reacción adversa poco común: eosinofilia en un paciente esquizofrénico paranoide usuario de olanzapina, situación documentada en contadas publicaciones a lo largo de la historia de uso de este medicamento. Se trata de una reacción adversa infrecuente, y por lo mismo poco conocida y estudiada.
Many adverse effects of antipsychotic drugs have been described, among which hematologic adverse effects stand out. Classically, blood discrasias have been associated to the use of olanzapine. On this paper we will focus on an uncommon adverse reaction: eosinophilia in a patient diagnosed with a paranoid schitzophrenia, who had been using olanzapine. There have been just a few reported cases of eosinophilia secondary to the use of olanzapine, which makes this an infrequent, rarely known and even less studied adverse reaction.
Subject(s)
Humans , Male , Adult , Schizophrenia , Antipsychotic Agents , Eosinophilia , OlanzapineABSTRACT
O estudo foi realizado para comparar a bioequivalência de duas formulações de olanzapina 2,5mg comprimidos (Olanzapina do Aché Laboratórios Farmacêuticos S/A., formulação teste e Zyprexa® da Eli Lilly do Brasil Ltda., formulação referência, Brasil) em 26 voluntários sadios. O estudo foi realizado através de um desenho aberto, randomizado, truncado, cruzado em dois períodos com tempo de washout de três semanas. As amostras de plasma foram obtidas ao longo de um intervalo de 72 horas. As concentrações de olanzapina foram determinadas através de um equipamento HPLC/MS/MS, utilizando citalopram como padrão interno. A partir dos dados de concentração plasmática obtidos individualmente se calcularam os seguintes parâmetros farmacocinéticos: ASC0-t, Cmax e Tmax. As médias para ASC0-72 para as formulações teste e referência foram 116657,480 pg.h/mL e 120619,617 pg.h/mL, para Cmax foram 4442,975 pg/mL e 4678,317 pg/mL e para Tmax foram 4,000 h e 4,667 h, respectivamente. As razões das médias geométricas foram de 96,60% para ASC0-72, e 94,00 % para Cmax. Os intervalos com 90% de confiança foram 94,12%-99,14% para ASC0-72, e 88,07%-100,33 % para Cmax. Uma vez que os intervalos de confiança de 90% para Cmax e ASC0-72 estiveram dentro da faixa de 80%-125% proposta pelo Food and Drug Administration (FDA) e pela ANVISA (Agência Nacional de Vigilância Sanitária) conclui-se que o comprimido de olanzapina de 2,5 mg é bioequivalente ao comprimido de Zyprexa® de 2,5 mg e, dessa forma, o produto teste pode ser considerado intercambiável na prática médica.
ABSTRACT
OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric); and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle), and Groups 2, 3, and 4 (liver). Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles. CONCLUSION: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.
OBJETIVOS: A olanzapina, uma droga antipsicótica atípica com afinidade por locais de ligação de dopamina, serotonina e histamina, parece se associar a um ganho de peso e a alterações metabólicas consideráveis. O objetivo desse estudo foi avaliar o ganho de peso e as alterações metabólicas em ratos tratados com olanzapina numa dieta hipercalórica. MÉTODOS: Usamos 40 ratos divididos em 4 grupos: Grupo 1, condições padrão de alimento e água (controle); Grupo 2, dieta padrão mais olanzapina; Grupo 3, dieta hipercalórica; e Grupo 4, olanzapina mais dieta hipercalórica. Olanzapina foi administrada por gavagem a uma dose de 3 mg/kg por 9 semanas. RESULTADOS: Não houve alterações significativas nos níveis de colesterol em qualquer um dos grupos. Os níveis de glicose aumentaram no Grupo 3 por volta da quarta semana. Os níveis de triglicerídeos estavam alterados no Grupo 2 ao final do experimento. Os níveis de leptina diminuíram nos Grupos 2 e 4. A atividade do complexo II nos músculos e no fígado se alterou no Grupo 2 (músculos) e nos Grupos 2, 3 e 4 (fígado). A atividade do complexo IV se alterou apenas no fígado no Grupo 2, sem alterações significativas nos músculos. CONCLUSÃO: Esses resultados sugerem que olanzapina se correlaciona ao ganho de peso e aos riscos associados à obesidade.
Subject(s)
Animals , Male , Rats , Antipsychotic Agents/adverse effects , Benzodiazepines/adverse effects , Energy Metabolism/drug effects , Leptin/blood , Weight Gain/drug effects , Random Allocation , Rats, WistarABSTRACT
Extended use of atypical neuroleptics in clinical practice, may be explained by their effectiveness as antipsychotics and also with recent approvals for therapeutic benefits of this drugs beyond psychotic disorders. Receptor adaptation mechanisms rises critical issues about treatment discontinuation strategies. Clinical data of two patients who have required the use of atypical antipsychotics are discussed. In both cases, abrupt discontinuation of the drug occurred followed by the emergence of extrapyramidal symptoms. Adaptation mechanisms in synaptic structures would be responsible for this phenomena and the subsequent amelioration of this extrapyramidal symptoms when initial treatment is replaced. The authors concluded that atypical antipsychotics, as other psychotropic agents shouldn't be abruptly discontinued even when they are replaced by other drugs from the same family.
El uso de los antipsicóticos atípicos ha ido aumentando con el tiempo entre otras cosas, por el hecho de que se están usando no sólo para los cuadros psicóticos sino que también para otras patologías. Como con otros fármacos que actúan a nivel de receptores deben considerarse los mecanismos de adaptación receptorial que se producen con su uso. Lo anterior es de suma importancia cuando pensamos en la discontinuación del tratamiento y en sus formas de hacerlo. En este trabajo presentamos dos casos clínicos de pacientes que han requerido el uso de antipsicóticos atípicos. En ambos casos se ha realizado una suspensión brusca del fármaco lo que ha generado la aparición de síntomas extrapiramidales, que en nuestra opinión, son explicados por mecanismos de adaptación a nivel sináptico y que han disminuido con el reinicio del tratamiento inicial. Debemos tener presente que estos fármacos no deben ser discontinuados en forma súbita aun cuando sean remplazados por otros de la misma familia.
Subject(s)
Humans , Female , Middle Aged , Antipsychotic Agents/adverse effects , Pirenzepine/adverse effects , Substance Withdrawal Syndrome/etiology , Bipolar Disorder/drug therapy , Antipsychotic Agents/administration & dosage , Benzodiazepines , Pirenzepine/administration & dosage , Pirenzepine/analogs & derivativesABSTRACT
Introducción: El delírium es una alteración aguda de la conciencia y la cognición que ha empezado a manejarse con antipsicóticos atípicos (AA). Debido a que las facultades mentales, por definición, se ven afectadas, los estudios en esta población generan dilemas éticos respecto a la participación voluntaria de los pacientes y su estado de vulnerabilidad. Objetivo: Valorar si los estudios realizados con AA para el tratamiento del delírium obtuvieron una aprobación por un comité de ética en investigación en seres humanos (CEISH), si hubo aplicación de un consentimiento informado (CI), si este era verbal o escrito y quién dio la aprobación para la participación en el protocolo. Diseño: Revisión sistemática en MedLine de los estudios de delírium que emplearon quetiapina y olanzapina y valoración de la existencia de aprobación por un CEISH y de la aplicación de un CI. Resultados: Se detectaron 11 estudios (6 de quetiapina y 5 de olanzapina), de los cuales 5 contaron con la aprobación del protocolo por un CEISH. Conclusiones: La mayoría de los estudios para el tratamiento del delírium no fueron sometidos a su aprobación por parte de un CEISH ni obtuvieron (de forma exclusiva) el CI de participación por parte del apoderado legal del paciente. Es fundamental que los futuros estudios de antipsicóticos y otros fármacos cuenten con la aprobación del protocolo por parte de un CEISH y de la firma del CI por parte del representante legal del paciente
Introduction: Delirium is an acute alteration of consciousness and cognition. Atypical antipsychotics (AA) have recently become a main part of its treatment. Studies in this population generate a series of ethical dilemmas concerning the voluntary participation of patients and their state of vulnerability since their mental faculties are, by definition, compromised. Objective: To assess whether studies with AA for the treatment of delirium obtained an approval by an ethics committee on human research (ECHR), if an informed consent (IC) was obtained, whether the IC was verbal or written, and who gave the approval to participate. Method: Systematic review of Medline for studies of delirium where quetiapine and olanzapine were the main treatment, assessing the existence of an ECHR approval and implementation of an IC. Results: 11 studies were identified (6 of quetiapine and 5 of olanzapine). 5 had an ECHR approval. Conclusions: Most studies examining the treatment of delirium with quetiapine or olanzapine were not subject to approval by an ECHR and most of them did not obtain an IC from the patients legal guardian. It is essential that future studies of antipsychotics and other drugs for the treatment of delirium have the protocol approved by an ECHR and a written IC signed by the patients legal representative, since by definition delirium is a condition that compromises superior mental processes
Subject(s)
Antipsychotic Agents , Mental DisordersABSTRACT
Introducción: En psiquiatría de enlace se logra obtener una visión integral del tratamiento y de las necesidades de cada paciente prestando especial atención a las interacciones medicamentosas y a las contraindicaciones. Algunos casos particulares motivaron la descripción, reporte y revisión bibliográfica acerca de otras posibles aplicaciones de fármacos antagonistas de los recetores 5HT2A y 3, particularmente mirtazapina y olanzapina, en síndrome de hiperalgesia, tinitus y leucoencefalopatía multifocal progresiva por virus JC. Método: reporte de casos. Resultados y Conclusiones: Se describen los casos de tres pacientes en los cuales fue necesario usar mirtazapina y olanzapina no solo para el control de los síntomas psiquiátricos (afectivos, comportamentales y trastorno del sueño), sino también como coadyuvantes en las patologías de base de cada paciente. El uso de cualquier medicamento en psiquiatría de enlace debe tener en cuenta el contexto del paciente, la comorbilidad, las contraindicaciones y las interacciones farmacológicas para garantizar un desenlace positivo, además de promover el trabajo multidisciplinario entre especialistas.
Introduction: In liaison psychiatry it is possible to get an integral view of patient's treatment and needs, paying special attention to pharmacological interactions and contraindications. Some particular cases motivated the description, report and review about other possible applications of 5HT2A and 5HT3 antagonist, particularly Mirtazapine and Olanzapine, in hyperalgesia syndrome, tinnitus and Progressive Multifocal Leukoencephalopathy by JC virus. Method: Cases report. Results: We describe 3 cases of patients in which Mirtazapine and Olanzapine were necessary not only to control psychiatric symptoms (affective / behavioral symptoms and insomnia) but to act as adjuvant therapy in axis III diseases. The use of any drug in psychiatry must take in to account the context of the patient, the presence of comorbidity, contraindications and pharmacological interactions so as to grant a positive outcome also promoting the multidisciplinary work between specialists.
Subject(s)
Humans , Adaptor Proteins, Signal Transducing/metabolism , Cell Nucleus/metabolism , Cysteine/metabolism , Neurons/metabolism , Thioredoxins/metabolism , Transcription Factors/metabolism , Amino Acid Motifs , Adaptor Proteins, Signal Transducing/genetics , Cell Line, Tumor , Cysteine/chemistry , Cytoplasm/metabolism , Disulfides/chemistry , Gene Expression Profiling , Gene Expression Regulation , Molecular Sequence Annotation , Molecular Sequence Data , Mutation , Neurons/cytology , Oxidation-Reduction , Protein Interaction Mapping , Signal Transduction , Transcription, Genetic , Thioredoxins/genetics , Transcription Factors/geneticsABSTRACT
INTRODUCTION: Delirium is an acute alteration of consciousness and cognition. Atypical antipsychotics (AA) have recently become a main part of its treatment. Studies in this population generate a series of ethical dilemmas concerning the voluntary participation of patients and their state of vulnerability since their mental faculties are, by definition, compromised. OBJECTIVE: To assess whether studies with AA for the treatment of delirium obtained an approval by an ethics committee on human research (ECHR), if an informed consent (IC) was obtained, whether the IC was verbal or written, and who gave the approval to participate. METHOD: Systematic review of Medline for studies of delirium where quetiapine and olanzapine were the main treatment, assessing the existence of an ECHR approval and implementation of an IC. RESULTS: 11 studies were identified (6 of quetiapine and 5 of olanzapine). 5 had an ECHR approval. CONCLUSIONS: Most studies examining the treatment of delirium with quetiapine or olanzapine were not subject to approval by an ECHR and most of them did not obtain an IC from the patient's legal guardian. It is essential that future studies of antipsychotics and other drugs for the treatment of delirium have the protocol approved by an ECHR and a written IC signed by the patient's legal representative, since by definition delirium is a condition that compromises superior mental processes.
ABSTRACT
INTRODUCTION: In liaison psychiatry it is possible to get an integral view of patient's treatment and needs, paying special attention to pharmacological interactions and contraindications. Some particular cases motivated the description, report and review about other possible applications of 5HT2A and 5HT3 antagonist, particularly Mirtazapine and Olanzapine, in hyperalgesia syndrome, tinnitus and Progressive Multifocal Leukoencephalopathy by JC virus. METHOD: Cases report. RESULTS: We describe 3 cases of patients in which Mirtazapine and Olanzapine were necessary not only to control psychiatric symptoms (affective / behavioral symptoms and insomnia) but to act as adjuvant therapy in axis III diseases. The use of any drug in psychiatry must take in to account the context of the patient, the presence of comorbidity, contraindications and pharmacological interactions so as to grant a positive outcome also promoting the multidisciplinary work between specialists.
ABSTRACT
The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with mannitol. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were selected from release data, dissolution parameters and their release profiles. Solid state characterization techniques like Fourier transform infrared (FT-IR) spectroscopy, X-ray diffractometry, differential scanning calorimetry, near-infrared and Raman spectroscopy were used to characterize the drug in selected dispersions. The dispersions were also evaluated by wettability studies and permeation studies. The results of phase solubility studies and the thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions compared to pure drug, and the release was found to increase with an increase in carrier content. The possible mechanism for increased release rate from dispersions may be attributed to solubilization effect of the carrier, change in crystal quality, phase transition from crystalline to amorphous state, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity of the drug, and increased wettability and dispersability of the drug in dissolution medium. The suggested reasons for increased release rate from dispersions were found to be well supported by results of solid state characterization, wettability and permeation studies. The absence of any interaction between the drug and the carrier was also proved by FT-IR analysis.
O objetivo do presente trabalho é estudar o comportamento de dissolução da olanzapina a partir de suas dispersões sólidas de manitol. As dispersões sólidas foram preparadas por dispersão por fusão e caracterizadas por estudos de solubilidade de fase, conteúdo de fármaco e dissolução in vitro. As melhores dispersões quanto à liberação foram selecionadas a partir dos dados de liberação, parâmetros de dissolução e perfis de liberação. Técnicas de caracterização de estado sólido como espectroscopia no infravermelho pela transformada de Fourier (FTIR), difratometria de raios X, calorimetria de varredura diferencial, infravermelho próximo e espectroscopia Raman foram utilizadas para caracterizar os fármacos a partir das dispersões selecionadas. As dispersões foram, também, avaliadas pelos estudos de capacidade de umedecimento e permeação. Os resultados dos estudos de solubilidade de fase e os parâmetros termodinâmicos indicaram a espontaneidade e o efeito de solubilização do transportador. Os resultados dos estudos de liberação mostraram maior aperfeiçoamento da liberação do fármaco das dispersões sólidas, comparativamente à do fármaco puro, e descobriu-se que a liberação aumenta com o aumento do conteúdo de transportador. O mecanismo possível para o aumento da taxa de liberação das dispersões pode ser atribuído ao efeito de solubilização do transportador, mudança da qualidade do cristal, transição de fase cristalina para estado amorfo, prevenção da aglomeração ou agregação das partículas do fármaco, mudança na superfície de hidrofobicidade do fármaco e aumento da capacidade de umedecimento e dispersividade do fármaco no meio de dissolução. As razões sugeridas para o aumento da taxa de liberação a partir das dispersões foram apoiadas pelos resultados da caracterização do estado sólido, capacidade de umedecimento e pelos estudos de permeação. A ausência de qualquer interação entre o fármaco e o transportador foi, também, comprovada pela análise no FTIR.
Subject(s)
In Vitro Techniques/classification , /analysis , Dissolution/analysis , Mannitol/pharmacokinetics , Pharmaceutical Preparations/analysisABSTRACT
El síndrome serotoninérgico (SS) se caracteriza por la presencia de disfunción autonómica, deterioro neuromuscular y alteraciones en el estado mental. El diagnóstico es clínico y por laboratorio. El tratamiento es mediante medidas de apoyo a base de líquidos, hipotermia, benzodiacepinas y, cuando lo amerite, intubación y ventilación mecánica. El pilar de la intervención farmacológica es ciproheptadina, un antagonista central H1, con un antagonismo periférico 5-HT2A. El medicamento disponible sólo se puede administrar por vía oral, por lo que en enfermos críticos debe administrarse a través de sonda nasoyeyunal. El objetivo de este trabajo es presentar un caso de SS y revisar la literatura al respecto.
The serotonin syndrome (SS) is characterized by a spectrum of signs characterized by autonomic dysfunction, neuromuscular impairment, and alterations in mental status. The diagnosis of the serotonin syndrome is clinical and by laboratory evaluation. Treatment is with active cooling and benzodiazepines to control agitation, and intubation, especially in patients with severe hyperthermia and delirium. The mainstay of pharmacologic intervention is cyproheptadine, a centrally acting H1-antagonist, with a prominent peripheral 5-HT2A antagonism. The drug is only available orally, and if the patient is unable to swallow, the drug should be administered nasogastrically. The objective of this paper is report a case of Serotonin Syndrome and review the literature related to this disease.
ABSTRACT
Introducción: Este es el reporte de caso de un hombre de 27 años con diagnóstico de esquizofrenia, quien desarrolló hipotensión y bradicardia inmediatamente después de la administración de una dosis única de 10 mg de olanzapina vía oral. Discusión: El paciente no tenía antecedentes importantes o de reacción adversa a medicamentos. Requirió manejo intrahospitalario, reanimación con cristaloides y atropina intravenosa para lograr la recuperación hemodinámica. El paciente posteriormente recibió tratamiento con haloperidol con adecuada recuperación y sin nuevos efectos adversos. Existe sólo un caso reportado de hipotensión o bradiarritmias asociados con la administración exclusiva de olanzapina oral...
Introduction: This is a case report of a 27-year-old man with a diagnosis of schizophrenia, who developed hypotension and bradycardia immediately after the administration of a single oral dose of 10 mg of olanzapine. Discussion: The patient had no medical history and no history of adverse reactions to medicines. He required hospitalization, reanimation with crystalloids, and IV atropine to achieve hemodynamic recovery. The patient later was treated with haloperidol with adequate recovery and without suffering new adverse effects. Only one case has been reported of hypotension or bradycardia associated with the administration of oral olanzapine...
Subject(s)
Bradycardia , Schizophrenia , Antipsychotic Agents , HypotensionABSTRACT
The aim of the present study was to develop an olanzapine freeze-dried tablet (FDT). The solubility and dissolution rate of poorly water-soluble olanzapine was improved by preparing a freeze-dried tablet of olanzapine using the freeze-drying technique . The FDT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was poured in to the pockets of blister packs and then was subjected to freezing and lyophilisation. The FDT was characterised by DSC, XRD and SEM and was evaluated for saturation solubility and dissolution. The samples were stored in a stability chamber to investigate their physical stability. Results obtained by DSC and X-ray were analysed and showed the crystalline state of olanzapine in FDT transformation to the amorphous state during the formation of FDT. Scanning electron microscope (SEM) results suggest reduction in olanzapine particle size. The solubility of olanzapine from the FDT was observed to be nearly four and a half times greater than the pure drug. Results obtained from dissolution studies showed that olanzapine FDT significantly improved the dissolution rate of the drug compared with the physical mixture (PM) and the pure drug. More than 90 percent of olanzapine in FDT dissolved within 5 minutes, compared to only 19.78 percent of olanzapine pure drug dissolved over the course of 60 minutes. In a stability test, the release profile of the FDT was unchanged, as compared to the freshly prepared FDT after 90 days of storing.
O objetivo do presente estudo foi desenvolver comprimidos liofilizados de olanzapina (FDT). A solubilidade e a taxa de dissolução da olanzapina, fracamente solúvel em água, foram melhoradas com a preparação de comprimidos liofilizados de olanzapina usando a técnica de liofilização. O FDT foi preparado por dispersão do fármaco em solução aquosa de materiais altamente solúveis em água, como gelatina, glicina e sorbitol. A mistura foi colocada em blisters e, então, submetida ao congelamento e liofilização. O FDT foi caracterizado por DSC, Difração de Raios X e microscopia eletrônica de varredura(SEM) e avaliaram-se a solubilidade de saturação e a dissolução. As amostras for5am armazenadas em câmara de estabilidade para investigar a estabilidade física. Os resultados obtidos com DSC e Raios X foram analisados e mostraram a transformação do estado cristalino da olanzepina em FDT no estado amorfo durante a formação do FDT. Os resultados da SEM sugerem a redução do tamanho das partículas de olanzapina. A solubilidade da olanzapina do FDT melhorou significativamente a taxa de dissolução do fármaco comparativamente à mistura física (PM) e ao fármaco puro. Mais do que 90 por cento da olanzepina no FDT dissolveu em 5 minutos, comparativamente aos 19,78 por cento do fármaco puro dissolvido em 60 minutos. No teste de estabilidade, o perfil de liberação da FDT mostrou-se inalterado, quando comparado com o FDT recém-preparado, após 90 dias de armazenamento.
Subject(s)
Solubility , Antipsychotic Agents/pharmacokinetics , Freezing , Dissolution/classification , Freeze DryingABSTRACT
El síndrome serotonínico es un cuadro neurológico agudo debido a hiperactividad serotoninérgica, por la interacción de drogas que refuerzan o mimetizan la acción del neurotrasmisor. La incidencia del síndrome de serotonina es ascendente por la disponibilidad creciente de fármacos serotoninérgicos como los antidepresivos. Por ello es importante que los médicos reconozcan y manejen adecuadamente el síndrome serotonínico. Este reporte de caso se refiere a una intoxicación accidental por el neuroléptico atípico olanzapina en un niño de 2 años, quien desarrolló manifestaciones clínicas como agitación, sudoración, mioclonías, clonus espontáneo e hipertermia, considerados como criterios diagnóstico del cuadro. La terapia consistió en descontaminación interna con lavado gástrico, carbón activado y sulfato de sodio, ciproheptadina, propranolol y furosemida. Su evolución fue satisfactoria. En nuestro país hay disponibilidad de la mayoría de los fármacos causales y tienen amplio uso, por lo que es probable el subregistro del síndrome. De allí la importancia de este reporte de caso
Serotonin syndrome is an acute neurologic picture due to serotonergic hyperactivity, due to the interaction of drugs that enhance or mimic the action of the serotonin. The incidence of serotonin syndrome is rising because of the growing availability of serotonergic drugs such as antidepressants. It is therefore important that clinicians recognize and manage appropriately this syndrome. This case report refers to an accidental poisoning by the atypical neuroleptic olanzapine in a 2 year old boy who developed clinical manifestations such as agitation, sweating, myoclonus, spontaneous clonus and hyperthermia, considered as diagnostic criteria for the syndrome. Therapy consisted of internal decontamination with gastric lavage, activated charcoal and sodium sulfate, cyproheptadine, propranolol and furosemide. The clinical outcome was satisfactory. In our country the majority of the causal drugs are easily available and widely employed, for which reason it is probable that this syndrome is under registered. Hence the importance of this case report
Subject(s)
Humans , Male , Child, Preschool , Cyproheptadine/therapeutic use , Poisoning/complications , Serotonin Agents/adverse effects , Serotonin Syndrome/diagnosis , Serotonin Syndrome/therapy , PediatricsABSTRACT
Two new spectrophotometric methods using permanganate as the oxidimetric reagent for the determination of olanzapine (OLP) were developed and validated as per the current ICH guidelines. The methods involved the addition of known excess of permanganate to OLP in either acid or alkaline medium followed by the determination of unreacted permanganate at 550 nm (method A) or bluish-green color of manganate at 610 nm (method B). The decrease in absorbance in method A or increase in absorbance in method B as a function of concentration of OLP was measured and related to OLP concentration. Under optimized conditions, Beer's law was obeyed over the ranges 2.0 to 20 and 1.0 to 10 μg mL-1 in method A and method B, respectively. The calculated molar absorptivity values were 1.34 x 10(4) and 2.54 x 10(4) l mol-1cm-1 for method A and method B respectively, and the respective Sandell sensitivities were 0.0233 and 0.0123 μg cm-2. The LOD and LOQ for method A were calculated to be 0.37 and 1.13 μg mL-1and the corresponding values for method B were 0.16 and 0.48 μg mL-1. Intermediate precision, expressed as RSD was in the range 0.51 to 2.66 percent, and accuracy, expressed as relative error ranged from 0.79 to 2.24 percent. The proposed methods were successfully applied to the assay of OLP in commercial tablets with mean percentage recoveries of 102 ±1.59 percent (method A) and 101 ±1.53 percent (method B). The accuracy and reliability of the methods were further confirmed by performing recovery tests via standard addition procedure.
Dois métodos espectrofotométricos novos, usando o permanganato como o reagente oxidimétrico para a determinação da olanzapina (OLP) foram utilizados e validados de acordo com as diretrizes atuais do ICH. Os métodos envolveram a adição de excesso conhecido de permanganato à OLP em meio ácido ou alcalino, determinando-se o permanganato que não reagiu em 550 nm (método A), ou pela cor verde-azulada do manganato a 610 nm (método B). A diminuição da absorbância no método A ou o aumento da absorbância no método B, em função da concentração de OLP, foi medida e relacionada à concentração de OLP. Sob condições otimizadas, a lei de Beer foi obedecida, nas faixas de concentração de 2,0 a 20 e 1,0 a 10 ao μg mL-1, no método A e no método B, respectivamente. Os valores de absortividade molar foram de 1,34 x 104 e 2,54 x 104 l mol-1cm-1 para o método A e para o método B, respectivamente, e as sensibilidades respectivas de Sandell foram de 0,0233 e 0,0123 μg cm-2. Os LOD e os LOQ para o método A calculados foram 0,37 e 1,13 μg mL-1e os valores correspondentes para o método B foram 0,16 e 0,48 μg mL-1. A precisão intermediária, expressa como RSD, encontrou-se na faixa de 0,51 a 2,66 por cento, e a exatidão, expressa como o erro relativo, variou de 0,79 a 2,24 por cento. Os métodos propostos foram aplicados com sucesso ao ensaio de OLP em comprimidos comerciais, com porcentagens médias de recuperação de 102± 1,59 por cento (método A) e de 101± 1,53 por cento (método B). A exatidão e a confiabilidade dos métodos foram confirmadas executando testes de recuperação através de procedimento padrão de adição.
Subject(s)
Drug Compounding , Diagnosis/methods , Laboratory Chemicals , Psychotropic Drugs/analysis , Spectrum Analysis , Chromatography, Liquid , PlacebosABSTRACT
Objetivo: comparar la efectividad de olanzapina versus haloperidol, en términos de tasas de recaída en pacientes venezolanos con esquizofrenia. Métodos: estudio abierto, aleatorizado, de 9 meses de seguimiento luego del alta hospitalaria o la estabilización clínica. El Medical Outcomes Study Form Health Survey (SF-36) y el Quality of Life Index from Mezzich & Cohen fueron usados para evaluar el estado de salud y la calidad de vida. Se registraron parámetros de seguridad. Resultados: se enrolaron 31 pacientes en olanzapina y 40 en haloperidol y las tasas de descontinuación fueron 65 y 68 respectivamente. Sólo un paciente en haloperidol recayó. El estado de salud mejoró más con olanzapina con diferencia estadística en 5 de los 8 dominios del SF-36. La olanzapina fue discretamente superior en mejorar la calidad de vida. Más eventos adversos se registraron con haloperidol (p = 0.036). Más síntomas extrapiramidales, acatisia e insomnio se reportaron con haloperidol y mayor aumento de peso con olanzapina sin diferencia estadística. Conclusiones: ambas medicaciones fueron similares en prevenir recaídas. El estado de salud y funcionalidad mejoró más con olanzapina vs. haloperidol. Los resultados de seguridad fueron consistentes con los perfiles conocidos de las drogas. Limitaciones en el diseño y conducción del estudio, acotan su generalización.
Objective: To compare olanzapine versus haloperidol effectiveness, in terms of relapse rates in Venezuela n patients with schizophrenia. Methods: A randomized, open label, follow-up study of 9-months after clinical stabilization or hospital discharged was conducted. The Medical Outcomes Study Form Health Survey (SF-36) and the Quality of Life Index from Mezzic & Cohen were used to evaluate the health state and quality of life. Safety parameters were collected. Results: Thirty-one patients in olanzapine and 40 in haloperidol were enrolled and discontinuation rates were 65 and 68 respectively. Only one patient in haloperidol relapsed. Health status improved more with olanzapine showing statistically significant improvement in five of the eight items of the SF-36. Olanzapine was slightly superior improving quality of life. More adverse events were registered with haloperidol (p = 0.036). More extrapyramidal symptoms, akathisia and insomnia were reported with haloperidol and more weight gain with olanzapine but the differences were not significant. Conclusions: Both medications were similar preventing relapses. Health status and functionality improved more with olanzapine versus haloperidol. Safety results are consistent with the known profile of the drug. Study limitations on design and conduction of this study restrict its generalization.
Subject(s)
Humans , Antipsychotic Agents , Schizophrenia/drug therapy , Haloperidol/therapeutic use , Antipsychotic Agents/adverse effects , Haloperidol/adverse effects , VenezuelaABSTRACT
Introducción: En 1956, Alan Lyell llamó necrólisis epidérmica tóxica (NTE) a los cuadros caracterizados histológicamente por necrosis de la epidermis y clínicamente por una epidermólisis difusa, con exfoliación o formación de lesiones bulosas, además de manifestaciones no cutáneas, lo que provoca trastornos hidroelectrolíticos, de termorregulación e hipercatabolismo. Objetivo: Describir un caso clínico con una reacción mayor y poco frecuente, secundaria al uso de olanzapina. Métodos: Se buscó información en la bases de datos de PubMed/Medline, Cochrane, SciELO, al igual que en referencias en artículos de revista y textos de los últimos cinco años. Se revisaron 16 artículos y se seleccionaron 10 de ellos para la discusión. Resultados: Las reacciones secundarias en la piel debido al uso Olanzapina se presentan en menos del 0,5% de los pacientes que la consumen; sin embargo, estas reacciones van desde exantema generalizado hasta NET, con un riesgo elevado de muerte. Conclusión: La piel es el órgano más frecuentemente afectado por las reacciones adversas a los medicamentos; pero sólo un pequeño porcentaje de las reacciones cutáneas supone un riesgo vital o conduce a secuelas importantes. La baja frecuencia de estas reacciones hace poco probable que se detecten en los ensayos clínicos previos a la comercialización de los medicamentos. El consumo de diferentes fármacos ha sido descrito como responsable de la aparición de reacciones cutáneas graves...
Introduction: In 1956, Alan Lyell used the term toxic epidermal necrolysis (TEN) to describe a histological and clinical pattern characterized by necrosis of the epidermis, diffuse epidermolysis with exfoliation and/or training bulosas injuries, as well as non-cutaneous manifestations such as hydro electrolytic, thermoregulatory and catabolic impairment. Objective: To describe a clinical case with a larger and unusual reaction, secondary to the use of olanzapine. Methods: Search for information in the databases: PubMed/Medline, Cochrane, SciELO, as well as in references from journals articles and textbooks, mainly in the last fi ve years. 16 articles were reviewed, 10 of which were included in the discussion. Results: The secondary reactions in the skin due to the use Olanzapine are present in <0,5% of patients who consumed it; however these reactions vary from a rash to TEN with a high risk of death. Conclusion: The skin is the organ most frequently affected by adverse reactions to medicines. However, only a small percentage of skin reactions are serious and life threatening. The low incidence of these reactions are unlikely to be detected in clinical trials prior to the marketing of medicines. The use of various drugs has been described as responsible for the occurrence of serious skin reactions...