Metabolic dysregulation in early onset psychiatric disorder before and after exposure to antipsychotic drugs

Antipsychotic Drugs (APDs) are being widely prescribed to treat various disorders, including schizophrenia and bipolar disorder; however, abnormal glucose metabolism and weight gain have been reported with Atypical Anti-Psychotic drugs (AAPDs) that can lead to insulin-resistance and type 2 diabetes mellitus. The study was designed to assess various biochemical parameters including insulin and blood sugar before and after exposure to APDs in order to exclude the involvement of psychiatric disorders and certain other factors in metabolic dysregulations. Fifty seven APDs-naïve patients with first episode psychosis were divided into six groups who received olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or combination of olanzapine with escitalopram and haloperidol. The serum samples were taken before the intake of the first dose and then on follow-up. Decrease in the level of elevated insulin and glucose was observed post-treatment in some patients, while others were observed whose insulin and glucose levels increased post-treatment, yet some patients did not show any disturbance in the insulin and glucose levels. It is concluded that psychiatric disorders by itself, narcotics, cigarette smoking and use of oral snuff may be also be implicated in metabolic dysregulations. The effects of APDs on insulin and glucose in healthy volunteers might be different than in patients with psychiatric disorders.

Comparative evaluation of pancreatic histopathology of rats treated with olanzapine, risperidone and streptozocin

Olanzapine and risperidone are widely prescribed atypical antipsychotics used in the treatment of schizophrenia and various other psychiatric disorders. Both of these drugs have been extensively reported to cause Type 2 diabetes mellitus and pancreatitis, however, the mechanism of olanzapine and risperidone-induced toxicity has not been so far unveiled. We, therefore, compared the streptozocin-induced pancreatic damage with that of pancreas isolated from olanzapine and risperidone treated rats. It was noticed that fibrotic growth, necrosis and derangement of the pancreatic islet cells caused by streptozocin were more pronounced than olanzapine and risperidone.

Caracterização no estado sólido e compatibilidade farmacêutica de cloridrato de ziprasidona / Solid-state characterization and pharmaceutical compatibility of ziprasidone hydrochloride

O cloridrato de ziprasidona foi físico-quimicamente caracterizado pelas técnicas de Calorimetria Exploratória Diferencial (DSC), Termogravimetria (TG), Espectroscopia no Infravermelho com Transformada de Fourier (FT-IR), Difração de Raios X de Pó (DRX) e Microscopia Eletrônica de Varredura (MEV). O estudo de compatibilidade foi realizado com 5 excipientes farmacêuticos diferentes (amido pré-gelatinizado, estearato de magnésio, celulose microcristalina, manitol e polivinilpirrolidona ­ PVP) . Amostras de misturas binárias fármaco: excipiente 1:1 m/m foram estocadas por 3 meses em câmara de estabilidade (75% ± 5% de umidade relativa e 40 ºC ± 1 ºC), e então analisadas por Cromatografia Líquida de Alta Eficiência (CLAE) para avaliar o efeito de cada excipiente na estabilidade química e, consequentemente, no teor do fármaco, em cada amostra . Os resultados de DRX e FT-IR identificaram a forma polimórfica F, correspondente ao cloridrato de ziprasidona monohidrato. A análise térmica demonstrou que o fármaco apresentou uma perda de massa de 4%, até 100ºC, correspondente à saída de uma molécula de água. A próxima perda de massa ocorreu a partir da temperatura de fusão (297ºC), e o fármaco foi totalmente degradado até 600ºC. Os resultados de CLAE demonstraram que o estearato de magnésio foi o único, entre os 5 excipientes testados, que provocou uma redução significativa de teor do fármaco na amostra (teor encontrado = 77% ± 3%). Dessa forma, o fármaco foi compatível com amido pré-gelatinizado, celulose microcristalina, manitol e PVP; e incompatível com estearato de magnésio nas condições estudadas.

Ziprasidone hydrochloride was fully characterized by Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FT-IR), Powder X-ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The stability study was carried out with 5 different pharmaceutical excipients (pregelatinized starch, magnesium stearate, microcrystalline cellulose, mannitol, polyvinylpyrrolidone ­ PVP). Binary mixtures of the drug-excipient were prepared in a 1:1(w/w) ratio and stored for 3 months in stability chamber (75% ± 5% of relative humidity and temperature of 40 ºC ± 1 ºC), then these samples were analyzed by High Performance Liquid Chromatography (HPLC) to evaluate the effect of each excipient on chemical stability and, consequently, on amount of drug in each sample. Data obtained by FT-IR and PXRD shown the polymorphic form F, corresponding to monohydrate ziprasidone hydrochloride. The thermal analysis demonstrated a mass loss of 4% until 100ºC, corresponding to a water molecule. The following mass loss occurred from melting temperature (297ºC) to 600ºC, with total sample degradation. The HPLC results shown that, between 5 tested excipients, only magnesium stearate caused significant amount reduction of drug in the sample (amount found = 77% ± 3%). Then, the drug was compatible with pregelatinized starch, microcrystalline cellulose, mannitol and PVP; and incompatible with magnesium stearate, in these work conditions.

Formulation and evaluation of bi-layer floating tablets of ziprasidone HCl and trihexyphenidyl HCl / Formulação e avaliação de bi-camada comprimidos flutuantes de ziprasidona HCl e HCl triexifenidila

The purpose of this research study was to establish ziprasidone HCl NR 40 mg and trihexyphenidyl HCl SR 4mg in the form of bi-layer sustained release floating tablets. The tablets were prepared using sodium HPMC K4M / HPMC K15M as bio-adhesive polymers and sodium bicarbonate acting as a floating layer. Tablets were evaluated based on different parameters such as thickness, hardness, friability, weight variation, in vitro dissolution studies, content of active ingredient and IR studies. The physico-chemical properties of the finished product complied with the specifications. In vitro release from the formulation was studied as per the USP XXIII dissolution procedure. The formulations gave a normal release effect followed by sustained release for 12 h which indicates bimodal release of ziprasidone HCl from the matrix tablets. The data obtained was fitted to Peppas models. Analysis of n values of the Korsmeyer equation indicated that the drug release involved non-diffusional mechanisms. By the present study, it can be concluded that bi-layer tablets of ziprasidone HCl and trihexyphenidyl HCl will be a useful strategy for extending the metabolism and improving the bioavailability of Ziprasidone HCl and Trihexyphenidyl HCl.

O propósito deste trabalho foi preparar ziprasidona. HCl NR 40 mg e triexifenidila.HCl SR 4 mg na forma de comprimidos efervescentes bicamada de liberação controlada. Os comprimidos foram preparados utilizando HPMC K4M / HPMC K15M sódico como polímero bioadesivo e bicarbonato como camada efervescente. Os comprimidos foram avaliados quanto a diferentes parâmetros, como espessura, dureza, friabilidade, variação de peso, dissolução in vitro, conteúdo do ingrediente ativo e estudos de IV. As propriedades físico-químicas dos produtos finais cumprem as especificações. A liberação in vitro da formulação foi estudada de acordo com o procedimento de dissolução da USP XXIII. As formulações resultaram em liberação normal, seguida por liberação controlada por 12 h, o que indica a liberação bimodal de cloridrato de ziprasidona dos comprimidos matriz. Os dados obtidos se adequaram aos modelos de Peppas. A análise de valores de n da equação de Korsmeyer indicou que a liberação do fármaco envolveu mecanismos não difusionais. Por este estudo, pode-se concluir que os comprimidos bicamada de ziprasidona.HCl e de triexifenidila.HCl serão um bom caminho para estender o metabolismo e para melhorar a biodisponibilidade de ziprasidona.HCl e de triexifenidila.HCl.

Disquinesia tardía inducida por neurolépticos y discapacidad en usuarios de larga estancia del Hospital Psiquiátrico Dr. Roberto Chacón Paut / Dyskinesia inducida by neuroleptics and discapacity in users of long stay of Hospital Psiquiátrico Dr. Roberto Chacón Paul

Justificación y objetivo: Los usuarios de larga estancia del Hospital Dr. Roberto Chacón Paut reciben trratamientos prolongados con neurolépticos, lo cual los expone a sufrir disquinesia tardía (DT). Este estudio tiene como objetivo determinar la prevalencia de DT inducida por neurolépticos, la discapacidad que genera, los factores de riesgo de sufrir disquinesia y sus efectos discapacitantes en esta población. Métodos: A 173 usuarios, se les administraron los instrumentos: Criterios de investigación DSM-IV para DT inducida por neurolépticos, Escala de movimientos involuntarios anormales e Indice de Barthel, con el fin de determinar la prevalencia de DT y la discapacida por movimientos anormales y para ABVD. Se utilizó un análisis de regresión logística para establecer los factores de riesgo de sufrir DT y sus efectos discapacitantes. Resultados: La prevalencia general de DT fue del 54 por ciento. Este porcentaje fue superior en mujeres y aumentó en los grupos de mayor edad y con tratamientos prolongados. Las mujeres presentaron discapacidad más severa que los varones. La edad avanzada y años de tratamiento con neurolépticos, se asociaron con una discapacidad menos severa. Se encontró un riesgo significativo de sufrir DT y discapacidad moderada por movimientos anormales, 1,06 veces más frecuente por cada año de tratamiento, y de total dependencia para ABVD, 10,07 veces más frecuente en mujeres que en varones. Conclusiones: Los años de tratamiento con neurolépticos fue el único factor de riesgo identificado en la ocurrencia de DT y discapacidad moderada por movimientos anormales. El sexo femenino se asoció con total dependecia para ABVD. Descriptores: Disquinesia, prevalencia, riesgo, discapacidad, movimientos anormales, vida diaria.

Detection of some antipsychotics in hair and nail

Measurement of therapeutic drug concentration have most commonly been determined from body fluids that reflect drug use within few days prior to sampling, therefore cannot distinguish between acute or chronic drug use. In the current study, human hair and nail were used for analysis to detect antipsychotic drugs [haloperidol and chlorpromazine] in cases of prolonged exposure. The patients selected were using the drugs for four months to give chance for nail and hair containing during to appear. Twenty patients were chosen, ten for each drug. Their ages were between 26-59 of either sex. Hair and nail samples taken after four months were positive

Condicionamento infantil com uso de neuroléptico / Management of children by using neuropletics

O presente trabalho considera o uso de um neuroléptico no condicionamento de 14 pacientes física e emocionalmente normais, em idade pré-escolar, acometidos de cárie rampante de aleitamento. Os resultados sugerem o emprego do fármaco na posologia administrativa, com êxito, livre dos possíveis efeitos colaterais dos mesmos, como um instrumento para o estabelecimento de uma futura aliança terapêutica satisfatória entre o paciente e o Odontopediatra