RESUMO
O relato discorre sobre a efetividade do antipsicótico cloridrato de ziprasidona como terapia farmacológica para desordens comportamentais em uma cadela apresentando sinais de transtornos neurológicos e episódios de crises convulsivas. Sabendo que há relatos onde a utilização de antipsicóticos em cães foi capaz de amenizar tais sinais, o intuito deste trabalho foi o de avaliar a eficiência da ziprasidona na melhora desta condição, visto que ainda não há registros da aplicabilidade da droga na espécie. No tratamento deste relato de caso foi administrada a dose de 20 mg de ziprasidona a cada 12 horas, com alimento, por um período de três meses. Resultados benéficos foram observados a partir do terceiro dia da administração, quando os sinais foram amenizados e o animal apresentou-se mais equilibrado. Concluiu-se que o fármaco foi capaz de suprimir os sinais indesejados sem causar sedação significativa, e sugere a diminuição na frequência de episódios convulsivos.
The report discusses the effectiveness of the antipsychotic ziprasidone hydrochloride as a pharmacological therapy for behavioral disorders in a dog showing signs of neurological disorders and episodes of seizures. Knowing that there are reports where the use of antipsychotics in dogs was able to mitigate such signs, the aim of this work was to evaluate the efficiency of ziprasidone in improving this condition, since there are still no records of the drugs applicability in the species. In the treatment of this case report, a dose of 20 mg of ziprasidone was administered every 12 hours, with food, for a period of three months. Beneficial results were observed from the third day of administration, when the signs were reduced and the animal was more balanced. It was concluded that the drug was able to suppress the unwanted signals without causing significant sedation, and suggests a decrease in the frequency of seizure episodes.
Assuntos
Animais , Cães , Antipsicóticos/administração & dosagem , Antipsicóticos/agonistas , Cães/fisiologia , Doenças do Sistema NervosoRESUMO
O relato discorre sobre a efetividade do antipsicótico cloridrato de ziprasidona como terapia farmacológica para desordens comportamentais em uma cadela apresentando sinais de transtornos neurológicos e episódios de crises convulsivas. Sabendo que há relatos onde a utilização de antipsicóticos em cães foi capaz de amenizar tais sinais, o intuito deste trabalho foi o de avaliar a eficiência da ziprasidona na melhora desta condição, visto que ainda não há registros da aplicabilidade da droga na espécie. No tratamento deste relato de caso foi administrada a dose de 20 mg de ziprasidona a cada 12 horas, com alimento, por um período de três meses. Resultados benéficos foram observados a partir do terceiro dia da administração, quando os sinais foram amenizados e o animal apresentou-se mais equilibrado. Concluiu-se que o fármaco foi capaz de suprimir os sinais indesejados sem causar sedação significativa, e sugere a diminuição na frequência de episódios convulsivos.(AU)
The report discusses the effectiveness of the antipsychotic ziprasidone hydrochloride as a pharmacological therapy for behavioral disorders in a dog showing signs of neurological disorders and episodes of seizures. Knowing that there are reports where the use of antipsychotics in dogs was able to mitigate such signs, the aim of this work was to evaluate the efficiency of ziprasidone in improving this condition, since there are still no records of the drugs applicability in the species. In the treatment of this case report, a dose of 20 mg of ziprasidone was administered every 12 hours, with food, for a period of three months. Beneficial results were observed from the third day of administration, when the signs were reduced and the animal was more balanced. It was concluded that the drug was able to suppress the unwanted signals without causing significant sedation, and suggests a decrease in the frequency of seizure episodes.(AU)
Assuntos
Animais , Cães , Cães/fisiologia , Antipsicóticos/administração & dosagem , Antipsicóticos/agonistas , Doenças do Sistema NervosoRESUMO
El síndrome neuroléptico maligno es una rara y potencialmente fatal reacción adversa medicamentosa, asociada usualmente al uso de antipsicóticos. Tiene por características la presencia de fiebre, rigidez muscular, estado mental alterado y disfunción autonómica. Los hallazgos de laboratorio son inespecíficos, sin embargo, la presencia de leucocitosis y elevación de la creatina fosfoquinasason hallazgos frecuentes. Presentamos el caso de un paciente varón de 51 años, natural de Lima con antecedentes médicos de tuberculosis pulmonar y esquizofrenia que acude a nuestro hospital con un cuadro de psicosis quien, luego de ser tratado con ziprasidona administrada por vía intramuscular, presentó los síntomas característicos de un síndrome neuroléptico maligno. Conocer la clínica y la fisiopatología de este síndrome nos permitirá un mejor abordaje, ya que por su poca frecuencia podría no llegar a plantearse dentro de los diagnósticos diferenciales, lo que resultaría perjudicial para el paciente.
Neuroleptic malignant syndrome is a rare and potentially fatal drug adverse reaction, usually associated with antipsychotics. Signs and symptoms include: fever, muscle rigidity, altered mental status and autonomic dysfunction. Laboratory findings are nonspecific, however the presence of leukocytosis and elevated creatinine phosphokinase are frequent findings. We present the case of a 51-year-old male patient from Lima with a medical history of pulmonary tuberculosis and schizophrenia that comes to our hospital with psychotic symptoms. After being treated with ziprasidone, administered by intramuscular injection presents with typical symptoms of neuroleptic malignant syndrome. Knowing the clinical features and the pathophysiology of this syndrome will allow us to better approach the condition. Due to its infrequent presentation, it may not be considered within the differential diagnosis, which could be harmful to the patient.
RESUMO
AIMS: Pregnancy is associated with physiological changes that alter the pharmacokinetics (PK) of drugs. The aim of this study was to predict the PK of ziprasidone in pregnant women. METHODS: A full physiologically-based pharmacokinetic (PBPK) model of ziprasidone was developed and validated for the non-pregnant population (healthy adults, paediatrics, geriatrics), and this was extended to the pregnant state to assess the change in PK profile of ziprasidone throughout pregnancy. RESULTS: The PBPK model successfully predicted the ziprasidone disposition in healthy adult volunteers, wherein the predicted and observed AUC, Cmax and tmax were within the fold-difference of 0.94-1.09, 0.89-1.40 and 0.80-1.08, respectively. The paediatric and geriatric population, also showed predicted AUC, Cmax and tmax within a two-fold range of the observed values. The simulated exposure in pregnant women using a p-PBPK model showed no significant difference when compared to non-pregnant women. CONCLUSIONS: The PBPK model predicted the impact of physiological changes during pregnancy on PK and exposure of ziprasidone, suggesting that dose adjustment is not necessary in this special population.
Assuntos
Antipsicóticos/farmacocinética , Simulação por Computador , Modelos Biológicos , Piperazinas/farmacocinética , Tiazóis/farmacocinética , Adulto , Fatores Etários , Idoso , Antipsicóticos/administração & dosagem , Área Sob a Curva , Células CACO-2 , Criança , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , Voluntários Saudáveis , Humanos , Transtornos Mentais/tratamento farmacológico , Piperazinas/administração & dosagem , Gravidez , Complicações na Gravidez/tratamento farmacológico , Tiazóis/administração & dosagemRESUMO
Antipsychotic drugs are used to treat schizophrenia and other psychiatric disorders. However, most of these drugs present side effects causing obesity and other serious metabolic alterations that correlate with grade of chronic inflammation. In contrast, ziprasidone's (ZIP) metabolic side effects are attenuated relative to those of other antipsychotic drugs, but some reports suggest that this drug could cause allergic, hypersensitive reactions in susceptible patients. At present, the mechanism of ZIP's effect on peripheral inflammatory metabolism is not well characterized. We conducted an in vitro study to evaluate the effect of ZIP on a macrophage cell line (RAW 264.1). Our results showed that in non-activated macrophage cells, ZIP exposure initiated macrophage spreading; increased cellular proliferation, as evaluated by MTT and flow cytometry assays; and presented higher levels of oxidant molecules involved in the inflammatory response (nitric oxide, superoxide, reactive oxygen species), and proinflammatory cytokines (IL-1, IL-6, TNFα, INFγ). Levels of IL-10, an anti-inflammatory cytokine were lower in ZIP-exposed cells. These effects were less potent than those caused by the positive control for inflammation induction (phytohemagglutinin), and more intense than the effects of lithium (LI), which was used as an anti-inflammatory molecule. ZIP also modulated cytokine gene expression. Taken together, these data suggest that ZIP can produce a peripheral inflammatory response, and this response may explain the allergen-inflammatory response observed in some patients treated with this antipsychotic drug.
Assuntos
Antipsicóticos/efeitos adversos , Inflamação/induzido quimicamente , Inflamação/patologia , Macrófagos/patologia , Piperazinas/efeitos adversos , Tiazóis/efeitos adversos , Animais , Antipsicóticos/química , Biomarcadores/metabolismo , Ciclo Celular/efeitos dos fármacos , Citocinas/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Oxirredução , Piperazinas/química , Células RAW 264.7 , Tiazóis/químicaRESUMO
Kounis syndrome (KS), described by Kounis and Zavras in 1991, is the manifestation of an allergic reaction preceding and leading to an acute coronary syndrome (ACS). There are three variants of Kounis Syndrome. Here we describe a novel case report of a type 1 variant secondary to Ziprasidone.
Assuntos
Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/imunologia , Transtorno Bipolar/tratamento farmacológico , Hipersensibilidade a Drogas/complicações , Piperazinas/efeitos adversos , Ideação Suicida , Tiazóis/efeitos adversos , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Serviço Hospitalar de Emergência , Humanos , Masculino , Piperazinas/uso terapêutico , Síndrome , Tiazóis/uso terapêuticoRESUMO
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.
Assuntos
Antipsicóticos/análise , Excipientes Farmacêuticos/química , Estabilidade de MedicamentosRESUMO
1. It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. In the present study, we investigated the effects of acute administration or withdrawal from long-term administration of haloperidol and/or ziprasidone on morphine-induced open-field behaviour in mice. 2. In the first experiment, mice were given a single injection of haloperidol (1 mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6 mg/kg, i.p.) and motor activity was quantified by the open-field test. The aim of the second experiment was to verify the effects of an acute injection of haloperidol (1 mg/kg) or ziprasidone (6 mg/kg) on 20 mg/kg morphine-induced behaviours in the open-field test. In the third experiment, mice were treated with 1 mg/kg haloperidol and/or 2, 4 or 6 mg/kg ziprasidone for 20 days. Seventy-two hours after the last injection, mice were injected with 20 mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. 3. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. The results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients.
Assuntos
Antipsicóticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Animais , Feminino , Haloperidol/farmacologia , Camundongos , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Tiazóis/farmacologiaRESUMO
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.
Assuntos
Antipsicóticos/análise , Comprimidos com Revestimento Entérico/uso terapêutico , Esquizofrenia/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodosRESUMO
OBJECTIVES: The aim of our study was to investigate the impact of typical and atypical antipsychotic drugs on leptin concentration in blood and changes in the receptor expression in the hypothalamus of male Wistar rats. METHODS: From the age of 13 to 18 weeks, three groups of 20 animals were fed an average dose of 3.5 + 0.03 mg/ kg body weight (BW) haloperidol; 30.6 + 0.22 mg/kg BW clozapine; or 14.9 + 0.13 mg/kg BW ziprasidone in ground food pellets containing 15 percent fat. Twenty control animals received no drugs. Blood samples were taken at week 14, 16, and 19. Locomotor activity and exploratory behavior were measured using the alcove test at weeks 15 and 17. The expression of the hypothalamic leptin receptor in rat brains was determined by using a Western blot. RESULTS: Rats medicated with haloperidol and ziprasidone showed a significantly decreased percentage weight gain and food consumption. We observed no differences in the alcove test, but locomotor activity was significantly reduced in the haloperidol group. Except for rats in the clozapine and ziprasidone groups, after 2 weeks of drug application, we found no changes in the leptin blood concentrations among the four groups or animals within each group. Moreover, we did not find specific differences in hypothalamic leptin receptor expression among the groups. CONCLUSION: We concluded that in male Wistar rats during this treatment period, the tested drugs did not act directly on the leptin regulatory system. We recommend further studies using long-term treatment of different rat strains.
Assuntos
Animais , Masculino , Ratos , Antipsicóticos/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/química , Leptina/sangue , Receptores para Leptina/análise , Aumento de Peso/efeitos dos fármacos , Western Blotting , Clozapina/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Haloperidol/farmacologia , Hipotálamo/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Ratos Wistar , Fatores de Tempo , Tiazóis/farmacologiaRESUMO
Atypical antipsychotic drugs have less extra pyramidal side effects and are more effective to control the clinical manifestations of schizophrenia. However, their use may be associated to a higher incidence of weight gain, dyslipidemia, metabolic syndrome, glucose intolerance and type 2 diabetes mellitus. We performed a systematic literature search to evaluate the risk of type 2 diabetes mellitus incidence associated to the use of atypical antipsychotic drugs, compared to conventional treatment. If users of all types of atypical antipsychotic drugs are compared with users of conventional treatment, no significant differences in the incidence of type 2 diabetes mellitus were observed. If individual drugs are evaluated, clozapine and risperidone are associated with a higher risk of diabetes than haloperidol. Quetiapine is associated with a lower risk of diabetes than conventional treatment. The quality of the evidence found was low; therefore, new studies should been performed.