Acompanhamento farmacoterapêutico na dor crônica geriátrica: relato de caso / Pharmacotherapeutic follow up in the geriatric chronic pain: a case report / Seguimiento farmacoterapéutico en dolor geriátrico crónico: relatode caso

O presente trabalho relata o caso de uma paciente idosa que sofrede dor crônica, destacando-seos principais diagnósticos farmacêuticos encontrados,e as intervenções realizadas. Os resultados obtidos permitem concluir que o acompanhamento farmacoterapêutico pode contribuir de forma direta com a melhora na qualidade de vida de um/apaciente. No caso de doenças crônicas, como a dor, o acompanhamento deve ser contínuo, no sentido de garantir a adesão do paciente ao tratamento.

The present study aims to report the case of an elderly patient withchronic pain, highlighting main pharmaceutical diagnostics and interventions. The obtained results allow us to conclude that the pharmacotherapeutic monitoring can contribute directly to improving the quality of life of the patient. In the case of chronic diseases, such as pain, monitoring should be continuous in order to ensure adherence to treatment.

El presente trabajo informa el caso de un paciente anciano con dolor crónico, destacando los principales diagnósticos farmacéuticos encontrados e intervenciones realizadas. Los resultados obtenidos nos permiten concluir que el seguimiento farmacoterapéutico puede contribuir directamente a mejorar la calidad de vida del paciente. En el caso de enfermedades crónicas, como el dolor, la monitorización debe ser continua para garantizar el cumplimiento del tratamiento por parte del paciente.

A possible role to nitric oxide in the anti-inflammatory effects of amitriptyline.

Antidepressants are reported to display anti-inflammatory effects. Nitric oxide (NO), in turn, has a key role in inflammation. The objective of the present study was to evaluate the effect of amitriptyline co-administered with L-NAME (a NO synthase inhibitor) on certain parameters of acute inflammatory response in rats, as a form to investigate a possible participation of NO in the anti-inflammatory effects of amitriptyline. For this, two animal models were used: carrageenan-induced paw edema and acute peritonitis. In the last one, peritoneal exudate, adhesion molecules expression by peripheral blood leukocytes and serum cytokines levels were evaluated. In a noninflammatory condition, serum levels of nitrates were determined. L-NAME induced a potentiation of the anti-inflammatory effects of amitriptyline (p < 0.05) in the paw edema model; however, these effects were not abrogated when L-NAME was substituted by L-arginine administration. A decrease in both leukocyte concentration and total number of cells in the peritoneal exudate and a reduction in the total serum levels of nitrates were observed with co-administration of L-NAME and amitriptyline (p < 0.05). No significant differences among groups were found concerning the expression of adhesion molecules by peripheral blood leukocytes (p > 0.05). There was a significant decrease on IL-1ß and TNF-α serum levels in the experimental groups when compared to the control animals. Together the present results and the literature suggest that the anti-inflammatory effects of amitriptyline may be due to a decrease in NO production. A decrease in IL-1ß/TNF-α serum levels may also be implicated in the results observed.

Odor cues from tumor-bearing mice induces neuroimmune changes.

Cohabitation for 14 days with an Ehrlich tumor-bearing mice was shown, among others, to increase locomotor activity, and hypothalamic noradrenaline levels and turnover, to decrease the innate immune responses and animal resistance to tumor growth. The present experiment was designed to access the relevance of tactile, olfactory, and visual communication to the neuroimmune changes induced by cohabitation with a tumor-bearing partner. Mice that were not allowed to perceive odor cues from their sick partners presented no alterations in neutrophil activity, a fact not observed after visual deprivation and physical isolation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. The present results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion.

Papel do antidepressivo amitriptilina sobre a resposta inflamatória aguda em ratos / Role of the antidepressant amitriptyline in the acute inflammatory response in rats

Diversos estudos têm sugerido uma ação anti-inflamatória para o antidepressivo amitriptilina; a presente investigação pretende analisar os mecanismos envolvidos com esta resposta. Mais especificamente, o objetivo do presente estudo é avaliar os efeitos da amitriptilina sobre a resposta inflamatória induzida pela carragenina em ratos e investigar os prováveis mecanismos relacionados a estes efeitos. Num primeiro momento, utilizando-se o modelo do edema de pata induzido pela carragenina, avaliamos o efeito anti-inflamatório da amitriptilina após administração em diferentes doses e intervalos de tempo, isto é, de forma aguda ou em múltiplas doses, por diferentes vias de administração. Verificamos que o tratamento com amitriptilina 10mg/kg, administrada a cada tempo de meia-vida de eliminação, produziu redução significante do edema de pata nos diversos tempos avaliados. Não houve reversão deste efeito anti-inflamatório quando os animais foram pré-tratados com um antagonista de receptores de glicocorticoides (RU-486); houve potencialização do efeito anti-inflamatório pelo pré-tratamento com antagonista de receptores alfa-1-adrenérgicos (prazosina). A administração de amitriptilina juntamente com um inibidor inespecífico de síntese de óxido nítrico (L-NAME) levou a uma potencialização do efeito anti-inflamatório avaliado pelo modelo do edema de pata; produziu, ainda, uma redução significante na concentração de leucócitos e no número total de leucócitos do exsudato peritoneal induzido por carragenina e uma redução significante do total de nitratos circulantes, quando comparados aos animais do grupo controle. Este efeito anti-inflamatório avaliado pelo edema de pata não foi revertido pela administração de um precursor da síntese de NO. O tratamento com amitriptilina ou L-NAME isoladamente (...)

... ou em conjunto não produziu alterações significantes na expressão das moléculas de adesão ICAM-1, PECAM-1, L-selectina e MAC-1 por leucócitos do sangue periférico. Quando avaliamos o comportamento dos leucócitos por microscopia intravital, observamos que a amitriptilina produziu uma redução significante no rolamento, adesão e transmigração de leucócitos avaliados em condição inflamatória. A administração de amitriptilina isoladamente ou em conjunto com L-NAME também mostrou produzir redução significante nos níveis de IL-1beta e TNF-alfa no soro de ratos. Podemos assim concluir que a amitriptilina apresentou um efeito anti-inflamatório na maioria dos modelos avaliados. Os mecanismos parecem envolver a participação dos receptores alfa-1-adrenérgicos, a inibição da NOS - com consequente redução na síntese de NO e das ações próinflamatórias a ele associadas - e a diminuição nos níveis das citocinas IL-1beta e TNF-alfa. Considerando-se a teoria que implica a depressão como um fenômeno inflamatório, a compreensão dos mecanismos envolvidos no efeito anti-inflamatório da amitriptilina poderia contribuir nas investigações envolvendo esta teoria

Depressão, antidepressivos e sistema imune: um novo olhar sobre um velho problema: [revisão] / Depression, antidepressants and immune system: a new look to an old problem: [review]

CONTEXTO: A hipótese monoaminérgica da depressão não responde a uma série de questões, tais como "quais as causas dos distúrbios monoaminérgicos?" e "como explicar uma taxa de 30 por cento de refratariedade aos antidepressivos?". Sendo assim, outras teorias têm sido propostas, entre elas, aquelas que enfocam as participações dos sistemas imune e endócrino. OBJETIVOS: Analisar criticamente o papel do sistema de resposta imunoinflamatória na depressão e discutir a interação dos antidepressivos com esse sistema, tanto do ponto de vista básico como clínico. MÉTODOS: Realizou-se pesquisa bibliográfica utilizando-se as bases de dados MedLine e SciELO. RESULTADOS: Pacientes vítimas de estresse crônico e depressão apresentam ativação das respostas imunoinflamatórias e do eixo hipotálamo-hipófise-adrenal, os quais, direta ou indiretamente, influenciam a neurotransmissão. Nesse sentido, a utilização de antidepressivos não apenas aumenta a disponibilidade de neurotransmissores na fenda sináptica, mas também induz mudança do padrão de resposta imune Th1 - pró-inflamatório - para o Th2, que é antiinflamatório. Além disso, sabe-se que pacientes não responsivos aos antidepressivos possuem o sistema imuneinflamatório mais ativo. No entanto, há uma série de dados controversos na literatura, havendo indícios de um perfil imune diferente de acordo com o tipo de depressão. CONCLUSÕES: A compreensão de aspectos neuroimunes presentes na depressão poderia contribuir para um melhor entendimento das bases biológicas desse transtorno e, possivelmente, para novas perspectivas na busca de uma terapêutica mais efetiva.

BACKGROUND: The monoaminergic hypothesis of depression does not answer certain questions, such as "what are the causes of the monoaminergic disturbances?" and "how to explain the existence of 30 percent refractory patients to antidepressants?". Therefore, other theories have emerged, such as those focusing on the immune and endocrine systems. OBJECTIVES: To analyze the role of the immune-inflammatory system on depression and, furthermore, the interactions between antidepressants and this system, from basic and clinical points of view. METHODS: Literature review was carried out in the MedLine and SciELO databases. Patients suffering of chronic stress and depression present an activation of both inflammatory responses and hypothalamic-pituitary-adrenal axis, which, directly or indirectly, influence neurotransmission. Therefore, the use of antidepressants not only increases the availability of neurotransmitters in the synaptic cleft, but also changes the pattern of Th1 immune response - pro-inflammatory - to the Th2, which is antiinflammatory. Moreover, it is known that patients who do not respond to antidepressant treatment have hyperactive immune-inflammatory response system. However, there are several controversies in the literature, and evidences suggest a different immune profile according to the type of depression. DISCUSSION: The understanding of the neuroimmune aspects of depression might contribute to a better comprehension of the biological basis of this disorder and, therefore, to a new perspective in the search for a more effective therapy.

Cohabitation with a sick cage mate: effects on ascitic form of Ehrlich tumor growth and macrophage activity.

The present study was designed to evaluate the effects of mice cohabitation with a sick conspecific cage mate on peritoneal macrophage activity and on resistance to Ehrlich tumor growth. Female mice housed in pairs were divided into control and experimental groups. One mouse of each control pair was inoculated with NaCl (0.1 ml/10 g) intraperitoneally and the other, called 'companion of healthy partner' (CHP), was kept undisturbed. One animal of each experimental pair of mice was inoculated with 5.0 x 10(6) Ehrlich tumor cells intraperitoneally and the other, the subject of this study, was called 'companion of sick partner' (CSP). Peritoneal macrophages were removed from CSP and CHP mice to analyze resident macrophage activity (experiment 1), macrophage activity after Mycobacterium bovis (experiment 2) or Ehrlich tumor cells (experiment 3) in vivo inoculations. The resistance of CSP and CHP mice to Ehrlich tumor growth was also analyzed (experiment 4). Differences between groups were not found on resident macrophage activity. However, Onco-BCG- and Ehrlich tumor-activated macrophages from CSP mice presented a decreased intensity and percentage of phagocytosis and an increased respiratory burst in the presence of Staphylococcus aureus stimulation in vitro. CSP animals at the same time displayed a decreased resistance to Ehrlich tumor growth. These data were discussed in light of a possible psychological stress effect imposed by the housing condition on mice's peritoneal macrophage activity and, as a consequence, on their resistance to Ehrlich tumor growth.

Cohabitation with a sick cage mate: Effects on noradrenaline turnover and neutrophil activity.

The present study was designed to evaluate the effects of cohabitation for 11 days with a sick conspecific on hypothalamic levels and turnover of noradrenaline NA (experiment 1) and on neutrophil oxidative burst and phagocytosis in mice (experiment 2). Female mice were divided into two groups: control and experimental. One mouse of each control pair was kept undisturbed and called "companion of health partner" (CHP). One animal of each experimental pair of mice was inoculated with 5 x 10(6) Ehrlich tumor cells i.p., and the other, the subject of this study, was called "companion of sick partner" (CSP). In experiment 3, CHP and CSP mice were treated with diazepam (1.0 mg/kg) or with control solution (vehicle of diazepam, 1.0 mL/kg) 1h before evaluation of neutrophil activity. The CSP mice presented (1) decreased levels and increased turnover of hypothalamic NA; (2) decreased neutrophil oxidative burst after PMA or Staphylococcus aureus induction; (3) decreased percentage and intensity of neutrophil phagocytosis. In CSP mice, diazepam induced no changes in neutrophil oxidative burst or intensity of phagocytosis, but abolished almost completely the percentage of neutrophils performing phagocytosis. These data were discussed in the light of possible neuroimmune interactions.

Bioavailability of immediate and controlled release formulations of lithium carbonate

INTRODUCTION/OBJECTIVES: Controlled-release lithium formulations were developed to minimize elevated blood peaks, related to side-effects and intoxications. However, there is little information about the bioavailability of the only controlled-release lithium formulation available in Brazil. The objective of this study was to compare the bioavailability of controlled-release and immediate-release lithium formulations, after single and multiple doses. METHODS: Twelve healthy volunteers received 900 mg of immediate-release or controlled-release lithium carbonate in single or multiple doses during 9 days. After single dose administration, the following parameters were analyzed for each formulation: maximum lithium concentration (Cmax); time to reach Cmax (t max); area under the curve of serum concentration versus time (AUC0-12 and AUC0-Ñ) and the elimination half-life (t1/2 elim.). After multiple doses, Cmax; t max; AUC0-12; mean (Cmean) and minimum drug concentration (Cmin) and degree of fluctuation (DF) were analyzed. A 90 percent confidence interval (90 percentCI) for the ratio between the AUCs for each formulation was constructed. RESULTS/DISCUSSION: Following single dose, the two formulations were bioequivalent; however, they were not after multiple doses. This fact could be a consequence of methodological limitations of lithium level's measurements since, following single dose, these levels could not be detected at time periods 24 and 48h in many volunteers, compromising the calculation of t1/2 elim ,and consequently of the AUC0-Ñ and the 90 percentCI to the ratio of these areas. Therefore, the bioequivalence found after single dose may be an unreliable result