Influência da atenção farmacêutica no seguimento do tratamento farmacológico de pacientes portadores de prolactinoma

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Farmacoterapia das perturbações do sono: insónia

Dissertação de mest., Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2011

La gestión electrónica de la farmacoterapia

Incluye bibliografía

Avaliação da eficácia e segurança da farmacoterapia da leishmaniose visceral

Pós-graduação em Doenças Tropicais - FMB

Perfil da farmacoterapia utilizada por idosos institucionalizados: uma análise dos problemas relacionados ao uso de medicamentos em instituições de longa permanência para idosos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes

Abstract Background Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to determine the pituitary level of pttg in three different experimental models of prolactinomas with altered dopaminergic control of the pituitary: the dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the senescent female rat. These three models shared the characteristics of increased pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or absent dopaminergic action at the pituitary level. We also studied samples from human macroprolactinomas, which were characterized as responsive or resistant to dopamine agonist therapy. Results When compared to female wild-type mice, pituitaries from female D2R knockout mice had decreased PTTG concentration, while no difference in pttg mRNA level was found. In senescent rats no difference in pituitary PTTG protein expression was found when compared to young rats. But, in young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg) PTTG protein expression was enhanced (P = 0.029). Therefore, in the three experimental models of prolactinomas, pituitary size was increased and there was hyperprolactinemia, but PTTG levels followed different patterns. Patients with macroprolactinomas were divided in those in which dopaminergic therapy normalized or failed to normalize prolactin levels (responsive and resistant, respectively). When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no differences were found. We next analyzed estrogen action at the pituitary by measuring pituitary estrogen receptor α levels. The D2R knockout female mice have low estrogen levels and in accordance, pituitary estrogen receptors were increased (P = 0.047). On the other hand, in senescent rats estrogen levels were slightly though not significantly higher, and estrogen receptors were similar between groups. The estrogen-treated rats had high pharmacological levels of the synthetic estrogen, and estrogen receptors were markedly lower than in controls (P < 0.0001). Finally, in patients with dopamine resistant or responsive prolactinomas no significant differences in estrogen receptor α levels were found. Therefore, pituitary PTTG was increased only if estrogen action was increased, which correlated with a decrease in pituitary estrogen receptor level. Conclusion We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level. Therefore it is increased only in prolactinomas generated by estrogen treatment, and not in prolactinomas arising from deficient dopamine control, or in dopamine resistant compared with dopamine responsive human prolactinomas. These results are important in the search for reliable prognostic indicators for patients with pituitary adenomas which will make tumor-specific therapy possible, and help to elucidate the poorly understood phenomenon of pituitary tumorigenesis.

Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists

Despite the fact that consensus guidelines recommend long-term dopamine agonist (DA) therapy as a first-line approach to the treatment of small prolactinoma, some patients continue to prefer a primary surgical approach. Concerns over potential adverse effects of long-term medical therapy and/or the desire to become pregnant and avoid long-term medication are often mentioned as reasons to pursue surgical removal. In this retrospective study, 34 consecutive patients (30 female, 4 male) preferably underwent primary pituitary surgery without prior DA treatment for small prolactinomas (microprolactinoma 1-10 mm, macroprolactinoma 11-20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients with microprolactinomas had significantly lower preoperative prolactin (PRL) levels compared to patients with macroprolactinomas (median 143 μg/l vs. 340 μg/l). Ninety percent of symptomatic patients experienced significant improvement of their signs and symptoms upon surgery. The postoperative PRL levels (median 3.45 μg/l) returned to normal in 94% of patients with small prolactinomas. There was no mortality and no major morbidities. One patient suffered from hypogonadotropic hypogonadism after surgery despite postoperative normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%) with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas after a median follow-up period of 33.5 months. Patients with small prolactinomas can safely consider pituitary surgery in a specialized centre with good chance of long-term remission as an alternative to long-term DA therapy.

Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma

The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this report, we determined the expression pattern of NNAT in individual cell types of the normal gland and within each of the different pituitary adenoma subtypes. In addition, we determined associations between expression and CpG island methylation and used colony forming efficiency assays (CFE) to gain further insight into the tumour-suppressor function of this gene. Immunohistochemical (IHC) co-localization studies of normal pituitaries showed that each of the hormone secreting cells (GH, PRL, ACTH, FSH and TSH) expressed NNAT. However, 33 out of 47 adenomas comprising, 11 somatotrophinomas, 10 prolactinomas, 12 corticotrophinomas and 14 non-functioning tumours, irrespective of subtype failed to express either NNAT transcript or protein as determined by quantitative real-time RT-PCR and IHC respectively. In normal pituitaries and adenomas that expressed NNAT the promoter-associated CpG island showed characteristics of an imprinted gene where approximately 50% of molecules were densely methylated. However, in the majority of adenomas that showed loss or significantly reduced expression of NNAT, relative to normal pituitaries, the gene-associated CpG island showed significantly increased methylation. Induced expression of NNAT in transfected AtT-20 cells significantly reduced CFE. Collectively, these findings point to an important role for NNAT in the pituitary and perhaps tumour development in this gland.

Farmacogenómica : aspectos éticos de la medicina personalizada

Las diferencias genéticas entre individuos (polimorfismos) condicionan los efectos de un fármaco en cuanto a la toxicología (efectos adversos) y farmacoterapia. Nuevas técnicas analíticas permiten estudiar el perfil genético de los individuos. Surge así una nueva disciplina, la Farmacogenómica, que es el estudio del total de genes farmacológicamente relevantes, así como la forma en que dichos genes manifiestan sus variaciones, y de qué manera estas variaciones pueden interaccionar para configurar el fenotipo de cada individuo, en lo que afecta a su respuesta a los medicamentos. La Bioética personalista ofrece un camino de reflexión que acompaña el quehacer científico en la búsqueda de fines verdaderos. En este sentido es fundamental acercar nuevas y mejores curas, así como disminuir el dolor de enfermedades crónicas y terminales, siempre y cuando se eviten nuevas clasificaciones de seres humanos e injusticias a la hora de distribuir los recursos.

Sedación paliativa

La fase de agonía es una etapa que experimentan las personas con una enfermedad progresiva debilitante varias horas o días antes de fallecer, durante este proceso el equipo interdisciplinar tiene que dar prioridad al confort y a los cuidados esenciales del paciente y de la familia para cubrir sus necesidades. En la fase de agonía puede aparecer una sintomatología imposible de controlar en un tiempo razonable con los medios y fármacos disponibles, entonces se recurre a la sedación como maniobra terapéutica para su adecuado control. El objetivo principal de este trabajo es adquirir unos conocimientos sobre la farmacoterapia utilizada. Idioma: Castellano

Psicoterapia grupal realizada por enfermería para pacientes con trastorno depresivo en atención primaria

La depresión es un trastorno mental habitual, siendo uno de los trastornos psiquiátricos más prevalentes, ya que afecta a 340 millones de personas en el mundo; y es uno de los trastornos que más problemas de discapacidad genera. La prevalencia de la depresión en el ámbito de Atención Primaria (AP) es alta, por lo que es importante hacer un buen abordaje terapéutico desde esta área. El tratamiento habitual para este tipo de pacientes es la farmacoterapia, sin embargo, diversos estudios señalan que junto con la psicoterapia se obtiene mejores resultados. Además, la realización de técnicas psicoterapéuticas por personal de enfermería previamente formado, como es la Enfermera de Salud Mental, ha demostrado ser eficaz, pero a pesar de ello, en los centros de AP no existe la figura de Enfermera de Salud Mental. Objetivo: Evaluar la efectividad de un programa psicoeducativo grupal realizado en un centro de AP por una Enfermera de Salud Mental en el tratamiento de pacientes con sintomatología depresiva, como complemento del tratamiento estándar aplicado por el Médico de AP. Metodología: Ensayo clínico aleatorizado con un grupo control que recibirá el tratamiento estándar, y un grupo experimental que recibirá además la intervención psicoeducativa. La población a estudio serán los pacientes con sintomatología depresiva pertenecientes a los Centros de Salud de Repélega y Castaños de Portugalete y la selección de la muestra se realizará con un muestreo no probabilístico consecutivo con un periodo de reclutamiento. Se compararán los resultados en cada grupo, tras la recogida de datos mediante el cuestionario de Salud SF-36 y el Inventario de depresión de Beck.

Terapias cognitivo-conductuales en la fobia social, en adultos

La fobia social es una enfermedad psiquiátrica que causa costes socioeconómicos significativos y que presenta una alta comorbilidad. Las terapias cognitivo-conductuales (TCC) pueden ser una alternativa de tratamiento efectiva, ya que buscan el cambio de pensamientos y comportamientos adquiridos en una enfermedad con un alto componente de aprendizaje. Objetivo: Verificar la efectividad de las terapias cognitivo-conductuales (TCC) con respecto a otros tratamientos empleados en la fobia social, en adultos (farmacoterapia y otras técnicas de psicoterapia). Metodología: Revisión bibliográfica de estudios de los últimos 10 años, en bases de datos (Pumed etc...). Se seleccionan 12 artículos, 10 ensayos clínicos y 2 meta-análisis. Resultados: Los estudios muestran una respuesta positiva de los pacientes (en términos de reducción de síntomas según escalas de medida estandarizadas para la fobia social) al tratamiento con terapias cognitivo-conductuales (TCC), en sus distintas modalidades de aplicación (individual, grupal y por internet). Estos ratios de respuesta son similares a los que se obtienen en otros tratamientos (farmacoterapia y terapia psicodinámica). Las TCC presentan como ventaja la ausencia de efectos secundarios; como desventaja, su efecto se produce a más largo plazo Conclusiones: No hay resultados concluyentes en relación al beneficio de estas terapias respecto de otras; los factores que determinan fundamentalmente el éxito de las mismas son la situación y la predisposición individual de cada paciente. Dadas las implicaciones de esta patología en la sociedad actual, sería conveniente invertir más medios en el desarrollo de nuevas técnicas.

Farmacogenética/Farmacogenómica

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas