Linaclotida en el tratamiento de pacientes con síndrome del intestino irritable con estreñimiento: análisis de una oportunidad / Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity

La linaclotida es un secretagogo que asocia un efecto combinado sobre el dolor visceral. La European Medicines Agency ha aprobado su indicación en el tratamiento sintomático en adultos del síndrome del intestino irritable con estreñimiento moderado o grave. El objetivo de esta revisión es analizar el marco clínico de aplicación de linaclotida en nuestro medio, las características del fármaco, su desarrollo preclínico y los estudios clínicos que apoyan su uso, con el fin de establecer los correspondientes juicios de validez y aplicabilidad clínica. Los resultados indican que el único efecto adverso, no grave, del fármaco es la diarrea. En cuanto a su eficacia, linaclotida presenta consistentemente favorables y significativas diferencias de riesgo absolutas frente a placebo en todas las variables resultado objetivas marcadas por las agencias reguladoras, con una respuesta combinada a dolor y estreñimiento entre el 12,6% y el 22,8%, según la variable y el ensayo considerados. Esta respuesta es sostenida y vinculada al fármaco, pues desaparece tras su retirada. Se concluye que linaclotida presenta un perfil de seguridad y eficacia que justifica, desde una perspectiva clínica, su uso en pacientes que cumplan criterios de síndrome del intestino irritable con estreñimiento con sintomatología de intensidad significativa que no pueda resolverse con otros tratamientos menos específicos. En ausencia de reglas de predicción de respuesta se recomienda que, si tras un periodo de prueba el paciente no responde, debe considerarse que no es candidato a tratamiento con linaclotida, reservando indicación y continuidad del tratamiento solo a los respondedores objetivos (AU)

Linaclotide is a secretagogue that provides a combined effect on visceral pain. The European Medicines Agency has authorized its indication for the symptomatic treatment of moderate to severe irritable bowel syndrome with constipation in adults. The purpose of this review is to discuss the clinical framework for linaclotide use in our setting, the drug’s characteristics and pre-clinical development, and the clinical studies supporting its use in order to establish relevant views regarding its validity and clinical applicability. The results suggest that the only —nonsevere— adverse effect associated with this drug is diarrhea. As regards effectiveness, linaclotide consistently shows favorable, significant differences in absolute risk versus placebo for all objective outcome variables described by regulatory agencies, with a combined pain and constipation response between 12.6% and 22.8% according to the variable and trial under consideration. This response is sustained and drug-related, as it goes away upon discontinuation. To conclude, linaclotide has a safety and efficacy profile that, from a clinical perspective, warrants its use for patients meeting irritable bowel syndrome and constipation criteria, with significant symptoms that cannot be relieved with other less specific measures. In the absence of predictive rules for response, it is recommended that, should the patient fail to respond, he or she should be considered not eligible for linaclotide therapy, and both indication and treatment continuity should be reserved for objective responders alone (AU)

Ghrelina e secretagogos do hormônio de crescimento (GHS): modulação da secreção do hormônio de crescimento e perspectivas terapêuticas: [revisão] / Ghrelin and growth hormone secretagogues (GHS): modulation of growth hormone secretion and therapeutic applications: [review]

A secreção do hormônio de crescimento (GH) é modulada pelo hormônio liberador de hormônio de crescimento (GHRH) e pela somatostatina. Na última década foi descoberto um terceiro mecanismo de controle, envolvendo os secretagogos de GH (GHS). A ghrelina, o ligante endógeno do receptor dos GHS, é um peptídeo acilado produzido no estômago, que também é sintetizado no hipotálamo. Este peptídeo é capaz de liberar GH, além de aumentar a ingesta alimentar. A ghrelina endógena parece amplificar o padrão básico de secreção de GH, ampliando a resposta do somatotrofo ao GHRH, estimulando múltiplas vias intracelulares interdependentes. Entretanto, seu local de atuação predominante é o hipotálamo. Neste trabalho, será apresentada revisão sobre a descoberta da ghrelina, os mecanismos de ação e o possível papel fisiológico dos GHS e da ghrelina na secreção de GH e, finalmente, as possíveis aplicações terapêuticas destes compostos.

Growth hormone-releasing hormone (GHRH) and somatostatin modulate growth hormone (GH) secretion. A third mechanism was discovered in the last decade, involving the action of growth hormone secretagogues (GHS). Ghrelin, the endogenous ligand of the GHS-receptor, is an acylated peptide mainly produced by the stomach, but also synthesized in the hypothalamus. This compound increases both GH release and food intake. Endogenous ghrelin might amplify the basic pattern of GH secretion, optimizing somatotroph responsiveness to GHRH, activating multiple interdependent intracellular pathways. However, its main site of action is the hypothalamus. In the current paper it is reviewed the available data on the discovery of this peptide, the mechanisms of action and possible physiological roles of the GHS and ghrelin on GH secretion, and finally, the possible therapeutic applications of these compounds.