Inhibidores de la bomba de protones: el impacto en la salud cognitiva de los adultos mayores / Proton pump inhibitors: the impact on cognitive health in older adults

RESUMEN Los inhibidores de la bomba de protones (IBP) son los medicamentos más potentes para inhibir la secreción gástrica ácida, y se utilizan en el tratamiento de la mayor parte de las afecciones inflamatorias de la mucosa gástrica. Forman parte de los fármacos más recetados y sobreprescritos en todo el mundo; por ejemplo, en los Estados Unidos, según la Encuesta nacional de salud y nutrición, casi duplicaron su uso en los adultos de 40 años de un 4,9 % hasta un 8,3 %, entre los años 1999 a 2012. Aunque, en general, se consideran bien tolerados, algunos estudios epidemiológicos ―que extraen información a partir de grandes bases de datos― han reportado una serie de efectos adversos asociados con su uso prolongado, entre los cuales están el deterioro cognitivo, la enfermedad renal crónica, el infarto de miocardio, el accidente cerebrovascular, las fracturas óseas e incluso la muerte, entre otros. El objetivo fue realizar una revisión narrativa de la literatura acerca de los efectos del uso crónico de los IBP sobre el deterioro cognitivo en los adultos mayores. Se revisaron artículos a partir de una búsqueda en las bases de datos Pudmed, Scopus y Scielo con las palabras clave y términos Mesh/DeCS relacionados tanto en inglés como en español. Los efectos secundarios a nivel neurológico inducidos por el uso crónico de los IBP pueden estar relacionados indirectamente con la presencia de alteraciones sistémicas secundarias (deficiencia de magnesio y vitamina B12) o con efectos directos sobre el funcionamiento neuronal después de pasar a través de la barrera hematoencefálica. Si bien se han descrito varios mecanismos neurobiológicos por medio de los cuales los IBP podrían favorecer el desarrollo de la demencia ―que comprenden el funcionamiento de la proteína tau, la acumulación de beta amiloide (βA) y la deficiencia de cobalamina, entre otros―, la mayor parte de la evidencia clínica disponible no ha encontrado una asociación significativa entre el uso de los IBP y el riesgo de demencia o el deterioro cognitivo. Para establecer de una manera más clara los efectos clínicos adversos del uso crónico de los IBP, en especial, en el funcionamiento cerebral, se necesitan estudios de cohorte bien diseñados, con tamaños de muestra grandes y periodos de seguimiento prolongados, con un método confiable para ajustar los factores de confusión estandarizados y, además, realizar análisis por subgrupos.

ABSTRACT Proton pump inhibitors (PPIs) are the most potent drugs to inhibit gastric acid secretion, being used in the treatment of most inflammatory conditions of the gastric mucosa. They are among the most prescribed and overprescribed medications worldwide; for example, in the United States, according to the National Health and Nutrition Examination Survey, they almost doubled their use in adults aged 40 years and older from 4.9 % to 8.3 % between 1999 and 2012. Although they are generally considered well tolerated, some epidemiological studies extracting information from large databases have reported a number of adverse effects associated with their prolonged use, including cognitive impairment, chronic kidney disease, myocardial infarction, stroke, bone fractures and even death, among others. The objective was to conduct a narrative review of the literature on the effects of chronic use of PPIs on cognitive impairment in older adults. Articles were reviewed based on a search in the PubMed, Scopus and SciELO databases using both English and Spanish keywords and related MeSH/DeCS terms. Neurological side effects induced by chronic PPI use may be indirectly related to secondary systemic disorders (magnesium and vitamin B12 deficiency) or to direct effects on neuronal functioning after passing through the blood-brain barrier. Although several neurobiological mechanisms by which PPIs could favor the development of dementia-which involve Tau protein function, beta-amyloid [βA] accumulation and cobalamin deficiency, among others-have been described, most of the available clinical evidence has not shown a significant association between PPI use and the risk of dementia or cognitive impairment. To establish the adverse clinical effects of chronic PPI use more clearly, especially on brain functioning, well-designed cohort studies with large sample sizes and long follow-up periods, with a reliable method to adjust for standardized confounders, as well as subgroup analyses are needed.

Avaliação do tratamento da psoríase com esomeprazol - estudo piloto / Evaluation of psoriasis treatment with esomeprazole - a pilot study

ABSTRACT BACKGROUND: Psoriasis is an inflammatory skin disease that affects 1%-3% of Caucasian populations and may be persistent, disfiguring and stigmatising. Proton pump inhibitors (PPI) are potent blockers of gastric acid secretion. They are widely regarded as the agents of choice for the treatment of acid-peptic disorders. In addition to anti-secretory effects PPI have been found to have anti-oxidant properties and direct effects on neutrophils, monocytes, endothelial, and epithelial cells that might prevent inflammation. OBJECTIVE: This study evaluated the treatment of psoriasis with esomeprazole. METHODS: Ten patients were selected and psoriasis was evaluated according to Psoriasis Area and Severity Index (PASI). Exclusion criteria included concomitant use of any treatment for Psoriasis, organic diseases, use of other PPI than esomeprazole. Patients were medicated with esomeprazole 40 mg B.I.D. for 90 days. At the 90th day the patients were evaluated according PASI score. RESULTS: Statistically significant results were seen when compared PASI before and at 90th day of treatment (P=0.0002). CONCLUSION: The use of esomeprazole for psoriasis resulted in excellent clinical results with a significant reduction of PASI score.

RESUMO CONTEXTO: A psoríase é uma doença inflamatória da pele que afeta 1%-3% das populações caucasianas e pode ser persistente, desfigurante e estigmatizante. Inibidores da bomba de prótons (IBP) são potentes bloqueadores da secreção de ácido no estômago. Eles são considerados como os agentes de escolha para o tratamento de doenças ácido-pépticas. No entanto, além dos efeitos anti-secretores, IBP apresentam propriedades anti-oxidantes e efeitos diretos sobre os neutrófilos, monócitos, células epiteliais e endoteliais que podem impedir a inflamação. OBJETIVO: Avaliar o tratamento da psoríase com esomeprazol. MÉTODOS: Foram selecionados pacientes adultos (18 anos ou mais) com psoríase. Os critérios de exclusão foram o uso concomitante de qualquer tratamento para a psoríase, doenças orgânicas e uso de outro IBP. Foram selecionados 10 pacientes e a psoríase foi avaliada pelo índice de gravidade e área da psoríase (Psoriasis Area and Severity Index - PASI). Os pacientes foram medicados com esomeprazol 40 mg BID por 90 dias. No nonagésimo dia os pacientes foram novamente avaliados por meio do PASI. RESULTADOS: Dados estatisticamente significativos foram vistos quando comparado PASI antes do tratamento e no nonagésimo dia de tratamento, P=0,0002. CONCLUSÃO: O uso do esomeprazol para psoríase apresentou excelentes resultados clínicos com redução importante do PASI. Este estudo piloto é a primeira publicação na literatura inglesa sobre o tratamento da psoríase com esomeprazol.

Un ensayo clínico piloto de la efectividad clínica de dos presentaciones de esomeprazol / Clinical effectiveness of two esomeprazole presentations in a pilot trial

Resumen Introducción: el presente estudio tuvo como fin investigar la efectividad clínica de dos presentaciones de esomeprazol en pacientes con dispepsia de causa no estudiada. Métodos: se realizó un ensayo clínico piloto de dos presentaciones de esomeprazol de 40 mg recibidos diariamente por 28 días. Se eligieron pacientes con diagnóstico de dispepsia no estudiada que asistieron a consulta de gastroenterología en un hospital de referencia. Se evaluaron a los pacientes inicialmente con endoscopia y biopsia, el seguimiento a 2 y 4 semanas con escalas clínicas de síntomas y calidad de vida con cuestionarios validados en español (SODA y QoL-PEI) y eventos adversos. Además, se midieron los niveles de pH gástrico con pH-metrías en 24 horas al día 14 de tratamiento. Se tomaron niveles séricos del medicamento al momento de la evaluación de la pH-metría. Para las escalas clínicas se aplicó un análisis de varianza (ANOVA) de dos factores con medidas repetidas y al encontrar diferencias significativas en los tiempos se realizó una corrección de Bonferroni. Resultados: se aleatorizó un total de 33 pacientes, 16 y 17 pacientes en cada grupo. No hubo diferencias en el porcentaje de inhibición del pH gástrico al día 14 de tratamiento (p = 0,9795). No hubo diferencias en concentraciones de niveles séricos el día 14 (p = 0,2199). No se encontraron diferencias significativas en las escalas de gravedad y calidad de vida en las dos primeras semanas de tratamiento, pero sí en las últimas dos semanas, en las cuales el producto de prueba demostró mayor disminución del dolor (p = 0,0048) y superioridad en conformidad (p = 0,01) en la subescala SODA. No se presentaron eventos adversos serios y no hubo diferencias estadísticas entre la presentación eventos adversos no serios. Conclusiones: los productos de prueba y el de referencia mostraron efectos similares en variables clínicamente relevantes.

Abstract Introduction: This pilot studied the clinical effectiveness of two presentations of esomeprazole in patients with dyspepsia with undiagnosed causes. Methods: We conducted a pilot clinical trial of two 40 mg Esomeprazole presentations. Patients with dyspepsia of unknown cause at a gastroenterology clinic in a referral hospital were included. They received one or the other presentation daily for 28 days. Patients were initially evaluated with endoscopy and biopsy and received follow-up examinations at two and four weeks. Adverse events were recorded, and clinical symptom scales and quality of life questionnaires validated in Spanish (SODA and QoL-PEI) were used. In addition, gastric pH levels were measured continuously for 24 hours on day 14 of treatment. Serum levels of the medication administered were also measured on day 14 of treatment. A two-way repeated measures ANOVA was used to compare mean differences between the two groups. When significant differences in times were found, a Bonferroni correction was made. Results: A total of 33 patients were randomized into two groups: 16 patients in one group and 17 in the other. There were no differences in the percentages of gastric pH inhibition at day 14 of treatment (p = 0.9795). There were no differences in serum level concentrations on day 14 (p = 0.2199). No significant differences were found in severity and quality of life scales in the first two weeks of treatment. However, in the last two weeks of treatment the test product showed a larger decrease in pain (p = 0.0048) and superiority in compliance (p = 0.01) on the SODA subscale. There were no serious adverse events, and there were no statistical differences between the presentations of non-serious adverse events. Conclusions: The Test product and the Reference product showed similar effects on clinically relevant variables.

Bioequivalencia clínica de dos marcas de esomeprazol administradas en pacientes con ulcus gastroduodenal / Clinical bioequivalence of 2 brands of esomeprazol administered in patients with gastroduodenal ulcus

Los inhibidores de bomba de protones son usados en el tratamiento de la gastropatía ácido-péptica. Objetivo: comparar la eficacia de dos marcas de esomeprazol en el tratamiento de gastropatía ácido-péptica, la evolución de síntomas y su tolerancia. Materiales y Métodos: Se incluyeron pacientes de ambos sexos, con edades entre 18-60 años, con o sin Helicobacter pylori, que en la gastroscopia presentaron una o más erosiones o úlceras ≥ 5 mm y < 25 mm en su diámetro mayor. Se distribuyeron aleatoriamente a recibir una de las marcas, 40 mg/día, oral, durante 4 semanas. Al final fueron evaluados con endoscopia, interrogatorio de efectos adversos y laboratorio, comparando tasa de curación y evolución de la endoscopia. Se evaluó la tasa de respondedores por disminución del score de síntomas y la tolerancia mediante interrogatorio de efectos adversos y pruebas de laboratorio. Resultados: Ingresaron 34 pacientes, analizando los resultados de 30. En ambos grupos observamos mejoría en la endoscopia (curación y/o mejoría). El score de síntomas mejoró en ambos grupos, con significancia intragrupo pero no intergrupal. Los efectos adversos no fueron significativos. Conclusiones: Observamos mejoría en los criterios de endoscopia, y en el score de síntomas, en ambos grupos.

Introduction: Proton pump inhibitors are used in the treatment of acid-peptic gastropathy. Objective: to compare the efficacy of two brands of esomeprazole in the treatment of acid-peptic gastropathy, the evolution of symptoms and their tolerance. Materials and methods: Patients of both sexes, aged 18-60 years, with or without Helicobacter pylori, who had one or more erosions or ulcers ≥ 5 mm and <25 mm in their largest diameter, in gastroscopy, were included. They were randomized to receive one of the brands, 40 mg / day, orally, for 4 weeks. At the end, they were evaluated with endoscopy, adverse event questioning and laboratory tests, comparing cure rate and evolution of endoscopy. We evaluated the rate of responders according to decreased symptom score, and tolerance through questioning of adverse effects and laboratory tests. Results: Thirty-four patients were enrolled, analyzing the results of 30 patients. In both groups we observed improvement in endoscopy (healing and / or improvement). The score of symptoms improved in both groups, with intragroup but not intergroup significance. Adverse events were not significant. Conclusions: Thirty-four patients were enrolled, analyzing the results of 30 patients. In both groups we observed improvement in endoscopy (healing and / or improvement). The score of symptoms improved in both groups, with intragroup but not intergroup significance. Adverse events were not significant.

Clinical observation on the curative effect of teprenone combined with esomeprazole for reflux esophagitis / 中国基层医药

Objective To investigate the curative effect of Teprenone combined with esomeprazole for reflux esophagitis. Methods 96 cases of reflux esophagitis comfirmed by endoscope were obtained and divied into observation group and control group randomly. Both groups were offered with esomeprazole and motilium. Teprenone was added to the observation group and sucralfate was added to the control group. Clinical effective rate,healing rate,adverse reactions and one-year follow up were observed closely after the course of 8 weeks. Results The relief time of clinical symptom and total effective rate in the observation group were(9.3 ±3.5)d and 95.8% respectively,which were significantly higher than those in the control group(P ＜0.05). Endoscopic effective rate was 93.8% in observation group and 81.2% in control group respectively and statistically significant difference was observed (P ＜0. 05). Recurrence rate after one year in the observation group was 8. 3% ,which was significantly lower than in the control group (P ＜ 0.05). One case of headache and nausea occurred in both groups but no severe adverse reaction was observed. Conclusion Teprenone combined with esomeprazole were more effective and more likely to approach the complete cure for reflux esophagitis.

Esomeprazol en la terapia triple para la erradicación de Helicobacter Pylori en pacientes dispépticos no ulcerosos / Esomeprazole based triple therapy for the eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia

OBJETIVO: El presente trabajo tiene como objetivo principal, evaluar la eficacia de la terapia triple con esomeprazol en la erradicación del Helicobacter pylori (Hp). METODOLOGÍA: Se realizó un estudio descriptivo, prospectivo en el Servicio de gastroenterología del Hospital Nacional Cayetano Heredia (HNCH), donde se seleccionaron pacientes dispépticos no ulcerosos con infección por Hp (determinada mediante biopsia) entre los meses de junio a agosto del 2008, a los cuales se les dividió en dos grupos: el ¨grupo control¨ se trató conamoxicilina 1g VO c/12h, claritromicina 500 mg VO c/12h y omeprazol 20 mg VO c/12h, y el ¨grupo en estudio¨ recibió amoxicilina 1g VO c/12h, claritromicina 500 mg VO c/12h y esomeprazol 20 mg VO c/12h, ambos esquemas se dieron por 10 días. A las 4 semanas de completado el tratamiento, a cada grupo se le hizo un control endoscópico con toma de biopsias y test de aliento para determinar la erradicación del Hp. RESULTADOS: Se incluyó un total de 83 pacientes, de los cuales 42 recibieron terapia triple con omeprazol (grupo control) y 41 recibieron terapia triple con esomeprazol (grupo en estudio). Se perdieron en el seguimiento 5 pacientes del grupo control y 7 pacientes en el grupo en estudio. Por no contar con Test de aliento se excluyeron 3 pacientes en el grupo control y 2 pacientes en el grupo en estudio. De los 34 pacientes del grupo control se erradicó el Hp en 25 (73,5%), mientras que los 32 pacientes del grupo en estudio se erradicó el Hp en 26 (81,2%). Los efectos adversos más importantes incluyeron: diarrea, cefalea, dolor abdominal y estreñimiento. CONCLUSIONES: El tratamiento con esomeprazol presentó una tasa de erradicación 8% mayor que el esquema con omeprazol y el porcentaje de reacciones adversas fue similar enambos grupos.

OBJECTIVE: To assess the efficacy of esomeprazole-based triple therapy in the eradication of helicobacter pylori (HP). METHODOLOGY: A descriptive, prospective study was carried out between the months of June and August, 2008, at the Gastroenterology Service of the Cayetano Heredia National Hospital (HNCH) in which patients with non-ulcer dyspepsia infected with HP (diagnosed by a biopsy) were randomized and divided into two groups: the "control group" was treated with Amoxicillin (1g VO e/12h), Clarithromycin (500 mg VO e/12h) and Omeprazole (20 mg VO e/12h) and the "study group" received Amoxicillin (1g VO e/12h), Clarithromycin (500 mg VO e/12h) and Esomeprazole (20 mg VO e/12h); both treatments were administered over a period of ten days. Four weeks after the conclusion of the treatment, each group underwent an endoscopic control, including biopsy tests and breath tests to determine the eradication of the HP infection. RESULTS: A total of 83 patients were included, out of which 42 received triple therapy with Omeprazole (control group) and 41 received triple therapy with Esomeprazole (study group). Five patients of the control group and 7 of the study group were lost in the follow-up stage and 3 patients of the control group and 2 of the study group were excluded due to the lackof a breath test. Out of the 34 patients of the control group, HP was eradicated in 25 of them (73,5%) while out of the 32 patients of the study group, HP was eradicated in 26 (81,2%). The most important adverse effects included: diarrhea, headaches, abdominal pain and constipation. CONCLUSIONS: Treatment with Esomeprazole showed an eradication rate of 8% greater than treatment with Omeprazole and the percentage of adverse effects was similar in both groups.