Famotidina en el tratamiento de pacientes hospitalizados con COVID-19. Revisión sistemática y metaanálisis / Famotidine in the treatment of hospitalized patients with COVID-19. Systematic review and meta-analysis

Introducción: El síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2), de alta morbimortalidad, carece a la fecha de preparar esta revisión, de una terapia específica altamente eficaz. Famotidina se ha postulado como una opción terapéutica viable, basado en trabajos de cohorte retrospectiva y modelos computacionales guiados por inteligencia artificial. Objetivo: Recopilar la mejor evidencia científica disponible para determinar la efectividad y eficacia de famotidina en el tratamiento de pacientes hospitalizados con COVID-19, para reducir el riesgo de progresión de la enfermedad, intubación, muerte y tiempo de estancia hospitalaria. Material y Métodos: Se realizó una búsqueda en PubMed, EBSCO, Scopus, Web of Science y Cochrane Central, de artículos originales que reporten las variables de interés asociadas al uso de famotidina en pacientes hospitalizados con COVID- 19. Los investigadores independientemente evaluaron y seleccionaron los estudios, se extrajeron los datos expuestos para las asociaciones de interés y se procesaron con el software Revman 5.3. Resultados: En la búsqueda se obtuvo un total de 126 artículos potenciales para la revisión, de los cuales 14 fueron seleccionados para el análisis. En el metaanálisis se incluyeron un total de 47.044 pacientes, de los cuales 6.647 fueron los usuarios de famotidina. El riesgo de intubación se vio reducido en el grupo no expuesto a famotidina, aunque sin significancia estadística, (RR 1,43 IC95% 0,42-4,83), en cuanto a la mortalidad no se evidenció reducción significativa en el grupo de famotidina (RR 0,95 IC 95% 0,70-1,29). Se observó reducción en el tiempo de estancia hospitalaria (DM -1,60 -2,89, -0,31) y finalmente se mostró que no hay presencia de asociación entre el uso de famotidina y el desenlace compuesto de reducción del riesgo de ingreso a UCI, intubación y muerte (RR 1,03 IC 95% 0,46-2,34). Conclusión: Famotidina no presenta efectividad ni eficacia en la reducción de riesgo de intubación o ingreso a UCI ni de mortalidad en pacientes hospitalizados por COVID-19. La eficacia en la reducción de la estancia hospitalaria no es consistente y se necesitan más ensayos clínicos con buena calidad metodológica para definirla.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high morbidity and mortality, lacks, at the time of preparing this review, a highly effective specific therapy. Famotidine has been postulated as a viable therapeutic option, based on retrospective cohort investigations and computational models guided by artificial intelligence. Aim: The objective of this study was to compile the best scientific evidence available to determine the effectiveness and efficacy of famotidine in the treatment of hospitalized patients with COVID-19, to reduce the risk of disease progression, intubation, death, and time to hospital stay. Methods: A search was carried out in PubMed, EBSCO, Scopus, Web of Science, and Central Cochrane, for original articles that report the variables of interest associated with the use of famotidine in hospitalized patients with COVID-19. The investigators independently evaluated and selected the studies, the exposed data for the associations of interest were extracted and processed with Revman 5.3 software. Results: The search yielded a total of 126 potential articles for the review, of which 14 were selected for analysis. A total of 47,044 patients were included in the meta-analysis of which 6,647 were famotidine users. The risk of intubation was reduced in the group not exposed to famotidine, although without statistical significance (RR 1.43 IC95% 0.42 - 4.83), regarding mortality there was no significant reduction in the famotidine group (RR 0.95 IC 95 % 0.70-1.29). A reduction in the length of hospital stay was observed (MD -1.60 -2.89, -0.31) and finally it was shown that there is no association between the use of famotidine and the composite outcome of reduced risk of ICU admission, intubation and death. (RR 1.03 95% CI 0.46-2.34). Conclusion: Famotidine does not show effectiveness or efficacy in reducing the risk of intubation or ICU admission or mortality in patients hospitalized for COVID-19. The efficacy in reducing hospital stay is not consistent and more clinical trials with good methodological quality are needed to define it.

Prescripción de protectores gástricos en pacientes reumatológicos: análisis desde Consulta Externa de Gastroenterología / Prescription of gastric protectors in rheumatological patients: Analysis from a gastroenterology outpatient clinic

Introducción: Los antinflamatorios no esteroideos son los medicamentos más recetados por reumatólogos y traumatólogos. Pero a pesar de tener una eficacia similar para controlar la inflamación y el dolor, los diferentes antinflamatorios no esteroideos disponibles presentan variabilidad en su perfil de seguridad. Objetivo: Brindar una panorámica sobre la prescripción de protectores gástricos en pacientes reumatológicos, en dos centros hospitalarios, desde una perspectiva gastroenterológica. Métodos: La investigación se inscribe en el paradigma cuantitativo con un estudio observacional. Se conformaron dos grupos de pacientes, uno de ellos provenientes del hospital A y el segundo grupo pertenecía al hospital B. Discusión: Los gastroprotectores se han convertido en los fármacos de mayor demanda en las farmacias comunitarias de Ecuador, y los más prescritos son los inhibidores de la bomba de protones y en menor frecuencia los antihistamínicos H2. Respecto a los gastroprotectores más frecuentemente prescritos, según nuestro estudio, estos valores podrían obedecer a la disponibilidad y los costos de la famotidina y el omeprazol con respecto a otros medicamentos de probada eficacia (ansoprazol, pantoprazol, rabeprazol y ranitidina). Conclusiones: Durante los últimos años, el uso de los fármacos gastroprotectores en América Latina ha experimentado un importante desarrollo, con la observancia de normas y guías clínicas de manejo de casos que ofrecen recomendaciones importantes al respecto. Por tanto, desde una perspectiva gastroenterológica, para tener éxito, es indispensable procurar un conocimiento de estos aportes y evidencias científicas(AU)

Introduction: Nonsteroidal anti-inflammatory drugs are the most prescribed medications by rheumatologists and traumatologists. However, despite having similar efficacy in controlling inflammation and pain, the different available nonsteroidal anti-inflammatory drugs show variability in their safety profile. Objective: To provide an overview of the prescription of gastric protectors in rheumatological patients, in two hospital centers, from a gastroenterological perspective. Methods: The research is part of the quantitative paradigm with an observational study. Two groups of patients were formed, one of them from hospital A and the second group belonged to hospital B. Discussion: Gastroprotectors have become the drugs in greatest demand in community pharmacies in Ecuador, the most prescribed being Proton Pump Inhibitors (IBPS) and, to a lesser extent, H2 antihistamines (anti-H2). Regarding the most frequently prescribed gastroprotectors, according to our study, these values ​​could be due to the availability and costs of famotidine and omeprazole compared to other drugs with proven effectiveness, such as ansoprazol, pantoprazole, rabeprazole and ranitidine. Conclusions: In recent years, the use of gastroprotective drugs in Latin America has undergone significant development, with the observance of clinical case management norms and guidelines that offer important recommendations in this regard. Therefore, from a gastroenterological perspective, to be successful, it is essential to seek knowledge of these contributions and scientific evidence(AU)

Perspectiva histórica do tratamento clínico da doença do refluxo gastroesofágico / Historical perspective of gastroesophageal reflux disease clinical treatment

ABSTRACT BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases. GERD generates significant impairment in patients' quality of life and it is associated to relevant medical resources utilization. A better understanding of GERD pathophysiology in the past five decades has favored the evolution of therapeutic strategies from non-drug interventions and antacids to more efficacious and safer alternatives. OBJECTIVE: To summarize data about the historical evolution of GERD management in Brazil, focusing on medical therapy and addressing evidence on efficacy and safety of drug classes currently recommended. METHODS: A narrative review was conducted by systematizing information about discoveries on GERD pathophysiology. We also addressed efficacy and safety of medications currently used to reduce symptoms and improve endoscopic healing of esophageal lesions. A structured search on Pubmed was performed to identify systematic reviews and meta-analysis investigating GERD outcomes positively impacted by proton pump inhibitors (PPIs), the first choice of pharmacotherapy for the disease. RESULTS: The chronological development of therapeutic measures for GERD in Brazil evolved from lifestyle interventions with relative poor effect on symptoms related to esophageal acid exposure, particularly heartburn, to effective and safe pharmacological interventions such as histamine H2-receptor antagonists and PPIs. In the present days, some drug classes play a minor role in disease management, namely prokinetics and antacids, due to their reduced efficacy and relevant safety concerns (particularly with prokinetics). The main challenge for prescribers and researchers seems to be finding long-acting acid suppressants strategies able to ameliorate patients' symptoms and quality of life, thereafter, reducing medical resource consumption. The dual delayed-release PPI dexlansoprazole seems to respond for some of the limitations other PPIs have. CONCLUSION: Recognizing the historical evolution of GERD management can help care providers to better understand therapeutic options for their patients, as well as focus on unmet needs that deserve further attention. PPIs are still the first choice therapy, with good evidence in favor of their efficacy, despite some safety concerns. However, as with any medical intervention, it is recommended to prescribe PPIs for patients with clear indication, using adequate dosing and monitoring for adverse events.

RESUMO CONTEXTO: A doença do refluxo gastroesofágico (DRGE) é uma das doenças gastrointestinais mais prevalentes, resultando em limitações significativas na qualidade de vida dos pacientes e, também, relevante utilização de recursos médicos. Um melhor entendimento da fisiopatologia da doença nas últimas cinco décadas tem favorecido a evolução das estratégias de tratamento, desde intervenções não farmacológicas e antiácidos, a alternativas mais eficazes e seguras. OBJETIVO: Resumir os dados sobre a evolução histórica do manejo da DRGE no Brasil, focando na terapia medicamentosa e abordando evidências sobre a eficácia e segurança de classes medicamentosas atualmente recomendadas. MÉTODOS: Uma revisão narrativa foi conduzida para sistematizar informações sobre descobertas na fisiopatologia da DRGE e, também, sobre a eficácia e segurança de medicamentos utilizados atualmente para reduzir os sintomas e melhorar a cicatrização endoscópica de lesões esofágicas. Uma busca estruturada na base de dados Pubmed foi realizada para identificar revisões sistemáticas e metanálises que investigassem desfechos da doença impactados positivamente pelos inibidores da bomba de prótons (IBPs), a primeira escolha farmacológica para a doença. RESULTADOS: O desenvolvimento cronológico das medidas terapêuticas para a DRGE no Brasil evoluiu de modificações no estilo de vida que demonstraram relativamente pouco efeito sobre os sintomas relacionados à exposição esofágico ao ácido, particularmente a azia, a intervenções farmacológicas eficazes e seguras como os anti-histamínicos H2 e os IBPs. Atualmente, algumas classes de medicamentos exercem um papel menor no manejo da doença, procinéticos e antiácidos por exemplo, devido à sua eficácia reduzida e a preocupações relevantes quanto a segurança (particularmente com os procinéticos). O principal desafio para os prescritores e pesquisadores parece ser encontrar estratégias supressoras de ácidos de longa duração capazes de melhorar os sintomas e a qualidade de vida dos pacientes, reduzindo assim o consumo de recursos médicos. O dexlansoprazol, um IBP de liberação retardada dupla, parece responder a algumas limitações que outros IBPs têm. CONCLUSÃO: O reconhecimento da evolução histórica do manejo da DRGE pode auxiliar aos profissionais assistentes a melhor entender as opções terapêuticas para seus pacientes, assim como focar em necessidades não atendidas que necessitem de maior atenção. IBPs ainda são a terapia de escolha inicial, com boas evidências a favor de sua eficácia, apesar algumas questões acerca da segurança de seu uso. No entanto, assim como para qualquer intervenção medicamentosa, é recomendada a prescrição dos IBPs para pacientes com indicação clara, utilizando doses adequadas e monitorando a ocorrência de eventos adversos.

Tratamento antissecretor da doença do refluxo gastroesofágico pediátrica - uma revisão sistemática / Antisecretory treatment for pediatric gastroesophageal reflux disease - a systematic review

ABSTRACT BACKGROUND: Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven. OBJECTIVE: To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review. METHODS: A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156). RESULTS: After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the treatment of children with cough, and there is no clear definition on the best strategy. Another study demonstrated that omeprazole performed better than ranitidine for the treatment of extraesophageal reflux manifestations. Ten studies failed to demonstrate significant benefits of proton pump inhibitors or histamine H2 receptor antagonists for the treatment of unspecific manifestations attributed to gastroesophageal reflux in infants. CONCLUSION: Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease, but not to treat asthma or unspecific symptoms.

RESUMO CONTEXTO: Inibidores de bomba de prótons e antagonistas dos receptores H2 da histamina são duas das mais comumente prescritas classes de medicações para a doença do refluxo gastroesofágico pediátrica, mas sua eficácia é controversa. Muitos pacientes são tratados com essas drogas por manifestações atípicas atribuídas ao refluxo gastroesofágico, mesmo que uma relação causal não esteja comprovada. OBJETIVO: Avaliar os inibidores da bomba de prótons e os antagonistas dos receptores H2 da histamina na doença do refluxo gastroesofágico pediátrica através de uma revisão sistemática. MÉTODOS: Realizou-se uma revisão sistemática, utilizando as bases de dados MEDLINE, EMBASE e Cochrane Central Register of Controlled Trials. A pesquisa foi limitada a estudos publicados em inglês, português e espanhol. Não houve limitação quanto à data de publicação. Os estudos foram considerados elegíveis se fossem ensaios controlados randomizados que avaliassem inibidores da bomba de prótons e/ou antagonistas dos receptores H2 da histamina para o tratamento da doença do refluxo gastroesofágico pediátrica. Estudos publicados apenas como resumos, estudos que não avaliassem desfechos clinicamente relevantes e estudos que comparassem exclusivamente diferentes doses do mesmo fármaco foram excluídos. A extração de dados foi realizada por pesquisadores independentes. O protocolo do estudo foi registrado na plataforma PROSPERO (CRD42016040156). RESULTADOS: Após a análise das 735 referências identificadas, 23 estudos (1598 pacientes randomizados) foram incluídos na revisão sistemática. Oito estudos demonstraram que tanto os inibidores da bomba de prótons como os antagonistas dos receptores H2 da histamina eram eficazes contra as manifestações típicas da doença de refluxo gastroesofágico e que não havia evidências de benefício na combinação dessas classes de drogas ou na prescrição rotineira de tratamentos de manutenção de longo prazo. Três estudos avaliaram o efeito dos tratamentos em crianças com asma e, nem os inibidores da bomba de prótons, nem os antagonistas dos receptores H2 da histamina se mostraram significativamente melhores do que o placebo. Um estudo comparou diferentes combinações de omeprazol, betanecol e placebo para o tratamento de crianças com tosse, e não há uma definição clara sobre a melhor estratégia terapêutica. Outro estudo demonstrou que o omeprazol apresentou melhor desempenho do que a ranitidina para o tratamento de manifestações extraesofágicas da doença do refluxo gastroesofágico. Dez estudos não tiveram sucesso em demonstrar benefícios significativos dos inibidores da bomba de prótons ou dos antagonistas dos receptores H2 da histamina para o tratamento de manifestações inespecíficas atribuídas ao refluxo gastroesofágico em crianças menores de 1 ano de idade. CONCLUSÃO: Inibidores da bomba de prótons ou antagonistas dos receptores H2 da histamina podem ser utilizados para tratar crianças com doença de refluxo gastroesofágico, mas não para tratar asma ou sintomas inespecíficos.

Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats / 浙江大学学报·医学版

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.

Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report / 대한마취과학회지

Serotonin syndrome is an unexpected fatal adverse event related to serotonergic medication. This case report is the first report describing the possible treatment effect of famotidine on serotonin syndrome. Furthermore, this is the first case report of serotonin syndrome induced by meperidine alone in a patient with no previous history suggesting a susceptibility to serotonin syndrome. A 70-year-old male with no recent history of serotonergic drug use presented with severe serotonin syndrome following ureteroscopy, possibly due to postoperative meperidine administration. The patient's symptoms included hypertension, tachycardia, tachypnea, hyperthermia, myoclonus, diaphoresis, retching, nausea, agitation, and semicoma mentality with no pupillary light reflex. Symptoms began to subside immediately after the administration of intravenous famotidine for prevention of aspiration pneumonia, with mental and neurological symptoms showing improvement initially, followed by autonomic symptoms. This case report suggests that the histamine type 2 receptor antagonist famotidine may be an effective emergency treatment for serotonin syndrome.

Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report / 대한마취과학회지

Serotonin syndrome is an unexpected fatal adverse event related to serotonergic medication. This case report is the first report describing the possible treatment effect of famotidine on serotonin syndrome. Furthermore, this is the first case report of serotonin syndrome induced by meperidine alone in a patient with no previous history suggesting a susceptibility to serotonin syndrome. A 70-year-old male with no recent history of serotonergic drug use presented with severe serotonin syndrome following ureteroscopy, possibly due to postoperative meperidine administration. The patient's symptoms included hypertension, tachycardia, tachypnea, hyperthermia, myoclonus, diaphoresis, retching, nausea, agitation, and semicoma mentality with no pupillary light reflex. Symptoms began to subside immediately after the administration of intravenous famotidine for prevention of aspiration pneumonia, with mental and neurological symptoms showing improvement initially, followed by autonomic symptoms. This case report suggests that the histamine type 2 receptor antagonist famotidine may be an effective emergency treatment for serotonin syndrome.

Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study / Prevalência de deficiência de vitamina B12 em pacientes diabéticos do tipo 2 usando metformina: um estudo transversal

ABSTRACT: CONTEXT AND OBJECTIVE: The prevalence of vitamin B12 deficiency varies from 5.8% to 30% among patients undergoing long-term treatment with metformin. Because of the paucity of data on Brazilian patients, this study aimed to determine the frequency of B12 deficiency and related factors among Brazilian patients with type 2 diabetes mellitus (T2DM) using metformin. DESIGN AND SETTING: Cross-sectional study at a public university hospital. METHODS: Patients with T2DM and a control group of non-diabetics were included. Serum B12 levels were measured and biochemical B12 deficiency was defined as serum levels < 180 pg/ml. Associations between B12 deficiency and age, duration of T2DM, duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) or histamine H2 antagonists were determined. RESULTS: 231 T2DM patients using metformin (T2DM-met) and 231 controls were included. No difference in the frequency of PPI or H2-antagonist use was seen between the groups. B12 deficiency was more frequent in the T2DM-met group (22.5% versus 7.4%) and this difference persisted after excluding PPI/H2-antagonist users (17.9% versus 5.6%). The factors that interfered with serum B12 levels were PPI/H2-antagonist use and duration of metformin use ≥ 10 years. Use of PPI/H2-antagonists was associated with B12 deficiency, with an odds ratio of 2.60 (95% confidence interval, 1.34-5.04). CONCLUSIONS: Among T2DM patients, treatment with metformin and concomitant use of PPI/H2-antagonists are associated with a higher chance of developing B12 deficiency than among non-diabetics.

RESUMO: CONTEXTO E OBJETIVO: A prevalência de deficiência de vitamina B12 varia de 5,8% a 30% nos pacientes em tratamento a longo prazo com metformina. Devido à escassez de dados em pacientes brasileiros, este estudo determinou a frequência de deficiência de B12 e fatores relacionados em pacientes brasileiros com diabetes mellitus tipo 2 (DM2) usando metformina. TIPO DE ESTUDO E LOCAL: Estudo transversal em hospital público universitário. MÉTODOS: Pacientes com DM2 e um grupo controle de não diabéticos foram incluídos. Os níveis séricos de vitamina B12 foram dosados e deficiência bioquímica de B12 foi definida como níveis séricos < 180 pg/ml. Foi investigada a associação entre deficiência de B12 e idade, duração do DM2, duração do uso e dose de metformina, uso de inibidores de bomba de prótons (IBP) ou antagonistas dos receptores histamínicos H2 (antagonistas-H2). RESULTADOS: 231 pacientes DM2 usando metformina (DM2-met) e 231 controles foram incluídos. Não houve diferença na frequência de uso de IBP/antagonistas-H2 entre os grupos. Deficiência de B12 foi mais frequente no grupo DM2-met (22,5% versus 7,4%) e essa diferença persistiu após exclusão dos usuários de IBP/antagonistas-H2 (17,9% versus 5,6%). Fatores que interferiram nos níveis séricos de B12 foram: uso de IBP/antagonistas-H2 e duração do uso de metformina ≥ 10 anos. O uso de IBP/antagonistas-H2 associou-se com deficiência de B12, com um risco relativo de 2,60 (95% intervalo de confiança, 1,34-5,04). CONCLUSÕES: Considerando pacientes com DM2, o tratamento com metformina e uso concomitante de IBP/antagonistas-H2 estão associados com maior chance de desenvolver deficiência de B12 quando comparado aos não diabéticos.

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.

RESUMO Contexto Anti-inflamatórios não esteroidais induzem lesões da mucosa gástrica devido às suas propriedades ácidas. Ranitidina, um antagonista dos receptores H2, revelou-se benéfico em pacientes com úlceras gástricas. Objetivo - O presente estudo foi realizado para avaliar o efeito da administração de ranitidina em gastropatia induzida por anti-inflamatórios não esteroidais (diclofenaco, nimesulida) e seu efeito sobre a histopatologia do estômago, dos rins e fígado. Métodos Diclofenaco, nimesulida e ranitidina foram administradas em doses de 2, 4 e 6 mg/kg, p.o. uma vez diariamente por 14 dias e seu efeito sobre o volume gástrico, acidez, significam o número de úlcera e o pH gástrico. Além disso, o exame histopatológico também foi realizado em seções do estômago, dos rins e fígado. Resultados Após a administração de diclofenaco ou nimesulida, todos os parâmetros gástricos foram significativamente alterados assim como a histopatologia do estômago, fígado e rim. No grupo controle, as seções renais mostraram glomérulos normais sem espessamento da membrana basal glomerular, enquanto em diclofenaco isolado, nimesulida isolado e grupos com ranitidina e nimesulida, foi observado espessamento da membrana basal glomerular. Estas alterações observou-se serem revertidas no grupo ranitidina com diclofenaco. As seções do fígado, o grupo controle mostrou placas e cordões de hepatócitos cuboidais anastomosados com núcleos bem demarcados e citoplasma abundante. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, leve dilatação dos sinusoides é vista acoplados com proeminência de veia central. Nos grupos diclofenaco e nimesulida sozinhos, túbulos proximais e distais contorcidos mostram necrose tubular focal leve. Nas secções gástricas, o grupo controle mostrou várias dobras formando vilosidades e a superfície do revestimento epitelial da mucosa. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, o duodeno mostrou dispersas células inflamatórias predominantemente compostas por linfócitos. Nos grupos diclofenaco e nimesulida sozinhos, as secções de áreas gástricas mostraram necrose parcial e inflamação crônica moderada respectivamente. Conclusão - O estudo, portanto, forneceu o fundamento terapêutico para administração simultânea de bloqueador de receptor H2 (ranitidina) com diclofenaco, sendo mais benéfica em comparação com ranitidina com nimesulida para minimizar a intolerância gástrica de diclofenaco no tratamento a longo prazo de condições inflamatórias.

Uso de inhibidores de la bomba de protones y antagonistas de los receptores H2 de histamina como profilaxis en úlceras por estrés: ¿una práctica justificada? / Use of proton pump inhibitors and Histamine-2 receptor antagonists in stress ulcers: a justified practice? / Uso de inibidores da bomba de prótons e antagonistas dos receptores H2 de histamina como profilaxia em úlceras por estresse: uma prática justificada?

La introducción de los moduladores de acidez gástrica como profilaxis contra las úlceras por estrés en pacientes críticos se ha \r\nido convirtiendo en una práctica de rutina tanto en la unidad de cuidados intensivos como fuera de esta; sin embargo, el desco\r\n-\r\nnocimiento de la fisiopatología de la enfermedad, las indicaciones de uso de moduladores de pH como profilácticos, los riesgos \r\nasociados a la prescripción indiscriminada y de las guías disponibles sobre esta práctica han llevado a un uso descontrolado \r\nde medicamentos como omeprazol y ranitidina, lo cual aumenta los costos para los hospitales y predispone a los pacientes a \r\npresentar enfermedades como neumonía. Con el objetivo de revisar los factores de riesgo asociados a esta patología, la eficacia \r\nde esta medida, sus indicaciones y posibles complicaciones tanto dentro como fuera de las unidades de cuidados intensivos, se \r\nrealizó una revisión de la literatura. Esta incluyó artículos disponibles en diferentes bases de datos que hicieran referencia al manejo \r\nprofiláctico de úlceras por estrés desde 1980 hasta 2014. Se encontró que, según la literatura actual, el uso de la profilaxis contra \r\núlceras por estrés es una práctica muy debatida en el caso de los pacientes críticos y, lo que es más importante, en los no críticos \r\naún no existen recomendaciones de uso o factores de riesgo establecidos. Por esta razón, la extrapolación de esta conducta a \r\npacientes fuera de la unidad de cuidados intensivos es injustificada hasta el momento.

The introduction of acid gastric modulators in critical patients \r\nas prophylaxis against stress ulcers has increasingly become \r\na routine practice both in the intensive care unit and outside \r\nof it. However, lack of knowledge about topics including \r\nthe physiopathology of the disease, directions for use of pH \r\nmodulators as a prophylactic, the associated risk of over-pre\r\n-\r\nscription, and guidelines available about this practice has led \r\nto an overuse of drugs like omeprazole and ranitidine, making \r\nhospitalization more expensive and predisposing patients \r\nto diseases like pneumonia. The objective of this article is \r\nto review the risk factors associated with this pathology, the \r\nefficacy of this action, and the complications and indications \r\ninside and outside of intensive care units using all available \r\ndata through 2014. In the end we conclude that at this time \r\nand with the new evidence, the use of prophylaxis against \r\nstress ulcers in critical patients is a widely debated practice and \r\nmore importantly there are no recommendations for its use or \r\nestablished risk factors in the non-critical population, leading \r\nus to conclude that extrapolation to patients outside of inten\r\n-\r\nsive care is not justified up to date.

A introdução dos moduladores de acidez gástrica como \r\nprofilaxia contra as úlceras por estresse em pacientes críticos \r\nconverteu-se em prática de rotina tanto na unidade de cuidados \r\nintensivos como fora desta. No entanto, o desconhecimento \r\nda fisiopatologia da doença, as indicações de uso de modula\r\n-\r\ndores de pH como profiláticos, os riscos associados à prescrição \r\nindiscriminada e as orientações disponíveis sobre esta prática \r\nlevaram a um uso descontrolado de medicamentos como \r\nomeprazol e ranitidina, aumentando o custo para os hospi\r\n-\r\ntais e predispondo os pacientes a doenças como pneumonia. \r\nCom o objetivo de revisar os fatores de risco associados a esta \r\npatologia, a eficácia desta medida, suas indicações e possí\r\n-\r\nveis complicações tanto dentro como fora das unidades de \r\ncuidado intensivo, foi realizada uma revisão da literatura. Esta \r\nincluiu artigos disponíveis em diferentes bancos de dados que \r\nse referiram ao manuseio profilático de úlceras por estresse, \r\ndesde 1980 até 2014. Descobriu-se que, segundo a literatura \r\natual, o uso de profilaxia contra úlceras por estresse é uma \r\nprática muito debatida no caso dos pacientes críticos e, o que \r\né mais importante, para os não críticos ainda não existem reco\r\n-\r\nmendações de uso ou fatores de risco estabelecidos. Por este \r\nmotivo, a extrapolação desta conduta com pacientes fora da \r\nunidade de cuidados intensivos é injustificada até o momento.

H[2] receptor activity; effect in isolated rabbit heart

Histamine can stimulate the heart by directly interacting with cardiac histamine receptors. In the present study we have investigated the H[2] receptor activity in isolated rabbit heart. Cimetidine, a specific H[2] receptor antagonist was used. The isolated heart was mounted in langendroff apparatus. The heart was perfused at a constant pressure with oxygenated Ringer's Locke solution. H[2] receptor antagonist produces negative inotropic effect in the presence of histamine. This indicates that H[2] receptors are present in rabbit heart, and plays a role in mediation of positive inotropic effect produced through CAMP by histamine

Current Status and Clinical Impact of Pediatric Endoscopy in Korea / 대한소화기학회지

BACKGROUND/AIMS: In pediatrics, endoscopic examination has become a common procedure for evaluation of gastrointestinal presentations. However, there are limited data on pediatric endoscopy in Korea. The aim of this study was to analyze the current status and clinical impacts of endoscopic examination in children and adolescents. METHODS: We retrospectively reviewed the medical records of outpatients who visited the tertiary hospital. Patients under 18 years of age who underwent endoscopy were included. Endoscopic findings were classified as specific and normal based on gross findings. Specific endoscopic findings were reflux esophagitis, peptic ulcers, and Mallory-Weiss tear. Other findings included acute gastritis classified according to the updated Sydney system. RESULTS: In 722 of 330,350 patients (0.2%), endoscopic examination (554 esophagogastroduodenoscopies [EGDs], 121 colonoscopies, 47 sigmoidoscopies) was performed between January 2008 and January 2013. In EGD, abdominal pain was the most frequent presentation (64.1%). The most common diagnosis was gastritis (53.2%), followed by reflux esophagitis. The frequency of peptic ulcer disease was 12.8%. Frequent symptoms leading to colonoscopic examination were abdominal pain, diarrhea, and hematochezia. In colonoscopy, a negative result was more likely in children younger than 7 years old. After the procedure, the diagnostic yield of EGD and colonoscopy was 88.1% and 45.8%, respectively, and the rate of change in management was 67.1%. CONCLUSIONS: In pediatrics, endoscopic examination was useful for the choice of therapeutic strategy and it would be a standard method for evaluation of gastrointestinal presentation.

The Antisecretory Therapy Improves Anxiety and Depression Symptoms in Patients with Symptomatic Gastroesophageal Reflux Disease

BACKGROUND/AIMS: Anxiety and depression are associated with reflux symptoms in patients with gastroesophageal reflux disease (GERD). The purpose of this study is to investigate whether the anxiety and depression in patients with GERD will improve with anti-secretory treatment. MATERIALS AND METHODS: Participants who had taken upper endoscopic evaluation and who had symptoms of heartburn or acid regurgitation more than once a week were included through questionnaires. The hospital anxiety and depression scale was used to compare the scores before and after anti-secretory drug (proton pump inhibitor [PPI] or histamine-2 receptor blocker [H2 blocker]) treatment for four weeks. RESULTS: Eighty-four out of a total 94 patients were randomly assigned to a four week treatment, in which, 46 and 38 patients were each assigned to PPI and H2 blocker, respectively. Regardless of the type of treatment, anxiety scores decreased significantly from 5.8+/-3.8 to 5.2+/-3.9 after treatment (P=0.033). Depression scores of 6.3+/-3.4 before treatment reduced to 5.5+/-3.4 after treatment (P=0.011). Anxiety scores and depression scores decreased significantly after treatment in the H2 blocker group. In the response group, anxiety and depression showed significant improvement (P=0.008, P=0.011). CONCLUSIONS: Regardless of the type of drugs, anti-secretory therapy is helpful in treating symptomatic GERD patients, not only in relieving symptoms, but also in relieving anxiety and depression accompanied with GERD.

The Antisecretory Therapy Improves Anxiety and Depression Symptoms in Patients with Symptomatic Gastroesophageal Reflux Disease

BACKGROUND/AIMS: Anxiety and depression are associated with reflux symptoms in patients with gastroesophageal reflux disease (GERD). The purpose of this study is to investigate whether the anxiety and depression in patients with GERD will improve with anti-secretory treatment. MATERIALS AND METHODS: Participants who had taken upper endoscopic evaluation and who had symptoms of heartburn or acid regurgitation more than once a week were included through questionnaires. The hospital anxiety and depression scale was used to compare the scores before and after anti-secretory drug (proton pump inhibitor [PPI] or histamine-2 receptor blocker [H2 blocker]) treatment for four weeks. RESULTS: Eighty-four out of a total 94 patients were randomly assigned to a four week treatment, in which, 46 and 38 patients were each assigned to PPI and H2 blocker, respectively. Regardless of the type of treatment, anxiety scores decreased significantly from 5.8+/-3.8 to 5.2+/-3.9 after treatment (P=0.033). Depression scores of 6.3+/-3.4 before treatment reduced to 5.5+/-3.4 after treatment (P=0.011). Anxiety scores and depression scores decreased significantly after treatment in the H2 blocker group. In the response group, anxiety and depression showed significant improvement (P=0.008, P=0.011). CONCLUSIONS: Regardless of the type of drugs, anti-secretory therapy is helpful in treating symptomatic GERD patients, not only in relieving symptoms, but also in relieving anxiety and depression accompanied with GERD.

Optimal Duration of Medical Treatment in Superior Mesenteric Artery Syndrome in Children

The aim of this study was to investigate the outcome, and optimal duration of medical treatment in children with superior mesenteric artery syndrome (SMAS). Eighteen children with SMAS were retrospectively studied. The data reviewed included demographics, presenting symptoms, co-morbid conditions, clinical courses, nutritional status, treatments, and outcomes. The three most common symptoms were postprandial discomfort (67.7%), abdominal pain (61.1%), and early satiety (50%). The median duration of symptoms before diagnosis was 68 days. The most common co-morbid condition was weight loss (50%), followed by growth spurt (22.2%) and bile reflux gastropathy (16.7%). Body mass index (BMI) was normal in 72.2% of the patients. Medical management was successful in 13 patients (72.2%). The median duration of treatment was 45 days. Nine patients (50%) had good outcomes without recurrence, 5 patients (27.8%) had moderate outcomes, and 4 patients (22.2%) had poor outcomes. A time limit of >6 weeks for the duration of medical management tended to be associated with worse outcomes (P=0.018). SMAS often developed in patients with normal BMI or no weight loss. Medical treatment has a high success rate, and children with SMAS should be treated medically for at least 6 weeks before surgical treatment is considered.

Tratamiento de erradicación de helicobacter pyroli en el paciente con úlcera péptica: guía clínica AUGE: serie de guías clínicas MINSAL, 2013 / Helicobacter pylori eradication treatment in patients with peptic ulcer: AUGE clinical guide, MINSAL clinical guide series, 2013

OBJETIVO Guía de referencia para la atención de pacientes con diagnóstico de úlcera péptica asociada a Helicobacter pylori (+) que requieran tratamiento de erradicación de la bacteria. La cual tiene como objetivos: -Mejorar el tratamiento de los pacientes con úlcera péptica y presencia del Helicobacter pylori. -Asegurar el seguimiento de los pacientes con úlcera péptica tratada mediante terapia de erradicación. -Optimizar el uso de los recursos terapéuticos. TIPO DE PACIENTES Y ESCENARIO CLÍNICO Pacientes con diagnóstico endoscópico de úlcera péptica y Helicobacter pylori (+). USUARIOS DE LA GUÍA -Médicos generales. -Médicos de servicios de urgencia. -Médicos internistas y gastroenterólogos. -Otros profesionales del equipo de salud. METODOLOGÍA Durante el año 2008, se realizó gran parte de esta guía de práctica clínica, elaborándose los capítulos iniciales, quedando el borrador en compás de espera, hasta el año 2012, fecha en la cual se completa el trabajo inicial, revisando la literatura relevante para los años 2008-2012 y ajustando las recomendaciones según la evidencia disponible y el juicio experto de los colaboradores. No existen versiones previas de esta guía clínica.

Two Cases of H2-Receptor Antagonist Hypersensitivity and Cross-Reactivity

H2-receptor antagonists, such as cimetidine, ranitidine and famotidine, are some of the most commonly prescribed medications for gastric acid-related disorders. These compounds are generally well-tolerated and anaphylactic reactions to them are rare. Here, we report two cases of H2-receptor antagonist-induced anaphylactic reactions: the first presented with sudden dyspnea, sneezing, urticaria, and swelling of the eyelids after ranitidine intake. The second presented with sudden severe urticaria, facial swelling, chest discomfort, dizziness, and hypotension. Possible cross-reactivity with other H2-receptor antagonists was assessed by oral challenge and skin tests. To date, only a few reports addressing cross-reactivity among H2-receptor antagonists have been published. We review the literature and summarize the data available on drug cross-reactivity in H2-receptor antagonist hypersensitivity.

Guidelines for the Treatment of Functional Dyspepsia / 대한소화기학회지

Functional dyspepsia (FD) is defined as the presence of symptoms thought to originate in the gastroduodenal area, in the absence of any organic, systemic, or metabolic disease that is likely to explain the symptoms. Based on the available evidence and consensus opinion, thirteen consensus statements for the treatment of FD were developed using the modified Delphi approach. Proton pump inhibitor, prokinetics, and histamine 2 receptor antagonists are effective for the treatment of FD. Mucosal protecting agents, fundus relaxant, and drugs for visceral hypersensitivity can improve symptoms in FD. Antacids and antidepressants may help improving symptoms in FD. Comparing endoscopy with 'test and treat' of Helicobacter pylori, endoscopy may be more effective initial strategy for managing patients with FD in Korea given high incidence of gastric cancer and low cost of endoscopy. Helicobacter pylori eradication can be one of the therapeutic options for patients with FD. Psychotherapy is effective for those who have severe symptoms and refractoriness. Further studies are strongly needed to develop better treatment strategies for Korean patients with FD.

Nuevos conceptos fisiológicos de la enfermedad ácido péptica: [revisión] / New physiologic concepts of the peptic acid disease: [review]

Fundamento: los trastornos ácido pépticos son el resultado de diferentes mecanismos patogénicos, producidos por un desbalance entre la secreción excesiva de ácido y/o la disminución de la barrera defensiva de la mucosa. Son enfermedades comúnmente presentes en la práctica médica diaria y producto a su cronicidad, representan un costo importante en la atención sanitaria. Desarrollo: los elementos claves en el éxito de controlar estas enfermedades son el desarrollo de drogas potentes y seguras sobre las bases fisiológicas. Los antagonistas de receptor de histamina II revolucionó el tratamiento de los trastornos ácido péptico debido a su inocuidad y eficacia. Los inhibidores de bomba de protón representan un avance terapéutico adicional debido a la inhibición más potente de la secreción ácida. Los datos obtenidos de los ensayos clínicos y la experiencia observacional confirman la eficacia de estos agentes en el tratamiento de la enfermedad ácido péptica con eficacia y seguridad. Los paradigmas en su velocidad y duración de acción subrayan la necesidad de nuevas variantes químicas que con sólo una dosis produzca una duración confiable del control ácido, particularmente por la noche. Conclusiones: esta evaluación provee una valoración del conocimiento en curso de la fisiología de la producción de ácido para poder enfrentar de las enfermedades ácido- pépticas, tanto como los desafíos en curso y las futuras instrucciones en el tratamiento de las enfermedades mediadas por ácido

Background: peptic acid disorders are the result of different pathogenic mechanisms, taken place by a misbalance between the acid excessive secretion and/or the decrease of the mucosa defensive barrier. These are commonly diseases in daily medical practice due to their chronicity; it represents an important cost in sanitary attention. Development: The key elements in the success of controlling these diseases are the development of potent and safe drugs on the physiologic bases. The histamine-2 receptor antagonists revolutionized the treatment of peptic acid disorders due to their innocuousness and effectiveness. The proton pump inhibitors represent an additional therapeutic advance due to the most potent inhibition in the acid secretion. The obtained data of the clinical trials and the observational experience has confirmed the effectiveness and security of these agents in the treatment of peptic acid disease. Paradigms in their speed and action duration underline the necessity of new chemical variants that just with a single dose produces a reliable duration of the acid control, particularly at night. Conclusions: this assessment provides a knowledge valuation in course of the physiology of acid production, to be able to face peptic-acid diseases as much as the challenges in course and the future instructions in the treatment of diseases mediated by acid