RESUMO
OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications, but their use can be associated with a number of adverse reactions, including upper gastrointestinal lesions. The aim of the study was to identify clinical and pharmacogenetic factors associated with upper gastrointestinal lesions, including those linked to NSAIDs, in patients at a multidisciplinary hospital. METHODS: The study included 92 patients (mean age 59.4±16.5 years; 47 women), who underwent esophagogastroduodenoscopy during inpatient treatment. Patients' intake of NSAIDs and gastroprotectors during the year before hospitalization was considered. Demographic, clinical, laboratory data of patients were compared between groups, including genotyping for CYP2C9*2 rs179985, CYP2C9*3 rs1057910, CYP2C8*3 rs11572080, CYP2C8*3 rs10509681, PTGS-1 rs10306135, PTGS-1 rs12353214, and PTGS-2 rs20417 using real-time PCR. RESULTS: In NSAIDs+ patients, PTGS1 rs10306135 AT+TT genotypes increased the chance of developing gastrointestinal complications by 5.4 times (95â¯% CI=1.30-22.27). In total sample, smoking (OR=3.12, 95â¯% CI=1.15-8.46), and alcohol intake (OR=4.09, 95â¯% CI=1.05-15.87) increased odds of gastrointestinal damage. In NSAIDs+ patients omeprazole, famotidine and both famotidine and omeprazole during the last year were as ineffective as not taking gastroprotectors; in total sample famotidine (OR=0.19, 95â¯% CI=0.04-0.93) and two gastroprotectors (OR=0.13, 95â¯% CI=0.02-0.75) reduced the chance of upper gastrointestinal lesions. CONCLUSIONS: Pharmacogenetic features of patients may significantly contribute to the development NSAIDs-induced upper gastrointestinal injuries.
Assuntos
Anti-Inflamatórios não Esteroides , Gastroenteropatias , Humanos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/genética , Adulto , Genótipo , Citocromo P-450 CYP2C9/genética , Trato Gastrointestinal Superior/efeitos dos fármacos , Trato Gastrointestinal Superior/patologia , Farmacogenética , Endoscopia do Sistema Digestório , Citocromo P-450 CYP2C8/genética , Ciclo-Oxigenase 1RESUMO
Brown seaweed-derived polysaccharides, notably fucoidan and laminarin, are known for their extensive array of bioactivities and physicochemical properties. However, the effects of upper digestive tract modification on the bioactive performance of fucoidan and laminarin fractions (FLFs) sourced from Australian native species are largely unknown. Here, the digestibility and bioaccessibility of FLFs were evaluated by tracking the dynamic changes in reducing sugar content (CR), profiling the free monosaccharide composition using LC-MS, and comparing high-performance gel permeation chromatography profile variation via LC-SEC-RI. The effects of digestive progression on bioactive performance were assessed by comparing the antioxidant and antidiabetic potential of FLFs and FLF digesta. We observed that molecular weight (Mw) decreased during gastric digestion indicating that FLF aggregates were disrupted in the stomach. During intestinal digestion, Mw gradually decreased and CR increased indicating cleavage of glycosidic bonds releasing free sugars. Although the antioxidant and antidiabetic capacities were not eliminated by the digestion progression, the bioactive performance of FLFs under a digestive environment was reduced contrasting with the same concentration level of the undigested FLFs. These data provide comprehensive information on the digestibility and bioaccessibility of FLFs, and shed light on the effects of digestive progression on bioactive expression.
Assuntos
Antioxidantes , Polissacarídeos , Alga Marinha , Polissacarídeos/química , Polissacarídeos/farmacologia , Alga Marinha/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Trato Gastrointestinal Superior/metabolismo , Trato Gastrointestinal Superior/efeitos dos fármacos , Peso Molecular , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Digestão/efeitos dos fármacos , Sulfatos/química , Glucanos/química , Glucanos/farmacologia , Phaeophyceae/química , HumanosRESUMO
BACKGROUND: Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. METHODS: Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. RESULTS: During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. CONCLUSION: In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.
Assuntos
Anticoagulantes/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Inibidores da Bomba de Prótons/uso terapêutico , Trato Gastrointestinal Superior/efeitos dos fármacos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Bases de Dados Factuais , Feminino , Hemorragia Gastrointestinal/epidemiologia , Humanos , Incidência , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Risco , Rivaroxabana/uso terapêutico , Varfarina/efeitos adversosRESUMO
Endothelial and epithelial cells form physical barriers that modulate the exchange of fluid and molecules. The integrity of these barriers can be influenced by signaling through G protein-coupled receptors (GPCRs) and ion channels. Serotonin (5-HT) is an important vasoactive mediator of tissue edema and inflammation. However, the mechanisms that drive 5-HT-induced plasma extravasation are poorly defined. The Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel is an established enhancer of signaling by GPCRs that promote inflammation and endothelial barrier disruption. Here, we investigated the role of TRPV4 in 5-HT-induced plasma extravasation using pharmacological and genetic approaches. Activation of either TRPV4 or 5-HT receptors promoted significant plasma extravasation in the airway and upper gastrointestinal tract of mice. 5-HT-mediated extravasation was significantly reduced by pharmacological inhibition of the 5-HT2A receptor subtype, or with antagonism or deletion of TRPV4, consistent with functional interaction between 5-HT receptors and TRPV4. Inhibition of receptors for the neuropeptides substance P (SP) or calcitonin gene-related peptide (CGRP) diminished 5-HT-induced plasma extravasation. Supporting studies assessing treatment of HUVEC with 5-HT, CGRP, or SP was associated with ERK phosphorylation. Exposure to the TRPV4 activator GSK1016790A, but not 5-HT, increased intracellular Ca2+ in these cells. However, 5-HT pre-treatment enhanced GSK1016790A-mediated Ca2+ signaling, consistent with sensitization of TRPV4. The functional interaction was further characterized in HEK293 cells expressing 5-HT2A to reveal that TRPV4 enhances the duration of 5-HT-evoked Ca2+ signaling through a PLA2 and PKC-dependent mechanism. In summary, this study demonstrates that TRPV4 contributes to 5-HT2A-induced plasma extravasation in the airways and upper GI tract, with evidence supporting a mechanism of action involving SP and CGRP release.
Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Serotonina , Canais de Cátion TRPV , Trato Gastrointestinal Superior/efeitos dos fármacos , Animais , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Pulmão/citologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Serotonina/genética , Serotonina/metabolismo , Serotonina/farmacologia , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Trato Gastrointestinal Superior/citologia , Trato Gastrointestinal Superior/metabolismoRESUMO
BACKGROUND: Delayed bleeding is the major adverse event in upper gastrointestinal endoscopic treatment (UGET). We aimed to investigate the efficacy of vonoprazan, which is the novel strong antisecretory agent, to reduce the risk for delayed bleeding in comparison with proton pump inhibitors (PPIs) in UGET. METHODS: This retrospective population-based cohort study used the Diagnosis Procedure Combination database in Japan. We included patients on vonoprazan or PPI in UGET between 2014 and 2019. The primary outcome was delayed bleeding. We conducted propensity score matching to balance the comparison groups, and logistic regression analyses to compare the bleeding outcomes. RESULTS: We enrolled 124,422 patients, in which 34,822 and 89,600 were prescribed with vonoprazan and PPI, respectively. After propensity score matching, the risk for delayed bleeding was lower in vonoprazan than in PPI (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.71-0.80), consistent with sensitivity analysis results. In the subgroup analyses of seven UGET procedures, vonoprazan was significantly advantageous in esophageal endoscopic submucosal dissection (E-ESD) (OR, 0.71; 95% CI, 0.54-0.94) and gastroduodenal endoscopic submucosal dissection (GD-ESD) (OR, 0.70; 95% CI, 0.65-0.75), although correction for multiple testing of the outcome data removed the significance in E-ESD. These results were also consistent with sensitivity analysis results. In the five other procedures, no significant advantage was found. CONCLUSIONS: This nationwide study found that, compared with PPI, vonoprazan can reduce delayed bleeding with approximately 30% in GD-ESD. Vonoprazan has the possibility to become a new treatment method for preventing delayed bleeding in this procedure.
Assuntos
Hemorragia/prevenção & controle , Pirróis/efeitos adversos , Sulfonamidas/efeitos adversos , Trato Gastrointestinal Superior/efeitos dos fármacos , Idoso , Estudos de Coortes , Feminino , Hemorragia/tratamento farmacológico , Humanos , Japão , Masculino , Pirróis/uso terapêutico , Estudos Retrospectivos , Sulfonamidas/uso terapêutico , Resultado do TratamentoRESUMO
Aerodigestive adverse effects (AD-AE) during intravenous pentamidine (IV-P) infusion for Pneumocystis jiroveci pneumonia prophylaxis are uncommon in retrospective chart review studies. We conducted a survey in patients on IV-P, which included 31 specific questions. Twenty-five patients were included in the analysis; AD-AE were observed in 22 (88%) with recurrence of symptoms in 88% participants with subsequent infusions. Five leading symptoms were congestion (48%), lip tingling (32%), nausea (28%), tongue tingling (24%), vomiting, and throat swelling (17%); multiple symptoms were reported in 72% of the patients. In conclusion, AD-AE of IV-P infusion are common, self-limited, and tend to be recurrent.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Leucemia/terapia , Pentamidina/efeitos adversos , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/tratamento farmacológico , Trato Gastrointestinal Superior/patologia , Adolescente , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infusões Intravenosas , Leucemia/patologia , Masculino , Michigan/epidemiologia , Pentamidina/administração & dosagem , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/patologia , Prognóstico , Autorrelato , Inquéritos e Questionários , Trato Gastrointestinal Superior/efeitos dos fármacos , Adulto JovemRESUMO
Background and objectives: Although treatment with novel oral non-vitamin K antagonist 3anticoagulants (NOACs) is associated with an overall decrease in hemorrhagic complications compared to warfarin, the incidence of gastrointestinal bleeding remains contradictory. Materials and Methods: After the exclusion of patients with pre-existing pathological lesions in the upper gastrointestinal tract (GIT) on esophageal-gastroduodenoscopy (EGD) at entry, a cohort of 80 patients (mean age of 74.8 ± 2.0 years) was randomly divided into four equivalent groups, treated with dabigatran, rivaroxaban, apixaban, or warfarin. Patients were prospectively followed up for three months of treatment, with a focus on anamnestic and endoscopic signs of bleeding. In addition, bleeding risk factors were evaluated. Results: In none of the patients treated with warfarin or NOACs was any serious or clinically significant bleeding recorded within the follow-up period. The incidence of clinical bleeding and endoscopically detected bleeding in the upper GT after three months of treatment was not statistically different among groups (χ2 = 2.8458; p = 0.41608). The presence of Helicobacter pylori (HP) was a risk factor for upper GIT bleeding (p < 0.05), while the use of proton pump inhibitors (PPIs) was a protective factor (p = 0.206; Spearman's correlation coefficient = 0.205). We did not record any post-biopsy continued bleeding. Conclusions: No significant GIT bleeding was found in any of the treatment groups, so we consider it beneficial to perform routine EGD before the initiation of any anticoagulant therapy in patients with an increased risk of upper GIT bleeding. Detection and eradication of HP as well as preventive PPI treatment may mitigate the occurrence of endoscopic bleeding. Endoscopic biopsy during the NOAC treatment is safe.
Assuntos
Anticoagulantes/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Trato Gastrointestinal Superior/efeitos dos fármacos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacologia , Endoscopia/métodos , Feminino , Mucosa Gástrica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Trato Gastrointestinal Superior/fisiopatologiaRESUMO
BACKGROUND: The most frequent etiologic cause is alkaline substances. We investigated the protective effects of the plant St. John 's Wort (Hypericum perforatum). METHODS: We included 42 Wistar albino rats weighing between 200-300 grams and divided into six groups as Group 1: Control, Group 2: Burn+Saline (BS), Group 3: Burn+St. John's Wort (BSJW), Group 4: Burn+Plasebo (BP), Group 5: St. John's Wort (SJW), Group 6: Placebo (P). After 15 days of treatment, esophagus, stomach and liver tissue samples were derived by dissection for histopathologic and biochemical markers. The cytotoxic effects of formulation on fibroblasts is evaluated in vitro on human dermoblast fibroblast line (HDFa, Gibco Invitrogen cell culture, C-013-5C). RESULTS: The weight of the rats increased in Group 1, 3, 4, 6, decreased in Group 2 and did not change in Group 5. In the BSJW group, submucosal collagen accumulation, muscularis mucosa damage, tunica muscularis damage and collagen accumulation in esophagus were similar to the control group but lesser than BS and placebo group. In the stomach, mucosal damage, gastric gland dilatation, submucosal polymorphonuclear infiltration were similar to the control group and lesser than the BS group. The lethal concentration of SJW was 2.58 gr/mL. CONCLUSION: SJW substrate is effective in protecting the esophagus and stomach in mild to moderate alcali corrosive burns in the subacute period. We should keep in mind the protective effects of STW substrate in alkaline corrosive burns of the gastrointestinal system.
Assuntos
Queimaduras Químicas , Cáusticos/efeitos adversos , Hypericum , Extratos Vegetais/farmacologia , Trato Gastrointestinal Superior , Animais , Queimaduras Químicas/tratamento farmacológico , Queimaduras Químicas/patologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Humanos , Ratos , Trato Gastrointestinal Superior/efeitos dos fármacos , Trato Gastrointestinal Superior/lesõesRESUMO
Gastrointestinal (GI) problems affect half of Western populations. Symptoms can vary from frequent reflux to irritable bowel syndrome. The Nutrition Care (NC) Gut Relief Formula contains a combination of herbs and nutrients including curcumin, Aloe vera, slippery elm, guar gum, pectin, peppermint oil, and glutamine shown to benefit the GI system. The 16-week pre-post study tested the hypothesis that the NC Gut Relief Formula would be tolerable and effective in improving GI symptoms and gut health in adults with digestive disorders. A total of 43 participants completed the study. After a control phase, participants took 5 g/d and then 10 g/d of the formula for 4 weeks. GI symptoms and GI health were assessed by a series of validated questionnaires, for example, Leeds Dyspepsia Questionnaire, Bristol Stool Chart, Birmingham IBS Symptom Questionnaire, and by intestinal permeability and gut microbiota profile. The NC Gut Relief Formula significantly improved the frequency and severity of upper and lower GI symptoms by 60%-80%, including indigestion, heartburn, nausea, constipation or diarrhea, abdominal pain, and troublesome flatulence, and significantly improved physical functioning, energy levels, mood, and sleep by 60%-80%. All participants with normal stool, 90% with hard stool, and 66% with soft stool recovered from intestinal permeability, evident by normal lactulose to mannitol ratios. The NC Gut Relief Formula generally improved microbial profile, with a marked increase in Lactobacillus, Clostridium, and Faecalibacterium prausnitzii. Almost half of the participants with upper GI symptoms taking proton pump inhibitors for heartburn no longer required proton pump inhibitors at the end of the study. A third of participants were able to reintroduce food triggers, such as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols garlic, onion, and beans, or reflux-causing acidic/spicy foods, for example, citrus, tomato, and caffeine, in their diet after 3 months without symptom aggravation. The NC Gut Relief Formula significantly improved GI symptoms and associated quality of life over 3 months while reducing intestinal permeability, improving the microbial profile, reducing the need for reflux medication, and enabling the consumption of previous food triggers.
Assuntos
Gastroenteropatias/tratamento farmacológico , Intestinos/efeitos dos fármacos , Magnoliopsida/química , Fitoterapia , Preparações de Plantas/uso terapêutico , Trato Gastrointestinal Superior/efeitos dos fármacos , Adulto , Aloe , Austrália , Curcumina , Dieta , Feminino , Galactanos , Gastroenteropatias/complicações , Gastroenteropatias/microbiologia , Gastroenteropatias/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glutamina , Humanos , Intestinos/microbiologia , Intestinos/patologia , Masculino , Mananas , Mentha piperita , Pessoa de Meia-Idade , Pectinas , Permeabilidade , Gomas Vegetais , Óleos de Plantas , Preparações de Plantas/farmacologia , Ulmus , Trato Gastrointestinal Superior/patologiaRESUMO
Introduction: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide. Areas covered: We searched PubMed using the key words 'metoclopramide', 'diabetic gastroparesis', and 'gastric emptying'. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible. Expert opinion: Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.
Assuntos
Complicações do Diabetes/complicações , Antagonistas dos Receptores de Dopamina D2/uso terapêutico , Esvaziamento Gástrico/efeitos dos fármacos , Gastroparesia/tratamento farmacológico , Metoclopramida/uso terapêutico , Trato Gastrointestinal Superior/efeitos dos fármacos , Antagonistas dos Receptores de Dopamina D2/efeitos adversos , Antagonistas dos Receptores de Dopamina D2/farmacologia , Gastroparesia/etiologia , Humanos , Metoclopramida/efeitos adversos , Metoclopramida/farmacologia , Resultado do Tratamento , Trato Gastrointestinal Superior/inervaçãoRESUMO
BACKGROUND: Upper gastrointestinal symptoms are major issues in various diseases such as postgastrectomy syndrome and functional dyspepsia. These symptoms cannot be fully controlled in such conditions and result in poorer quality of life. Rikkunshito has been traditionally used in Japan to relieve these symptoms. This systematic review assessed the efficacy and safety of rikkunshito for relieving upper gastrointestinal symptoms. METHODS: A systematic literature search was conducted using Ovid MEDLINE, Scopus, the Cochrane Central Register of Controlled Trials, and ICHUSHI. Randomized controlled trials comparing rikkunshito to alternative drugs for the treatment of upper gastrointestinal symptoms were searched without language restriction. Two review authors independently assessed the literature and extracted data from identified studies. The risk of bias in each study was assessed. RESULTS: Twenty-four studies with a combined total of 2175 participants were included in this review. Rikkunshito did not significantly relieve upper gastrointestinal symptoms when compared with other treatments via the Gastrointestinal Symptom Rating Scale (standardized mean difference, -0.07; 95% confidence interval [CI], -0.31 to 0.17; P = 0.59), while it significantly relieved the symptoms on a 5-point scale (mean difference, -0.38; 95% CI, -0.55 to -0.21; P < 0.001). No drug-related severe adverse events were reported. Most of the included studies had high or unclear overall risk of bias. CONCLUSIONS: It remains still unclear whether rikkunshito is effective for the relief of upper gastrointestinal symptoms. Further high-quality studies are needed.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Trato Gastrointestinal Superior/efeitos dos fármacos , Animais , Humanos , Japão , Medicina Tradicional do Leste Asiático/métodos , Qualidade de VidaRESUMO
Importance: Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment. Objectives: To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk. Design, Setting, and Participants: Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015. Exposures: Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy. Main Outcomes and Measures: Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10â¯000 person-years of anticoagulant treatment, incidence rate ratios (IRRs). Results: There were 1â¯643â¯123 patients with 1â¯713â¯183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651â¯427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870â¯330 person-years [74.9%]). During 754â¯389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n = 7119) was 115 per 10â¯000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n = 1278) was 144 per 10â¯000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n = 279; 73 per 10â¯000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n = 629; 120 per 10â¯000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n = 4933; 113 per 10â¯000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, -47.5 [95% CI,-60.6 to -34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, -40.5 [95% CI, -50.0 to -31.0]). When anticoagulant treatment with PPI cotherapy (264â¯447 person-years; 76 per 10â¯000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, -24 [95% CI, -38 to -11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, -61.1 [95% CI, -74.8 to -47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, -35.5 [95% CI, -48.6 to -22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, -39.3 [95% CI, -44.5 to -34.2]). Conclusions and Relevance: Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.
Assuntos
Anticoagulantes/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Hospitalização/estatística & dados numéricos , Inibidores da Bomba de Prótons/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Dabigatrana/efeitos adversos , Quimioterapia Combinada , Feminino , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Trato Gastrointestinal Superior/efeitos dos fármacos , Varfarina/efeitos adversosRESUMO
Liraglutide is a glucagon-like peptide type 1 (GLP-1) analogue that is approved for long-term obesity management in North America. While bariatric surgery remains the gold standard for weight loss, an increasing number of patients are on liraglutide in the setting of ongoing workup for bariatric surgery. The presence of gastrointestinal symptoms prior to bariatric surgery may prompt testing for dysmotility, which affects surgical decision making. Here we report six cases where treatment with liraglutide was associated with reversible reduction in gastric and esophageal motility in screening for bariatric surgery. While liraglutide is known to delay gastric emptying, there are minimal reports of how this medication affects gastrointestinal investigations used in this context. The implications of these abnormal screening investigations on candidacy for bariatric surgery are discussed.
Assuntos
Cirurgia Bariátrica , Refluxo Gastroesofágico/complicações , Motilidade Gastrointestinal/efeitos dos fármacos , Liraglutida/farmacologia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Trato Gastrointestinal Superior/efeitos dos fármacos , Adulto , Cirurgia Bariátrica/métodos , Transtornos da Motilidade Esofágica/complicações , Transtornos da Motilidade Esofágica/cirurgia , Feminino , Refluxo Gastroesofágico/tratamento farmacológico , Hérnia Hiatal/complicações , Hérnia Hiatal/tratamento farmacológico , Hérnia Hiatal/cirurgia , Humanos , Liraglutida/uso terapêutico , Pessoa de Meia-Idade , Seleção de Pacientes , Trato Gastrointestinal Superior/fisiologia , Redução de PesoRESUMO
Hydrocortisone sodium succinate (HSS) is an anti-inflammatory drug, but its application on ulcerative colitis (UC) treatment is limited by its associated side-effects. To solve this problem, a kind of pH-sensitive P(LE-IA-MEG) hydrogel microspheres (HMSs) were prepared as the drug carrier of hydrocortisone sodium succinate (HSS) for the treatment of UC. The P(LE-IA-MEG) HMSs were spherical in shape with good dispersion and the mean particle size was 34.87±0.90µm. HSS was successfully loaded into the P(LE-IA-MEG) HMSs. The in vitro release study of HSS-loaded HMSs (HSS-HMSs) revealed that the HSS-HMSs possessed desirable pH-sensitivity, the cumulative release rate was 4.07% and 94.64% in the solution with pH 1.2 and pH 7.4 solution during 12h, respectively. Furthermore, the study on pharmacokinetic, gastrointestinal drug residue and side-effects were conducted to evaluate the in vivo colon-targeting property of the HSS-HMSs. All the results showed that the HSS-HMSs could deliver HSS to the colon as well as reduce its premature absorption in the upper gastrointestinal tract. Finally, the HSS-HMSs showed better ameliorative effects and therapeutic effects on mice with experimental colitis as compared to HSS. In conclusion, the HSS-HMSs had great potential in the treatment of UC.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Hidrocortisona/análogos & derivados , Hidrocortisona/farmacologia , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Microesferas , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Trato Gastrointestinal Superior/efeitos dos fármacosAssuntos
Pesquisa Biomédica , Descoberta de Drogas , Gastroenterologia , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Trato Gastrointestinal Superior/efeitos dos fármacos , Animais , Dispepsia/diagnóstico , Dispepsia/tratamento farmacológico , Dispepsia/fisiopatologia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/fisiopatologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/fisiopatologia , Fármacos Gastrointestinais/efeitos adversos , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Motilidade Gastrointestinal/efeitos dos fármacos , Gastroparesia/diagnóstico , Gastroparesia/tratamento farmacológico , Gastroparesia/fisiopatologia , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Trato Gastrointestinal Superior/patologia , Trato Gastrointestinal Superior/fisiopatologiaRESUMO
AIMS: Lanthanum carbonate is used as an alternative to calcium-based phosphate binders to manage hyperphosphataemia in patients with renal failure. The deposition of lanthanum within gastroduodenal mucosa of patients treated with the medication has been described, but given the relative novelty of this entity, the histiocytic deposits in the gastroduodenal mucosa can be confused with a variety of other processes, including infections and other drug-induced forms of injury. METHODS AND RESULTS: We describe five cases of lanthanum phosphate deposition in upper gastrointestinal (GI) tract biopsies. Three cases were confirmed with scanning electron microscopy and energy dispersive X-ray analysis, including one unique patient, status post-renal transplant for polycystic kidney disease, who had last taken lanthanum 7 years prior to biopsy. CONCLUSION: Lanthanum deposition in the upper GI tract is a mimic of other drug-related forms of GI injury, including iron pill-related gastropathy. The key to making this diagnosis is a thorough drug history and awareness of the histological features.
Assuntos
Hiperfosfatemia/tratamento farmacológico , Lantânio/efeitos adversos , Trato Gastrointestinal Superior/efeitos dos fármacos , Trato Gastrointestinal Superior/patologia , Adulto , Idoso , Feminino , Humanos , Hiperfosfatemia/etiologia , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis. METHODS: We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases. RESULTS: A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied. CONCLUSIONS: This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.
Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Neoplasias Esofágicas/epidemiologia , Neoplasias Gastrointestinais/epidemiologia , Osteoporose/epidemiologia , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Bases de Dados Factuais , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Neoplasias Gastrointestinais/etnologia , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Razão de Chances , Osteoporose/tratamento farmacológico , Osteoporose/etnologia , Osteoporose/patologia , República da Coreia/epidemiologia , Fatores Sexuais , Trato Gastrointestinal Superior/efeitos dos fármacos , Trato Gastrointestinal Superior/patologiaRESUMO
Both the stomach and small intestine play important roles in sensing the arrival of a meal, and its physico-chemical characteristics, in the gastrointestinal lumen. The presence of a meal in the stomach provides a distension stimulus, and, as the meal empties into the small intestine, nutrients interact with small intestinal receptors, initiating the release of gut hormones, associated with feedback regulation of gastrointestinal functions, including gut motility, and signaling to the central nervous system, modulating eating behaviours, including energy intake. Lipid appears to have particularly potent effects, also in close interaction with, and modulating the effects of, gastric distension, and involving the action of gut hormones, particularly cholecystokinin (CCK). These findings have not only provided important, and novel, insights into how gastrointestinal signals interact to modulate subjective appetite perceptions, including fullness, but also laid the foundation for an increasing appreciation of the role of altered gastrointestinal sensitivities, e.g. as a consequence of excess dietary intake in obesity, or underlying the induction of gastrointestinal symptoms in functional dyspepsia (a condition characterized by symptoms, including bloating, nausea and early fullness, amongst others, after meals, particularly those high in fat, in the absence of any structural or functional abnormalities in the gastrointestinal tract). This paper will review the effects of dietary nutrients, particularly lipid, on gastrointestinal function, and associated effects on appetite perceptions and energy intake, effects of interactions of gastrointestinal stimuli, as well as the role of altered gastrointestinal sensitivities (exaggerated, or reduced) in eating-related disorders, particularly obesity and functional dyspepsia.
Assuntos
Apetite/fisiologia , Refeições/fisiologia , Trato Gastrointestinal Superior/inervação , Trato Gastrointestinal Superior/fisiologia , Adulto , Afasia/patologia , Afasia/fisiopatologia , Apetite/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ingestão de Energia/efeitos dos fármacos , Ingestão de Energia/fisiologia , Humanos , Refeições/efeitos dos fármacos , Obesidade/patologia , Obesidade/fisiopatologia , Trato Gastrointestinal Superior/efeitos dos fármacosRESUMO
Proton pump inhibitors (PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding (LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Hemorragia Gastrointestinal/prevenção & controle , Probióticos/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Hemorragia Gastrointestinal/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Prescrição Inadequada/prevenção & controle , Trato Gastrointestinal Inferior/efeitos dos fármacos , Medição de Risco , Fatores de Risco , Trato Gastrointestinal Superior/efeitos dos fármacosRESUMO
In recent years, metronomic chemotherapy, consisting of continuous administration of low doses of cytotoxic agents, has being used as rescue therapy for different tumours. The aim of this study was to retrospectively assess the efficacy and safety of low-dose metronomic, oral capecitabine in pretreated or frail patients with recurrent upper gastrointestinal tract cancer. Patients with pretreated upper gastrointestinal tract cancer or who were not candidates for standard chemotherapy because of toxicity concerns received capecitabine at 1500 mg per day continuously until disease progression or occurrence of toxicity. Forty-seven patients (25 oesophagogastric cancer, 22 pancreatobiliary cancer; 25 men, 22 women; median age 69 years, range 42-90) were included in the study. Forty-five percent of the patients had received at least two previous lines of treatment and the median number of previous treatments was 1 (range 0-5). Twelve (31.6%) patients achieved clinical benefit (one partial response, 11 stable disease), whereas nine (23.7%) patients were progression free for at least 6 months. In an exploratory analysis, there was a significant relationship between performance status and clinical benefit (hazard ratio=8.25; P=0.01). The median overall survival was 5 months. A good performance status was associated with a longer survival (hazard ratio=0.26; P<0.01). No severe toxicity or treatment-related death was reported. Metronomic capecitabine showed good safety and moderate activity in frail or pretreated patients with advanced, upper gastrointestinal tract cancer.