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1.
Gastroenterology ; 157(2): 403-412.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31054846

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.


Assuntos
Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento
2.
Gastrointest Endosc ; 89(2): 357-363.e2, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30670179

RESUMO

BACKGROUND AND AIMS: Although erosions and ulcerations are the most common small-bowel abnormalities found on wireless capsule endoscopy (WCE), a computer-aided detection method has not been established. We aimed to develop an artificial intelligence system with deep learning to automatically detect erosions and ulcerations in WCE images. METHODS: We trained a deep convolutional neural network (CNN) system based on a Single Shot Multibox Detector, using 5360 WCE images of erosions and ulcerations. We assessed its performance by calculating the area under the receiver operating characteristic curve and its sensitivity, specificity, and accuracy using an independent test set of 10,440 small-bowel images including 440 images of erosions and ulcerations. RESULTS: The trained CNN required 233 seconds to evaluate 10,440 test images. The area under the curve for the detection of erosions and ulcerations was 0.958 (95% confidence interval [CI], 0.947-0.968). The sensitivity, specificity, and accuracy of the CNN were 88.2% (95% CI, 84.8%-91.0%), 90.9% (95% CI, 90.3%-91.4%), and 90.8% (95% CI, 90.2%-91.3%), respectively, at a cut-off value of 0.481 for the probability score. CONCLUSIONS: We developed and validated a new system based on CNN to automatically detect erosions and ulcerations in WCE images. This may be a crucial step in the development of daily-use diagnostic software for WCE images to help reduce oversights and the burden on physicians.


Assuntos
Endoscopia por Cápsula , Doenças do Íleo/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Intestino Delgado/patologia , Doenças do Jejuno/diagnóstico , Redes Neurais (Computação) , Reconhecimento Automatizado de Padrão , Úlcera/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Área Sob a Curva , Aprendizado Profundo , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/etiologia , Úlcera Duodenal/patologia , Feminino , Humanos , Doenças do Íleo/etiologia , Doenças do Íleo/patologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Doenças do Jejuno/etiologia , Doenças do Jejuno/patologia , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/diagnóstico , Úlcera Péptica/patologia , Curva ROC , Sensibilidade e Especificidade , Software , Úlcera/etiologia , Úlcera/patologia
3.
Digestion ; 99(1): 66-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554208

RESUMO

BACKGROUND AND AIM: Helicobacter pylori infection is a primary cause of gastroduodenal ulcers. To investigate whether there is an association between H. pylori infection and small intestinal mucosal injury. METHODS: Patients were selected from a general pool of subjects who underwent capsule endoscopy for current or past obscure gastrointestinal bleeding. Characteristics including age, gender, history, treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acid suppressant, diagnosis, and H. pylori infection were investigated. Patients infected with H. pylori had positive test result, ranging 30 days before to 30 days after capsule endoscopy. Patients diagnosed with inflammatory diseases, malignant tumors, etc. were excluded. All video images were re-evaluated to count small intestinal mucosal breaks. Eligible patient variables were compared. RESULTS: A total of 92 patients (30 infected with H. pylori/62 uninfected) were eligible. By univariate analysis of the number of mucosal breaks, patients treated with NSAIDs were found to have more mucosal breaks than patients untreated (38%: 8/21 vs. 18%: 13/71; p = 0.004), and the possible association was detected between patients infected with H. pylori and those who were not (67%: 14/21 vs. 37%: 26/71; p = 0.081). When comparing the H. pylori infected and uninfected patients, the rate of patients with mucosal breaks was greater in infected patients (47%: 14/30 vs. 11%: 7/62; p = 0.001). After excluding patients treated with NSAIDs, the number of mucosal breaks was also greater in patients infected with H. pylori (1.2 ± 1.5 vs. 0.38 ± 0.62; p = 0.001). CONCLUSION: There is a possibility that H. pylori infection induces small intestinal mucosal injury.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori , Enteropatias/microbiologia , Úlcera Péptica/microbiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Endoscopia por Cápsula , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Humanos , Enteropatias/induzido quimicamente , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/microbiologia , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Projetos Piloto , Estudos Retrospectivos
4.
Life Sci ; 217: 164-168, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30528722

RESUMO

AIMS: Memantine is a commonly used drug in treating Alzheimer disease. In the current work, we aimed to evaluate the gastro-protective effect of memantine in indomethacin-induced peptic ulcer in rats. MAIN METHODS: Peptic ulcer induced by indomethacin and memantine administered either alone or in combination with glibenclamide or nitric oxide synthase (NOS) inhibitor. Ulcer index done and malondialdehyde (MDA), superoxide dismutase (SOD), total nitrites, expression of tumor necrosis factor-α (TNF-α) and expression of nuclear factor kappa B (NF-κB) were measured in gastric mucosa. KEY FINDINGS: Memantine reduced ulcer index, reduced MDA, increased SOD, increased total nitrites and reduced expression of both TNF-α and NF-κB. Glibenclamide and not NOS inhibitor abolished the gastroprotective effect of memantine. SIGNIFICANCE: Memantine was protective against indomethacin-induced peptic ulcer in rats mostly by affecting potassium channels, antioxidative stress and anti-inflammatory actions.


Assuntos
Antiulcerosos/uso terapêutico , Indometacina , Memantina/uso terapêutico , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/tratamento farmacológico , Canais de Potássio/metabolismo , Animais , Glibureto/uso terapêutico , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Úlcera Péptica/metabolismo , Úlcera Péptica/patologia , Ratos , Ratos Wistar
5.
Int J Pharm Pract ; 26(4): 369-372, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29159948

RESUMO

OBJECTIVES: To identify prescribing patterns of antiulcer agents in patients on low-dose aspirin (LDA) and to evaluate the number of gastrointestinal (GI) risk factors of the patients. METHODS: A retrospective chart review of patients taking LDA was conducted at the National Cerebral and Cardiovascular Center in Japan. The rate of concomitant use of antiulcer agents and the risk of each patient to develop GI complications were evaluated. RESULTS: Of the 314 patients, 64 were not on antiulcer agents and 55 of them had >1 risk factor. More patients not on antiulcer agents had started LDA before hospitalization. CONCLUSION: The rate of coprescribing antiulcer agents with LDA was high. However, the timing of initiating LDA therapy affected the prescribing pattern of antiulcer agents.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Aspirina/efeitos adversos , Prescrições de Medicamentos/estatística & dados numéricos , Úlcera Péptica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
6.
J Physiol Pharmacol ; 69(6)2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30802217

RESUMO

Capsaicin-sensitive sensory nerves are densely distributed in the gastrointestinal system and involved in maintenance of gastrointestinal mucosal integrity. capsaicin selectively stimulates nociceptive neurons and its action is mediated through the transient receptor potential channel vanilloid type 1 (TRPV1) receptor. Activation TRPV1 receptors that play a fundamental role in pain signaling, may also exert protective effects against gastrointestinal injury. The present study was performed to investigate and compare the vulnerability of gastric as well as small intestinal mucosa to ulcerogenic action of indomethacin (IM) in mice with genetically deleted TRPV1 receptor (TRPV1 KO) and in C57/BL6/J mice. IM-induced injury was assessed macroscopically as well as histologically; the somatic pain sensitivity was estimated by tail flick latency (tail flick test); plasma corticosterone levels and body weight were also monitored. A single IM administration (35 mg/kg, subcutaneously) into pre-starving (24 h) mice caused the formation of gastric erosions 4 h later and, then, after refeeding, induced formation of the small intestinal injury which was visible 24, 48, 72 h after IM administration. Although IM-induced gastrointestinal injury was detectable in both C57/BL6/J and TRPV1 KO mice, area of gastric damage was greater in C57/BL6/J than in TRPV1 KO mice, whereas the small intestinal injury (48 and 72 h after IM injection), on the contrary, prevailed in TRPV1 KO mice compared to C57/BL6/J mice. In 24 h after IM injection, the total area of intestinal injury did not differ in C57BL6/J and TRPV1 KO mice, however histological score was higher in TRPV1 KO mice than C57BL6/J mice. TRPV1 KO mice showed the increased tail flick latencies and the lacking IM-induced corticosterone rise. The data suggest that in TRPV1 KO mice the gastric mucosa is less vulnerable to ulcerogenic action of IM compared to C57/BL6/J mice, however, their small intestinal mucosa, on the contrary, is more vulnerable to the ulcerogenic action than in C57/BL6/J mice.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Indometacina/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Canais de Cátion TRPV/genética , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Capsaicina/farmacologia , Mucosa Gástrica/patologia , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Fatores de Tempo
7.
Ter Arkh ; 90(8): 95-100, 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30701943

RESUMO

The review analyzes the main etiological and pathogenetic mechanisms of the development of NSAID-enteropathy. Particular attention is paid to the role of intestinal microbiota in the manifestation and progression of NSAID-enteropathy. The special role of probiotics in the prevention and treatment of NSAIDs enteropathy is considered.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Gastroenterite/induzido quimicamente , Úlcera Péptica/induzido quimicamente , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Gastroenterite/microbiologia , Gastroenterite/prevenção & controle , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Microbiota/efeitos dos fármacos , Úlcera Péptica/microbiologia , Úlcera Péptica/prevenção & controle , Probióticos/uso terapêutico
8.
J Gastrointestin Liver Dis ; 26(4): 395-402, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29253055

RESUMO

BACKGROUND AND AIMS: Aspirin is one of the most widely used medication for its analgesic and anti-platelet properties and thus a major cause for gastrointestinal (GI) bleeding. This study compared the preventive effect of histamine-2 receptor antagonists (H2RAs) and proton-pump inhibitors (PPIs) against chronic low-dose aspirin (LDA)-related GI bleeding and ulcer formation. METHODS: Electronic databases of Pubmed, Embase and Cochrane Central Register of Controlled Trials were searched for human observations (randomised controlled trials and observational studies) comparing the long term effects of PPIs and H2RAs treatment in the prevention of GI bleeding or ulcer formation in patients on chronic LDA treatment listed up till September 30, 2016. Two independent authors searched databases using PICO questions (aspirin, H2RA, PPI, GI bleeding or ulcer), and reviewed abstracts and articles for comprehensive studies keeping adequate study quality. Data of weighted odds ratios were statistically evaluated using Comprehensive Metaanalysis (Biostat, Inc., Engelwood, MJ, USA), potential bias was checked. RESULTS: Nine studies for GI bleeding and eight studies for ulcer formation were found meeting inclusion criteria, altogether 1,879 patients were included into review. The H2RAs prevented less effectively LDA-related GI bleeding (OR= 2.102, 95% CI: 1.008-4.385, p<0.048) and ulcer formation (OR= 2.257, 95% CI: 1.277-3.989, p<0.005) than PPIs. CONCLUSION: The meta-analysis showed that H2RAs were less effective in the prevention of LDA-related GI bleeding and ulcer formation suggesting the preferable usage of PPIs in case of tolerance.


Assuntos
Aspirina/efeitos adversos , Hemorragia Gastrointestinal/prevenção & controle , Antagonistas dos Receptores Histamínicos H2/uso terapêutico , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Aspirina/administração & dosagem , Esquema de Medicação , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle
9.
Int J Risk Saf Med ; 29(1-2): 57-68, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28885223

RESUMO

BACKGROUND: The use of non-steroidal anti-inflammatory drug (NSAIDs) is deemed a major risk factor for peptic ulcer disease in elderly population that requires concomitant therapy with gastroprotective agents (GPAs). OBJECTIVE: This study evaluated the rational prescribing of NSAIDs and GPAs, and extent of adherence to the guideline recommendations in primary care. METHODS: Nationwide audit of prescriptions issued to elderly patients (≥65 years) with hypertension or diabetic hypertension in primary care. RESULTS: Among 2090 elderly, 45.9% were on low-dose aspirin, and 13.5% on other NSAIDs. Diclofenac-XR was the most frequently prescribed NSAIDs to three-quarter patients whereas naproxen, the safest NSAID for patients with high cardiovascular (CV) risk, was rarely prescribed. Among those on NSAID, 82.9% were on a scheduled dosing regimen; of these 78.8% received long-term NSAID therapy (3.9±0.9 months). The prescription rate of GPAs was low: 29.2% for aspirin and 33.3% for other NSAIDs. A quarter of the patients on histamine type-2 receptor antagonists received ranitidine at subtherapeutic single-dose for gastroprotection. Approximately half of the patients on proton pump inhibitors (PPIs) were prescribed supra-therapeutic double-dose regimen: omeprazole and esomeprazole accounted for 63.2% of overall prescribed PPIs. CONCLUSIONS: The rational choice of NSAIDs and physicians' adherence to gastroprotective measures was suboptimal in primary care. The choice of NSAIDs and gastroprotective strategy in elderly be guided by the CV and gastrointestinal adverse events likelihood due to the NSAIDs and risk profile of patients for such adverse events.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antiulcerosos/administração & dosagem , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Complicações do Diabetes/epidemiologia , Feminino , Fidelidade a Diretrizes , Humanos , Hipertensão/epidemiologia , Masculino , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Fatores de Risco
10.
Am J Ther ; 24(5): e559-e569, 2017 Sep/Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28763306

RESUMO

BACKGROUND: Long-term aspirin use in cardiovascular disease prevention may result in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long-term aspirin users in the randomized controlled trials, there are safety concerns about the long-term use of PPI. STUDY QUESTION: What is the safety and efficacy of PPI in patients using aspirin in long term for prevention of cardiovascular diseases and stroke? METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, ProQuest, and relevant references from inception through February 2015, and used random-effects model for meta-analysis. RESULTS: A total of 10 publications from 9 studies (n = 6382) were included in the meta-analysis. Compared with control, PPI reduced the risks of peptic ulcers [risk ratio (RR): 0.19; 95% confidence interval: 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P < 0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22 (0.10-0.51); P = 0.0004], and erosive esophagitis [0.14 (0.07-0.28); P < 0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P = 0.01], heartburn [1.24 (1.18-1.31); P < 0.00001], and regurgitation [1.26 (1.13-1.40); P < 0.0001], but did not increase the risks of all-cause mortality [1.72 (0.61-4.87); P = 0.31], cardiovascular mortality [1.80 (0.59-5.44); P = 0.30], nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P = 0.22], ischemic stroke/transient ischemic attack [1.09 (0.34-3.53); P = 0.89] and other adverse events. CONCLUSIONS: The PPI seems to be effective in preventing peptic ulcers and erosive esophagitis and in resolution of dyspeptic symptoms without increasing adverse events, cardiac risks or mortality in long-term aspirin users.


Assuntos
Aspirina/uso terapêutico , Esofagite Péptica/epidemiologia , Infarto do Miocárdio/prevenção & controle , Úlcera Péptica Hemorrágica/epidemiologia , Úlcera Péptica/epidemiologia , Inibidores da Bomba de Prótons/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Esofagite Péptica/induzido quimicamente , Esofagite Péptica/prevenção & controle , Humanos , Infarto do Miocárdio/mortalidade , Razão de Chances , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/complicações , Úlcera Péptica/prevenção & controle , Úlcera Péptica Hemorrágica/etiologia , Úlcera Péptica Hemorrágica/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
11.
PLoS One ; 12(6): e0180612, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28666006

RESUMO

The primary study objectives were to estimate the frequencies and rates of gastrointestinal bleeding and peptic ulcerative disorder in HIV-positive patients compared with age- and sex-matched HIV-negative subjects. Data from a US insurance claims database was used for this analysis. Among 89,207 patients with HIV, 9.0% had a GI bleed, 1.0% had an upper gastrointestinal bleed, 5.6% had a lower gastrointestinal bleed, 1.9% had a peptic ulcerative disorder diagnosis, and 0.6% had both gastrointestinal/peptic ulcerative disorder. Among 267,615 HIV-negative subjects, the respective frequencies were 6.9%, 0.6%, 4.3%, 1.4%, and 0.4% (p<0.0001 for each diagnosis subcategory). After combining effect measure modifiers into comedication and comorbidity strata, gastrointestinal bleeding hazard ratios (HRs) were higher for HIV-positive patients without comedication/comorbidity, and those with comedication alone (HR, 2.73; 95% confidence interval [CI], 2.62-2.84; HR, 1.59; 95% CI, 1.47-1.71). The rate of peptic ulcerative disorder among those without a history of ulcers and no comorbidity/comedication was also elevated (HR, 2.72; 95% CI, 2.48-2.99). Hazard ratios of gastrointestinal bleeding, and peptic ulcerative disorder without a history of ulcers were lower among patients infected with HIV with comedication/comorbidity (HR, 0.64; 95% CI, 0.56-0.73; HR, 0.46; 95% CI, 0.33-0.65). Rates of gastrointestinal bleeding plus peptic ulcerative disorder followed a similar pattern. In summary, the rates of gastrointestinal/peptic ulcerative disorder events comparing HIV-infected subjects to non-HIV-infected subjects were differential based on comorbidity and comedication status.


Assuntos
Hemorragia Gastrointestinal/epidemiologia , Infecções por HIV/complicações , Formulário de Reclamação de Seguro , Úlcera Péptica/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/complicações , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Biol Pharm Bull ; 40(6): 910-915, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28566633

RESUMO

In a study to find ways to prevent the side effects of indomethacin (IMC), we previously reported that magnesium ion (Mg2+) can prevent the onset of IMC-induced gastric mucosa in adjuvant-induced arthritis (AA) rats, a model for rheumatoid arthritis (RA). In this study we investigated whether the co-administration of IMC and Mg2+ prevents the formation and aggravation of intestinal ulcerogenic lesions in AA rats. The single oral administration of an excessive dose of IMC (40 mg/kg) induces hemorrhagic lesions and nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) in the jejunal and ileal mucosa of AA rats, and the extent of the lesions, as well as iNOS and NO levels in AA rats are higher than in normal rats. On the other hand, the co-administration of 200 mg/kg Mg2+ attenuates intestinal ulceration and the elevation in the iNOS and NO levels in AA rats. Further, hemorrhagic lesioning and enhanced iNOS and NO levels in AA rats also result from the repetitive oral administration of 3 mg/kg IMC (therapeutic dose) for 42 d (once a day), and these changes are also prevented by the co-administration of 200 mg/kg Mg2+. In conclusion, the co-administration of Mg2+ suppresses the ulcerogenic response to IMC in the jejunal and ileal mucosa of AA rats, probably by preventing the elevation of iNOS and NO levels in the region.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Artrite Experimental/tratamento farmacológico , Indometacina/efeitos adversos , Magnésio/uso terapêutico , Úlcera Péptica/prevenção & controle , Substâncias Protetoras/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Quimioterapia Combinada , Íleo/efeitos dos fármacos , Íleo/metabolismo , Indometacina/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/metabolismo , Úlcera Péptica/patologia , Ratos
13.
World J Gastroenterol ; 23(11): 1954-1963, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28373761

RESUMO

Novel oral anticoagulants (NOACs), which include direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding (GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran (150 mg b.i.d), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/prevenção & controle , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/terapia , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Fatores de Coagulação Sanguínea/agonistas , Fatores de Coagulação Sanguínea/antagonistas & inibidores , Ensaios Clínicos como Assunto , Endoscopia Gastrointestinal , Hemorragia Gastrointestinal/prevenção & controle , Infecções por Helicobacter/complicações , Humanos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/complicações , Fatores de Risco
14.
Pharmacoepidemiol Drug Saf ; 26(10): 1141-1148, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28370857

RESUMO

PURPOSE: To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. METHODS: A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs). RESULTS: At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47). CONCLUSIONS: Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Hemorragia Gastrointestinal/epidemiologia , Manejo da Dor/efeitos adversos , Dor/tratamento farmacológico , Úlcera Péptica Perfurada/epidemiologia , Úlcera Péptica/epidemiologia , Inibidores da Bomba de Prótons/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Manejo da Dor/métodos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/complicações , Úlcera Péptica/prevenção & controle , Úlcera Péptica Perfurada/etiologia , Úlcera Péptica Perfurada/prevenção & controle , Fatores de Risco
15.
Adv Ther ; 34(5): 1070-1086, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28429247

RESUMO

Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.


Assuntos
Esofagite/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Úlcera Péptica/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Humanos , Inibidores da Bomba de Prótons/farmacologia
16.
Inflammopharmacology ; 25(2): 255-264, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28255738

RESUMO

We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.


Assuntos
Arginina/administração & dosagem , Ciclofosfamida/toxicidade , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/metabolismo , Úlcera Péptica/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Sequência de Aminoácidos , Animais , Antiulcerosos/administração & dosagem , Quimioterapia Combinada , Feminino , Óxido Nítrico/antagonistas & inibidores , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/tratamento farmacológico , Distribuição Aleatória , Ratos , Ratos Wistar
17.
J Clin Psychopharmacol ; 37(2): 239-245, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28166082

RESUMO

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been reported to have an increased risk of gastrointestinal adverse events, and the risk may be further increased by combined use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, little has been known about the risk of peptic ulcer associated with other classes of antidepressants or individual antidepressants combined with NSAIDs. METHODS: We conducted a retrospective cohort study to define the risk of peptic ulcer associated with combined use of antidepressants and NSAIDs, as compared with use of antidepressants alone. Using the Korean Health Insurance Review and Assessment Service database, we identified a total of 1,127,622 patients who began receiving antidepressants between 2009 and 2012. Propensity-based matching and Cox proportional hazards models were used to compare the risk of peptic ulcer between antidepressant users with NSAIDs and those without NSAIDs matched in a 1:1 ratio, for a total of 768,850 patients. RESULTS: The risk of peptic ulcer did not increase with combined use of overall antidepressants and NSAIDs, as compared with antidepressant use alone (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.99-1.06). A slightly increased risk was observed for combined use of NSAIDs with tricyclic antidepressants (HR, 1.15; 95% CI, 1.09-1.21) and with SSRIs (HR, 1.08; 95% CI, 1.01-1.16). CONCLUSION: We found that although concomitant use of NSAIDs and antidepressants was not associated with an increased risk of peptic ulcer for antidepressants in general, it was so for some specific classes including tricyclic antidepressants and SSRIs. However, we cannot rule out the possibility that the increased risk was solely due to NSAID use.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antidepressivos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Úlcera Péptica/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos Tricíclicos/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Inibidores de Captação de Serotonina/efeitos adversos , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-28215165

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) exert gastrointestinal upset by inhibiting mucosal cyclooxygenase (COX) activity and complexation technique with metals has been adopted to overcome this drawback. OBJECTIVE: The study aimed to overcome the gastrointestinal side effects associated with indomethacin treatment by synthesizing copper (Cu) and zinc (Zn) complexes of indomethacin along with assessing potential pharmacological effects of these complexes. METHOD: The characterization of synthesized complexes was done by FT-IR, XRD, UV-Vis, Atomic Absorption Spectroscopy (AAS) and Differential Scanning Calorimetry (DSC). Biological properties as local analgesic activity, anti-inflammatory activity and antiulcerogenic activity were evaluated following radiant heat tail flick, inhibition of rat hind paw edema and inhibition of NSAID induced gastroenteropathy method respectively. RESULTS: 0.3 ml of indomethacin-copper complex demonstrated prominent analgesia at 25 µg/ml dose and 0.3 ml of indomethacin-zinc complex, after 30, 60 and 90 minutes of oral administration, shown significant local analgesia at 25, 50 and 100 µg/ml dose. In antiinflammatory activity assay, indomethacin-copper exhibited significant inhibition at 20 mg/kg dose after 2nd, 3rd and 4th hour of administration whereas indomethacin-zinc illustrated significant inhibition at 10 mg/kg dose after 2nd, 3rd and 4th hour of administration. Anti-ulcerogenic activity study of the complexes exhibited no macroscopic damage to the stomach and intestine, except minor microscopic damage. CONCLUSION: In view of the results, the copper and zinc complexes of indomethacin may be used as better substitutes of the parent indomethacin owing to their minimal side effects with additional pharmacological effects.


Assuntos
Analgésicos , Anti-Inflamatórios não Esteroides , Complexos de Coordenação , Cobre , Indometacina , Zinco , Analgésicos/efeitos adversos , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina , Complexos de Coordenação/efeitos adversos , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Cobre/química , Cobre/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Temperatura Alta , Indometacina/efeitos adversos , Indometacina/química , Indometacina/uso terapêutico , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Masculino , Camundongos , Dor/tratamento farmacológico , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/patologia , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/patologia , Zinco/química , Zinco/uso terapêutico
19.
Ann Pharmacother ; 51(4): 354-356, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28228058

RESUMO

The scaffold of this commentary is oriented to gravitate toward shedding light on the misconception regarding the use of enteric-coated, extended-release or sustained-release forms of nonsteroidal anti-inflammatory drugs (NSAIDs) and the reduction in gastrointestinal (GI) risks. Although evidence is sufficiently available with regard to the inability of these forms to ameliorate GI risks, it has been widely neglected by health care professionals. This dilemma will be approached and elaborated by uncovering historical evidence about the topic of interest followed by theoretical pharmacological explanations.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Úlcera Péptica Hemorrágica/induzido quimicamente , Úlcera Péptica/induzido quimicamente , Preparações de Ação Retardada , Humanos , Risco , Comprimidos com Revestimento Entérico
20.
Zhonghua Nei Ke Za Zhi ; 56(1): 81-85, 2017 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-28056333

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are a broad class of non glucocorticoid drugs which are extensively used in anti-inflammatory, analgesic, and antipyretic therapies. However, NSAIDs may cause many side effects, most commonly in gastrointestinal(GI) tract. Cardiovascular system, kidney, liver, central nervous system and hematopoietic system are also involved. NSAID-induced GI side effects not only endanger the patients' health, increase mortality, but also greatly increase the cost of medical care. Therefore, how to reduce GI side effects is of particular concern to clinicians. The Chinese Rheumatism Data Center(CRDC) and Chinese Systemic Lupus Erythematosus Treatment and Research Group(CSTAR) compose a "Recommendation for the prevention and treatment of non-steroidal anti-inflammatory drug-induced gastrointestinal ulcers and its complications" , as following: (1) GI lesions are the most common side effects of NSAIDs. (2) NSAID-induced GI side effects include gastritis, esophagitis, gastric and duodenal ulcers, bleeding, perforation and obstruction. (3) With the application of capsule endoscopy and small intestinal endoscopy, growing attention is being paid to the NASID-induced small intestine mucosa damage, which is mainly erosion and ulcer. (4) Risk factors related to NSAID-induced GI ulcers include: Helicobacter pylori (Hp) infection, age> 65 years, past history of GI ulcers, high doses of NSAIDs, multiple-drug combination therapy, and comorbidities, such as cardiovascular disease and nephropathy.(5) GI and cardiovascular function should be evaluated before using NSAIDs and gastric mucosal protective agents. (6) The risk of GI ulcers and complications caused by selective cyclooxygenase-2 (COX-2) inhibitors is less than that of non-selective COX-2 inhibitors. (7)Hp eradication therapy helps to cure GI ulcers and prevent recurrence when Hp infection is positive in NSAID-induced ulcers. (8) Proton pump inhibitor (PPI) is the first choice for the prevention and treatment of NSAID-induced GI injury. Gastric mucosal protective agents also suggested.(9) H2 receptor antagonist (H2RA) can reduce the risk of NSAID-induced duodenal injury, however, the therapeutic effect of NSAID-induced gastric ulcer remains to be further confirmed. (10) Endoscopic treatment is the first recommendation for NSAID-induced peptic ulcers combined with upper GI bleeding, high-dose PPI effectively prevent rebleeding, reduce the possibility of surgery and mortality rate.


Assuntos
Dor Abdominal/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Hemorragia Gastrointestinal/prevenção & controle , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Guias de Prática Clínica como Assunto , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/efeitos adversos , Sistema Digestório/efeitos dos fármacos , Sistema Digestório/patologia , Mucosa Gástrica , Gastroenteropatias , Infecções por Helicobacter , Helicobacter pylori , Antagonistas dos Receptores Histamínicos H2 , Humanos , Inibidores da Bomba de Prótons , Fatores de Risco , Úlcera
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