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1.
Expert Opin Investig Drugs ; 28(10): 871-889, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31566013

RESUMO

Introduction: Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low-grade duodenal inflammation.Areas covered: This review summarizes recent and ongoing drug development for FD as identifiedExpert opinion: Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassiumcompetitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may be efficacious in PDS. There are emerging data with pro-and antibiotics and with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.


Assuntos
Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/farmacologia , Gastroenteropatias/tratamento farmacológico , Dor Abdominal/etiologia , Desenvolvimento de Medicamentos/métodos , Dispepsia/fisiopatologia , Fármacos Gastrointestinais/administração & dosagem , Gastroenteropatias/fisiopatologia , Gastroparesia/tratamento farmacológico , Gastroparesia/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacologia
3.
Expert Opin Drug Saf ; 18(11): 1043-1053, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31498687

RESUMO

Introduction: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs worldwide. However, concerns are growing about the serious adverse events and mortality linked to their long-term use. Areas covered: The authors review the main approved clinical indications and adverse events associated with PPIs, including, among others, pneumonia, Clostridium difficile infection, cardiovascular diseases, bone fractures, kidney diseases, and several nutrient deficiencies. Recent studies have reported that patients taking PPIs displayed increased mortality, linked to cardiovascular diseases, gastrointestinal malignancies, and chronic kidney diseases. Expert opinion: PPIs represent an important advance in the medical treatment of acid-related diseases. PPIs have contributed to profound reductions in hospitalizations and mortality due to upper GI complications. However, concern is growing about the wide range of potentially serious adverse events and mortality linked to chronic PPI use. Nevertheless, the level of evidence on adverse events is low; it is based on observational studies, and most findings have not been confirmed in the limited number of clinical trials available. PPI overuse and off-label prescriptions must be eradicated, but long-term PPI use for clear indications must continue, until we have stronger evidence to support claims of serious adverse events and mortality.


Assuntos
Uso Off-Label/estatística & dados numéricos , Uso Excessivo de Medicamentos Prescritos/prevenção & controle , Inibidores da Bomba de Prótons/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/mortalidade , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/mortalidade
4.
Rev Med Suisse ; 15(661): 1551-1555, 2019 Sep 04.
Artigo em Francês | MEDLINE | ID: mdl-31496188

RESUMO

Proton pump inhibitors (PPI) have long been considered as devoid of any toxicity, but recent studies have uncovered significant potential side effects related to long-term use. In addition, stopping treatment with PPI may cause a symptomatic rebound effect of acid production. This article reviews the current literature on strategies for rationalizing their use, limiting potential adverse effects and progressive discontinuation.


Assuntos
Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico
6.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
7.
Orv Hetil ; 160(34): 1340-1345, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31423829

RESUMO

Introduction and aim: As the efficacy of the first-line traditional treatment used to eradicate Helicobacter pylori (H. p.) decreased below 75% in Hungary, a new protocol had to be created. Method: Supposing the success rate of the traditional therapy (14-day double dose of proton pump inhibitor [PPI], 1000 mg amoxicillin b.i.d., 500 mg clarithromycin b.i.d. [PAC]) to be 75% and the efficacy of the new protocol (10-day 120 mg bismuth dicitrate q.i.d., double dose PPI b.i.d., 500 mg tetracycline q.i.d. and 500 mg tinidazole b.i.d. [BQT]) to be 90%, we calculated 109 patients on each arm. Patients were recruited after upper gastrointestinal endoscopy from 5 endoscopic units in Vas county. The heterogeneity of groups, success rate and side effects of both therapies were evaluated by Fisher exact test; p<0.05 was considered significant. Results: 110 patients were included in the BQT and 109 patients in the PAC group. There was no heterogeneity between the two groups in age, gender and indication of eradication. H. p. eradication was successful in 103/110 (93.6%) in the BQT and 81/109 (74.3%) in the PAC group (p<0.001). The odds ratio in the BQT group for successful eradication was 5.05 (95% confidence interval: 2.02-14.42) as compared to the PAC group (p<0.001). The side effects of the two groups were similar, in the BQT group the frequency was 34.5%. Conclusion: 10 day-long BQT containing double dose PPI with 120 mg bismuth dicitrate q.i.d., 500 mg tetracycline q.i.d. and 500 mg tinidazole b.i.d. is recommended as the first-line treatment for the eradication of H. p. because of its high efficacy and tolerable side effects. Orv Hetil. 2019; 160(34): 1340-1345.


Assuntos
Antiácidos/administração & dosagem , Antibacterianos/administração & dosagem , Bismuto/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antiácidos/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Claritromicina/administração & dosagem , Claritromicina/uso terapêutico , Esquema de Medicação , Farmacorresistência Bacteriana , Quimioterapia Combinada , Endoscopia Gastrointestinal , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Humanos , Hungria , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Tetraciclina/administração & dosagem , Tetraciclina/uso terapêutico , Tinidazol/administração & dosagem , Tinidazol/uso terapêutico , Resultado do Tratamento
8.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
9.
J Oncol Pharm Pract ; 25(7): 1705-1711, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31081468

RESUMO

BACKGROUND: Capecitabine is a commonly used oral chemotherapy agent. Recent data suggest that concurrent use of proton pump inhibitors may reduce the efficacy of capecitabine by decreasing its absorption through increased gastric pH. Since proton pump inhibitors are widely used, we evaluated the supportive evidence for the probability of occurrence and potential seriousness of this drug interaction. METHODS: The probability of occurrence was evaluated based on the clinical, pharmacokinetic and in vitro evidence using the Drug Interaction Probability Scale. The possibility of seriousness was assessed based on the potential impact on the therapeutic intent of capecitabine therapy. RESULTS: The probability of occurrence of the interaction is doubtful. Clinical findings from two retrospective post hoc analyses showed inconsistent trends towards reduced survival. Pharmacokinetics studies found no significant decrease in systemic capecitabine level with concurrent gastric acid suppression with antacid or food intake. In vitro data do not support the proposed mechanism of reduced capecitabine absorption due to increased gastric pH. The possibility of seriousness varies depending on the treatment intent of capecitabine therapy. The most and least serious possible outcome would be reduced possibility of cure or survival and symptom control, respectively. CONCLUSION: Although the possible outcome may be serious, the probability of interaction between capecitabine and proton pump inhibitors is doubtful. Therefore, we suggest that intervention should be limited to minimal change to existing therapy plan. This may include routinely ascertaining the need for proton pump inhibitor use. Alternate acid suppressing agents may be considered based on the therapeutic intent of capecitabine therapy.


Assuntos
Capecitabina/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Antiácidos/administração & dosagem , Antiulcerosos/administração & dosagem , Capecitabina/efeitos adversos , Interações de Medicamentos , Ácido Gástrico/metabolismo , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos
10.
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
11.
World J Gastroenterol ; 25(17): 2110-2121, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31114137

RESUMO

BACKGROUND: Reflux esophagitis (RE) is a common digestive disorder, and its frequent recurrences cause significant physical pain and are financially burdensome to patients. However, studies on the natural history of treated RE are few. Although proton pump inhibitors (PPIs) as the first-line treatment provide notable symptomatic relief, disordered gut microbiota has been observed among PPI users. Probiotics are commonly administered to patients to regulate the disordered intestinal flora. AIM: To evaluate the therapeutic effects in RE patients treated with a combination of esomeprazole and probiotics [Bacillus subtilis (B. subtilis) and Enterococcus faecium (E. faecium)]. METHODS: One hundred and thirty-four RE patients were randomized into two groups of 67 subjects each. The probiotics group was administered with esomeprazole 20 mg b.i.d. and live combined B. subtilis and E. faecium enteric-coated capsules 500 mg t.i.d. for eight weeks; the placebo group was administered with esomeprazole 20 mg b.i.d. and placebo for eight weeks. Subsequently, 12-wk follow-up was carried out on patients who achieved both endoscopic and clinical cure. Endoscopy, reflux diagnostic questionnaire (RDQ), gastrointestinal symptom rating scale (GSRS), and lactulose hydrogen breath test were performed to evaluate the therapeutic effects. A difference of P < 0.05 was considered statistically significant. RESULTS: Sixty-six patients in the probiotics group and 64 patients in the placebo group completed the 8-wk treatment. The healing rate and RDQ score had no significant difference between the two groups (P > 0.05). However, the GSRS diarrhea syndrome score was decreased significantly in the probiotics group (P = 0.002), and the small intestinal bacterial overgrowth negative rate in the probiotics group was significantly higher than that in the placebo group (P = 0.002). Of 114 endoscopically and clinically cured patients, 96 completed the follow-up. The log-rank test showed that the time to relapse was shorter in the placebo group than in the probiotics group (P = 0.041). Furthermore, the therapy had a significant influence on relapse time, and the risk of relapse in the probiotics group was lower than that in the placebo group at any time point during the 12-wk follow-up (hazard ratio = 0.52, P = 0.033). CONCLUSION: Esomeprazole combined with probiotics (B. subtilis and E. faecium) have a beneficial effect on RE treatment and patient management.


Assuntos
Esomeprazol/administração & dosagem , Esofagite Péptica/terapia , Probióticos/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Adolescente , Adulto , Idoso , Bacillus subtilis , Índice de Massa Corporal , Suplementos Nutricionais , Endoscopia , Enterococcus faecium , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
12.
Internist (Berl) ; 60(6): 597-607, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31076795

RESUMO

Gastrointestinal bleeding is a common and sometimes life-threatening event in older people. There is often a drug-induced cause. Drugs that can lead to gastrointestinal bleeding include non-steroidal anti-inflammatory drugs (NSAIDs) like diclofenac and ibuprofen, platelet inhibitors such as acetylsalicylic acid (ASS), clopidogrel and prasugrel, as well as anticoagulants like vitamin-K antagonists, heparin or direct oral anticoagulants (DOAKs). Combination antiplatelet therapy or combined medication with platelet inhibitor and anticoagulants increase the risk of gastrointestinal bleeding compared to monotherapy. Primary and secondary prevention options include Helicobacter pylori eradication and co-medication with a proton pump inhibitor (PPI).


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Helicobacter pylori , Humanos , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Risco
14.
Int J Mol Sci ; 20(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003453

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) eradication therapy may improve gastric atrophy and intestinal metaplasia, but the results of previous studies have not always been consistent. The aim of this study was to compare the histological changes of intestinal metaplasia and gastric atrophy among the use of acid-suppressing drugs after H. pylori eradication. METHODS: A cohort of 242 patients who underwent successful eradication therapy for H. pylori gastritis and surveillance endoscopy examination from 1996 to 2015 was analyzed. Changes in the histological scores of intestinal metaplasia and atrophy according to drug use (proton-pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), and non-acid suppressant use) were evaluated in biopsies of the antrum and corpus using a generalized linear mixed model in all patients. RESULTS: The mean follow-up period and number of biopsies were 5.48 ± 4.69 years and 2.62 ± 1.67 times, respectively. Improvement in the atrophy scores of both the antrum (p = 0.042) and corpus (p = 0.020) were significantly superior in patients with non-acid suppressant drug use compared with those of PPI and H2RA use. Metaplasia scores in both the antrum and corpus did not improve in all groups, and no significant differences were observed among groups in the antrum (p = 0.271) and corpus (p = 0.077). CONCLUSIONS: Prolonged acid suppression by PPIs or H2RAs may limit the recovery of gastric atrophy following H. pylori eradication.


Assuntos
Atrofia/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/microbiologia , Atrofia/fisiopatologia , Atrofia/prevenção & controle , Endoscopia , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/fisiopatologia , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Gastrite/fisiopatologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidade , Humanos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/fisiopatologia , Masculino , Metaplasia/tratamento farmacológico , Metaplasia/microbiologia , Metaplasia/fisiopatologia , Pessoa de Meia-Idade
15.
Pharm Dev Technol ; 24(6): 788-793, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30885016

RESUMO

The purpose of this research was to develop a novel revaprazan-loaded surface-modified solid dispersion (SMSD) with improved drug solubility and oral bioavailability. The impact of carriers on aqueous solubility of revaprazan was investigated. HPMC and Cremophor A25 were selected as an appropriate polymer and surfactant, respectively, due to their high drug solubility. Numerous SMSDs were prepared with various concentrations of carriers, using distilled water, and the drug solubility of each was assessed. Moreover, the physicochemical properties, dissolution and pharmacokinetics of selected SMSD in rats were assessed in comparison to revaprazan powder. Of the SMSDs assessed, the SMSD composed of revaprazan/HPMC/Cremophor A25 at the weight ratio of 1:0.28:1.12 had the most enhanced drug solubility (∼6000-fold). It was characterized by particles with a relatively rough surface, suggesting that the carriers were attached onto the surface of the unchanged crystalline revaprazan powder. It had a significantly higher dissolution rate, AUC and Cmax, and a faster Tmax value in comparison to revaprazan powder, with a 5.3-fold improvement in oral bioavailability of revaprazan. Therefore, from an environmental perspective, this SMSD system prepared with water, and without organic solvents, should be recommended as a revaprazan-loaded oral pharmaceutical alternative.


Assuntos
Portadores de Fármacos/química , Derivados da Hipromelose/química , Polietilenoglicóis/química , Inibidores da Bomba de Prótons/química , Pirimidinonas/química , Tensoativos/química , Tetra-Hidroisoquinolinas/química , Administração Oral , Cristalização , Inibidores da Bomba de Prótons/administração & dosagem , ATPases Translocadoras de Prótons/antagonistas & inibidores , Pirimidinonas/administração & dosagem , Solubilidade , Tetra-Hidroisoquinolinas/administração & dosagem
16.
J Gastrointestin Liver Dis ; 28(1): 11-14, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30851166

RESUMO

BACKGROUND AND AIM: Standard 10-day sequential therapy is advised as first-line therapy for Helicobacter pylori (H. pylori) eradication by current Italian guidelines. Some data suggested that a 14-day regimen may achieve higher eradication rates. This study compared the efficacy of sequential therapy administered for either 10- or 14-days. METHODS: This prospective, multicenter, open-label study enrolled patients with H. pylori infection without previous treatment. Patients were receiving a sequential therapy for either 10 or 14 days with esomeprazole 40 mg and amoxicillin 1 g (5 or 7 days) followed by esomeprazole 40 mg, clarithromycin 500 mg and tinidazole 500 mg (5 or 7 days), all given twice daily. Bacterial eradication was checked using 13C-urea breath test. Eradication cure rates were calculated at both Intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: A total of 291 patients were enrolled, including 146 patients in 10-day and 145 in the 14-day regimen. The eradication rates were 87% (95% CI = 81.5-92.4) and 90.3% (95% CI = 85.5-95.1) at ITT analysis with the 10- and 14-day regimen, respectively, and 92.7% (95% CI = 88.3-97) and 97% (95% CI = 94.2-99.9) at PP analysis (p =0.37). Among patients, who earlier had interrupted therapy, bacterial eradication was achieved in 8 out of 9 who completed the first therapy phase and performed at least >/=3 days of triple therapy in the second phase. CONCLUSION: This study found that both 10- and 14-day sequential therapies achieved a high eradication rate for first-line H. pylori therapy in clinical practice.


Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Claritromicina/administração & dosagem , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Tinidazol/administração & dosagem , Adulto , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Carga Bacteriana , Claritromicina/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Esomeprazol/efeitos adversos , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Tempo , Tinidazol/efeitos adversos , Resultado do Tratamento
18.
BMJ Case Rep ; 12(2)2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30814100

RESUMO

Acute oesophageal necrosis, also known as 'black oesophagus', is a rare condition characterised by the black discolouration of the oesophageal mucosa on endoscopy and involves the distal oesophagus in majority of cases but may also extend proximally. A number of conditions are found to be associated with it and it is thought to occur due to a combination of hypovolaemia and inadequate oesophageal protective mucosal barrier function. Gastric secretions may have a direct effect on the oesophageal mucosa. We present a case of a woman who presented with haematemesis and significant hypotension after a session of haemodialysis. Black oesophagus was confirmed on esophagogastroduodenoscopy. She was given two units of packed red blood cells and one unit of platelets, and started on a pantoprazole infusion. However, despite rigorous attempts at resuscitation the patient failed to recover.


Assuntos
Doenças do Esôfago/diagnóstico por imagem , Doenças do Esôfago/patologia , Doença Aguda , Idoso de 80 Anos ou mais , Transfusão de Sangue , Endoscopia do Sistema Digestório/métodos , Doenças do Esôfago/terapia , Esôfago/diagnóstico por imagem , Esôfago/patologia , Evolução Fatal , Feminino , Humanos , Necrose , Pantoprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem
19.
J Gastroenterol Hepatol ; 34(4): 666-672, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30726563

RESUMO

BACKGROUND AND AIM: Failure of bismuth quadruple therapy for Helicobacter pylori eradication is frequently observed. To increase the eradication rate, comprehensive analyses need to be performed regarding risk factors of bismuth quadruple therapy failure based on complete standard culture and antimicrobial susceptibility testing results. METHODS: Patients with history of failed first therapy who had H. pylori colonies isolated from culture and successful minimum inhibitory concentration (MIC) test were enrolled. Esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapies for 7 or 14 days were given. Eradication rate, treatment compliance, adverse events, and risk factors for the failure of bismuth quadruple therapy were analyzed. RESULTS: A total 54 patients were enrolled. Overall eradication rate in the present study was 88.8%. The eradication rate for cases with metronidazole resistance such as MIC 8-16 µg/mL or 16-32 µg/mL was 92.8% (13/14). For cases with high level metronidazole resistance (MIC > 32 µg/mL), the eradication rate was only 60% (6/10). Multivariate analysis regarding compliance, treatment duration, age > 60, three kinds of metronidazole MICs, tetracycline MIC > 4 µg/mL, adverse events and any other parameters, "metronidazole resistance, high level (MIC > 32 µg/mL)" was the only independent risk factor for eradication failure (P = 0.007). CONCLUSION: For cases with metronidazole resistance at MIC > 32 µg/mL, rescue therapy other than bismuth-containing quadruple therapy is needed.


Assuntos
Antibacterianos/administração & dosagem , Bismuto/administração & dosagem , Bismuto/efeitos adversos , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter , Helicobacter pylori , Falha de Tratamento , Antibacterianos/farmacologia , Bismuto/farmacologia , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Quimioterapia Combinada , Esomeprazol/administração & dosagem , Feminino , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Metronidazol/administração & dosagem , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Risco , Tetraciclina/administração & dosagem , Tetraciclina/farmacologia
20.
Expert Opin Drug Saf ; 18(3): 163-172, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30704306

RESUMO

OBJECTIVE: We aimed to summarize the current evidence regarding the risk of pneumonia associated with proton pump inhibitors (PPI) treatment. METHODS: We searched PubMed, Embase, and CENTRAL from the 1970 through December 2017. We included both randomized controlled trials (RCTs) and observational studies. We used random-effect model to calculate the summary effect estimates and quantified the heterogeneity by I2 statistics. RESULTS: A total of 7,643,982 patients from 10 RCTs and 48 observational studies were included in this meta-analysis. The primary meta-analysis demonstrated PPIs use was significantly associated with increased risk of pneumonia, but the heterogeneity was high (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30-1.57; I2, 95.4%). The sensitivity analysis indicated PPIs were not statistically associated with increased risk of pneumonia among patients concomitantly taking nonsteroidal anti-inflammatory drugs (OR, 1.11; 95% CI, 0.94-1.31; I2, 5.8%). The funnel plot demonstrated significant publication bias, especially for observational studies. CONCLUSIONS: The presence of significant between-study heterogeneity and publication bias raised concerns regarding the validity of the primary meta-analytic result. Protopathic bias, or reverse causality, may cause overestimated association. Studies that adopted a design to account for protopathic bias did not show a significant association between PPI use and risk of pneumonia.


Assuntos
Modelos Estatísticos , Pneumonia/epidemiologia , Inibidores da Bomba de Prótons/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Interpretação Estatística de Dados , Humanos , Pneumonia/etiologia , Inibidores da Bomba de Prótons/efeitos adversos , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
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