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Journal of Veterinary Internal Medicine Nov 2018The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of...
The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of inflammatory, erosive, and ultimately ulcerative lesions. This report offers a consensus opinion on the rational administration of GI protectants to dogs and cats, with an emphasis on proton pump inhibitors (PPIs), histamine type-2 receptor antagonists (H RAs), misoprostol, and sucralfate. These medications decrease gastric acidity or promote mucosal protective mechanisms, transforming the management of dyspepsia, peptic ulceration, and gastroesophageal reflux disease. In contrast to guidelines that have been established in people for the optimal treatment of gastroduodenal ulcers and gastroesophageal reflux disease, effective clinical dosages of antisecretory drugs have not been well established in the dog and cat to date. Similar to the situation in human medicine, practice of inappropriate prescription of acid suppressants is also commonplace in veterinary medicine. This report challenges the dogma and clinical practice of administering GI protectants for the routine management of gastritis, pancreatitis, hepatic disease, and renal disease in dogs and cats lacking additional risk factors for ulceration or concerns for GI bleeding. Judicious use of acid suppressants is warranted considering recent studies that have documented adverse effects of long-term supplementation of PPIs in people and animals.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Gastrointestinal Agents; Gastrointestinal Diseases; Misoprostol; Proton Pump Inhibitors; Sucralfate
PubMed: 30378711
DOI: 10.1111/jvim.15337 -
International Journal of Molecular... Sep 2022Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+... (Review)
Review
Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adenosine Triphosphatases; Antacids; Bone Density; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Omeprazole; Osteoporotic Fractures; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; United States
PubMed: 36142643
DOI: 10.3390/ijms231810733 -
Digestive Diseases and Sciences May 2022Gastroesophageal reflux disease (GERD) has consistently been the most frequently diagnosed gastrointestinal malady in the USA. The mainstay of therapy has traditionally... (Review)
Review
Gastroesophageal reflux disease (GERD) has consistently been the most frequently diagnosed gastrointestinal malady in the USA. The mainstay of therapy has traditionally been medical management, including lifestyle and dietary modifications as well as antacid medications. In those patients found to be refractory to medical management or with a contraindication to medications, the next step up has been surgical anti-reflux procedures. Recently, though innovative advancements in therapeutic endoscopy have created numerous options for the endoscopic management of GERD, in this review, we discuss the various endoscopic therapy options, as well as suggested strategies we use to recommend the most appropriate therapy for patients.
Topics: Anti-Ulcer Agents; Endoscopy; Esophagitis, Peptic; Fundoplication; Gastroesophageal Reflux; Humans; Treatment Outcome
PubMed: 35258754
DOI: 10.1007/s10620-022-07390-2 -
BMJ (Clinical Research Ed.) Sep 2019To assess the effects of treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To assess the effects of 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 were randomly assigned to treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design.
INTERVENTIONS
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 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 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 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
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. treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00339768.
Topics: Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Biopsy; China; Dietary Supplements; Drug Therapy, Combination; Female; Follow-Up Studies; Garlic; Gastric Mucosa; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Male; Middle Aged; Plant Extracts; Precancerous Conditions; Proton Pump Inhibitors; Stomach Neoplasms; Survival Analysis; Survival Rate; Time Factors; Treatment Outcome; Vitamins
PubMed: 31511230
DOI: 10.1136/bmj.l5016 -
The Turkish Journal of Gastroenterology... Dec 2017Gastroesophageal reflux disease (GERD) is frequently seen during pregnancy. In the medical treatment of pregnant women with GERD, alginic acid and sucralfate can be...
Gastroesophageal reflux disease (GERD) is frequently seen during pregnancy. In the medical treatment of pregnant women with GERD, alginic acid and sucralfate can be used. Calcium- and magnesium-based antacids can also be used, particularly for patients with preeclampsia. In particular, ranitidine -a histamine-2 receptor blocker- is preferred. In the case of non-responsiveness to the abovementioned treatments, proton pump inhibitors (PPIs), except omeprazole, can be given considering the benefit-harm ratio for the mother and fetus after the first trimester. In cases with GERD during the lactation period, drugs having minimum systemic absorption, such as sucralfate and alginic acid, are preferable but there is no data.
Topics: Alginates; Antacids; Female; Gastroesophageal Reflux; Glucuronic Acid; Hexuronic Acids; Humans; Lactation; Omeprazole; Pregnancy; Pregnancy Complications; Proton Pump Inhibitors; Ranitidine; Sucralfate
PubMed: 29199169
DOI: 10.5152/tjg.2017.14 -
BMC Pharmacology & Toxicology Jul 2020The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole, rabeprazole, and pantoprazole.
SETTING
The study population comprised 186 healthy volunteers participating in 6 bioequivalence clinical trials.
METHOD
Subjects were evaluated to determine the effect of a high-fat breakfast on the pharmacokinetics of omeprazole (n = 36), rabeprazole (n = 69), and pantoprazole (n = 81).
MAIN OUTCOME MEASURE
Drug plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry.
RESULTS
Food affected the pharmacokinetics of omeprazole (increased T and decreased AUC and C), pantoprazole (increased T and decreased AUC), and rabeprazole (increased T, C and half-life). Food increased variability in T for all 3 drugs, delaying absorption around 3 to 4 h and until 20 h in some subjects.
CONCLUSION
As food delays the absorption of PPIs and increases their variability, it would be better to administer these drugs under fasting conditions.
TRIAL REGISTRATION
European Union Drug Regulating Authorities Clinical Trials Database: EudraCT : 2004-003863-59 (registration date 05/MAR/2004), EudraCT 2006-001162-17 (registration date 17-MAR-2006), EudraCT: 2007-002489-37 (registration date 12-JUN-2007), EudraCT: 2007-002490-31 (registration date 12-JUN-2007), EudraCT: 2010-024029-19 (registration date 23-NOV-2010).
Topics: Adult; Anti-Ulcer Agents; Cross-Over Studies; Cytochrome P-450 CYP2C19; Dietary Fats; Fasting; Female; Food-Drug Interactions; Genotype; Humans; Male; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Young Adult
PubMed: 32711578
DOI: 10.1186/s40360-020-00433-2 -
The Korean Journal of Gastroenterology... Feb 2019Dyspepsia is a common problem, and when dyspeptic symptoms develop within a short period of time, organic diseases such as gastroesophageal reflux disease, peptic ulcer... (Review)
Review
Dyspepsia is a common problem, and when dyspeptic symptoms develop within a short period of time, organic diseases such as gastroesophageal reflux disease, peptic ulcer diseases, pancreatoduodenal diseases, and gastrointestinal cancers should be suspected. Furthermore, functional dyspepsia (FD) should be considered if chronic or recurrent symptoms persist after eliminating underlying disease. FD is classified as epigastric pain syndrome (EPS) or postprandial distress syndrome (PDS), but these two conditions may overlap. Patients with the EPS subtype can be treated with proton pump inhibitors (PPIs), whereas patients with the PDS subtype may be managed primarily with prokinetics, and patients with EPS and PDS can be co-administered PPIs and prokinetics. eradication therapy can be administered on a test-and-treat basis when PPIs and prokinetics are ineffective or to younger patients with chronic dyspepsia, and tricyclic antidepressants can be used as a secondary treatment because they are effective in patients with the EPS subtype. In addition, because the pathophysiology of FD is diverse, dietary education and stress management are required in addition to medical therapy, and should substantially aid treatment and long-term management. Here, we introduce and summarize recently published guidelines for the treatment of FD.
Topics: Anti-Anxiety Agents; Anti-Bacterial Agents; Anti-Ulcer Agents; Antipsychotic Agents; Dyspepsia; Guidelines as Topic; Helicobacter Infections; Humans; Life Style; Proton Pump Inhibitors
PubMed: 30845383
DOI: 10.4166/kjg.2019.73.2.77 -
Alimentary Pharmacology & Therapeutics Sep 2020Tegoprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tegoprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders.
AIMS
To assess whether tegoprazan is non-inferior to lansoprazole in terms of efficacy and safety in patients with gastric ulcers.
METHODS
In this phase 3, double-blind, active control, multicentre study, 306 gastric ulcer patients were randomised to one of three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg once daily for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed ulcers confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms and safety were assessed.
RESULTS
In the full analysis set, the cumulative healing rates at week 8 were 94.8% (91/96) for the tegoprazan 50 mg, 95.0% (94/99) for the tegoprazan 100 mg and 95.7% (89/93) for the lansoprazole 30 mg groups. At week 4, the respective healing rates were 90.6% (87/96), 91.9% (91/99), and 89.2% (83/93). In per protocol analysis, 4-week healing rates were 95.4% (84/88), 94.6% (88/93) and 92.9% (79/85) for tegoprazan 50 mg, tegoprazan 100 mg and lansoprazole 30 mg, respectively. Both doses of tegoprazan were non-inferior to lansoprazole in ulcer healing at 4 and 8 weeks. The incidence of drug-related treatment-emergent adverse events did not differ among groups. The increase in serum gastrin concentration was not higher in tegoprazan-treated patients than in lansoprazole-treated patients.
CONCLUSIONS
Tegoprazan 50 or 100 mg were not inferior to lansoprazole 30 mg once daily in the treatment of gastric ulcers.
Topics: Adult; Aged; Anti-Ulcer Agents; Benzene Derivatives; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Imidazoles; Lansoprazole; Male; Middle Aged; Potassium; Proton Pump Inhibitors; Republic of Korea; Stomach Ulcer; Treatment Outcome; Wound Healing
PubMed: 32701188
DOI: 10.1111/apt.15865 -
The Lancet. Gastroenterology &... Apr 2018Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs.
METHODS
We searched MEDLINE and Embase from Jan 1, 1950, to Dec 31, 2015, to identify unconfounded, randomised trials of a gastroprotectant drug (defined as a PPI, prostaglandin analogue, or H2RA) versus control, or versus another gastroprotectant. Two independent researchers reviewed the search results and extracted the prespecified outcomes and key characteristics for each trial. We did meta-analyses of the effects of gastroprotectant drugs on ulcer development, bleeding, and mortality overall, according to the class of gastroprotectant, and according to the individual drug within a gastroprotectant class.
FINDINGS
We identified comparisons of gastroprotectant versus control in 849 trials (142 485 participants): 580 prevention trials (110 626 participants), 233 healing trials (24 033 participants), and 36 trials for the treatment of acute upper gastrointestinal bleeding (7826 participants). Comparisons of one gastroprotectant drug versus another were available in 345 trials (64 905 participants), comprising 160 prevention trials (32 959 participants), 167 healing trials (28 306 participants), and 18 trials for treatment of acute upper gastrointestinal bleeding (3640 participants). The median number of patients in each trial was 78 (IQR 44·0-210·5) and the median duration was 1·4 months (0·9-2·8). In prevention trials, gastroprotectant drugs reduced development of endoscopic ulcers (odds ratio [OR] 0·27, 95% CI 0·25-0·29; p<0·0001), symptomatic ulcers (0·25, 0·22-0·29; p<0·0001), and upper gastrointestinal bleeding (0·40, 0·32-0·50; p<0·0001), but did not significantly reduce mortality (0·85, 0·69-1·04; p=0·11). Larger proportional reductions in upper gastrointestinal bleeding were observed for PPIs than for other gastroprotectant drugs (PPIs 0·21, 99% CI 0·12-0·36; prostaglandin analogues 0·63, 0·35-1·12; H2RAs 0·49, 0·30-0·80; p=0·0005). Gastroprotectant drugs were effective in preventing bleeding irrespective of the use of non-steroidal anti-inflammatory drugs (p=0·56). In healing trials, gastroprotectants increased endoscopic ulcer healing (3·49, 95% CI 3·28-3·72; p<0·0001), with PPIs more effective (5·22, 99% CI 4·00-6·80) than prostaglandin analogues (2·27, 1·91-2·70) and H2RAs (3·80, 3·44-4·20; p<0·0001). In trials among patients with acute bleeding, gastroprotectants reduced further bleeding (OR 0·68, 95% CI 0·60-0·78; p<0·0001), blood transfusion (0·75, 0·65-0·88; p=0·0003), further endoscopic intervention (0·56, 0·45-0·70; p<0·0001), and surgery (0·72, 0·61-0·84; p<0·0001), but did not significantly reduce mortality (OR 0·90, 0·72-1·11; p=0·31). PPIs had larger protective effects than did H2RAs for further bleeding (p=0·0107) and blood transfusion (p=0·0130).
INTERPRETATION
Gastroprotectants, in particular PPIs, reduce the risk of peptic ulcer disease and its complications and promote healing of peptic ulcers in a wide range of clinical circumstances. However, this meta-analysis might have overestimated the benefits owing to small study bias.
FUNDING
UK Medical Research Council and the British Heart Foundation.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Histamine H2 Antagonists; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Prostaglandins, Synthetic; Proton Pump Inhibitors; Secondary Prevention
PubMed: 29475806
DOI: 10.1016/S2468-1253(18)30037-2 -
Alimentary Pharmacology & Therapeutics Apr 2019Tegoprazan is a novel potassium-competitive acid blocker that has a fast onset of action and can control gastric pH for a prolonged period, which could offer clinical... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Tegoprazan is a novel potassium-competitive acid blocker that has a fast onset of action and can control gastric pH for a prolonged period, which could offer clinical benefit in acid-related disorders.
AIM
To confirm the non-inferiority of tegoprazan to esomeprazole in patients with erosive oesophagitis (EE).
METHODS
In this multicentre, randomised, double-blind, parallel-group comparison study, 302 Korean patients with endoscopically confirmed EE (Los Angeles Classification Grades A-D) were randomly allocated to either tegoprazan (50 or 100 mg) or esomeprazole (40 mg) treatment groups for 4 or 8 weeks. The primary endpoint was the cumulative proportion of patients with healed EE confirmed by endoscopy up to 8 weeks from treatment initiation. Symptoms, safety and tolerability were also assessed.
RESULTS
The cumulative healing rates at week 8 were 98.9% (91/92), 98.9% (90/91) and 98.9% (87/88) for tegoprazan 50 mg, tegoprazan 100 mg and esomeprazole 40 mg, respectively. Both doses of tegoprazan were non-inferior to esomeprazole 40 mg. The incidence of adverse events was comparable among the groups, and tegoprazan was well-tolerated.
CONCLUSION
Once daily administration of tegoprazan 50 or 100 mg showed non-inferior efficacy in healing EE and tolerability to that of esomeprazole 40 mg.
Topics: Adult; Aged; Anti-Ulcer Agents; Benzene Derivatives; Double-Blind Method; Esomeprazole; Esophagitis; Female; Humans; Imidazoles; Male; Middle Aged; Potassium; Proton Pump Inhibitors; Treatment Outcome; Wound Healing; Young Adult
PubMed: 30843245
DOI: 10.1111/apt.15185