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Therapie 2021The long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria and in some cases to achlorhydria when compared to other... (Meta-Analysis)
Meta-Analysis Review
The long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria and in some cases to achlorhydria when compared to other acid-suppressing agents like histamine-2 (H2) receptor blockers and antacids. These consequences by the use of long-term PPIs may lead to significant vitamin (B and C) and mineral (iron, calcium and magnesium) deficiencies which needs gastric acid for their absorption and bioavailability. Long-term use of PPIs by the pregnant patients may impose a potential risk of congenital malformations. Various studies have recommended the life style modifications and antacid use as first choice among pregnant womens by preserving PPIs (omeprazole as a safe choice of PPI) for severe conditions of gastroesophageal reflux disease. The long-term acid suppression by PPIs can also lead to enteric, respiratory and urinary tract infections. The hypochlorhydria by chronic PPIs use may induce hypergastrinemia, which ultimately mediates the gastric polyps, gastric carcinoids and gastric cancer. The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose the patients to major adverse cardiac events. This review has enlisted the comprehensive information regarding the adverse effects induced by long-term use of PPIs and their possible relations. Considerable studies like case-control, randomized trials, cohort studies and meta-analysis were reported in supporting these adverse effects. The clinicians and patients should be cautious about these effects so that they can avoid the serious outcomes. PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication.
Topics: Aged; Anti-Ulcer Agents; Female; Gastric Acid; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Risk Factors
PubMed: 32718584
DOI: 10.1016/j.therap.2020.06.019 -
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 -
Annual Review of Medicine Jan 2021Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of... (Review)
Review
Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.
Topics: Anti-Ulcer Agents; Colitis, Ulcerative; Fecal Microbiota Transplantation; Humans; Hyperbaric Oxygenation; Immunologic Factors; Janus Kinase Inhibitors; Sphingosine 1 Phosphate Receptor Modulators
PubMed: 33502898
DOI: 10.1146/annurev-med-052919-120048 -
Drugs Jan 2021Historically, there has been a scarcity of evidence-based topical therapy to hasten the healing of diabetic foot ulcers. But recently new evidence-based treatments have... (Review)
Review
Historically, there has been a scarcity of evidence-based topical therapy to hasten the healing of diabetic foot ulcers. But recently new evidence-based treatments have emerged from multicentre, randomised, controlled trials. This article highlights those trials, and describes the current pharmacological management of the diabetic foot ulcer and the advances that have been made in wound therapy to date. It provides an overview of topical and systemic pharmacotherapies in current use and those in development for future use in managing the diabetic foot. For each treatment, proposed mechanisms of action and evidence available to support their clinical use are presented. There is supporting randomised, controlled evidence for sucrose octasulfate in the treatment of neuro-ischaemic ulcers, and multi-layered patch of autologous leucocytes, platelets and fibrin in ulcers with or without ischaemia. There is also evidence for placentally derived products and for topical and systemic oxygen therapy in the healing of diabetic foot ulcers. Growth factors, bio-engineered tissues, stem cell therapy, gene therapy and peptide therapy also have some supporting evidence in the healing of diabetic foot ulcers. Nonsurgical debriding agents may be useful when the optimum approach of sharp debridement is not possible, and immunomodulators may be helpful for their antimicrobial effects, but robust data is still required to strengthen the case for general use. The review does not cover antimicrobials as their primary role are as anti-infectives and not in wound healing. The development of nanotechnology has created a means of prolonging the bioavailability of target molecules at the wound site, with the use of glass/hydrogel nanoparticles, polyethylene glycol and hyaluronic acid. Looking forward, novel therapies, including traction force-activated payloads, local delivery of short-interfering RNA and finally hydrogels incorporating bioactive agents or cells may provide possibilities for pharmacotherapy in the future.
Topics: Anti-Ulcer Agents; Diabetes Mellitus; Diabetic Foot; Humans; Hypoglycemic Agents; Wound Healing
PubMed: 33382445
DOI: 10.1007/s40265-020-01415-8 -
Digestive Diseases and Sciences Jul 2020As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide.... (Review)
Review
As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.
Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Antigens, Bacterial; Biopsy; Bismuth; Breath Tests; Clarithromycin; Culture Techniques; Doxycycline; Drug Resistance, Bacterial; Drug Therapy, Combination; Dyspepsia; Feces; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Lymphoma, B-Cell, Marginal Zone; Metronidazole; Nitro Compounds; Organometallic Compounds; Peptic Ulcer; Polymerase Chain Reaction; Proton Pump Inhibitors; Rifabutin; Salicylates; Salvage Therapy; Serologic Tests; Stomach Neoplasms; Tetracycline; Thiazoles; Treatment Outcome; Urea
PubMed: 32170476
DOI: 10.1007/s10620-020-06193-7 -
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 -
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 -
JAMA Oct 2022In arthroscopic knee and shoulder surgery, there is growing evidence that opioid-sparing protocols may reduce postoperative opioid consumption while adequately... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of a Postoperative Multimodal Opioid-Sparing Protocol vs Standard Opioid Prescribing on Postoperative Opioid Consumption After Knee or Shoulder Arthroscopy: A Randomized Clinical Trial.
IMPORTANCE
In arthroscopic knee and shoulder surgery, there is growing evidence that opioid-sparing protocols may reduce postoperative opioid consumption while adequately addressing patients' pain. However, there are a lack of prospective, comparative trials evaluating their effectiveness.
OBJECTIVE
To evaluate the effect of a multimodal, opioid-sparing approach to postoperative pain management compared with the current standard of care in patients undergoing arthroscopic shoulder or knee surgery.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial was performed at 3 clinical sites in Ontario, Canada, and enrolled 200 patients from March 2021 to March 2022 with final follow-up completed in April 2022. Adult patients undergoing outpatient arthroscopic shoulder or knee surgery were followed up for 6 weeks postoperatively.
INTERVENTIONS
The opioid-sparing group (100 participants randomized) received a prescription of naproxen, acetaminophen (paracetamol), and pantoprazole; a limited rescue prescription of hydromorphone; and a patient educational infographic. The control group (100 participants randomized) received the current standard of care determined by the treating surgeon, which consisted of an opioid analgesic.
MAIN OUTCOMES AND MEASURES
The primary outcome was postoperative oral morphine equivalent (OME) consumption at 6 weeks after surgery. There were 5 secondary outcomes, including pain, patient satisfaction, opioid refills, quantity of OMEs prescribed at the time of hospital discharge, and adverse events at 6 weeks all reported at 6 weeks after surgery.
RESULTS
Among the 200 patients who were randomized (mean age, 43 years; 73 women [38%]), 193 patients (97%) completed the trial; 98 of whom were randomized to receive standard care and 95 the opioid-sparing protocol. Patients in the opioid-sparing protocol consumed significantly fewer opioids (median, 0 mg; IQR, 0-8.0 mg) than patients in the control group (median, 40.0 mg; IQR, 7.5-105.0; z = -6.55; P < .001). Of the 5 prespecified secondary end points, 4 showed no significant difference. The mean amount of OMEs prescribed was 341.2 mg (95% CI, 310.2-372.2) in the standard care group and 40.4 mg (95% CI, 39.6-41.2) in the opioid-sparing group (mean difference, 300.8 mg; 95% CI, 269.4-332.3; P < .001). There was no significant difference in adverse events at 6 weeks (2 events [2.1%] in the standard care group vs 3 events [3.2%] in the opioid-sparing group), but more patients reported medication-related adverse effects in the standard care group (32% vs 19%, P = .048).
CONCLUSIONS AND RELEVANCE
Among patients who underwent arthroscopic knee or shoulder surgery, a multimodal opioid-sparing postoperative pain management protocol, compared with standard opioid prescribing, significantly reduced postoperative opioid consumption over 6 weeks.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04566250.
Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Ulcer Agents; Arthroscopy; Clinical Protocols; Drug Therapy, Combination; Female; Humans; Hydromorphone; Knee Joint; Male; Naproxen; Ontario; Pain, Postoperative; Pantoprazole; Patient Education as Topic; Postoperative Care; Shoulder Joint
PubMed: 36194219
DOI: 10.1001/jama.2022.16844 -
The American Journal of Gastroenterology Nov 2023In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are... (Randomized Controlled Trial)
Randomized Controlled Trial
Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.
INTRODUCTION
In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure.
METHODS
In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed.
RESULTS
A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm.
DISCUSSION
Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).
Topics: Humans; Omeprazole; Heartburn; Anti-Ulcer Agents; Esophagitis; Proton Pump Inhibitors; Dyspepsia; Peptic Ulcer; Abdominal Pain; Treatment Outcome; Double-Blind Method
PubMed: 37307528
DOI: 10.14309/ajg.0000000000002360