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The Medical Letter on Drugs and... May 2022
Topics: Dexlansoprazole; Esomeprazole; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors
PubMed: 35536912
DOI: No ID Found -
The Medical Letter on Drugs and... Apr 2022
Topics: Histamine H2 Antagonists; Humans; Proton Pump Inhibitors
PubMed: 35348553
DOI: No ID Found -
The Medical Letter on Drugs and... Apr 2022
Topics: Gastroesophageal Reflux; Helicobacter Infections; Humans; Peptic Ulcer
PubMed: 35348552
DOI: No ID Found -
Frontiers in Cardiovascular Medicine 2022Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of...
BACKGROUND
Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.
METHODS
This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.
RESULTS
In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC/ROR = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC/ROR = 0.01/1.08) to renal haemangioma (IC/ROR = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC/ROR = 0.07/1.28) to hypertensive nephropathy (IC/ROR = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.
CONCLUSIONS
PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.
PubMed: 35282344
DOI: 10.3389/fcvm.2022.767987 -
The Cochrane Database of Systematic... Jan 2022Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to... (Review)
Review
BACKGROUND
Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.
OBJECTIVES
To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (HRA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
Topics: Acute Disease; Endoscopy; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors
PubMed: 34995368
DOI: 10.1002/14651858.CD005415.pub4 -
Electrophoresis Sep 2021Proton pump inhibitors (PPIs) are benzimidazole-derivative chiral sulfoxides, frequently used in the treatment of gastric hyperacidity-related disorders. Due to their... (Review)
Review
Proton pump inhibitors (PPIs) are benzimidazole-derivative chiral sulfoxides, frequently used in the treatment of gastric hyperacidity-related disorders. Due to their stereoselective metabolism, the eutomeric forms of PPIs can present a more advantageous pharmacokinetic profile by comparison with the distomers or racemates. Moreover, two representatives of the class are used in therapy both as racemates and as pure enantiomers (esomeprazole, dexlansoprazole). A relatively large number of enantioseparation methods employed for the stereoselective determination of PPIs from pharmaceutical, biological, and environmental matrices were published in the past three decades. The purpose of the current overview is to provide a systematic survey of the available chiral separation methods published since the introduction of PPIs in the therapy up to the present. Analytical and bioanalytical methods using different chromatographic and electromigration techniques reported for the enantioseparation of omeprazole, lansoprazole, pantoprazole, rabeprazole, ilaprazole, and tenatoprazole are included. The analytical conditions of the presented methods are summarized in three comprehensive tables, while a critical discussion of the applied techniques, possible mechanism of enantiorecognition, and future perspectives on the topic are also presented.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Electrophoresis; Esomeprazole; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole
PubMed: 34004039
DOI: 10.1002/elps.202100032 -
Applied Microbiology and Biotechnology Apr 2021Biocatalytic synthesis of pharmaco-chiral sulfoxides has gained interest in recent years for its environmental friendliness. However, only a few natural biocatalysts can...
Biocatalytic synthesis of pharmaco-chiral sulfoxides has gained interest in recent years for its environmental friendliness. However, only a few natural biocatalysts can be used for the efficient synthesis of pharmaco-sulfoxides, including (R)-lansoprazole, a chiral proton pump inhibitor used to treat gastrointestinal diseases. In this study, the sequence of BoBVMO (Baeyer-Villiger monooxygenase from Bradyrhizobium oligotrophicum) was used as a probe to identify BVMOs via genomic mining for the highly efficient synthesis of (R)-lansoprazole and other pharmaco-sulfoxides. After virtual sequence filtering, target gene cloning, heterologous expression, and activity screening for lansoprazole sulfide (LPS) monooxygenation, seven new BVMOs were identified among more than 10,000 homologous BVMOs. According to the conserved sequence and phylogenetic tree analysis, these discovered enzymes belong to the family of type I BVMOs and the ethionamide monooxygenase subtype. Among them, CbBVMO, Baeyer-Villiger monooxygenase from Cupriavidus basilensis, showed the highest efficiency and excellent enantioselectivity for converting LPS into (R)-lansoprazole. Moreover, CbBVMO showed a wide substrate spectrum toward other bulky prazole-family sulfides. The results indicate that CbBVMO is a potential enzyme for extending the application of BVMOs in pharmaceutical industry. KEY POINTS: • CbBVMO is the most efficient biocatalyst for (R)-lansoprazole biosynthesis. • CbBVMO catalyzes the conversion of various bulky prazole sulfides. • CbBVMO is a promising enzyme for the biosynthesis of pharmaco-sulfoxides.
Topics: Bradyrhizobium; Cupriavidus; Dexlansoprazole; Mixed Function Oxygenases; Oxidation-Reduction; Phylogeny; Substrate Specificity; Sulfoxides
PubMed: 33779786
DOI: 10.1007/s00253-021-11230-0 -
Luminescence : the Journal of... Aug 2021New spectroscopic methods were developed for dexlansoprazole estimation in capsule formulation based on the formation of a reaction between dexlansoprazole and...
New spectroscopic methods were developed for dexlansoprazole estimation in capsule formulation based on the formation of a reaction between dexlansoprazole and Mercurochrome (MER) at pH 3.7. The formed complex was measured spectrophotometrically (Method I) at 557 nm and spectrofluorometrically (Method II) at 300 nm/538 nm, because the drug caused quantitative quenching of the native fluorescence of Mercurochrome. The spectrophotometric method was linear over the concentration 25-55 μg/ml with a limit of detection (LOD) of 1.15 μg/ml and a limit of quantification (LOQ) of 3.48 μg/ml. The spectrofluorometric method had a linear range 20-45 μg/ml with an LOD of 1.13 μg/ml and an LOQ of 3.45 μg/ml. The suggested methods were used to analyze capsules to test the interference from excipients and the data indicated good selectivity. Data obtained were statistically analyzed and were favourably good. The new methods are environmentally benign and depend on distilled water mainly as the diluting solvent. This property was confirmed by assessing their greenness.
Topics: Dexlansoprazole; Merbromin; Solvents; Spectrometry, Fluorescence; Spectrophotometry
PubMed: 33724687
DOI: 10.1002/bio.4043 -
Frontiers in Medicine 2021Non-cardiac chest pain is common with two-thirds due to gastroesophageal reflux disease (GERD). To evaluate the effectiveness and safety of guided vs. empirical...
Non-cardiac chest pain is common with two-thirds due to gastroesophageal reflux disease (GERD). To evaluate the effectiveness and safety of guided vs. empirical therapy in non-cardiac chest pain. Adults with normal angiogram or stress test were randomized into either a guided or empirical group. In the guided group, after the ambulatory pH-impedance test, if GERD then dexlansoprazole 30 mg/day for 8 weeks, but if functional or hypersensitive chest pain, then theophylline SR 250 mg/day for 4 weeks. In the empirical group, dexlansoprazole 60 mg/day was given for 2 weeks. The primary outcome was global chest pain visual analog score (VAS) and secondary outcomes were Quality of Life in Reflux and Dyspepsia (QOLRAD), GERD questionnaire (GERDQ), and pH parameters, all determined at baseline, 2nd and 8th weeks. Of 200 screened patients, 132 were excluded, and of 68 randomized per-protocol, 33 were in the guided group and 35 in the empirical group. For between-group analysis, mean global pain scores were better with guided vs. empirical group at 8th week ( = 0.005) but not GERDQ or QOLRAD or any of pH measures (all > 0.05). For within-group analysis, mean QOLRAD improved earliest at 8th week vs. baseline ( = 0.006) in the guided group and 2nd week vs. baseline ( = 0.011) in the empirical group but no differences were seen in other secondary outcomes ( > 0.05). No serious adverse events were reported. Guided approach may be preferred over short-term empirical therapy in symptom response, however QOLRAD, acid-related symptoms, or pH measures are not significantly different (trial registration ID no. NCT03319121).
PubMed: 33659261
DOI: 10.3389/fmed.2021.605647