-
Clinical Nephrology. Case Studies 2024Drug-induced hypomagnesemia is an adverse effect with the potential for serious and fatal outcomes. Although rare, chronic use of proton pump inhibitors (PPIs) can cause...
Drug-induced hypomagnesemia is an adverse effect with the potential for serious and fatal outcomes. Although rare, chronic use of proton pump inhibitors (PPIs) can cause hypomagnesemia due to impaired intestinal absorption, mainly attributed to reduced transcellular transport of magnesium via transient receptor potential melastatin 6 (TRPM6) and 7 (TRPM7) channels. However, a reduction of magnesium paracellular absorption due to the downregulation of intestinal claudins has also been reported. PPI-induced hypomagnesemia can trigger other concomitant electrolyte derangements, including hypokalemia, hypocalcemia, hypophosphatemia, and hyponatremia. Here we report two cases of multiple electrolyte disorders associated with PPI-induced hypomagnesemia, the clinical manifestations of which were cardiac arrhythmia, cognitive changes, and seizure crisis. These cases illustrate the need to monitor serum magnesium levels in patients on long-term PPI use, especially in the elderly and those with malabsorptive bowel syndromes or taking loop diuretics and thiazides.
PubMed: 38222324
DOI: 10.5414/CNCS111284 -
The Journal of Biological Chemistry Aug 2023Cytochrome P450 CYP102A1 is a prototypic biocatalyst that has great potential in chemical synthesis, drug discovery, and biotechnology. CYP102A1 variants engineered by...
Cytochrome P450 CYP102A1 is a prototypic biocatalyst that has great potential in chemical synthesis, drug discovery, and biotechnology. CYP102A1 variants engineered by directed evolution and/or rational design are capable of catalyzing the oxidation of a wide range of organic compounds. However, it is difficult to foresee the outcome of engineering CYP102A1 for a compound of interest. Here, we introduce UniDesign as a computational framework for enzyme design and engineering. We tested UniDesign by redesigning CYP102A1 for stereoselective metabolism of omeprazole (OMP), a proton pump inhibitor, starting from an active but nonstereoselective triple mutant (TM: A82F/F87V/L188Q). To shift stereoselectivity toward (R)-OMP, we computationally scanned three active site positions (75, 264, and 328) for mutations that would stabilize the binding of the transition state of (R)-OMP while destabilizing that of (S)-OMP and picked three variants, namely UD1 (TM/L75I), UD2 (TM/A264G), and UD3 (TM/A328V), for experimentation, based on computed energy scores and models. UD1, UD2, and UD3 exhibit high turnover rates of 55 ± 4.7, 84 ± 4.8, and 79 ± 5.7 min, respectively, for (R)-OMP hydroxylation, whereas the corresponding rates for (S)-OMP are only 2.2 ± 0.19, 6.0 ± 0.68, and 14 ± 2.8 min, yielding an enantiomeric excess value of 92, 87, and 70%, respectively. These results suggest the critical roles of L75I, A264G, and A328V in steering OMP in the optimal orientation for stereoselective oxidation and demonstrate the utility of UniDesign for engineering CYP102A1 to produce drug metabolites of interest. The results are discussed in the context of protein structures.
Topics: Bacterial Proteins; Cytochrome P-450 Enzyme System; Hydroxylation; NADPH-Ferrihemoprotein Reductase; Omeprazole; Oxidation-Reduction; Protein Engineering
PubMed: 37451479
DOI: 10.1016/j.jbc.2023.105050 -
Gels (Basel, Switzerland) Jan 2024Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless,... (Review)
Review
Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless, conventional dosage forms often lead to low therapeutic efficacy, safety issues, and patient noncompliance. To tackle these issues, novel topical and transdermal platforms involving nanotechnology have been developed. This review focuses on the latest advances regarding the development of nanoemulgels for skin application, encapsulating a wide variety of molecules, including already marketed drugs (miconazole, ketoconazole, fusidic acid, imiquimod, meloxicam), repurposed marketed drugs (atorvastatin, omeprazole, leflunomide), natural-derived compounds (eucalyptol, naringenin, thymoquinone, curcumin, chrysin, brucine, capsaicin), and other synthetic molecules (ebselen, tocotrienols, retinyl palmitate), for wound healing, skin and skin appendage infections, skin inflammatory diseases, skin cancer, neuropathy, or anti-aging purposes. Developed formulations revealed adequate droplet size, PDI, viscosity, spreadability, pH, stability, drug release, and drug permeation and/or retention capacity, having more advantageous characteristics than current marketed formulations. In vitro and/or in vivo studies established the safety and efficacy of the developed formulations, confirming their therapeutic potential, and making them promising platforms for the replacement of current therapies, or as possible adjuvant treatments, which might someday effectively reach the market to help fight highly incident skin or systemic diseases and conditions.
PubMed: 38247768
DOI: 10.3390/gels10010045 -
European Review For Medical and... Nov 2023Peptic ulcer (PU) and hypertension are chronic diseases affecting up to 10% and 30% of the adult population worldwide. Most of these patients will require treatment with...
Assessing the hypolipidemic and gastro-liver protective activity of herbal combination with emphasis on PPI amid selected multiple antihypertensive drug combination in experimental animal models.
OBJECTIVE
Peptic ulcer (PU) and hypertension are chronic diseases affecting up to 10% and 30% of the adult population worldwide. Most of these patients will require treatment with a combination of antihypertensive medicines, which have adverse effects on the body's different organs. This study specifically focused on antihypertensive multi-drug induced PU disease and disturbance of liver function.
MATERIALS AND METHODS
During a 14-day oral administration of antihypertensive drugs, Cilnidipine (1 mg/kg), Rosuvastatin (1 mg/kg), Bisoprolol (0.52 mg/kg), and Clopidogrel (7.81 mg/kg) were observed for their effects on the stomach lining and liver function in Wister albino rats. This study aimed to assess the potential of an herbal combination of (BO) + (BA) + (ZO) 0.26 mg/kg body weight (b.w.) Powder and water mixture on the ulcer, lipid profile, and liver function for 14 days in the treatment of the indomethacin-induced gastric ulcers in rats at doses of 30 mg/kg b.w. for three days. Esomeprazole (20 mg/kg b.w.) is used as a standard reference to evaluate antiulcer activity in rat models. The experiment suggests that the gastroprotective effect of the herbal combination can be attributed to its reducing effect on the peptic and the Serum Glutamic Pyruvic Transaminase (SGPT) levels and within the normal range of 34.67 ± 0.88 IU/L.
RESULTS
The results for Total Cholesterol (TC), Triglyceride (TG), High-density lipoprotein (HDL) and Low-density lipoprotein (LDL) of the herbal combination were 52 ± 9.81495 (mg/dl), 70 ± 12.12435 (mg/dl), 23.33 ± 6.06446 (mg/dl), 14.5 ± 1.32790 (mg/dl), respectively, where the standard group (atorvastatin) 5 mg/kg TC, TG, HDL and LDL were 69.77 ± 9.92 (mg/dl), 47.7 ± 10.35 (mg/dl), 33.43 ± 5.70 (mg/dl), 26.8 ± 3.70 (mg/dl), and control group total cholesterol, triglyceride, HDL and LDL were 68.67 ± 2.20 (mg/dl), 124.07 ± 2.94 (mg/dl), 49.14 ± 1.05 (mg/dl), 54.11 ± 1.15 (mg/dl).
CONCLUSIONS
CThis investigation reported that antihypertensive drugs did not produce gastrointestinal (GI) toxicity, and the morphological structure of the organ was not changed. So, it could be concluded that the herbal combination used in this experiment has a promising role in controlling lipid profile, liver function, and antiulcer effects. Moreover, multiple drug therapy for hypertension does not cause any harm to the stomach. Further investigations might be carried out on a larger scale to make these statements more valid.
Topics: Humans; Adult; Rats; Animals; Antihypertensive Agents; Cholesterol, LDL; Rats, Wistar; Liver; Triglycerides; Stomach; Hypertension; Models, Animal; Cholesterol, HDL
PubMed: 38039033
DOI: 10.26355/eurrev_202311_34471 -
Gut and Liver Jan 2024H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis.
METHODS
A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared.
RESULTS
According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different.
CONCLUSIONS
DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).
Topics: Humans; Famotidine; Histamine H2 Antagonists; Gastritis; Proton Pump Inhibitors; Double-Blind Method
PubMed: 37309193
DOI: 10.5009/gnl220446 -
JPMA. the Journal of the Pakistan... Mar 2024To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. (Randomized Controlled Trial)
Randomized Controlled Trial
Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.
OBJECTIVE
To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection.
METHODS
The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27.
RESULTS
Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B.
CONCLUSIONS
Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration.
CLINICAL TRIAL NUMBER
Iranian Registry of Clinical Trials: IRCT20221207056738N1.
Topics: Male; Female; Humans; Adult; Middle Aged; Helicobacter Infections; Esomeprazole; Levofloxacin; Anti-Bacterial Agents; Helicobacter pylori; Pakistan; Iran; Amoxicillin; Drug Therapy, Combination; Treatment Outcome; Clarithromycin; Proton Pump Inhibitors; Pyrroles; Sulfonamides
PubMed: 38591272
DOI: 10.47391/JPMA.9545 -
Food Technology and Biotechnology Dec 2023The role of dietary habits of patients with laryngopharyngeal reflux (LPR) is comparatively underexplored. The aim of the study is to examine dietary habits, onset and...
RESEARCH BACKGROUND
The role of dietary habits of patients with laryngopharyngeal reflux (LPR) is comparatively underexplored. The aim of the study is to examine dietary habits, onset and course of the disease as well as the quality of life of patients with LPR.
EXPERIMENTAL APPROACH
The results of the modified food frequency questionnaire (FFQ-m) and laryngopharyngeal reflux health-related quality of life (LPR-HRQL) questionnaires were compared between subjects with and without LPR. There were a total of 100 subjects with LPR and 65 subjects in the control group. The group of subjects with LPR was further randomly divided into two subgroups; the first subgroup was treated with esomeprazole at a dose of 20 mg twice daily combined with the instructions for dietary and general lifestyle changes, and the other with pantoprazole at a dose of 20 mg twice daily combined with the instructions for dietary and general lifestyle changes. Participants were instructed to fill out FFQ-m and LPR-HRQL questionnaires immediately after the initial examination and then after control examinations 30 and 60 days after the initial examination.
RESULTS AND CONCLUSIONS
Patients with LPR consume more food with high reflux potential, drink more carbonated drinks and juices and have a worse quality of life than the control group (p<0.001). Taking proton pump inhibitors at a dose of 20 mg twice daily in combination with a change in dietary habits such as substituting acidic, spicy, fermented, sweet, fried foods and other foods with a high reflux potential as well as carbonated drinks and juices with the food with a low reflux potential and water significantly reduced the symptoms of LPR and increased the quality of life of the patients (p<0.001).
NOVELTY AND SCIENTIFIC CONTRIBUTION
This is the first study showing the correlation between dietary habits and the quality of life of patients with LPR. The contribution of this research is an objective assessment of the follow-up of patients with LPR that could be used in their regular assessment.
PubMed: 38205049
DOI: 10.17113/ftb.61.04.23.8222 -
Obesity Surgery Apr 2024To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile...
PURPOSE
To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS).
METHODS
Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated.
RESULTS
HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (-14.6 ± 27.5 mg/dL HP-treated vs -22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (-13.7 ± 29.4 mg/dL HP-treated vs -26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023).
CONCLUSIONS
Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS.
Topics: Humans; Helicobacter pylori; Retrospective Studies; Prospective Studies; Obesity, Morbid; Helicobacter Infections; Amoxicillin; Clarithromycin; Omeprazole; Metronidazole; Bariatric Surgery; Weight Loss; Drug Therapy, Combination; Anti-Bacterial Agents
PubMed: 38400943
DOI: 10.1007/s11695-024-07091-x -
Veterinary Medicine and Science Nov 2023Fungal and yeast infections, including those caused by Malassezia spp., are becoming increasingly difficult to treat, likely due to the occurrence of drug resistance.
BACKGROUND
Fungal and yeast infections, including those caused by Malassezia spp., are becoming increasingly difficult to treat, likely due to the occurrence of drug resistance.
OBJECTIVES
This study aimed to evaluate the antifungal effects of omeprazole (OME), a proton pump inhibitor, against antifungal-resistant Malassezia pachydermatis and to investigate the potential synergistic effects between OME and other antifungal compounds.
METHODS
In total, 15 samples of M. pachydermatis isolated from the skin of dogs were tested. The susceptibility of M. pachydermatis to itraconazole, ketoconazole, miconazole, terbinafine and OME was assessed using a modified broth microdilution (BM) method. The in vitro efficacy of OME alone and in combination with other antifungal compounds was evaluated for all isolates using the BM chequerboard method. The data obtained were analysed using the fractional inhibitory concentration index (FICI).
RESULTS
The minimum inhibitory concentration (MIC) values of antifungal compounds and OME against quality control strain (M. pachydermatis CBS1879) were lower than the MIC values of same drugs against clinically collected strains. There was no significant difference in MIC values between drugs alone and combination. According to the analysis by the FICI method, no interaction was observed with OME and antifungal compounds.
CONCLUSIONS
Most M. pachydermatis strains were resistant to azole antifungal compounds. OME exerted antifungal effects against Malassezia spp. and even showed good effects on antifungal-resistant strains. No synergistic effects were observed between the antifungal compounds and OME.
Topics: Animals; Dogs; Antifungal Agents; Malassezia; Omeprazole; Drug Resistance, Fungal
PubMed: 37872836
DOI: 10.1002/vms3.1305 -
Allergy, Asthma & Immunology Research Mar 2024Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid...
Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs) have more potent and durable effects on anti-acid secretion. However, whether vonoprazan and esomeprazole have different therapeutic effects on GERC remains unknown. Patients diagnosed with GERC were enrolled in our study and randomly treated with vonoprazan (20 mg, once daily, P-CAB) or esomeprazole (20 mg, twice daily, PPI) for two months. A prokinetic agent was also administered. Patients were followed up once a month. Cough severity visual analogue scale (VAS) was measured as the primary outcome, while cough symptom score (CSS) and scores for cough-related quality-of-life or reflux-related symptoms were the secondary endpoints. A total of 50 patients completed the study, with 25 patients in each group. P-CAB and PPI groups showed similar decreases in cough severity VAS and CSS scores after the 2-month treatment (all < 0.001). For quality-of-life, the Leicester Cough Questionnaire (LCQ) score increased significantly from baseline in both groups, but the P-CAB group had greater improvement and a higher LCQ score in month 2 (all ≤ 0.05). For reflux-related symptoms, the Hull Airway Reflux Questionnaire (HARQ) score declined substantially over time in the P-CAB group, while the reflux symptom index (RSI) score decreased in both groups. The P-CAB group tended to have a lower HARQ ( = 0.051) and RSI ( = 0.069) scores in month 2. In conclusion, vonoprazan may be comparable to esomeprazole in cough symptom relief in GERC during the 2-month treatment period, but possibly provides better gains on classic reflux symptoms and quality-of-life. The long-term efficacy of P-CABs on GERC may be worth further exploration. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200067089.
PubMed: 38528386
DOI: 10.4168/aair.2024.16.2.191