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Journal of Veterinary Internal Medicine Mar 2020Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors...
BACKGROUND
Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors or histamine-2 receptor blockers administered IV is commonly recommended.
HYPOTHESIS/OBJECTIVES
To evaluate the efficacy of IV administered esomeprazole, pantoprazole, and famotidine constant rate infusion (CRI) on increasing the intragastric pH of dogs. We hypothesized that esomeprazole and famotidine CRI would provide superior acid suppression compared to pantoprazole and reach pH goals for the treatment of GI bleeding.
ANIMALS
Nine healthy research Beagles.
METHODS
Randomized, 3-way crossover. Dogs received pantoprazole or esomeprazole at 1 mg/kg IV q12h and famotidine with a loading dose of 1 mg/kg followed by 8 mg/kg IV CRI daily for 3 consecutive days. The intragastric pH was recorded at baseline and for 72 hours of treatment. The mean pH and the mean percentage time (MPT) the intragastric pH was ≥3 or ≥4 were compared among and within treatment groups.
RESULTS
Significant increases in mean pH (P < 0.0001), MPT ≥3 (P < 0.001), and MPT ≥4 (P = 0.0006) were noted over time with all 3 treatments. The time effect did not differ by treatment for mean pH, MPT ≥3, and MPT ≥4 (P = .29, .56, and .37, respectively); however, only esomeprazole and famotidine CRI achieved the goals established for the treatment of gastroduodenal ulceration in people.
CONCLUSIONS AND CLINICAL IMPORTANCE
Famotidine CRI and esomeprazole might be superior acid suppressants compared to standard doses of pantoprazole for the first 72 hours of treatment.
Topics: Animals; Anti-Ulcer Agents; Cross-Over Studies; Dogs; Esomeprazole; Famotidine; Female; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Pantoprazole
PubMed: 32020689
DOI: 10.1111/jvim.15718 -
Cardiovascular Therapeutics Apr 2015The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI... (Comparative Study)
Comparative Study
BACKGROUND
The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI pantoprazole on ventricular arrhythmias induced by either ischemia or ischemia-reperfusion (I/R) was studied.
METHODS
The left main coronary artery (LAD) was ligated for 30 or 10 min followed by a 30-min reperfusion in anesthetized rats. Rats were pretreated with pantoprazole (1.3 mg/kg) or vehicle by gastric gavage (daily for 3 weeks) before ligation. Serum electrolytes levels were measured by the end of the third week before coronary ligation. Lactate dehydrogenase (LDH) activity and nitric oxide (NO) concentrations were measured at the end of the ischemia and IR injury.
RESULTS
Pantoprazole caused significant hyperkalemia by the end of third week compared with vehicle-treated rats. After LAD ligation (30 min), ventricular premature contractions (VPC), ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded in rats of the vehicle ischemia group. Pantoprazole pretreatment aggravate these arrhythmias and increased mortality. A 10-min period of ischemia followed by a 30-min reperfusion induced high incidence of VT (100%) and VF (80%) in the vehicle-treated group. The group of rats administered pantoprazole had significantly lower incidence and durations of VT and VF together with reduction of mortality rate. Pantoprazole significantly reduced serum LDH activity and NO release from myocardial tissue after both ischemia and I/R injury.
CONCLUSION
Pantoprazole aggravated ischemia-induced arrhythmias but had a significant antiarrhythmic effect on I/R-induced ventricular arrhythmias.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Disease Models, Animal; Heart Conduction System; Hyperkalemia; L-Lactate Dehydrogenase; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Nitric Oxide; Pantoprazole; Proton Pump Inhibitors; Rats, Wistar; Tachycardia, Ventricular; Time Factors; Ventricular Fibrillation; Ventricular Premature Complexes
PubMed: 25677801
DOI: 10.1111/1755-5922.12107 -
Geriatrics (Basel, Switzerland) Aug 2023Pharmacogenomic factors affect the susceptibility to drug-drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of...
Identification of Drugs Acting as Perpetrators in Common Drug Interactions in a Cohort of Geriatric Patients from Southern Italy and Analysis of the Gene Polymorphisms That Affect Their Interacting Potential.
BACKGROUND
Pharmacogenomic factors affect the susceptibility to drug-drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of 290 older adults and analysed the prevalence of gene polymorphisms that can increase their interacting potential. We also pinpointed clinical decision support systems (CDSSs) that incorporate pharmacogenomic factors in DDI risk evaluation.
METHODS
Perpetrator drugs were identified using the Drug Interactions Flockhart Table, the DRUGBANK website, and the Mayo Clinic Pharmacogenomics Association Table. Allelic variants affecting their activity were identified with the PharmVar, PharmGKB, dbSNP, ensembl and 1000 genome databases.
RESULTS
Amiodarone, amlodipine, atorvastatin, digoxin, esomperazole, omeprazole, pantoprazole, simvastatin and rosuvastatin were perpetrator drugs prescribed to >5% of our patients. Few allelic variants affecting their perpetrator activity showed a prevalence >2% in the European population: CYP3A4/5*22, *1G, *3, CYP2C9*2 and *3, CYP2C19*17 and *2, CYP2D6*4, *41, *5, *10 and *9 and SLC1B1*15 and *5. Few commercial CDSS include pharmacogenomic factors in DDI-risk evaluation and none of them was designed for use in older adults.
CONCLUSIONS
We provided a list of the allelic variants influencing the activity of drug perpetrators in older adults which should be included in pharmacogenomics-oriented CDSSs to be used in geriatric medicine.
PubMed: 37736884
DOI: 10.3390/geriatrics8050084 -
The Canadian Journal of Cardiology Aug 2017Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone... (Review)
Review
BACKGROUND
Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy.
METHODS
Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo.
RESULTS
Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD.
CONCLUSIONS
COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.
Topics: Anticoagulants; Cardiovascular Diseases; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thrombolytic Therapy
PubMed: 28754388
DOI: 10.1016/j.cjca.2017.06.001 -
Scientific Reports May 2023Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated...
Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated anticancer and hypoglycemic effects, but their mechanisms of action are not yet fully understood. We used the GeneCards and PharmMapper databases to identify therapeutic targets for diabetes, breast cancer and PPIs. We identified common targets and constructed a regulatory network of diseases and drugs using the STRING database and Cytoscape software. We also explored the binding between small molecule ligands and protein receptors using Discovery Studio software. We identified 33 shared targets for breast cancer, diabetes, and PPIs including lansoprazole, omeprazole, and pantoprazole, which play a critical role in fatty acid transport, insulin resistance, apoptosis, and cancer-related signaling pathways. Our findings demonstrated that PPIs had a strong affinity for AKT1 and MMP9. This study provides insights into the mechanisms of action of PPIs in breast cancer and diabetes and identifies AKT1 and MMP9 as critical targets for future drug development. Our findings highlight the potential of PPIs as a novel therapeutic approach for these challenging diseases.
Topics: Humans; Female; Proton Pump Inhibitors; Matrix Metalloproteinase 9; Anti-Ulcer Agents; Breast Neoplasms; Network Pharmacology; Diabetes Mellitus; 2-Pyridinylmethylsulfinylbenzimidazoles
PubMed: 37165049
DOI: 10.1038/s41598-023-34524-x -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well...
OBJECTIVE
The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well as to study the impact of pantoprazole on the gastric mucosa to optimize the prophylaxis and treatment of gastropathies induced by ASA and clopidogrel.
PATIENTS AND METHODS
Materials and methods: The experiments were performed on 77 non-linear white male rats with the average weight of 150-180 g. Depending on the aim of research, the animals were divided into 7 groups.
RESULTS
Results: The administration of pantoprazole in combination with ASA and clopidogrel presented positive trends in neutral glycoproteins amount and contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.
CONCLUSION
Conclusions: 1. According to our study findings, administration of ASA in combination with clopidogrel results in 2,5 times higher risk of GM erosive lesions. 2. One of the most significant morphological manifestations of gastropathy in ASA and clopidogrel regimen is the development of microerosions, which are poorly diagnosed by macroscopic examination. 3. The use of PAS-reaction makes possible to identify damage to the basal membrane of superficial epitheliocytes, which may be a top-priority morphological criterion of gastropathy induced by ASA or clopidogrel in the absence of an inflammatory reaction. 4. Administration of pantoprazole in combination with ASA and clopidogrel contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.
Topics: Animals; Aspirin; Clopidogrel; Gastric Mucosa; Male; Pantoprazole; Rats; Ticlopidine
PubMed: 33813477
DOI: No ID Found -
Frontiers in Veterinary Science 2020Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as...
Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.
PubMed: 33330703
DOI: 10.3389/fvets.2020.580735 -
Journal of Clinical Medicine Apr 2023Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin...
BACKGROUND AND OBJECTIVES
Long-term proton pump inhibitor (PPI) use is frequently encountered in primary care. Its effect on micronutrient absorption is known, as vitamin B12, calcium or vitamin D insufficiency may occur in such patients.
MATERIALS AND METHODS
We recruited patients using a PPI (pantoprazole) for >12 months. The control group was represented by subjects attending the general practitioner not taking any PPI in the last 12 months. We excluded subjects using nutritional supplements or with diseases interfering with micronutrient blood levels. All subjects underwent blood sampling with full blood count, iron, ferritin, vitamin D, calcium, sodium, potassium, phosphate, zinc and folate.
RESULTS
We recruited 66 subjects: 30 in the PPI group and 36 in the control group. Long-term pantoprazole users had lower red blood cell count but similar hemoglobin. We did not find any significant difference in blood iron, ferritin, vitamin B12 and folate. Vitamin D deficit was observed more frequently in the PPI group (100%) than in controls (30%, < 0.001), with blood levels lower in pantoprazole consumers. No differences in calcium, sodium and magnesium were observed. Pantoprazole users had lower phosphate levels than controls. Finally, a non-significant trend for zinc deficiency was found in PPI users.
CONCLUSIONS
Our study confirms that chronic PPI users may encounter alterations in some micronutrients involved in bone mineral homeostasis. The effect on zinc levels deserves further investigation.
PubMed: 37109245
DOI: 10.3390/jcm12082910 -
Cureus Jan 2021Metronidazole is a very commonly used drug for the treatment of ailments caused by bacteria and parasites. It can treat a vast array of conditions like rosacea, sexually...
Metronidazole is a very commonly used drug for the treatment of ailments caused by bacteria and parasites. It can treat a vast array of conditions like rosacea, sexually transmitted diseases (STDs), liver abscess, bedsores, etc. Metronidazole comes with generic side-effects like nausea, vomiting, dizziness, metallic taste, and also rare side-effects like paresthesia, syncope, cerebellar symptoms, psychosis but mania is a rare side-effect. Here, we present a case of metronidazole induced mania in a 50-year-old male with no past medical history who initially presented with a complaint of mild fever, loss of appetite, and fatigue from the past 10-12 days. On further examination and investigations, diagnosis of the amebic liver abscess was made on the basis of USG, serum serology for amebiasis IgG, and a CT scan. Consequently, the patient was started on the drug of choice for amebic liver abscess; IV metronidazole 1.5g/day divided over the day into three doses. Other drugs that were administered were pantoprazole, paracetamol, and ondansetron. On the ninth day of admission, the patient's wife as well as the physician-daughter of the patient reported a change in the behavior of the patient which became a major concern for the family. The patient was restless, energetic, unable to sleep, had racing thoughts, elated mood, petulant, and kept singing loudly in the private patient room. There was no history of any psychiatric illness in the family. Mr. K´s manic symptoms were managed using haloperidol and lorazepam. Upon discontinuing metronidazole, there was a gradual improvement in the manic symptoms, and symptoms improved, haloperidol and lorazepam were able to be tapered down and eventually stopped. Mr. K did not require any use of any selective serotonin reuptake inhibitor (SSRIs), monoamine oxidase inhibitors (MAOIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), or any other atypical psychotropic drug. Manic-psychosis side-effect is a rare entity caused by antibiotics and the symptoms of which would disappear in a few days after stopping the antibiotic. It is also notable that this patient recovered without the use of any psychotropic drugs. Physicians should be aware of the possible neuropsychiatric side-effects of antibiotics which can lead to unnecessary workup. This side-effect did not require the use of any psychotropic drugs in this patient.
PubMed: 33409111
DOI: 10.7759/cureus.12414 -
Scientific Reports Jun 2022Gastric cancer is the fourth cause of cancer death globally, and gastric adenocarcinoma is its most common type. Efforts for the treatment of gastric cancer have...
Gastric cancer is the fourth cause of cancer death globally, and gastric adenocarcinoma is its most common type. Efforts for the treatment of gastric cancer have increased its median survival rate by only seven months. Due to the relatively low response of gastric cancer to surgery and adjuvant therapy, as well as the complex role of risk factors in its incidences, such as protein-pomp inhibitors (PPIs) and viral and bacterial infections, we aimed to study the pathological pathways involved in gastric cancer development and investigate possible medications by systems biology and bioinformatics tools. In this study, the protein-protein interaction network was analyzed based on microarray data, and possible effective compounds were discovered. Non-coding RNA versus coding RNA interaction network and gene-disease network were also reconstructed to better understand the underlying mechanisms. It was found that compounds such as amiloride, imatinib, omeprazole, troglitazone, pantoprazole, and fostamatinib might be effective in gastric cancer treatment. In a gene-disease network, it was indicated that diseases such as liver carcinoma, breast carcinoma, liver fibrosis, prostate cancer, ovarian carcinoma, and lung cancer were correlated with gastric adenocarcinoma through specific genes, including hgf, mt2a, mmp2, fbn1, col1a1, and col1a2. It was shown that signaling pathways such as cell cycle, cell division, and extracellular matrix organization were overexpressed, while digestion and ion transport pathways were underexpressed. Based on a multilevel systems biology analysis, hub genes in gastric adenocarcinoma showed participation in the pathways such as focal adhesion, platelet activation, gastric acid secretion, HPV infection, and cell cycle. PPIs are hypothesized to have a therapeutic effect on patients with gastric cancer. Fostamatinib seems a potential therapeutic drug in gastric cancer due to its inhibitory effect on two survival genes. However, these findings should be confirmed through experimental investigations.
Topics: Adenocarcinoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Stomach Neoplasms; Systems Biology
PubMed: 35650297
DOI: 10.1038/s41598-022-13052-0