RESUMEN
Proton pump inhibitors (PPIs) are a commonly used class of drugs with a good safety profile. However, their use is associated with rare cases of severe skin reaction. Herein, we present details of a patient who developed two episodes of omeprazole-induced delayed-onset hypersensitivity (atypical drug reaction with eosinophilia and systemic symptoms [DRESS]). Lymphocytes from the patient were stimulated to proliferate and secrete cytokines and cytolytic molecules when treated with the drug. T-cell cross-reactivity was observed with structurally related PPIs. Hence, other PPIs have the potential to cause further serious immune-related adverse events in patients who present with hypersensitivity to a primary PPI.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos , Omeprazol , Inhibidores de la Bomba de Protones , Humanos , Omeprazol/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Femenino , Persona de Mediana Edad , MasculinoRESUMEN
RATIONALE: Stevens-Johnson syndrome (SJS) is a rare but severe skin-mucosal reaction with a high mortality rate. It is characterized by sudden, painful blistering lesions on the skin, often accompanied by high fever and systemic toxicity. Lesions typically appear on the dorsal surfaces of the hands, feet, forearms, legs, and soles of the feet. They can also affect the conjunctiva, oral mucosa, labial mucosa, and vaginal mucosa. Patients may experience complications such as pneumonia, severe comorbidities, and liver and renal failure. PATIENT CONCERNS: A 51-year-old female patient was admitted to the hospital due to "abdominal distention and skin yellowing for 20 days." After using omeprazole, she developed a rash all over her body, and her liver function further deteriorated, ultimately leading to chronic acute liver failure. DIAGNOSES: The diagnosis included fever, rash suspected to be drug-induced, chronic and acute liver failure, and decompensation of post-Hepatitis B cirrhosis. INTERVENTIONS: During hospitalization, suspected adverse drug reactions were discontinued, and symptomatic supportive treatment with methylprednisolone and fluid replacement was promptly provided. OUTCOMES: The patient's symptoms and follow-up showed that the rash disappeared and liver and kidney function improved significantly after treatment. LESSONS: We explored how chronic acute liver failure can cause immune system abnormalities and immune paralysis in patients, manifested as susceptibility to infection. This case report describes a drug-induced allergic reaction - SJS - in patients with chronic acute liver failure, as well as subsequent treatment, including hormone dosage and treatment duration. I hope this report will help enrich the relevant literature on drug-induced SJS combined with chronic and acute liver failure, laying the foundation for improving the survival rate of patients with the disease.
Asunto(s)
Omeprazol , Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/etiología , Femenino , Persona de Mediana Edad , Omeprazol/efectos adversos , Fallo Hepático Agudo/inducido químicamenteRESUMEN
BACKGROUND: Insulin autoantibody syndrome (IAS), or Hirata disease, is caused by high concentrations of insulin autoantibodies, which result in spontaneous, mainly post-prandial, hypoglycemic episodes. We report a case of a previously healthy 67-year-old man presenting with recurrent fasting hypoglycemia culminating in a diagnosis of insulin autoimmune syndrome linked to omeprazole and probably spices, namely, coriander, and ginger. CASE PRESENTATION: A previously healthy 67-year-old Sinhalese man presented with recurrent syncopal attacks for 3 months, which were found to be hypoglycemic episodes. He experienced mainly fasting hypoglycemic attacks, at a frequency gradually increasing to daily attacks. His cardiovascular, respiratory, abdominal, and neurologic examinations were normal. He was found to have insulin levels > 6000 mU/L and a post-polyethylene glycol insulin recovery of less than 9.5%. Contrast-enhanced computed tomography of the pancreas was normal. The diagnosis of insulin autoantibody syndrome was confirmed by testing for the insulin autoantibody level, yielding a level of > 300 U/mL. With regard to a possible trigger, he had a history of omeprazole intake for 2 weeks, 4 weeks prior to the onset of symptoms. He also consumed an herbal supplement containing coriander and ginger extracts daily for a period of 1 year, approximately 2 years prior to the onset of hypoglycemic attacks. He was commenced on prednisolone 30 mg daily, and hypoglycemic episodes responded dramatically, and thus he was tapered off corticosteroids. CONCLUSION: Omeprazole-induced insulin autoantibody syndrome is likely in this patient; however, the known hypoglycemic effects of coriander and ginger make it worthwhile to consider a possible association with insulin autoantibody syndrome. In addition, this case report highlights the need to consider insulin autoantibody syndrome even in patients presenting with fasting hypoglycemic attacks.
Asunto(s)
Hipoglucemia , Humanos , Masculino , Anciano , Hipoglucemia/inmunología , Hipoglucemia/inducido químicamente , Anticuerpos Insulínicos/sangre , Anticuerpos Insulínicos/inmunología , Omeprazol/efectos adversos , Omeprazol/uso terapéutico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/diagnóstico , Insulina/inmunología , Zingiber officinale/efectos adversos , Síndrome , Autoanticuerpos/sangreRESUMEN
Introduction: PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Methods: Healthy adult male BALB/c mice were randomly divided into three equal groups (n = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 µl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. Result: The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in ß-cell numbers between groups. Conclusion: Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated.
Asunto(s)
Glucemia , Gastrinas , Homeostasis , Resistencia a la Insulina , Ratones Endogámicos BALB C , Omeprazol , Animales , Omeprazol/farmacología , Omeprazol/efectos adversos , Gastrinas/sangre , Gastrinas/metabolismo , Masculino , Ratones , Homeostasis/efectos de los fármacos , Glucemia/metabolismo , Insulina/metabolismo , Insulina/sangre , Regulación de la Expresión Génica/efectos de los fármacos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/inducido químicamente , Prueba de Tolerancia a la Glucosa , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/efectos adversos , Glucosa/metabolismoRESUMEN
BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.
Asunto(s)
Clopidogrel , Hemorragia Gastrointestinal , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Inhibidores de la Bomba de Protones , Humanos , Clopidogrel/administración & dosificación , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/prevención & control , Terapia Antiplaquetaria Doble/métodos , Esomeprazol/administración & dosificación , Esomeprazol/uso terapéutico , Omeprazol/administración & dosificación , Omeprazol/uso terapéutico , Omeprazol/efectos adversos , Interacciones Farmacológicas , Quimioterapia Combinada , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Antagonistas de los Receptores H2 de la Histamina/uso terapéuticoRESUMEN
BACKGROUND: A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. METHODS: The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. RESULTS: The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings. CONCLUSION: This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.
Asunto(s)
Bancos de Muestras Biológicas , Análisis de la Aleatorización Mendeliana , Omeprazol , Osteoartritis , Humanos , Omeprazol/efectos adversos , Osteoartritis/genética , Reino Unido/epidemiología , Factores de Riesgo , Femenino , Masculino , Persona de Mediana Edad , Biobanco del Reino UnidoRESUMEN
Omeprazole, a gastric acid pump inhibitor, is repeatedly administered and is oxidatively metabolized mainly by polymorphic cytochrome P450 2C19. The prescribed dosage of omeprazole was discontinued or reduced in 47 of the 135 patients who received omeprazole alone in this survey, as recorded in the Japanese Adverse Drug Event Report database. The days to onset of omeprazole-related disorders were 3-4 d (median) and 16 d for intravenous 20-40 mg and oral 20 mg daily doses, respectively, in 34 patients for whom relevant data were available. The maximum plasma concentration of omeprazole was pharmacokinetically modeled after a single oral 40-mg dose in P450 2C19-defective poor metabolizers and was 2.4-fold higher than that in extensive metabolizers. The modeled area under the hepatic concentration curves of omeprazole in P450 2C19 poor metabolizers after virtual daily 40-mg doses for 7 d was 5.2-fold higher than that in the extensive metabolizers. Omeprazole-induced P450 2C19 (approx. 2-fold), resulting in increased hepatic intrinsic clearance in repeated doses, was considered after the second day. Virtual plasma/hepatic exposure estimated using pharmacokinetic modeling in subjects with P450 2C19 poor metabolizers indicated that these exposure levels virtually estimated could be one of causal factors for unexpected hepatic disorders induced by prescribed omeprazole, such as those resulting from drug interactions with repeatedly co-administered medicines.
Asunto(s)
Citocromo P-450 CYP2C19 , Hígado , Omeprazol , Inhibidores de la Bomba de Protones , Humanos , Sistemas de Registro de Reacción Adversa a Medicamentos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Bases de Datos Factuales , Pueblos del Este de Asia , Japón , Hígado/metabolismo , Hígado/efectos de los fármacos , Modelos Biológicos , Omeprazol/farmacocinética , Omeprazol/efectos adversos , Omeprazol/sangre , Omeprazol/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/farmacocinética , Inhibidores de la Bomba de Protones/sangreRESUMEN
Drug-induced liver injury (DILI) is a frequent cause of clinical trial failures during drug development. While inhibiting bile salt export pump (BSEP) is a well-documented DILI mechanism, interference with genes related to bile acid (BA) metabolism and transport can further complicate DILI development. Here, the effects of twenty-eight compounds on genes associated with BA metabolism and transport were evaluated, including those with discontinued development or use, boxed warnings, and clean labels for DILI. The study also included rifampicin and omeprazole, pregnane X receptor and aryl hydrocarbon receptor ligands, and four mitogen-activated protein kinase kinase (MEK1/2) inhibitors. BSEP inhibitors with more severe DILI, notably pazopanib and CP-724714, significantly upregulated the expression of 7 alpha-hydroxylase (CYP7A1), independent of small heterodimer partner (SHP) expression. CYP7A1 expression was marginally induced by omeprazole. In contrast, its expression was suppressed by mometasone (10-fold), vinblastine (18-fold), hexachlorophene (2-fold), bosentan (2.1-fold), and rifampin (2-fold). All four MEK1/2 inhibitors that show clinical DILI were not potent BSEP inhibitors but significantly induced CYP7A1 expression, accompanied by a significant SHP gene suppression. Sulfotransferase 2A1 and BSEP were marginally upregulated, but no other genes were altered by the drugs tested. Protein levels of CYP7A1 were increased with the treatment of CYP7A1 inducers and decreased with obeticholic acid, an farnesoid X receptor ligand. CYP7A1 inducers significantly increased bile acid (BA) production in hepatocytes, indicating the overall regulatory effects of BA metabolism. This study demonstrates that CYP7A1 induction via various mechanisms can pose a risk for DILI, independently or in synergy with BSEP inhibition, and it should be evaluated early in drug discovery. SIGNIFICANCE STATEMENT: Kinase inhibitors, pazopanib and CP-724714, inhibit BSEP and induce CYP7A1 expression independent of small heterodimer partner (SHP) expression, leading to increased bile acid (BA) production and demonstrating clinically elevated drug-induced liver toxicity. MEK1/2 inhibitors that show BSEP-independent drug-induced liver injury (DILI) induced the CYP7A1 gene accompanied by SHP suppression. CYP7A1 induction via SHP-dependent or independent mechanisms can pose a risk for DILI, independently or in synergy with BSEP inhibition. Monitoring BA production in hepatocytes can reliably detect the total effects of BA-related gene regulation for de-risking.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Indazoles , Pirimidinas , Sulfonamidas , Humanos , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Omeprazol/efectos adversos , Ácidos y Sales Biliares , Colesterol 7-alfa-Hidroxilasa/metabolismoRESUMEN
We aimed to present a drug monitoring profile of tacrolimus and proton pump inhibitor coadministration in a 23-year-old male patient with a history of high blood pressure who underwent kidney transplant. The patient's serum trough levels of tacrolimus were in the therapeutic range until omeprazole 20 mg daily was prescribed. Tacrolimus trough serum level increased to 29.5 ng/mL under the same daily dose and to 13.9 ng/mL after tacrolimus daily dose was decreased to 6 mg/day. This increase in tacrolimus serum level was behind a renal function alteration. After withdrawal of omeprazole, tacrolimus trough serum level returned to the therapeutic range. Because interactions between tacrolimus and omeprazole could result in toxicities, careful monitoring of tacrolimus serum levels should be considered to adjust the dosage.
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Trasplante de Riñón , Tacrolimus , Masculino , Humanos , Adulto Joven , Adulto , Inhibidores de la Bomba de Protones/efectos adversos , Inmunosupresores , Trasplante de Riñón/efectos adversos , Omeprazol/efectos adversos , Interacciones FarmacológicasRESUMEN
Most proton pump inhibitors (PPIs) inhibit the bioactivation of clopidogrel to its active metabolite. There is controversy concerning whether PPIs alter the effectiveness of clopidogrel in reducing the risk of ischemic stroke (IS). We therefore aimed to examine the risk of IS associated with concomitant use of clopidogrel and omeprazole, a PPI commonly used in clinical settings. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohorts comprised 407 patients diagnosed with acute coronary syndrome (ACS) and with concomitant use of clopidogrel and omeprazole (the exposed cohort), 814 ACS patients with single use of clopidogrel (the comparison cohort), and 230 ACS patients with concurrent use of clopidogrel and pantoprazole (the reference cohort). The primary outcome was incident IS. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the time-dependent Cox regression model were used to assess the association between concomitant use of clopidogrel and omeprazole and the risk of IS. The incidence rate of IS was significantly higher in the exposed cohort (81.67 per 1000 person-years) than in the comparison cohort (57.45 per 1000 person-years), resulting in an adjusted HR of 1.39 (95% CI 1.03-1.74). By contrast, there was no significant difference in the risk of IS between the exposed and reference cohorts (adjusted HR 1.11; 95% CI 0.81-1.52). The present study revealed that patients taking both clopidogrel and omeprazole was associated with an increased risk of IS.
Asunto(s)
Síndrome Coronario Agudo , Accidente Cerebrovascular Isquémico , Humanos , Clopidogrel/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Estudios de Cohortes , Omeprazol/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/efectos adversos , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/inducido químicamente , Interacciones FarmacológicasRESUMEN
The objectives of the present study were to evaluate the acute toxicity, gastroprotective, therapeutic, anti-inflammatory and anti H. pylori activities of T. vulgaris total plant extract against ethanol-induced gastric ulcers in Sprague Dawley rats. Animals were divided into five groups i.e G-1 (Normal Control), Group 2 (ulcer control) were administered orally with 0.5% Carboxymethylcellulose (CMC), Group 3 (omeprazole treated) was administered orally with 20 mg/kg of omeprazole and Groups 4 and 5 (Low dose and High dose of the extract) were administered orally with 250, and 500 mg/ kg of Thymus vulgaris extract, respectively. After 1 hour, the normal group was orally administered with 0.5% CMC (5 ml/kg), whereas absolute alcohol (5ml/ kg) was orally administered to the ulcer control group, omeprazole group, and experimental groups. Stomachs were examined macroscopically and microscopically. Grossly, rats pre-treated with T. vulgaris demonstrated significantly decreased ulcer area and an increase in mucus secretion and pH of gastric content compared with the ulcer control group. Microscopy of gastric mucosa in the ulcer control group showed severe damage to gastric mucosa with edema and leukocytes infiltration of the submucosal layer. However, rats pretreated with omeprazole or Thyme vulgaris exhibited a mild to moderate disruption of the surface epithelium and lower level of edema and leukocyte infiltration of the submucosal layer. The T. vulgaris extract caused up-regulation of Hsp70 protein, down-regulation of Bax protein, and intense periodic acid Schiff uptake of the glandular portion of the stomach. Gastric mucosal homogenate of rats pre-treated with T. vulgaris exhibited significantly increased superoxide dismutase (SOD) and catalase (CAT) activities while malondialdehyde (MDA) level was significantly decreased. Based on the results showed in this study, Thymus vulgaris extract can be proposed as the safe medicinal plants for use and it has considerable gastroprotective potential via stomach epithelium protection against gastric ulcers and stomach lesions.
Asunto(s)
Antiulcerosos , Úlcera Gástrica , Thymus (Planta) , Ratas , Animales , Ratas Sprague-Dawley , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Úlcera/tratamiento farmacológico , Etanol/toxicidad , Etanol/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Mucosa Gástrica/metabolismo , Omeprazol/efectos adversos , Antioxidantes/metabolismo , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Edema/tratamiento farmacológicoRESUMEN
OBJECTIVE: To estimate the incidence rates (IR) of prespecified outcomes of interest in pediatric patients (1 month to < 1 year) treated with intravenous (IV) pantoprazole using Optum's longitudinal electronic health records database (Optum Market Clarity) from the United States (US). METHODS: This real-world, non-interventional, retrospective cohort study was conducted from 01 January 2007 to 31 December 2020 in patients who received IV pantoprazole. Premature patients and those weighing < 2.36 kg were excluded. Patients were categorized based on diagnosis of gastroesophageal reflux disease (GERD) and erosive esophagitis (EE) into: Subgroup 1 (GERD and EE), Subgroup 2 (GERD and no EE), and Subgroup 3 (absence of GERD and EE). Overall IRs (per 1000 person-years [PY]) and 95% confidence intervals (CI) of outcomes were estimated (overall and subgroups) and stratified by duration of IV pantoprazole treatment (< 4 days versus ≥ 4 days). RESULTS: Of 1879 eligible patients, none were identified in Subgroup 1; 851 (45.3%) and 1028 (54.7%) patients were identified in Subgroups 2 and 3, respectively. IRs of outcomes of interest ranged from 0.0 to 742.8 per 1000 PY. IRs were highest for vomiting (742.80), diarrhea (377.77), abdominal distension (214.31), hyponatremia (204.99), and hypokalemia (203.49). IRs were comparable between Subgroups 2 and 3. For most outcomes, IRs were higher among patients treated with IV pantoprazole for ≥ 4 days versus those treated for < 4 days. CONCLUSION: These results are consistent with the known safety profile of pantoprazole and emphasize the utility of using real-world data from pediatric populations for assessment of safety outcomes.
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Antiulcerosos , Reflujo Gastroesofágico , Humanos , Niño , Pantoprazol/uso terapéutico , Antiulcerosos/efectos adversos , Omeprazol/efectos adversos , 2-Piridinilmetilsulfinilbencimidazoles/efectos adversos , Estudios Retrospectivos , Bencimidazoles/efectos adversos , Sulfóxidos/efectos adversos , Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/inducido químicamenteRESUMEN
BACKGROUND AND AIM: The association between proton-pump inhibitors (PPIs) and rhabdomyolysis were unclear. The aim of this study was to explore and systematically analyze the potential link between five PPIs and the rhabdomyolysis events using the FDA Adverse Event Reporting System (FAERS) database. METHODS: Suspected rhabdomyolysis events associated with PPIs were identified by data mining with the reporting odds ratio (ROR), proportional reporting ratio (PRR), the information component (IC), and Empirical Bayes Geometric Mean (EBGM). Demographic information, drug administration, and outcomes of PPI-induced rhabdomyolysis events were also analyzed. RESULTS: There were 3311 reports associated with PPI-induced rhabdomyolysis that were identified. After removing duplicates, 1899 cases were determined to contain complete patient demographic data. The average age was 65 ± 18 year and 57% were male. Omeprazole and pantoprazole had the same largest percentage of reports. Lansoprazole had the highest ROR index of 12.67, followed by esomeprazole (11.18), omeprazole (10.27), rabeprazole (10.06), and pantoprazole (9.24). PRR, IC, and EBGM showed similar patterns. This suggested that lansoprazole exhibited the strongest correlation with rhabdomyolysis. In rhabdomyolysis events, PPIs were mainly "concomitant" (>60%), and only a few cases were "primary suspects" (<15%). Rabeprazole showed the lowest death rate while lansoprazole showed the highest. CONCLUSIONS: The study suggested that significant rhabdomyolysis signals were associated with PPIs. Further research should be performed in drug safety evaluation for a more comprehensive association.
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Inhibidores de la Bomba de Protones , Rabdomiólisis , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Inhibidores de la Bomba de Protones/efectos adversos , Pantoprazol , Rabeprazol , Farmacovigilancia , Teorema de Bayes , Omeprazol/efectos adversos , Lansoprazol , Rabdomiólisis/inducido químicamente , Rabdomiólisis/epidemiologíaRESUMEN
The objective of this study was to explore the causal relationship between the use of proton pump inhibitors (PPIs) and 16 types of digestive system tumors. We utilized a 2-sample Mendelian randomization (MR) approach to investigate this relationship. We obtained exposure and outcome data from the UK Biobank and the Finland Biobank, respectively. The genetic data used in the analysis were derived from genome-wide association studies (GWAS) studies conducted on European populations. We screened single nucleotide polymorphisms significantly associated with the use of omeprazole, a commonly used PPIs, as instrumental variables. We then performed MR analyses using the inverse variance weighting (IVW) method, MR-Egger regression, and the weighted median method to evaluate the causal effect of omeprazole use on the 16 types of digestive system tumors. Our MR analysis revealed a significant causal relationship between the use of omeprazole and pancreatic malignancies, but not with any other types of digestive system tumors. The IVW analysis showed an odds ratio of 4.33E-05 (95%CI: [4.87E-09, 0.38], Pâ =â .03) and the MR-Egger analysis showed an odds ratio of 5.81E-11 (95%CI: [2.82E-20, 0.12], Pâ =â .04). We found no significant heterogeneity or pleiotropy, and sensitivity analysis confirmed the robustness of our results. Furthermore, statistical power calculations suggested that our findings were reliable. Conclusion The use of PPIs is a protective factor for pancreatic malignancies, but no causal relationship has been found with other digestive system tumors.
Asunto(s)
Neoplasias del Sistema Digestivo , Neoplasias Gastrointestinales , Neoplasias Pancreáticas , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neoplasias del Sistema Digestivo/inducido químicamente , Neoplasias del Sistema Digestivo/epidemiología , Neoplasias del Sistema Digestivo/genética , Neoplasias Gastrointestinales/inducido químicamente , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/genética , Omeprazol/efectos adversosRESUMEN
Kounis syndrome is a rare type of acute coronary syndrome (ACS) that occurs as a result of an allergic or anaphylactic reaction. Kounis syndrome can be induced by various medications including antibiotics, proton pump inhibitors, antihypertensive medications, corticosteroids, and antineoplastic medications. Additionally, cases of Kounis syndrome associated with lansoprazole and pantoprazole have been previously reported in the literature. In this report, we present a case of Kounis syndrome associated with omeprazole use, and discuss the need for a high index of suspicion as it is often underrecognised.
Asunto(s)
Anafilaxia , Síndrome de Kounis , Humanos , Anafilaxia/inducido químicamente , Anafilaxia/diagnóstico , Síndrome de Kounis/etiología , Síndrome de Kounis/complicaciones , Omeprazol/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
BACKGROUND/AIMS: Proton pump inhibitors are frequently used to treat gastroesophageal reflux disease, but their effect is restricted. The present study aimed to investigate whether the addition of sublingual melatonin to omeprazole was effective in the treatment of gastro gastroesophageal reflux disease symptoms. MATERIALS AND METHODS: This was a randomized double-blind clinical trial. A total of 78 patients with gastro gastroesophageal reflux disease were randomly allocated to either omeprazole 20 mg/d plus sublingual melatonin (3 mg/d) or omeprazole 20 mg/d plus placebo for 4 weeks. The selected patients had histories of heartburn and regurgitation and a score ≤32 on the Frequency Scale for the Symptoms of gastroesophageal reflux disease (FSSG). The outcome measures for the assessment of treatment efficacy were heartburn, epigastric pain and the Frequency Scale for the Symptoms of gastroesophageal reflux disease score. Safety and quality of life were evaluated in the patients as the secondary outcomes too. RESULTS: Seventy-two out of 78 eligible patients completed this trial (35 in the melatonin group and 37 in the placebo group). Heartburn, epigastric pain, and Frequency Scale for the Symptoms of gastroesophageal reflux disease score declined significantly in the melatonin group compared to the placebo group (P = .04, P = .03, and P = .0001, respectively). Moreover, the quality of life score was significantly higher in the melatonin group compared with the placebo group (P = .0001). Adverse events were similarly observed in the 2 groups (P = .55), and there were no serious adverse events. CONCLUSION: The combination of sublingual melatonin (3 mg/day) with omeprazole (20 mg/day) may be more effective than omeprazole (20 mg/day) alone in the treatment of gastroesophageal reflux disease.
Asunto(s)
Reflujo Gastroesofágico , Melatonina , Humanos , Omeprazol/efectos adversos , Pirosis/tratamiento farmacológico , Pirosis/etiología , Melatonina/uso terapéutico , Calidad de Vida , Reflujo Gastroesofágico/complicaciones , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del Tratamiento , Dolor/inducido químicamente , Dolor/complicaciones , Dolor/tratamiento farmacológico , Método Doble CiegoRESUMEN
BACKGROUND: Vonoprazan is a new acid-suppressing drug that received FDA approval in 2022. It reversibly inhibits gastric acid secretion by competing with the potassium ions on the luminal surface of the parietal cells (potassium-competitive acid blockers or P-CABs). Vonoprazan has been on the market for a short time and there are many clinical trials to support its clinical application. However, medical experience and comprehensive clinical data is still limited, especially on how and if, gastric histology is altered due to therapy. METHODS: A 12-week experiment trial with 30 Wistar rats was to assess the presence of gastrointestinal morphologic abnormalities upon administration of omeprazole and vonoprazan. At six weeks of age, rats were randomly assigned to one of 5 groups: (1) saline as negative control group, (2) oral omeprazole (40 mg/kg), as positive control group, (3) oral omeprazole (40 mg/kg) for 4 weeks, proceeded by 8 weeks off omeprazole, (4) oral vonoprazan (4 mg/kg), as positive control group, and (5) oral vonoprazan (4 mg/kg) for 4 weeks, proceeded by 8 weeks off vonoprazan. RESULTS: We identified non-inflammatory alterations characterized by parietal (oxyntic) cell loss and chief (zymogen) cell hyperplasia and replacement by pancreatic acinar cell metaplasia (PACM). No significant abnormalities were identified in any other tissues in the hepatobiliary and gastrointestinal tracts. CONCLUSION: PACM has been reported in gastric mucosa, at the esophagogastric junction, at the distal esophagus, and in Barrett esophagus. However, the pathogenesis of this entity is still unclear. Whereas some authors have suggested that PACM is an acquired process others have raised the possibility of PACM being congenital in nature. Our results suggest that the duration of vonoprazan administration at a dose of 4 mg/kg plays an important role in the development of PACM.