ABSTRACT
The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.
Subject(s)
Celecoxib , Cyclooxygenase 2 Inhibitors , Humans , Celecoxib/administration & dosage , Celecoxib/adverse effects , Cyclooxygenase 2 Inhibitors/adverse effects , Cyclooxygenase 2 Inhibitors/administration & dosage , Cyclooxygenase 2 Inhibitors/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Comorbidity , Drug InteractionsABSTRACT
Fixed drug eruptions (FDE) are adverse cutaneous drug reactions and a form of delayed type 4 hypersensitivity reaction characterised by recurrent lesions at the same site each time a specific drug is taken. They most commonly result in cutaneous lesions presenting as an erythematous round or oval macule or plaque. FDEs have rarely been reported to affect oral mucous membranes and tend to have a bullous or aphthous-like appearance with erythema. Almost half of patients report an increase in the severity of symptoms with prolonged exposure to the offending medication. The most commonly attributed classes of drug are antibiotics (tetracyclines and sulphonamides) alongside non-steroidal anti-inflammatory drugs. Cutaneous adverse reactions to etoricoxib, a highly selective COX-2 inhibitor, have been reported. Here we describe an adverse reaction restricted to the oral mucosa.
Subject(s)
Cyclooxygenase 2 Inhibitors , Drug Eruptions , Etoricoxib , Pyridines , Sulfones , Humans , Etoricoxib/adverse effects , Drug Eruptions/etiology , Pyridines/adverse effects , Cyclooxygenase 2 Inhibitors/adverse effects , Sulfones/adverse effects , Female , Male , Middle Aged , Mouth Mucosa/pathology , Mouth Mucosa/drug effects , Hypersensitivity, Delayed/chemically inducedABSTRACT
Imrecoxib, a cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug (NSAID), was discovered via the balanced inhibition strategy of COX-1/COX-2. It is indicated for the relief of painful symptoms of osteoarthritis. There have been some pharmacological and therapeutic advances since the approval of imrecoxib in 2011. However, an update review in this aspect is not yet available. Relevant literature until January 2024 was identified by search of PubMed, Web of science, Embase and CNKI. From the perspective of efficacy, imrecoxib provides relief of osteoarthritis symptoms, and potential off-label use for treatment of idiopathic pulmonary fibrosis, perioperative pain, hand-foot syndrome, axial spondyloarthritis, COVID-19, cartilage injury, and malignancies such as lung and colon cancer. From a safety point of view, imrecoxib showed adverse effects common to NSAIDs; however, it has lower incidence of new-onset hypertension than other types of selective COX-2 inhibitors, less gastrointestinal toxicities than non-selective NSAIDs, weaker risk of drug interaction than celecoxib, and more suitable for elderly patients due to balanced inhibition of COX-1/COX-2. From a pharmacoeconomic perspective, imrecoxib is more cost-effective than celecoxib and diclofenac for osteoarthritis patients. With the deepening of the disease pathophysiology study of osteoarthritis, new therapeutic schemes and pharmacological mechanisms are constantly discovered. In the field of osteoarthritis treatment, mechanisms other than the analgesic and anti-inflammatory effects of COX-2 inhibitors are also being explored. Taken together, imrecoxib is a moderate selective COX-2 inhibitor with some advantages, and there would be more clinical applications and research opportunities in the future.
Subject(s)
Cyclooxygenase 2 Inhibitors , Osteoarthritis , Humans , Cyclooxygenase 2 Inhibitors/adverse effects , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/therapeutic use , Osteoarthritis/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase 2/metabolism , AnimalsABSTRACT
BACKGROUND: Adenotonsillectomy and tonsillectomy (referred to as tonsillectomy hereafter) are common pediatric surgeries. Postoperative complications include hemorrhage requiring surgery (2 to 3% of cases) and pain. Although nonsteroidal anti-inflammatory drugs are commonly administered for postsurgical pain, controversy exists regarding bleeding risk with cyclooxygenase-1 inhibition and associated platelet dysfunction. Preliminary evidence suggests selective cyclooxygenase-2 inhibitors, for example celecoxib, effectively manage pain without adverse events including bleeding. Given the paucity of data for routine celecoxib use after tonsillectomy, this study was designed to investigate the association between postoperative celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery using chart-review data from the Children's Hospital of Eastern Ontario. METHODS: After ethics approval, a retrospective single-center observational cohort study was performed in children less than 18 yr of age undergoing tonsillectomy from January 2007 to December 2017. Cases of adenoidectomy alone were excluded due to low bleed rates. The primary outcome was the proportion of patients with post-tonsillectomy hemorrhage requiring surgery. The association between a celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery was estimated using inverse probability of treatment weighting based on propensity scores and using generalized estimating equations to accommodate clustering by surgeon. RESULTS: An initial patient cohort of 6,468 was identified, and 5,846 children with complete data were included in analyses. Median (interquartile range) age was 6.10 (4.40, 9.00) yr, and 46% were female. In the cohort, 28.1% (n = 1,644) were prescribed celecoxib. Among the 4,996 tonsillectomy patients, 1.7% (n = 86) experienced post-tonsillectomy hemorrhage requiring surgery. The proportion with post-tonsillectomy hemorrhage requiring surgery among patients who had a tonsillectomy and were or were not prescribed celecoxib was 1.94% (30 of 1,548; 95% CI, 1.36 to 2.75) and 1.62% (56 of 3,448; 95% CI, 1.25 to 2.10), respectively. Modeling did not identify an association between celecoxib prescription and increased odds of post-tonsillectomy hemorrhage requiring surgery (odds ratio = 1.4; 95% CI, 0.85 to 2.31; P = 0.20). CONCLUSIONS: Celecoxib does not significantly increase the odds of post-tonsillectomy hemorrhage requiring surgery, after adjusting for covariates. This large pediatric cohort study of celecoxib administered after tonsillectomy provides compelling evidence for safety but requires confirmation with a multisite randomized controlled trial.
Subject(s)
Celecoxib , Pain, Postoperative , Postoperative Hemorrhage , Tonsillectomy , Humans , Celecoxib/therapeutic use , Tonsillectomy/adverse effects , Retrospective Studies , Female , Male , Child , Pain, Postoperative/drug therapy , Child, Preschool , Cohort Studies , Postoperative Hemorrhage/epidemiology , Pain Management/methods , Cyclooxygenase 2 Inhibitors/therapeutic use , Cyclooxygenase 2 Inhibitors/adverse effects , AdolescentSubject(s)
Anti-Inflammatory Agents, Non-Steroidal , Cyclooxygenase 2 Inhibitors , Renal Insufficiency, Chronic , Humans , Cyclooxygenase 2 Inhibitors/therapeutic use , Cyclooxygenase 2 Inhibitors/adverse effects , Renal Insufficiency, Chronic/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cyclooxygenase 2/metabolismABSTRACT
Prostanoids are biologically active lipids generated from arachidonic acid by the action of the COX (cyclooxygenase) isozymes. NSAIDs, which reduce the biosynthesis of prostanoids by inhibiting COX activity, are effective anti-inflammatory, antipyretic, and analgesic drugs. However, their use is limited by cardiovascular adverse effects, including myocardial infarction, stroke, hypertension, and heart failure. While it is well established that NSAIDs increase the risk of atherothrombotic events and hypertension by suppressing vasoprotective prostanoids, less is known about the link between NSAIDs and heart failure risk. Current evidence indicates that NSAIDs may increase the risk for heart failure by promoting adverse myocardial and vascular remodeling. Indeed, prostanoids play an important role in modulating structural and functional changes occurring in the myocardium and in the vasculature in response to physiological and pathological stimuli. This review will summarize current knowledge of the role of the different prostanoids in myocardial and vascular remodeling and explore how maladaptive remodeling can be counteracted by targeting specific prostanoids.
Subject(s)
Heart Failure , Hypertension , Humans , Prostaglandins , Vascular Remodeling , Cyclooxygenase 2 Inhibitors/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cyclooxygenase 2 , Heart Failure/chemically induced , Hypertension/chemically inducedABSTRACT
No disponible
Subject(s)
Humans , Female , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Infertility/drug therapy , Cyclooxygenase 2 Inhibitors/adverse effects , Fertility , Fertility/immunology , Fertility Agents/administration & dosage , Fertility Agents/pharmacology , Fertility Agents, Female/pharmacologyABSTRACT
Abstract: Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.
Subject(s)
Humans , Female , Aged , Pyridines/adverse effects , Sulfones/adverse effects , Patch Tests/methods , Drug Eruptions/etiology , Cyclooxygenase 2 Inhibitors/adverse effects , Drug Eruptions/pathologyABSTRACT
Abstract The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p < 0.05). Treatment with either LDA or etoricoxib alone was not associated with gastric damage. No significant damage was observed on kidney morphology and function (F = 0.5418, p > 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.
Subject(s)
Animals , Male , Platelet Aggregation Inhibitors/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/administration & dosage , Cyclooxygenase 2 Inhibitors/adverse effects , Gastric Mucosa/drug effects , Kidney/drug effects , Pyridines/adverse effects , Stomach Diseases/chemically induced , Sulfones/adverse effects , Time Factors , Cardiovascular Diseases/prevention & control , Random Allocation , Ibuprofen/adverse effects , Risk Factors , Treatment Outcome , Rats, Wistar , Creatinine/blood , Etoricoxib , Kidney Diseases/chemically inducedABSTRACT
No disponible
Subject(s)
Humans , Male , Adult , Cyclooxygenase 2 Inhibitors/adverse effects , Drug Hypersensitivity/diagnosis , Analgesics/adverse effectsABSTRACT
No disponible
Subject(s)
Humans , Drug Hypersensitivity/diagnosis , Etodolac/adverse effects , Skin Diseases, Vesiculobullous/chemically induced , Cyclooxygenase 2 Inhibitors/adverse effectsABSTRACT
No disponible
Subject(s)
Humans , Female , Adult , Exanthema/chemically induced , Cyclooxygenase 2 Inhibitors/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Patch TestsABSTRACT
This is a cross-sectional observational study undertaken to explore the current prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) and the prevalence of NSAID-induced gastrointestinal (GI) risk factors of orthopaedic patients in real clinical practice in Korea. Study cohort included 3,140 orthopaedic outpatients at 131 hospitals and clinics between January 2008 and August 2008. A self-administered questionnaire was completed by each patient and physician. A simplified risk scoring scale (the Standardized Calculator of Risk for Events; SCORE) was used to measure patients' risk for GI complications. The pattern of NSAIDs prescription was identified from medical recordings. Forty-five percents of the patients belonged to high risk or very high risk groups for GI complications. The cyclooxygenase-2 enzyme (COX-2) selective NSAID showed a propensity to be prescribed more commonly for high/very high GI risk groups, but the rate was still as low as 51%. In conclusion, physician's considerate prescription of NSAIDs with well-understanding of each patient's GI risk factors is strongly encouraged in order to maximize cost effectiveness and to prevent serious GI complications in Korea. Other strategic efforts such as medical association-led education programs and application of Korean electronic SCORE system to hospital order communication system (OCS) should also be accompanied in a way to promote physician's attention.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cohort Studies , Cross-Sectional Studies , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/adverse effects , Drug Prescriptions , Gastrointestinal Diseases/chemically induced , Musculoskeletal Diseases/complications , Prevalence , Surveys and Questionnaires , Republic of Korea , Risk FactorsABSTRACT
Introducción y objetivo: Se ha señalado que la ciclooxigenasa-2 (COX-2) ejerce una función protectora en pacientes con asma mediante la producción de la prostaglandina E2. Con el objetivo de reproducir dicho efecto en un modelo experimental y dilucidar los mecanismos implicados, hemos evaluado, en un modelo de asma alérgica en el ratón, el efecto de la inhibición de la COX-2 en la respuesta de las vías aéreas expuestas a ovalbúmina y en la actividad de los mastocitos. Material y métodos: Se sensibilizaron ratones a la ovalbúmina (10 μg, vía intraperitoneal) y se reexpusieron a ovalbúmina al 0,5% por vía intranasal. La mitad de los animales sensibilizados recibió tratamiento con rofecoxib (15mg/kg al día, por vía oral, durante la fase de reexposición). Se evaluó la función pulmonar mediante pletismografía corporal antes y después de la reexposición a ovalbúmina, y se estableció el grado de inflamación broncovascular. También se midió la concentración sérica de la proteasa-1 de los mastocitos de ratón. Resultados: Los ratones sensibilizados y tratados con rofecoxib mostraron una hiperreactividad bronquial 2,4 veces mayor que los del grupo control a una concentración de 100mg/ml de metacolina. Asimismo, se apreció una clara tendencia hacia el empeoramiento del proceso inflamatorio en presencia de rofecoxib, aunque sin significación estadística. Estos cambios se acompañaron de un aumento significativo de la actividad de los mastocitos de la mucosa. Conclusiones: La inhibición farmacológica de la COX-2 durante la reexposición a ovalbúmina agrava la función pulmonar, un fenómeno que consideramos se debe, al menos en parte, al incremento de la actividad de los mastocitos de las vías aéreas(AU)
Background: Cyclooxygenase (COX)-2 activity has been said to have a protective effect in asthmatic patients as a result of prostaglandin E2 production. In order to elucidate the mechanisms involved, we evaluated the impact of selective inhibition of COX-2 with rofecoxib during ovalbumin challenge, assessing mast cell activity and airway response in a murine model of asthma. Material and methods: Mice were sensitized to ovalbumin (10μg injected intraperitoneally) and further challenged with 0.5% intranasal ovalbumin. Half the sensitized animals were treated orally with rofecoxib (15mg/kg/d during the challenge phase). Lung function was measured by whole body plethysmography before and after exposure to ovalbumin. The severity of airway inflammation was evaluated by means of a scoring system. Finally, the serum level of mouse mast cell protease-1 was determined as an indicator of mucosal mast cell activity. Results: Sensitized mice treated with rofecoxib exhibited 2.4-fold greater airway hyperresponsiveness than did vehicle-treated mice at a methacholine concentration of 100mg/ml. A clear trend toward worsening airway inflammation in the presence of rofecoxib was observed, although the difference between rofecoxib-treated and vehicle-treated animals was not significant. These changes were accompanied by a significant increase in mucosal mast cell activity. Conclusions: Selective pharmacological inhibition of COX-2 during the challenge phase worsens airway function in the ovalbumin -induced murine model of acute asthma. We suggest that this effect might be at least partially explained by the increase in airway mast cell activity(AU)
Subject(s)
Animals , Mice , Female , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/adverse effects , Cyclooxygenase 2/adverse effects , Cyclooxygenase 2/therapeutic use , Mast Cells/physiology , Ovalbumin/adverse effects , Ovalbumin/analysis , Models, Animal , Cyclooxygenase 2 Inhibitors/adverse effects , Cyclooxygenase 2 Inhibitors/therapeutic use , Respiratory Tract Diseases/complications , Respiratory Tract Diseases/drug therapyABSTRACT
No disponible
Subject(s)
Humans , Male , Aged , Cyclooxygenase 2 Inhibitors/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Gastrointestinal Hemorrhage/chemically induced , Osteoarthritis, Spine/drug therapy , Drug Interactions , Drug-Related Side Effects and Adverse Reactions/epidemiologyABSTRACT
No disponible