Comparing pre- and postoperative etoricoxib administration versus only postoperative on third molar extraction sequelae and oral health quality of life: a prospective quasi-experimental study.

OBJECTIVES: This study aimed to compare the impact of pre- and postoperative etoricoxib administration versus only postoperative on third molar extraction sequelae and oral health quality of life. MATERIALS AND METHODS: This prospective quasi experimental study involved 56 patients, divided into a study group receiving preemptive etoricoxib 120 mg before surgery and postoperative etoricoxib 120 mg (n = 28), and a control group receiving preemptive placebo before surgery and postoperative etoricoxib 120 mg (n = 28). Follow-up assessments were conducted at 3- and 7-days post-surgery, recording swelling, trismus, and adverse events. Patients rated perceived pain using the visual analog scale (VAS) and completed an oral health-related quality of life (OHRQoL) questionnaire at specified intervals. Statistical analysis employed non-parametric tests (i.e., the Mann-Whitney test, Friedman test, and Wilcoxon sign test) with P < 0.05. RESULTS: Significantly lower VAS scores were reported in the study group throughout the follow-up period (P < 0.05). Pharmacological protocol did not have a significant impact on postoperative edema and trismus (P > 0.05). However, double etoricoxib intake significantly improved postoperative quality of life on day 3 after surgery (P < 0.05). CONCLUSIONS: Pre- and postoperative etoricoxib 120 mg intake in third molar surgery reduced postoperative pain and enhanced postoperative quality of life on day 3 after surgery. Importantly, it was equally effective in managing swelling and trismus compared to exclusive postoperative intake. CLINICAL RELEVANCE: Preemptive etoricoxib use may decrease patient discomfort following impacted mandibular third molar extraction.

The Cyclooxygenase 2 Inhibitor Etoricoxib as Adjunctive Therapy in Tuberculosis Impairs Macrophage Control of Mycobacterial Growth.

BACKGROUND: Current tuberculosis treatment regimens could be improved by adjunct host-directed therapies (HDT) targeting host responses. We investigated the antimycobacterial capacity of macrophages from patients with tuberculosis in a phase 1/2 randomized clinical trial (TBCOX2) of the cyclooxygenase-2 inhibitor etoricoxib. METHODS: Peripheral blood mononuclear cells from 15 patients with tuberculosis treated with adjunctive COX-2i and 18 controls (standard therapy) were collected on day 56 after treatment initiation. The ex vivo capacity of macrophages to control mycobacterial infection was assessed by challenge with Mycobacterium avium, using an in vitro culture model. Macrophage inflammatory responses were analyzed by gene expression signatures, and concentrations of cytokines were analyzed in supernatants by multiplex. RESULTS: Macrophages from patients receiving adjunctive COX-2i treatment had higher M. avium loads than controls after 6 days, suggesting an impaired capacity to control mycobacterial infection compared to macrophages from the control group. Macrophages from the COX-2i group had lower gene expression of TNF, IL-1B, CCL4, CXCL9, and CXCL10 and lowered production of cytokines IFN-ß and S100A8/A9 than controls. CONCLUSIONS: Our data suggest potential unfavorable effects with impaired macrophage capacity to control mycobacterial growth in patients with tuberculosis receiving COX-2i treatment. Larger clinical trials are required to analyze the safety of COX-2i as HDT in patients with tuberculosis. CLINICAL TRIALS REGISTRATION: NCT02503839.

COX-2 inhibitor delivery system aiming intestinal inflammatory disorders.

Selective COX-2 inhibitors such as etoricoxib (ETX) are potentially indicated for the treatment of intestinal inflammatory disorders. However, their systemic administration provokes some off-site secondary effects, decreasing the desirable local effectiveness. To circumvent such limitations, herein an ETX delivery system based on electrospun fibrous meshes (eFMs) was proposed. ETX at different concentrations (1, 2, and 3 mg mL-1) was loaded into eFMs, which not affect the morphology and the mechanical properties of this drug delivery system (DDS). The ETX showed a burst release within the first 12 h, followed by a faster release until 36 h, gradually decreasing over time. Importantly, the ETX studied concentrations were not toxic to human colonic cells (i.e. epithelial and fibroblast). Moreover, the DDS loading the highest concentration of ETX, when tested with stimulated human macrophages, promoted a reduction of PGE2, IL-8 and TNF-α secretion. Therefore, the proposed DDS may constitute a safe and efficient treatment of colorectal diseases promoted by inflammatory disorders associated with COX-2.

[Investigation of the effect of ethylmethylhydroxypyridine succinate on the effectiveness of non-steroidal anti-inflammatory drugs for visceral and somatic pain in mice and rats]. / Izuchenie vliyaniya etilmetilgidroksipiridina suktsinata na effektivnost' nesteroidnykh protivovospalitel'nykh preparatov pri vistseral'noi i somaticheskoi boli v eksperimente na myshakh i krysakh.

OBJECTIVE: To study the effect of ethylmethylhydroxypyridine succinate (EMHPS) on the analgesic effect of the non-selective cyclooxygenase (COX) inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib in models of acute visceral and somatic pain and to evaluate the possibility of using EMHPS in combination with COX inhibitors to reduce their doses while maintaining analgesic efficiency. MATERIAL AND METHODS: We studied the effect of EMHPS with a single oral administration on the analgesic effects of non-steroidal anti-inflammatory drugs (NSAIDs): the non-selective COX inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib - on models of acute visceral (vinegar writhing test) and somatic pain (formalin test and mechanical hyperalgesia during inflammation) in an experiment on mice and rats. RESULTS: In a model of acute visceral pain in mice, EMGPS (25-100 mg/kg) does not have a significant effect on its severity, but enhances the analgesic effect of diclofenac sodium (0.5 mg/kg) and etoricoxib (1 mg/kg). In the formalin test in rats, which simulates pain during surgical incisions (trauma), EMGPS (25 mg/kg) increases the severity of the analgesic effect of COX inhibitors (1 mg/kg), primarily by reducing pain in the acute phase caused by the effect of formalin on afferent neurons. In a model of mechanical hyperalgesia in rats caused by exudative inflammation after injection of a carrageenan solution into the paw, EMHPS enhances the effect of diclofenac to a greater extent than etoricoxib. CONCLUSION: The data obtained indicate the feasibility of a clinical study of the use of EMGPS in combination with NSAIDs for visceral and somatic pain in order to assess its ability to increase the therapeutic effect of NSAIDs.

Etoricoxib enhances aryl hydrocarbon receptor activity.

Etoricoxib is a nonsteroidal anti-inflammatory drug (NSAID) that possesses properties that include reducing inflammation and relieving pain and fever. Etoricoxib is an oral medication that selectively inhibits cyclooxygenase-2 with high efficacy. Controversies about its cardiovascular side effects have long existed. The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor that plays a key role in the metabolism of xenobiotics and many physiological functions. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is a tryptophan metabolite and endogenous AhR agonist. Activation of AhR by its ligand induces upregulation of AhR-targeted cytochrome P450 (CYP) 1A1 expression. We found that etoricoxib (10-60 µM) induced CYP1A1 mRNA and protein expressions and the transcriptional activity of AhR mediated by the aryl hydrocarbon response element (AHRE) in both mouse Hepa-1c1c7 and human HepG2 cells. Its induction did not appear in AhR signaling-deficient cells, and was inhibited by the AhR antagonist, CH-223191. Etoricoxib was able to induced the translocalization of AhR from cytosol into nucleus. Etoricoxib also worked synergistically with ITE to further increase the expression of CYP1A1 mRNA and protein in human cells. The synergistic effect was higher in cells with than cells without overexpression of AhR. In summary, etoricoxib is an agonist of AhR in both mouse and human cells. Etoricoxib has a synergistic effect on ITE-induced CYP1A1 expression in human cells. The effect of etoricoxib on AhR and ITE on endothelial cells and cardiomyocytes should be further elucidated to in hope to clarify the mechanism of increased cardiovascular events in COX-2 inhibitors and etoricoxib.

Remission of Dowager's hump by manipulative correction of spinal alignment: a case report.

Dowager's hump is described as excessive kyphotic curvature in the thoracic spine with a Cobb angle of more than 40 degrees. This case report presents a 61 years old female office clerk who experienced headaches and neck pain for 3 years that extended into her right shoulder and upper chest. She consulted her primary care physician two months before seeing the chiropractor when the neck pain worsened. A diagnosis of cervicalgia related to osteoarthritis was made based on cervical and thoracic X-ray findings. The patient received non-steroid anti-inflammatory drugs (celecoxib and etoricoxib) and stretching exercises at home. At the onset of chiropractic care, radiographs showed loss of cervical lordosis, narrowing at the C4-5, C5-C6, and C6-7 intervertebral disc space with marginal osteophytes. Based on these findings, a working diagnosis of cervicogenic headache was established. After treatment for 9 months, the patient showed improvement in symptoms and function from cervical curve radiographic change and dextro-convexity of the thoracic spine. Avoiding forward head flexion and maintaining correct posture in daily activities will be key mechanisms to prevent the reoccurrence of Dowager's hump. The improvement of symptoms following chiropractic therapy has been shown to correlate with radiographic markers of spinal realignment.

Preemptive effects of etoricoxib, acetaminophen, nimesulide, and ibuprofen on postoperative pain management after single-implant surgery: A randomized clinical trial.

BACKGROUND: There is insufficient evidence for pain control in preemptive analgesia (PA) after dental implant surgery, signaling the need for further studies. The objective of this study was to evaluate the efficacy of PA in single dental implant surgeries (SDIS), seeking to identify among the etoricoxib (ETOR), ibuprofen (IBU), nimesulide (NIME), and acetaminophen (ACETA)], which one has the higher efficacy effectiveness in relieving postoperative pain and reducing the use of rescue medication compared to placebo. METHODS: In this triple-blind, parallel, randomized controlled clinical trial, 135 individuals with a mean age of 57.6 years (±11.7), both genders, were randomly divided into five groups according to the test drug: I-PLACEBO; II-IBU (600 mg); III-NIME (100 mg); IV-ACETA (750 mg); and V-ETOR (90 mg). The occurrence, duration, and intensity of pain were analyzed using the Chi-square, Fisher's exact and ANOVA tests, and the generalized estimating equation models, when appropriate. RESULTS: Test drugs provided a reduction in postoperative pain scores and lower use of rescue medication when compared to placebo. The ETOR group presented significantly lower pain scores, when compared to other active treatments. The IBU group showed the highest mean number of rescue medication used. CONCLUSIONS: All test drugs provided a beneficial preemptive effect demonstrated by the reduced postoperative pain and reduced use of rescue medication. The ETOR group presented lower pain scores, and the IBU group showed the highest mean number of rescue medication used among the test groups.

Etoricoxib nanostructured lipid carriers attenuate inflammation by modulating Cyclooxygenase-2 signaling and activation of nuclear factor-κB-p65 pathways in radiation-induced acute cardiotoxicity in rats.

The current investigation aimed to explore the potential of etoricoxib nanostructured lipid carriers (ET-NLCs) as an anti-inflammatory drug in radiation-exposed rats, with a focus on assessing its efficacy in reducing inflammation while minimizing cardiac toxicity compared to conventional etoricoxib (ET) treatment. The ET-NLCs were prepared by the low-temperature melt emulsification solidification technique. Various techniques were employed to characterize the NLCs. Rats were exposed to gamma-irradiation (6 Gy) to induce cardiac inflammation and injury, followed by oral administration of ET or ET-NLCs (10 mg/kg b.w.) for 14 consecutive days. Results demonstrated a significant increase in the levels of malondialdehyde (MDA), cyclooxygenase-2 (COX-2), nuclear factor kappa-B p65 (NF-κB-p65), and poly ADP-ribose polymerase (PARP-1) in the heart tissues of gamma-irradiated rats compared to the control group. This increase was accompanied by a reduction in the activity of antioxidant enzymes. However, treatment with ET and ET-NLCs exhibited a positive impact on these levels. Interestingly, the efficacy of ET-NLCs in mitigating radiation-induced inflammation in heart tissue was found to be superior to that of ET. In conclusion, the study suggests that the utilization of NLCs as a drug delivery system for ET may not only enhance its therapeutic efficacy but also help reduce the cardiovascular risks associated with ET, specifically focused on individuals who had been exposed to gamma radiation. These findings open new avenues for further research in the development of effective and safer therapeutic strategies for managing inflammatory diseases and their impact on cardiovascular health.

The Efficacy of Oral Etoricoxib in Pain Control During Colposcopy-Directed Cervical Biopsy: A Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness and safety of oral etoricoxib administration before colposcopic procedure for pain relief during and after colposcopy. METHODS: A prospective double-blind, randomized controlled trial was conducted at the colposcopy unit of Thammasat University Hospital, Thailand from August 2022 to January 2023. The participants were women undergoing colposcopy. They were allocated into two groups: etoricoxib group and control group. Thirty minutes prior to colposcopy, the participants received etoricoxib or placebo tablet. A numerical rating scale was used to evaluate pain upon speculum insertion, 3% acetic acid application, directed cervical biopsy (CDB), endocervical curettage (ECC), and 10 minutes and 24 hours after colposcopy. RESULT: One hundred and ten women were recruited and were divided equally into study and control groups. The mean age of participants was 42.6 years old. One-fourth of cases (29/110) had cervical intraepithelial neoplasia grade 2 or more histology. Subjects in etoricoxib group had less median pain scores during CDB, ECC, and 10-minute and 24-hour post procedure than the control group with statistical significance. Both groups had comparable side effects. CONCLUSION: Administration of oral etoricoxib 30 minutes before colposcopy could reduce pain during and up to 24-hour post colposcopy with minimal side effects.

Selective COX-2 inhibitors after bariatric surgery: Celecoxib, etoricoxib and etodolac post-bariatric solubility/dissolution and pharmacokinetics.

Anatomical/physiological gastrointestinal changes after bariatric surgery may influence the fate of orally administered drugs.Since non-selective NSAIDs are not well-tolerated post-surgery, selective cyclooxygenase-2 (COX-2) inhibitors may be important for these patients. In this work we investigated celecoxib, etoricoxib and etodolac, for impaired post-bariatric solubility/dissolution and absorption. Solubility was studied in-vitro, and ex-vivoin aspirated gastric contents from patients pre- vs. post-surgery. Dissolution was studied in conditions simulating pre- vs. post-surgery stomach. Finally, the experimental solubility data were used in physiologically-based biopharmaceutics model (PBBM) (GastroPlus®) to simulate pre- vs. post-surgery celecoxib/etoricoxib/etodolac pharmacokinetic (PK) profiles.For etoricoxib and etodolac (but not celecoxib), pH-dependent solubility was demonstrated: etoricoxib solubility decreased âˆ¼1000-fold, and etodolac solubility increased 120-fold, as pH increased from 1 to 7, which was also confirmed ex-vivo. Hampered etoricoxib dissolution and improved etodolac dissolution post-surgery was revealed. Tablet crushing, clinically recommended after surgery, failed to improve post-bariatric dissolution. PBBM simulations revealed significantly impaired etoricoxib absorption post-surgery across all conditions; for instance, 79% lower Cmax and 53% decreased AUC was simulated post-gastric bypass procedure, after single 120 mg dose. Celecoxib and etodolac maintained unaffected absorption after bariatric surgery.This mechanistically-based analysis suggests to prefer the acidic drug etodolac or the neutral celecoxib as selective COX-2 inhibitors, over the basic drug etoricoxib, after bariatric surgery.

Comparison of preemptive etoricoxib and dexamethasone in third molar surgery - a randomized controlled clinical trial of patient-reported and clinical outcomes.

OBJECTIVES: To compare preemptive single-dose etoricoxib and dexamethasone on postoperative patient satisfaction (pPS) and clinical parameters following the impacted mandibular third molar (IMTM) extraction. MATERIALS AND METHODS: A parallel-group, triple-blinded, controlled clinical study included a total of 90 patients (n = 30), randomized to receive: etoricoxib 90 mg, dexamethasone 4 mg, or no premedication (control group) 1 h before surgery. Paracetamol 500 mg was prescribed as rescue medication (RM). Check-ups were scheduled at 24 h, 48 h, and day 7 post-surgery. At each time point, pPS was assessed using the 5-point Likert scale. RM parameters, swelling, trismus, and the occurrence of adverse events were also recorded, and patients were instructed to rate the perceived pain on Visual Analogue Scale. RESULTS: In all the follow-up periods, data indicated significantly higher pPS scores in the preemptive medication groups when compared to the control group (p < 0.05). Both regimens delayed the first RM intake when compared to controls. In the etoricoxib group, a significantly lower total RM consumption was observed (p < 0.05). Dexamethasone significantly decreased swelling at each check-up and increased mouth opening at day 7 after the surgery (p < 0.05). CONCLUSIONS: Preemptive etoricoxib and dexamethasone elevate pPS after IMTM surgery. Etoricoxib improves RM parameters, while dexamethasone ameliorates the patient's postoperative functional ability. CLINICAL RELEVANCE: Preemptive etoricoxib and dexamethasone use may decrease patients' discomfort following the impacted mandibular third molar extraction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05791721. Date of Registration: 28/03/2023 (retrospectively registered).

Transient depersonalisation/derealisation syndrome from tramadol.

Depersonalisation/derealisation (DD) syndrome is often associated with severe traumatic experiences and the use of certain medications. Our patient reported experiencing a transient DD phenomenon a few hours after taking 37.5 mg of tramadol, together with etoricoxib, acetaminophen and eperisone. His symptoms subsided upon tramadol discontinuation, suggesting the possibility of tramadol-induced DD. A study of the patient's cytochrome P450 (CYP) 2D6 polymorphism, which mainly metabolises tramadol, indicated normal metaboliser status with reduced function. The concomitant administration of the CYP2D6 inhibitor, etoricoxib, would have led to higher concentrations of the serotonergic parent tramadol, providing an explanation for the patient's symptoms.

Merging konjac glucomannan with other copolymeric hydrogels as a cutting-edge liquid raft system for dual delivery of etoricoxib and famotidine.

This study aimed to formulate and evaluate a floating raft system for the co-delivery of etoricoxib (ETO) and famotidine (FAM) using a combination of glucomannan with natural/semi-synthetic polysaccharides. Formulation variables affect gelation lag time (GLT), floating lag time (FLT), and release percentage of drugs after 1-8 h, Stability, and viscosity parameters were evaluated. In vivo X-ray studies, followed by the pharmacokinetic study, were performed on human volunteers. Formulations exhibited pseudoplastic behavior for ease of swallowing. The optimum raft system (ORS) comprised 1% Na alginate, 0.1% Low Methoxyl (LM) pectin, 0.8% Konjac glucomannan (KGL), 1% Precirol, and 1% CaCO3. ORS exhibited rapid GLT and FLT (around 42 and 8 sec respectively) in 0.1 N HCl as well as controlled release of ETO (15% in 1 h and 82% in 8 h) and FAM (29% in 1 h and 85% in 8 h). Formulation stability with the absence of any drug-excipient interactions was observed. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. Compared with marketed products, ORS showed superior relative bioavailability for both drugs. These findings revealed the successful preparation of a promising raft system with improved dual drug delivery.

[Selective cyclooxygenase-2 inhibitor hypersensitivity]. / Hipersensibilidad selectiva a inhibidores de la ciclooxigenasa-2.

BACKGROUND: The cyclooxygenase-2 inhibitors are usually recommended as a safe alternative in patients with multiple hypersensitivity to non-steroidal antiinflammatory drugs. Nevertheless, both immediate and delayed hypersensitivity reactions have been described, and the possibility of cross-reactivity with sulphonamides. CASE REPORT: A 66-year-old patient who, after taking a celecoxib tablet, presented with latency of several hours a skin reaction. Previously, he had presented a minor reaction during treatment with etoricoxib without establishing the correlation at that time. The patient underwent an allergological study by means of skin tests with negative results and an oral challenged test with etoricoxib with positive results. Tolerance to sulfonamides was proven. CONCLUSIONS: We present a singular case of a cross-reactivity skin reaction to etoricoxib and celecoxib, suggesting the need to perform challenge tests to confirm the tolerance or not of each drug before allowing their use. On the contrary, trimethropim/sulfamethoxazole could be safely used in our patients, if needed.

INTRODUCCIÓN: Los inhibidores de la ciclooxigenasa-2 suelen indicarse en pacientes con hipersensibilidad múltiple a los antiinflamatorios no esteroides. Sin embargo, se han descrito reacciones de hipersensibilidad inmediata y retardada, además de posible reactividad cruzada con sulfonamidas. REPORTE DE CASO: Paciente masculino de 66 años, que acudió al servicio de Alergia por una reacción cutánea, luego de haber consumido un comprimido de celecoxib. Previamente, durante el tratamiento con etoricoxib, tuvo una reacción menor, sin establecer la correlación farmacológica. Se realizaron pruebas cutáneas (intraepidérmicas y epicutáneas), con resultados negativos, y un examen de exposición oral controlada con etoricoxib, con resultado positivo. Se comprobó la tolerancia a las sulfamidas. CONCLUSIONES: El caso de reacción cutánea, mediante reactividad cruzada, entre etoricoxib y celecoxib expuesto en este artículo sugiere la necesidad de realizar pruebas de provocación para confirmar la tolerancia de cada fármaco antes de su prescripción. Por el contrario, trimetropim-sulfametoxazol pueden indicarse con seguridad, si fuese necesario.

Secondary cough headache: Independent course of headache and response to a COX-2 inhibitor.

We report on two patients with secondary cough headache who responded to the cyclo-oxygenase-2 (COX-2) inhibitor etoricoxib and showed an independent temporal course. This case report shows that secondary cough headache can also respond to medical treatment and can respond to a COX-2 inhibitor, not previously reported. As is seen in primary cough headache, the headache disorder can go into natural remission (case 1) while the secondary pathology progresses and conversely, persist once the secondary pathology has resolved (case 2). The course of the headache and that of the secondary pathology do not necessarily correlate. It is, therefore, proposed that any treatment of the secondary pathology is independent to that of the headache. In NSAID-intolerant cases a COX-2 inhibitor can be trialled first line.

Selective COX-2 Inhibitor Etoricoxib's Liposomal Formulation Attenuates M2 Polarization of TAMs and Enhances its Anti-metastatic Potential.

INTRODUCTION: COX-2 inhibition in pro-tumoral M2 polarization of Tumor-Associated Macrophages (TAMs) underscore the improved prognosis and response to cancer therapy. Thus, etoricoxib, a COX-2 inhibiting NSAID drug is highly effective against tumorigenesis, but its compromised solubility and associated hepatotoxicity, and cardiotoxicity limit its clinical translation. OBJECTIVE: In view of the consequences, the proposed study entails the development of a liposomal formulation for etoricoxib and evaluates its anticancer potential. METHODS AND RESULT: Etoricoxib loaded liposome was prepared by thin layer hydration method and characterized as a nearly monodisperse system with particle size (91.64 nm), zeta potential (-44.5 mV), drug loading (17.22%), and entrapment efficiency (94.76%). The developed formulation was administered subcutaneously into the orthotopic 4T1/Balb/c mice model. Its treatment significantly reduced tumor size and skewed M2 polarization of TAMs to a greater extent against free etoricoxib. Furthermore, Tumor tissues analyzed through immunoblotting study confirmed the reduction in Akt phosphorylation at Thr308 residue and pro-tumoral VEGF, MMP-9, and MMP-2 proteins; Moreover, histology studies and microCT analysis of bones revealed the enhanced anti-metastatic potential of etoricoxib delivered through developed formulation against free etoricoxib. CONCLUSION: As an epilogue, the developed formulation efficiently delivers poorly soluble etoricoxib, enhances its therapeutic potential as an anti-tumor and anti-metastatic agent, and directs explorative research for clinical translation.

Comparative Risks of Nonsteroidal Anti-inflammatory Drugs on Cardiovascular Diseases: A Population-Based Cohort Study.

Through examining the incidence of cardiovascular diseases (CVDs) among nonsteroidal anti-inflammatory drug (NSAID) users and nonusers, this study aims to compare the risks contributed by different NSAIDs in a Chinese population. The retrospective cohort including 4 298 368 adults without CVD from electronic health records between 2008 and 2017 in Hong Kong was adopted. A total of 4.5% of individuals received NSAIDs including celecoxib, etoricoxib, diclofenac, ibuprofen, indomethacin, mefenamic acid, or naproxen for ≥4 consecutive weeks at baseline. Cox regression, including NSAID use as a time-dependent covariate and adjusted with patient's characteristics, was conducted to examine the association between NSAID exposure and incident CVD. After a median follow-up of 6.9 years (30 million person-years), a total of 258 601 cases of incident CVD was recorded. NSAID use was shown to be associated with a significantly higher risk of CVD (hazard ratio [HR], 1.32 [95%CI, 1.28-1.37]) compared to non-NSAID use. Similar results in coronary heart disease (HR, 1.37 [95%CI, 1.31-1.43]), stroke (HR, 1.27 [95%CI, 1.21-1.33]), and heart failure (HR, 1.25 [95%CI, 1.16-1.34]) were obtained. Overall, similar CVD risk was observed across users of NSAIDs except for etoricoxib, which showed a higher risk (HR, 2.01 [95%CI, 1.63-2.48]). Considering that a higher CVD risk was consistently displayed among NSAID users, NSAIDs should be used cautiously, and the usage of etoricoxib in the Chinese population should be reviewed.

Evaluating the efficacy of Etoricoxib in reducing post-operative pain associated with minor oral surgery. A randomized clinical trial / Avaliação da eficácia do Etoricoxibe na redução da dor pós-operatória associada à cirurgia oral menor: ensaio clínico randomizado

Etoricoxib, a new cyclooxygenase-2-selective inhibitor has demonstrated a rapid onset analgesic effect for relieving acute pain especially when prescribed as a pre-emptive medication. On these bases, this study may provide useful information and guidance for clinicians working in the field of oral surgery, as regards handling odontogenic pain and postoperative pain precisely with cyclooxygenase-2 inhibitors. Objective: the study aimed to measure the quantifiable efficacy of Etoricoxib in reducing post-extraction pain in subjects undergoing minor oral surgical intervention as compared to Naproxen (a traditional NSAID) which is commonly used to control postoperative pain. Material and Methods: a 120 mg film-coated tablet of Etoricoxib was given to each of the twenty patients representing the study group, and a 500 mg tablet of Naproxen was given to each of the other twenty subjects representing the positive control group. According to manufacturer instructions, the tablets were given to the subjects 30 minutes pre-operatively (before dental extraction). Post-operative pain was assessed for each subject using eleven points from zero to ten, visual analog scale. Results: showed no statistically significant difference between Etoricoxib and Naproxen in decreasing post-extraction odontogenic pain, suggesting that Etoricoxib is as efficient as Naproxen in the control of discomfort with dental origin taking into consideration the patient's status when prescribing the medication. Conclusion: this study suggests that Etoricoxib can be handled as a pre-emptive medication to reduce post-operative pain for subjects seeking traditional or surgical extraction of any of their teeth (AU)

O Etoricoxibe, um novo inibidor seletivo da ciclooxigenase-2, demonstrou um efeito analgésico de início rápido para aliviar a dor aguda, especialmente quando prescrito como medicação preventiva. Com base nesses fundamentos, este estudo pode fornecer informações úteis e orientação para clínicos que trabalham no campo da cirurgia oral, no que diz respeito ao manejo da dor odontogênica e da dor pós-operatória de forma precisa com inibidores da ciclooxigenase-2. Objetivo: o estudo teve como objetivo medir a eficácia quantificável do Etoricoxibe na redução da dor pós-extração em indivíduos submetidos a intervenção cirúrgica oral menor, comparado ao Naproxeno (AINE tradicional) que é comumente usado para controlar a dor pós-operatória. Material e Métodos: um comprimido revestido com um filme de 120 mg de Etoricoxibe foi administrado a cada um dos 20 pacientes representando o grupo de estudo, e um comprimido de 500 mg de Naproxeno foi administrado a cada um dos outros vinte sujeitos representando o grupo de controle positivo. De acordo com as instruções do fabricante, os comprimidos foram administrados aos indivíduos 30 minutos antes da cirurgia (antes da extração dentária). A dor pós-operatória foi avaliada para cada sujeito usando uma escala analógica visual de onze pontos, de zero a dez. Resultados: não mostraram diferença estatisticamente significativa entre o Etoricoxibe e o Naproxeno na diminuição da dor odontogênica pós-extração, sugerindo que o Etoricoxibe é tão eficiente quanto o Naproxeno no controle do desconforto de origem dentária, levando em consideração o estado do paciente ao prescrever a medicação. Conclusão: este estudo sugere que o Etoricoxibe pode ser administrado como medicação preventiva para reduzir a dor pós-operatória em indivíduos que buscam extração dentária tradicional ou cirúrgica de qualquer um de seus dentes. (AU)

Cyclooxygenase-2 plays a crucial role during myocardial patterning of developing chick.

Cyclooxygenase-2 (COX-2), a member of the Cyclooxygenase family, initiates the biosynthesis of prostanoids that regulates various cellular functions. Our pilot attempt revealed that the administration of etoricoxib, an inhibitor specific for COX-2, induces abnormal looping in the chicken heart. The present study attempts to reveal the mechanistic details of etoricoxib-induced abnormal cardiac looping. The activity of COX-2 was inhibited by administering 3.5 µg of etoricoxib into the egg's air cell on day zero of incubation. The gene and protein expression patterns of key mediators of heart development were then analyzed on day 2 (HH12) and day 3 (HH20). Reduced COX-2 activity altered the expressions of upstream regulators of organogenesis like Wnt11, BMP4, and SHH in the etoricoxib-exposed embryos. The observed expression shifts in the downstream regulators of myocardial patterning (MYOCD, HAND2, GATA4, GATA5, and GATA6) in the treated embryos corroborate the above results. In addition, the reduction in COX-2 activity hampered cardiomyocyte proliferation with a concomitant increase in the apoptosis rate. In conclusion, the collective effect of altered expression of signaling molecules of myocardial patterning and compromised cardiomyocyte turnover rate could be the reason behind the looping defects observed in the heart of etoricoxib-treated chick embryos.

The effect of non-steroidal anti-inflammatory drugs with different mechanisms of action on the body temperature and cyclooxygenase pathway of the arachidonic acid cascade on the model of acute general cooling (air hypothermia) in rats.

NSAIDs are promising agents for preventing cold injury (frigoprotectors). The influence of prophylactic administration of the non-selective COX inhibitor diclofenac sodium (7 mg/kg) and the highly selective COX-2 inhibitor etoricoxib (5 mg/kg) on cyclooxygenase pathway biomarkers was studied on the model of acute general cooling (air hypothermia at -18 °С for 2 hours). Diclofenac completely prevented a decrease in body temperature, surpassing etoricoxib. In the liver of the rats immediately after cold exposure, the content of COX-1 was increased moderately and the content of COX-2 highly significantly. Very significantly, the level of PGE2 decreased, and the levels of PGF2α, especially PGI2 and TXB2, were elevated. In the blood serum, the level of COX-1 was decreased, and the changes in COX-2 and prostaglandins levels were similar to those in the liver. Diclofenac exerted a moderate effect towards the normalization of both COX isoforms in the liver, moderately increased the content of PGE2, and decreased - PGF2α and TXB2 without changing the level of PGI2. In serum, diclofenac reduced COX-1 level to subnormal values, and its effect on other biomarkers was similar to that in the liver, except for a moderate decrease in PGI2. Thus, diclofenac was inferior to etoricoxib, which normalized COX-1, COX-2, PGE2, and PGI2 in the liver and reduced the content of PGF2α and TXB2 in the liver to subnormal values. At the same time, in the blood serum, it decreased COX-1, COX-2, and PGE2 to subnormal values, normalized PGF2α, and PGI2, and significantly reduced TXB2. The opposite degree of intensity of the influence of diclofenac and etoricoxib on the cyclooxygenase pathway and body temperature indicates a dissociation of anti-inflammatory and frigoprotective activity. Inhibition of oxidative stress is not determinative for the frigoprotective activity of NSAIDs since diclofenac, despite the weaker influence on the content of 8-isoprostane in the liver, still exerts the maximum frigoprotective activity.