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1.
Behav Neurol ; 2021: 9536054, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539935

RESUMO

Background: The purpose of this meta-analysis was to assess the clinical efficacy of etoricoxib in comparison with traditional NSAIDs for postoperative pain after third molar surgery. Methods: The quality of studies found in PubMed and Google Scholar was evaluated with Cochrane Collaboration's risk of bias tool. Data on total consumption of rescue analgesics, number of patients using rescue analgesics, global assessment of study treatments, and adverse effects were extracted exclusively from high-quality clinical trials. Each meta-analysis was performed with the Review Manager Software 5.3 for Windows. Results: The qualitative analysis showed that etoricoxib has better analgesic activity when compared with ibuprofen (2 clinical trials) and diclofenac (1 clinical trial). A similar analgesic efficacy between etoricoxib and nonselective Cox-2 NSAIDs was informed in 3/8 studies (2 compared to ibuprofen and 1 to naproxen sodium). Moreover, the number of patients requiring rescue analgesics in the postoperative period showed a statistical difference in favor of etoricoxib when compared to NSAIDs. Conclusion: Etoricoxib significantly reduces the number of patients needing rescue analgesics compared to NSAIDs after third molar surgery.


Assuntos
Dente Serotino , Sulfonas , Analgésicos , Etoricoxib , Humanos , Dente Serotino/cirurgia , Piridinas/uso terapêutico , Sulfonas/uso terapêutico
2.
BMC Oral Health ; 21(1): 462, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556118

RESUMO

BACKGROUND: How to prevent pain after the extraction of impacted teeth is a serious challenge for all patients. The purpose of this clinical trial was to investigate whether pre-emptive low dose of etoricoxib can reduce postoperative pain in patients undergoing third molars surgery. METHODS: Patients were randomised to receive etoricoxib 60 mg or placebo 30 min before surgery. Post-operative pain was recorded using a visual analogue scale during 24 h within the post-operative period. The total dose of ibuprofen rescue intake was recorded. Kaplan-Meier curves and log-rank analyses were used to evaluate the proportion of patients without rescue analgesic. RESULTS: Scores for the post-operative pain in the etoricoxib group were significantly lower than those in the placebo group during first 12 h (p < 0.05). The number of patients without analgesic rescue medication was significantly lower in the etoricoxib group than in the placebo group. The average amount of rescue medication in the etoricoxib group (0.4 ± 0.9 dose) was lower than that in the placebo group (1.1 ± 0.9 doses, p = 0.004). Etoricoxib resulted in the long-term survival of patients without rescue analgesic (p < 0.001). CONCLUSIONS: This study revealed that etoricoxib has a substantial pre-emptive analgesic effect, resulting in the reduced use of analgesics after third molar removal. TRIAL REGISTRATION: Registered on ChiCTR1900024503. Date of Registration: 13/07/2019.


Assuntos
Dente Serotino , Dente Impactado , Método Duplo-Cego , Etoricoxib , Humanos , Dente Serotino/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Extração Dentária , Dente Impactado/cirurgia
3.
J Med Chem ; 64(15): 11570-11596, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34279934

RESUMO

Selective cyclooxygenase (COX)-2 inhibitors have been extensively studied for colorectal cancer (CRC) chemoprevention. Celecoxib has been reported to reduce the incidence of colorectal adenomas and CRC but is also associated with an increased risk of cardiovascular events. Here, we report a series of gut-restricted, selective COX-2 inhibitors characterized by high colonic exposure and minimized systemic exposure. By establishing acute ex vivo 18F-FDG uptake attenuation as an efficacy proxy, we identified a subset of analogues that demonstrated statistically significant in vivo dose-dependent inhibition of adenoma progression and survival extension in an APCmin/+ mouse model. However, in vitro-in vivo correlation analysis showed their chemoprotective effects were driven by residual systemic COX-2 inhibition, rationalizing their less than expected efficacies and highlighting the challenges associated with COX-2-mediated CRC disease chemoprevention.


Assuntos
Antineoplásicos/farmacologia , Celecoxib/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Etoricoxib/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Celecoxib/química , Celecoxib/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Etoricoxib/química , Etoricoxib/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Relação Estrutura-Atividade
4.
Biochemistry ; 60(31): 2407-2418, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34293856

RESUMO

Long residence time enzyme inhibitors with a two-step binding mechanism are characterized by a high internal energy barrier for target association. This raises the question of whether optimizing residence time via further increasing this internal energy barrier would inevitably lead to insufficient target occupancy in vivo due to slow, time-dependent binding. We attempted to address this question during optimization of cyclooxygenase-2 (COX-2) inhibitors. Defining long residence time drugs with acceptable association and dissociation rate constants required for sufficient target occupancy and sustained efficacy, which we termed "balanced internal energetics", provides an important criterion for successful progression during lead optimization. Despite the advancement of several COX-2 inhibitors to marketed drugs, their detailed inhibition kinetics have been surprisingly limiting especially during the structure-activity relationship process mainly due to the lack of robust kinetic assays. Herein, we describe a reoptimized COX enzymatic assay and a novel MS-based assay enabling detailed mechanistic studies for identifying long residence time COX-2 inhibitors with balanced internal energetics. These efforts led to the discovery of promising leads possessing dissociation half-lives of ≤40 h, much greater than the values of 6 and 0.71 h for two marketed drugs, etoricoxib and celecoxib, respectively. Importantly, the inhibition rate constants remain comparable to those of the marketed drugs and above the lower limits set by the criteria of balanced internal energetics, predicting sufficient target occupancy required for efficacy. Taken together, this study demonstrates the feasibility of increasing the internal energy barrier as a viable approach for lead optimization toward discovering long residence time drug candidates.


Assuntos
Inibidores de Ciclo-Oxigenase 2/química , Descoberta de Drogas/métodos , Ensaios Enzimáticos/métodos , Furanos/química , Espectrometria de Massas/métodos , Piridinas/química , Celecoxib/química , Celecoxib/farmacologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Etoricoxib/química , Etoricoxib/farmacologia , Fluorescência , Furanos/farmacologia , Humanos , Hidrogênio/química , Cinética , Modelos Teóricos , Oxigênio/química , Pirazóis/química , Pirazóis/farmacologia , Piridinas/farmacologia , Termodinâmica , Fatores de Tempo
5.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 56(6): 565-569, 2021 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-34098672

RESUMO

Objective: To evaluate the effect of preventive use of etocoxib-induced preemptive analgesia on three types of pain (wound pain, swallowing pain, mouth opening pain) after extraction of impacted teeth. Methods: In this study, 60 patients (60 teeth) with impacted mandibular third molars in Department of Jinyintan Outpatient, School of Stomatology, Wuhan University from May to October 2020 were enrolled. The patients were numbered by SPSS 21.0 and randomly divided into two groups. The odd number was included in the etocoxib group, and the even number was included in the control group, with 30 cases in each group. Patients in the two groups were given etocoxib 60 mg or placebo vitamin C 100 mg 30 min before operation. Pain at 2, 4, 6, 8, 10, 12, and 24 hours after tooth extraction was recorded with numeric rating scale (NRS) score. The total dose of ibuprofen rescue intake was recorded. Kaplan-Meier curves and Log-Rank analyses were used to evaluate the proportion of patients without rescue analgesic. Results: The NRS scores of wound pain, swallowing pain and mouth opening pain in the etoricoxib group were lower than those in the control group within 24 hours after tooth extraction (P<0.05). The total dose of emergency analgesics in the etoricoxib group [(0.7±0.7) dose] was lower than that in the control group [(1.4±0.9) dose] (P<0.01). The mean time between first application of analgesics was 11.5 hours in etoricoxib group and 3.5 hours in the placebo group, respectively (P<0.05). Conclusions: This study revealed that etoricoxib has a substantial preemptive analgesic effect, resulting in the reduced use of analgesics after third molar removal.


Assuntos
Analgesia , Dente Impactado , Método Duplo-Cego , Etoricoxib , Humanos , Dente Serotino/cirurgia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Extração Dentária , Dente Impactado/cirurgia
6.
BMC Cancer ; 21(1): 493, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941107

RESUMO

BACKGROUND: Glioblastoma (GBM) is the deadliest and the most common primary brain tumor in adults. The invasiveness and proliferation of GBM cells can be decreased through the inhibition of Wnt/ß-catenin pathway. In this regard, celecoxib is a promising agent, but other COXIBs and 2,5-dimethylcelecoxib (2,5-DMC) await elucidation. Thus, the aim of this study was to analyze the impact of celecoxib, 2,5-DMC, etori-, rofe-, and valdecoxib on GBM cell viability and the activity of Wnt/ß-catenin pathway. In addition, the combination of the compounds with temozolomide (TMZ) was also evaluated. Cell cycle distribution and apoptosis, MGMT methylation level, COX-2 and PGE2 EP4 protein levels were also determined in order to better understand the molecular mechanisms exerted by these compounds and to find out which of them can serve best in GBM therapy. METHODS: Celecoxib, 2,5-DMC, etori-, rofe- and valdecoxib were evaluated using three commercially available and two patient-derived GBM cell lines. Cell viability was analyzed using MTT assay, whereas alterations in MGMT methylation level were determined using MS-HRM method. The impact of COXIBs, in the presence and absence of TMZ, on Wnt pathway was measured on the basis of the expression of ß-catenin target genes. Cell cycle distribution and apoptosis analysis were performed using flow cytometry. COX-2 and PGE2 EP4 receptor expression were evaluated using Western blot analysis. RESULTS: Wnt/ß-catenin pathway was attenuated by COXIBs and 2,5-DMC irrespective of the COX-2 expression profile of the treated cells, their MGMT methylation status, or radio/chemoresistance. Celecoxib and 2,5-DMC were the most cytotoxic. Cell cycle distribution was altered, and apoptosis was induced after the treatment with celecoxib, 2,5-DMC, etori- and valdecoxib in T98G cell line. COXIBs and 2,5-DMC did not influence MGMT methylation status, but inhibited COX-2/PGE2/EP4 pathway. CONCLUSIONS: Not only celecoxib, but also 2,5-DMC, etori-, rofe- and valdecoxib should be further investigated as potential good anti-GBM therapeutics.


Assuntos
Neoplasias Encefálicas/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Glioblastoma/metabolismo , Proteínas de Neoplasias/efeitos dos fármacos , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Idoso , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Celecoxib/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Metilases de Modificação do DNA/efeitos dos fármacos , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/efeitos dos fármacos , Enzimas Reparadoras do DNA/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Etoricoxib/farmacologia , Feminino , Glioblastoma/tratamento farmacológico , Humanos , Isoxazóis/farmacologia , Lactonas/farmacologia , Masculino , Metilação , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Receptores de Prostaglandina E Subtipo EP4/efeitos dos fármacos , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Sulfonas/farmacologia , Temozolomida/farmacologia , Proteínas Supressoras de Tumor/efeitos dos fármacos , Proteínas Supressoras de Tumor/metabolismo , beta Catenina/efeitos dos fármacos , beta Catenina/metabolismo
7.
Biomed Pharmacother ; 139: 111625, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33895524

RESUMO

OBJECTIVE: The current study was to evaluate the association of Etoricoxib treatment and incident hypoxia among type-B aortic dissection (AD) patients undergoing endovascular aortic repair (EVAR). METHODS: Patients undergoing EVAR were retrospectively recruited. Based on Etoricoxib use, patients were divided into the non-treated and Etoricoxib-treated groups. Baseline characteristics including demographics, laboratory parameters, characteristics of aortic computer tomography and echocardiography, medications used, and procedural characteristics were collected from the electronic health record. RESULTS: Compared to non-treated group (n = 36), prevalence of obesity and fever at baseline was higher in Etoricoxib-treated group (n = 24; P < 0.05). Mean number of neutrophils, and mean serum CRP and D-dimer levels were higher in Etoricoxib-treated group (P < 0.05). The overall incidence of hypoxia was lower in Etoricoxib-treated group (44.4% vs 33.4%, P < 0.05). Increase in neutrophils count, serum CRP and D-dimer levels was associated with incident hypoxia, with an odds ratio (OR) of 1.36 (95% confidence interval [CI] 1.07-1.65), 1.44 (95% CI 1.12-1.78) and 1.25 (95% CI 1.01-1.47) respectively. In unadjusted model, Etoricoxib use was associated with a 44% lower odds of incident hypoxia. After adjustment for inflammatory markers, the association between Etoricoxib and incident hypoxia was non-significant, with OR of 0.95% and 95% CI of 0.78-1.06. CONCLUSION: Compared to patients who did not receive Etoricoxib during hospitalization, those treated with Etoricoxib had lower incidence of hypoxia, which might be attributed to its anti-inflammatory effects.


Assuntos
Aneurisma Dissecante/cirurgia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Procedimentos Endovasculares/métodos , Etoricoxib/uso terapêutico , Hipóxia/epidemiologia , Hipóxia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Dissecante/complicações , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Ecocardiografia , Etoricoxib/efeitos adversos , Feminino , Febre/complicações , Febre/epidemiologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Prevalência , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
J Bone Miner Res ; 36(8): 1459-1468, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33852188

RESUMO

Primary hypertrophic osteoarthropathy (PHO) is a rare disease inherited as a recessive or irregular dominant trait and characterized by digital clubbing, pachydermia, and periostosis. Biallelic mutations in HPGD and SLCO2A1, disturbing prostaglandin E2 (PGE2 ) catabolism and leading to increased circulating PGE2 level, cause PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2), respectively. However, no causative genes have been reported for PHO autosomal dominant (PHOAD). Here, we performed Sanger sequencing and whole-genome sequencing (WGS) on DNA samples from seven Chinese PHOAD families; after excluding other single-nucleotide variants (SNVs), structural variations (SVs), and copy number variations (CNVs) in the genomes, we reported six SLCO2A1 monoallelic mutations (c.1660G>A [p.G554R], c.664G>A [p.G222R], c.1106G>A [p.G369D], c.1065dupA [p.Q356TfsX77], c.1293delT [p.S432AfsX48], and c.1807C>T [p.R603X]) in the probands and affected family members. Then, in five other PHO families with probands carrying SLCO2A1 biallelic mutations, we verified that parents with SLCO2A1 monoallelic mutations also displayed PHO manifestations, which further confirmed the pathogenicity of SLCO2A1 monoallelic mutations and illustrated the allelic nature of PHOAD and PHOAR2. Subsequently, through comparison of seven PHOAD probands and 50 PHOAR2 patients, we found onset age in puberty and skewed penetrance rate were similar in both PHO types, but symptoms and signs of PHOAD were milder, including less severe pachydermia (p = .027) and periostosis (p = .005), and less frequent cutis verticis gyrata (p = .011), acne (p = .005), arthralgia (p = .037), and anemia (p = .023). The median urinary PGE2 level in PHOAD probands was almost half that in PHOAR2 patients (PHOAD 277.58 ng/mmoL creatinine, PHOAR2 473.19 ng/mmoL creatinine; p = .038). Moreover, through the 3-month trial of oral administration of etoricoxib, an effective response similar to that we reported previously in PHOAR2 patients was observed in PHOAD probands. In conclusion, our findings confirm that SLCO2A1 monoallelic mutations are the cause of PHOAD and broaden phenotypic spectrum of PHO. © 2021 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Transportadores de Ânions Orgânicos , Osteoartropatia Hipertrófica Primária , Variações do Número de Cópias de DNA , Etoricoxib , Humanos , Mutação/genética , Transportadores de Ânions Orgânicos/genética , Osteoartropatia Hipertrófica Primária/genética , Linhagem
9.
Med Hypotheses ; 150: 110557, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33730601

RESUMO

The worldwide spread of COVID-19 has caused an unprecedented disaster. The emergence of COVID-19-mediated cytokine storm is one of the most important contributors to the development of acute and severe illness in patients. At present, there is an urgent need for drugs that can inhibit cytokine storm to treat COVID-19. In the absence of specific drugs and vaccines, it is important to screen existing drugs as potential treatments. This article introduces a potential repositioning of the existing drug etoricoxib, which may inhibit cytokine storm to treat COVID-19 through reducing the activity of Cyclooxygenase-2 in the conversion of arachidonic acid to prostaglandin.


Assuntos
COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Etoricoxib/uso terapêutico , Reposicionamento de Medicamentos , Humanos
10.
Biomed Res Int ; 2021: 8888151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748282

RESUMO

This study was aimed at evaluating the use of oral etoricoxib for preemptive analgesia on the health-related quality of life (QoL) outcome after the extraction of mandibular third molar. The study population consisted of 60 participants that required extraction of a single partial bony impacted mandibular third molar under local anesthesia and met the inclusion criteria. The participants were randomized into two groups. The etoricoxib group orally received 60 mg etoricoxib 30 min before surgery, whereas the control group was given a placebo. The patients were assessed postoperatively after 1, 2, 3, 4, 5, 6, and 7 days using the United Kingdom oral health-related QoL questionnaire and visual analog scale for maximum postoperative pain. The total dose of ibuprofen rescue intake and total number of days the drug was taken were recorded. Surgical removal of impacted teeth had a negative influence on the patient's QoL across various physical, social, and psychological aspects. The scores for postoperative pain in the etoricoxib group were significantly lower than those in the control group on each postoperative observation day. The number of patients without analgesic rescue medication, the average amount, and total number of days emergency analgesics were taken were significantly lower in the etoricoxib group than in the control group. The etoricoxib group showed better QoL score than the control group. Preemptive oral etoricoxib is an effective therapeutic strategy for improving the QoL after surgical removal of the impacted lower third molar.


Assuntos
Etoricoxib/administração & dosagem , Dente Serotino/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Qualidade de Vida , Extração Dentária , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Medição da Dor , Dor Pós-Operatória/etiologia
11.
Int Arch Allergy Immunol ; 182(5): 433-439, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33592604

RESUMO

BACKGROUND: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative. OBJECTIVE: The aim of the study was to demonstrate the safety of meloxicam and etoricoxib administered by open oral challenge in 2 equal steps in patients with NSAID hypersensitivity. METHODS: A cross-sectional, descriptive study of patients with a diagnosis of NSAID hypersensitivity who underwent an oral drug provocation test (DPT) with meloxicam or etoricoxib between January 2011 and August 2017 was conducted. The analysis was performed from a database in BD Clinic. RESULTS: Two hundred and twenty-eight oral provocations were performed with an alternative NSAID (203 with meloxicam and 25 with etoricoxib) in 217 patients with hypersensitivity to NSAIDs. The median age was 38 years. Ninety-eight percent of meloxicam and 100% of etoricoxib DPTs were performed in 2 steps (without previous placebo), and 52% and 64% of meloxicam and etoricoxib DPTs, respectively, were performed with 50% of the therapeutic dose in each step. Tolerance to meloxicam was demonstrated in 192 patients (94.5%) and in 100% of patients receiving etoricoxib. CONCLUSIONS: Open oral provocation with meloxicam and etoricoxib carried out in 2 steps without placebo seems to be safe and implies less costs and less time expenditure. Also, it could be performed with 2 equal doses.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Hipersensibilidade a Drogas/etiologia , Substituição de Medicamentos , Etoricoxib/administração & dosagem , Meloxicam/administração & dosagem , Testes de Provocação Brônquica , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Quimioterapia Combinada , Etoricoxib/efeitos adversos , Humanos , Meloxicam/efeitos adversos
12.
J Orthop Surg Res ; 16(1): 163, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639986

RESUMO

BACKGROUND: Heterotopic ossifications are a common complication after total hip arthroplasty. Low-dose radiation therapy and non-steroidal anti-inflammatory drugs have proven to effectively reduce the rate of heterotopic ossification after total hip arthroplasty. However, a low number of studies describe an equal efficiency of etoricoxib. This work shows first results on the examination of a larger group with 194 subjects to analyze efficiency and rate of side effects under treatment with etoricoxib. METHODS: Clinical examinations were performed the day before surgery and after at least 12 months. The survey of clinical and functional outcome was done with Harris Hip Score (HHS). Conventional antero-posterior radiographs and second plane in frog leg position were assessed. RESULTS: In total, 14 undesirable side effects (7.4%) and only four early terminations of therapy (2.1%) were documented. A complete 1-year follow-up examination including radiographs could be done in 143 subjects (79.4%). Only 28 subjects (19.6%) developed heterotopic ossifications from which 92.9% were classified in type 1 and 7.1% in type 2 using the method described by Brooker. The results do not show correlations with body mass index, extended treatment (more than ten days), or clinical and functional outcome (measured by "Harris Hip Score"). However, male subjects show a significantly higher rate of heterotopic ossifications. CONCLUSIONS: The investigations presented in this study confirm a good efficiency of etoricoxib for the prevention of heterotopic ossifications in comparison with classical methods such as radiation or drug therapy and show a low rate of undesirable side effects.


Assuntos
Artroplastia de Quadril/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Etoricoxib/uso terapêutico , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 131(4): e100-e107, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33468439

RESUMO

Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by recurrence of lesions at the same sites each time a specific drug is taken. Oral mucosal involvement is rare. Nonsteroidal anti-inflammatory drugs are one of the most common offending drug groups in FDE; however, selective cyclooxygenase-2 inhibitors, such as etoricoxib, are rarely implicated. We present a case of oral mucosal and cutaneous FDE induced by etoricoxib that, to the best of our knowledge, is the first reported case of this nature. We describe the diagnostic challenges and review the pertinent literature. The value of drug provocation testing and patch testing in FDE is also discussed.


Assuntos
Erupção por Droga , Mucosa Bucal , Erupção por Droga/diagnóstico , Erupção por Droga/etiologia , Etoricoxib , Humanos , Testes do Emplastro , Pele
14.
Cancer Lett ; 502: 44-57, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33429006

RESUMO

Obesity is a major risk factor for breast cancer, especially in post-menopausal women. In the breast tissue of obese women, cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production has been correlated with inflammation and local estrogen biosynthesis via aromatase. Using a mouse model of 7,12-dimethylbenz[a]anthracene/medroxyprogesterone-acetate (DMBA/MPA)-induced carcinogenesis, we demonstrated that an obesogenic diet promotes mammary tissue inflammation and local estrogen production, and accelerates mammary tumor formation in a COX-2-dependent manner. High-sugar/fat (HSF) diet augmented the levels of the pro-inflammatory mediators MCP-1, IL-6, COX-2, and PGE2 in mammary tissue, and this was accompanied by crown-like structures of breast (CLS-B) formation and aromatase/estrogen upregulation. Treatment with a COX-2 selective inhibitor, etoricoxib, decreased PGE2, IL-6, MCP-1, and CLS-B formation as well as reduced aromatase protein and estrogen levels in the mammary tissue of mice fed a HSF diet. Etoricoxib-treated mice showed increased latency and decreased incidence of mammary tumors, which resulted in prolonged animal survival when compared to HSF diet alone. Inhibition of tumor angiogenesis also seemed to account for the prolonged survival of COX-2 inhibitor-treated animals. In conclusion, obesogenic diet-induced COX-2 is sufficient to trigger inflammation, local estrogen biosynthesis, and mammary tumorigenesis.


Assuntos
Neoplasias da Mama/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dinoprostona/biossíntese , Açúcares/efeitos adversos , Regulação para Cima , 9,10-Dimetil-1,2-benzantraceno/efeitos adversos , Animais , Aromatase/metabolismo , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Etoricoxib/administração & dosagem , Etoricoxib/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-6/metabolismo , Células MCF-7 , Acetato de Medroxiprogesterona/efeitos adversos , Camundongos
15.
J Control Release ; 329: 316-327, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33278481

RESUMO

Medical prescriptions for the alleviation of post-surgical pain are the most abundant source of opioids in circulation. As a systemic drug delivery source, opioids leave patients at high risk for side effects after being dosed. Given the significant rate of unauthorized use, distribution, addiction, and opioid related deaths, an alternative method of post-surgical analgesia is needed. Herein, we report the use of bio-resorbable poly(ester urea) (PEU) films that controllably deliver a non-opioid COX-2 inhibitor, etoricoxib, in vivo and in vitro as a model system for post-surgical pain control. PEU composition, drug-load, and film thickness were varied to selectively control etoricoxib elution. Elution data were fit to a Higuchi model, and the diffusion constant of etoricoxib was calculated in each of the films. Pharmacokinetic (pK) data from an in vivo rat model showed the local tissue concentration of etoricoxib at the study endpoint to be up to 23-fold higher in tissue then plasma. In a well-established mouse model of diabetic neuropathic pain in vivo film implantation showed effective relief of pain for more than 4 days post-implantation and efficacious local etoricoxib delivery. Overall, implementation of local drug delivery systems such as this could reduce the need for opioid prescriptions associated with current pain management strategies.


Assuntos
Ésteres , Ureia , Animais , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Ésteres/uso terapêutico , Etoricoxib/uso terapêutico , Humanos , Camundongos , Dor Pós-Operatória/tratamento farmacológico , Piridinas/uso terapêutico , Ratos , Sulfonas/uso terapêutico
16.
BMJ Open ; 10(9): e036748, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912981

RESUMO

OBJECTIVE: To assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Web of Science, China National Knowledge Infrastructure and Wanfang Data published as of 4 April 2020. METHODS: We performed meta-analysis of randomised controlled trials (RCTs) of traditional non-selective NSAIDs versus cyclo-oxygenase-2 inhibitors and RCTs of various cyclo-oxygenase-2 inhibitors in patients with acute gout. The main outcome measures were mean change in pain Visual Analogue Scale (VAS) score and 5-point Likert scale score on days 2-8. RESULTS: Twenty-four trials involving five drugs were evaluated. For pain Likert scale, etoricoxib was comparable to indomethacin (standardised mean difference (SMD): -0.09, 95% CI: -0.27 to 0.08) but better than diclofenac 50 mg three times a day (SMD: -0.53, 95% CI: -0.98 to 0.09). Regarding pain VAS score, etoricoxib was comparable to diclofenac 75 mg two times per day (SMD: -1.63, 95% CI: -4.60 to 1.34) and diclofenac 75 mg four times a day (SMD: -1.82, 95% CI: -5.18 to 1.53), while celecoxib was comparable to diclofenac 100 mg four times a day (SMD: -2.41, 95% CI: -5.91 to 1.09). Etoricoxib showed similar patients' global assessment of response (SMD: -0.10, 95% CI: -0.27 to 0.07) and swollen joint count (SMD: -0.25, 95% CI: -0.74 to 0.24), but better investigator's global assessment of response (SMD: -0.29, 95% CI: -0.46 to 0.11) compared with indomethacin. Etoricoxib showed more favourable pain VAS score than celecoxib (SMD: -2.36, 95% CI: -3.36 to 1.37), but was comparable to meloxicam (SMD: -4.02, 95% CI: -10.28 to 2.24). Etoricoxib showed more favourable pain Likert scale than meloxicam (SMD: -0.56, 95% CI: -1.10 to 0.02). Etoricoxib 120 mg four times a day was more likely to achieve clinical improvement than celecoxib 200 mg two times per day (OR: 4.84, 95% CI: 2.19 to 10.72). CONCLUSION: Although cyclo-oxygenase-2 inhibitors and traditional non-selective NSAIDs may be equally beneficial in terms of pain relief, cyclo-oxygenase-2 inhibitors (especially etoricoxib) may confer a greater benefit.


Assuntos
Anti-Inflamatórios não Esteroides , Gota , Anti-Inflamatórios não Esteroides/uso terapêutico , China , Diclofenaco/uso terapêutico , Etoricoxib/uso terapêutico , Gota/tratamento farmacológico , Humanos
17.
J Dtsch Dermatol Ges ; 18(12): 1405-1414, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32989835

RESUMO

BACKGROUND: The aim of this study was to verify the validity of clinical history and oral provocation challenges of patients with NSAID hypersensitivity and to identify safe alternatives. The COX-2 inhibitor etoricoxib, in particular, was studied. PATIENTS AND METHODS: In all, 104 patients with confirmed diagnoses of NSAID hypersensitivity treated at the Department of Dermatology, Frankfurt University Hospital, Germany between 2004 and 2012 were retrospectively studied. RESULTS: The medical history and hypersensitivity symptoms during oral provocation testing (OPT) largely coincided and were mostly mild to moderate. Acetylsalicylic acid (ASA) was the most frequent trigger both anamnestically (27.9 %) and during OPT (47.8 %). Etoricoxib caused the fewest reactions during OPT (4.2 %). Acetaminophen led to reactions in only 6.7 % of the cases studied although it was named more often in clinical histories (14 %). CONCLUSIONS: OPT should be the aim whenever possible as most symptoms are mild to moderate. To distinguish between selective and cross-hypersensitivity reactions, ASA should be part of the test protocol. Furthermore, the findings of this study indicate that etoricoxib and acetaminophen are safe treatment alternatives in case of NSAID hypersensitivity. However, these drugs should not be administered without prior OPT in an inpatient setting, as severe symptoms can occur.


Assuntos
Hipersensibilidade a Drogas , Preparações Farmacêuticas , Anti-Inflamatórios não Esteroides/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Etoricoxib , Humanos , Estudos Retrospectivos
18.
Ann Anat ; 232: 151585, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32818660

RESUMO

OBJECTIVES: The non-steroidal anti-inflammatory drug etoricoxib is the most highly selective inhibitor of cyclooxygenase-2 available (344:1) and has been approved for postoperative pain therapy following dental interventions in Europe. At clinically relevant doses it has been reported to only have marginal effects on the velocity of orthodontic tooth movement (OTM). Its effects on associated dental root resorptions, osteoclastogenesis, trabecular number in the alveolar bone and periodontal bone loss during OTM, however, have not yet been investigated. MATERIAL AND METHODS: 40 male Fischer344 rats were divided into four groups: 1.5ml tap water/day p.o. (control, 1), additional 7.8mg/kg/day etoricoxib (normal dose) for three (2) or seven (3) days/week and 13.1mg/kg/day (high dose) for seven days/week, respectively (4). After a week of premedication, OTM in anterior direction of the first left upper molar was performed for 28 days by means of a nickel-titanium coil spring (0.25N). We quantified OTM-associated dental root resorptions, osteoclastogenesis, trabecular number and periodontal bone loss by histomorphometrical, histochemical and µCT analyses of the disected tooth-bearing upper jaw sections. RESULTS: After 28 days of OTM, associated reduction of trabecular number seemed to be slightly alleviated by high doses of etoricoxib, whereas no significant other etoricoxib effects in the doses administered could be detected regarding OTM-induced or -associated dental root resorptions, osteoclastogenesis or periodontal bone loss. CONCLUSIONS: Dental root resorptions, osteoclastogenesis and periodontal bone loss during OTM in rats were not significantly affected by etoricoxib in the clinically relevant dosages investigated with only a slight inhibitory effect on bone remodelling to be expected at high dosages. Etoricoxib is therefore not suitable for the prevention of these detrimental effects, but could be a suitable analgesic during OTM, as it has been reported not to affect tooth movement.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Etoricoxib/farmacologia , Técnicas de Movimentação Dentária/efeitos adversos , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Etoricoxib/uso terapêutico , Masculino , Modelos Animais , Osteogênese/efeitos dos fármacos , Dor/tratamento farmacológico , Dor/etiologia , Ratos Endogâmicos F344 , Coloração e Rotulagem , Fosfatase Ácida Resistente a Tartarato , Reabsorção de Dente/tratamento farmacológico , Reabsorção de Dente/prevenção & controle
19.
Int J Nanomedicine ; 15: 3965-3980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606658

RESUMO

Aim: Etoricoxib is a selective inhibitor of COX-2 enzyme. It is proposed as a potent anti-inflammatory drug intended for the control of irritable bowel syndrome. The current work aimed at developing etoricoxib-loaded nanoparticles for colon- targeting. Materials and Methods: PLGA nanoparticles were developed via nano-spray drying technique. The D-optimal design was adopted for the investigation of the influence of i) DL-lactide-coglycolide (PLGA) concentration, ii) polyvinylpyrrolidone K30 (PVP K30) concentration and iii) lactide:glycolide ratio in the copolymer chain on the yield%, the encapsulation efficiency (EE%), particle size (PS) and percentage of drug release after 2h (P2h), 4h (P4h) and 12h (P12h). To promote colon targeting of the systems, the best achieved system (M14) was either directly coated with poly(methacrylic acid-co-methyl methacrylate) [Eudragit®-S100] or loaded into hard gelatin capsules and the capsules were coated with poly(methacrylic acid-co-methyl methacrylate) (E-M14C). The pharmacokinetic parameters of etoricoxib following oral administration of E-M14C in healthy volunteers were assessed relative to commercial etoricoxib tablets. Results: M14 system was prepared using PLGA (0.5% w/v) at a lactide:glycolide ratio of 100:0, in the presence of PVP K30 (2% w/v). M14 system was nano-spherical particles of 488 nm size possessing promising yield% (63.5%) and EE% (91.2%). The percentage drug released after 2, 4 and 12 hours were 43.41%, 47.34 and 64.96%, respectively. Following M14-loading into hard gelatin capsules and coating with poly(methacrylic acid-co-methyl methacrylate) [Eudragit-S100], the respective P2h, P4h and P12h were 10.1%, 28.60% and 65.45%. Significant (p < 0.05) differences between the pharmacokinetic parameter of E-M14C in comparison with the commercial product were revealed with a delay in Tmax (from 2.5h to 6h), a prolongation in MRT0-∞ (from 24.4h to 34.7h) and an increase in the relative oral bioavailability (4.23 folds). Conclusion: E-M14C is a potential system for possible colon targeting of etoricoxib.


Assuntos
Colo/efeitos dos fármacos , Etoricoxib/farmacologia , Etoricoxib/farmacocinética , Voluntários Saudáveis , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ácidos Polimetacrílicos/química , Administração Oral , Adulto , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Colo/metabolismo , Liberação Controlada de Fármacos , Humanos , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Adulto Jovem
20.
Medicina (Kaunas) ; 56(6)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32486104

RESUMO

Background and objectives: The main objective of this study is to highlight the efficiency of different therapeutic means in patients with ankylosing spondylitis, resulting in the improvement of their quality of life. Materials and Methods: We conducted a randomized, longitudinal, controlled trial on 92 patients with ankylosing spondylitis over a period of 6 years. Disease activity was assessed using the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score. The assessment of functional disabilities was performed using BASFI (Bath Ankylosing Spondylitis Functional Index). We assessed the quality of life using the HAQ questionnaire (Health Assessment Questionnaire). Based on the HAQ, we calculated the minimum number of patients to be treated for 52 weeks to prevent a decrease in the quality of life for at least one of them (the number needed to treat (NNT)). Results: For the combination therapy group, the result we obtained was 2, lower than the other therapies compared (the medication group and the group with physical exercise). We point out a correlation between the improvement of the functional status (BASFI) and the increase of the quality of life (HAQ), estimated as moderately high (0.8). The superiority of the effects of the combined treatment, in which we combined a nonsteroidal anti-inflammatory drug (etoricoxib) to the exercise program, is reflected by the model of the significant improvements (p < 0.05) obtained for the functional status and quality of life scores (BASFI and HAQ). Conclusions: The nonsteroidal anti-inflammatory drugs, in our case, etoricoxib, facilitate the application of individualized exercise programs in patients with ankylosing spondylitis.


Assuntos
Etoricoxib/farmacologia , Terapia por Exercício/métodos , Amplitude de Movimento Articular/efeitos dos fármacos , Espondilite Anquilosante/tratamento farmacológico , Adulto , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/análise , Proteína C-Reativa/efeitos dos fármacos , Etoricoxib/uso terapêutico , Terapia por Exercício/instrumentação , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Romênia , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Inquéritos e Questionários
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