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1.
Medicine (Baltimore) ; 100(7): e24512, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607780

RESUMO

BACKGROUND: The postoperative pain associated with total knee arthroplasty (TKA) is severe for most patients. The analgesic efficacy and safety of preoperative use of selective cyclooxygenase-2 (COX-2) inhibitors for patients undergoing TKA are unclear. OBJECTIVES: We conducted a systematic review and meta-analysis to assess whether the use of selective COX-2 inhibitors before TKA decreases the postoperative pain intensity. METHODS: Data sources: The PubMed, Embase, EBSCO, Web of Science, and Cochrane Controlled Register of Trials databases from inception to January 2020. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials (RCTs) in which the intervention treatment was preoperative selective COX-2 vs placebo in patients undergoing TKA and that had at least one of the quantitative outcomes mentioned in the following section of this paper were included. Letters, review articles, case reports, editorials, animal experimental studies, and retrospective studies were excluded. INTERVENTIONS: All RCTs in which the intervention treatment was preoperative selective COX-2 vs placebo in patients undergoing TKA. STUDY APPRAISAL AND SYNTHESIS METHODS: The quality of the RCTs was quantified using the Newcastle-Ottawa quality assessment scale. RevMan 5.3 software was used for the meta-analysis. RESULTS: Six RCTs that had enrolled a total of 574 patients were included in the meta-analysis. The visual analog scale pain score at rest was significantly different between the experimental group and control group at 24 hours (P < .05) and 72 hours (P < .05) postoperatively. The experimental group exhibited a significant visual analog scale pain score during flexion at 24 hours postoperatively (P < .05), and it was not different at 72 hours postoperatively (P = .08). There was a significant difference in opioid consumption (P < .05), but there was no difference in the operation time (P = .24) or postoperative nausea/vomiting (P = .64) between the groups. CONCLUSION: The efficacy of preoperative administration of selective COX-2 inhibitors to reduce postoperative pain and opioid consumption after TKA is validated. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202090101.


Assuntos
Analgesia/métodos , Artroplastia do Joelho/métodos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Cuidados Pré-Operatórios/métodos , Idoso , Analgésicos Opioides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Front Immunol ; 11: 2167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013911

RESUMO

The inflammatory response to and the subsequent development of Adult Respiratory Distress Syndrome (ARDS) is considered to underpin COVID-19 pathogenesis. With a developing world catastrophe, we need to examine our known therapeutic stocks, to assess suitability for prevention and/or treatment of this pro-inflammatory virus. Analyzing commonly available and inexpensive immunomodulatory and anti-inflammatory medications to assess their possible effectiveness in improving the host response to COVID-19, this paper recommends the following: (1) optimize current health-cease (reduce) smoking, ensure adequate hypertension and diabetes control, continue exercising; (2) start on an HMG CoA reductase inhibitor "statin" for its immunomodulatory and anti-inflammatory properties, which may reduce the mortality associated with ARDS; and (3) consider using Diclofenac (or other COX-2 inhibition medications) for its anti-inflammatory and virus toxicity properties. For purposes of effectiveness, this needs to be in the early course of the disease (post infection and/or symptom presentation) and given in a high dose. The downsides to these recommended interventions are considered manageable at this stage of the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , /tratamento farmacológico , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Diclofenaco/efeitos adversos , Diclofenaco/uso terapêutico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , /virologia , Internalização do Vírus/efeitos dos fármacos
3.
Medicine (Baltimore) ; 99(40): e22544, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019464

RESUMO

BACKGROUND: Clinical studies have shown that celecoxib can significantly inhibit the development of tumors, and basic experiments and in vitro experiments also provide a certain basis, but it is not clear how celecoxib inhibits tumor development in detail. METHODS: A literature search of all major academic databases was conducted (PubMed, China National Knowledge Internet (CNKI), Wan-fang, China Science and Technology Journal Database (VIP), including the main research on the mechanisms of celecoxib on tumors. RESULTS: Celecoxib can intervene in tumor development and reduce the formation of drug resistance through multiple molecular mechanisms. CONCLUSION: Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis and thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. Meanwhile, it was found that celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy. Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.


Assuntos
Celecoxib/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Celecoxib/efeitos adversos , Celecoxib/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Dinoprostona/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
Cochrane Database Syst Rev ; 4: CD011459, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32352165

RESUMO

BACKGROUND: Dementia is a worldwide concern. Its global prevalence is increasing. At present, there is no medication licensed to prevent or delay the onset of dementia. Inflammation has been suggested as a key factor in dementia pathogenesis. Therefore, medications with anti-inflammatory properties could be beneficial for dementia prevention. OBJECTIVES: To evaluate the effectiveness and adverse effects of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for the primary or secondary prevention of dementia. SEARCH METHODS: We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group up to 9 January 2020. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP) and six other databases to ensure that the searches were as comprehensive and up-to-date as possible. We also reviewed citations of reference lists of included studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing aspirin or other NSAIDs with placebo for the primary or secondary prevention of dementia. We included trials with cognitively healthy participants (primary prevention) or participants with mild cognitive impairment (MCI) or cognitive complaints (secondary prevention). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the strength of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included four RCTs with 23,187 participants. Because of the diversity of these trials, we did not combine data to give summary estimates, but presented a narrative description of the evidence. We identified one trial (19,114 participants) comparing low-dose aspirin (100 mg once daily) to placebo. Participants were aged 70 years or older with no history of dementia, cardiovascular disease or physical disability. Interim analysis indicated no significant treatment effect and the trial was terminated slightly early after a median of 4.7 years' follow-up. There was no evidence of a difference in incidence of dementia between aspirin and placebo groups (risk ratio (RR) 0.98, 95% CI 0.83 to 1.15; high-certainty evidence). Participants allocated aspirin had higher rates of major bleeding (RR 1.37, 95% CI 1.17 to 1.60, high-certainty evidence) and slightly higher mortality (RR 1.14, 95% CI 1.01 to 1.28; high-certainty evidence). There was no evidence of a difference in activities of daily living between groups (RR 0.84, 95% CI 0.70 to 1.02; high-certainty evidence). We identified three trials comparing non-aspirin NSAIDs to placebo. All three trials were terminated early due to adverse events associated with NSAIDs reported in other trials. One trial (2528 participants) investigated the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib (200 mg twice daily) and the non-selective NSAID naproxen (220 mg twice daily) for preventing dementia in cognitively healthy older adults with a family history of Alzheimer's disease (AD). Median follow-up was 734 days. Combining both NSAID treatment arms, there was no evidence of a difference in the incidence of AD between participants allocated NSAIDs and those allocated placebo (RR 1.91, 95% CI 0.89 to 4.10; moderate-certainty evidence). There was also no evidence of a difference in rates of myocardial infarction (RR 1.21, 95% CI 0.61 to 2.40), stroke (RR 1.82, 95% CI 0.76 to 4.37) or mortality (RR 1.37, 95% CI 0.78 to 2.43) between treatment groups (all moderate-certainty evidence). One trial (88 participants) assessed the effectiveness of celecoxib (200 mg or 400 mg daily) in delaying cognitive decline in participants aged 40 to 81 years with mild age-related memory loss but normal memory performance scores. Mean duration of follow-up was 17.6 months in the celecoxib group and 18.1 months in the placebo group. There was no evidence of a difference between groups in test scores in any of six cognitive domains. Participants allocated celecoxib experienced more gastrointestinal adverse events than those allocated placebo (RR 2.66, 95% CI 1.05 to 6.75; low-certainty evidence). One trial (1457 participants) assessed the effectiveness of the COX-2 inhibitor rofecoxib (25 mg once daily) in delaying or preventing a diagnosis of AD in participants with MCI. Median duration of study participation was 115 weeks in the rofecoxib group and 130 weeks in the placebo group. There was a higher incidence of AD in the rofecoxib than the placebo group (RR 1.32, 95% CI 1.01 to 1.72; moderate-certainty evidence). There was no evidence of a difference between groups in cardiovascular adverse events (RR 1.07, 95% CI 0.68 to 1.66; moderate-certainty evidence) or mortality (RR 1.62, 95% CI 0.85 to 3.05; moderate-certainty evidence). Participants allocated rofecoxib had more upper gastrointestinal adverse events (RR 3.53, 95% CI 1.17 to 10.68; moderate-certainty evidence). Reported annual mean difference scores showed no evidence of a difference between groups in activities of daily living (year 1: no data available; year 2: 0.0, 95% CI -0.1 to 0.2; year 3: 0.1, 95% CI -0.1 to 0.3; year 4: 0.1, 95% CI -0.1 to 0.4; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is no evidence to support the use of low-dose aspirin or other NSAIDs of any class (celecoxib, rofecoxib or naproxen) for the prevention of dementia, but there was evidence of harm. Although there were limitations in the available evidence, it seems unlikely that there is any need for further trials of low-dose aspirin for dementia prevention. If future studies of NSAIDs for dementia prevention are planned, they will need to be cognisant of the safety concerns arising from the existing studies.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Demência/prevenção & controle , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Celecoxib/administração & dosagem , Celecoxib/efeitos adversos , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Demência/epidemiologia , Demência/mortalidade , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Lactonas/uso terapêutico , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Naproxeno/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia , Sulfonas/uso terapêutico
6.
Arterioscler Thromb Vasc Biol ; 40(6): 1454-1463, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295420

RESUMO

Prostanoids are a group of bioactive lipids that are synthesized de novo from membrane phospholipid-released arachidonic acid and have diverse functions in normal physiology and disease. NSAIDs (non-steroidal anti-inflammatory drugs), which are among the most commonly used medications, ameliorate pain, fever, and inflammation by inhibiting COX (cyclooxygenase), which is the rate-limiting enzyme in the biosynthetic cascade of prostanoids. The use of NSAIDs selective for COX-2 inhibition increases the risk of a thrombotic event (eg, myocardial infarction and stroke). All NSAIDs are associated with an increased risk of heart failure. Substantial variation in clinical responses to aspirin exists and is associated with cardiovascular risk. Limited clinical studies suggest the involvement of prostanoids in vascular restenosis in patients who received angioplasty intervention. mPGES (microsomal PG [prostaglandin] E synthase)-1, an alternative target downstream of COX, has the potential to be therapeutically targeted for inflammatory disease, with diminished thrombotic risk relative to selective COX-2 inhibitors. mPGES-1-derived PGE2 critically regulates microcirculation via its receptor EP (receptor for prostanoid E) 4. This review summarizes the actions and associated mechanisms for modulating the biosynthesis of prostanoids in thrombosis, vascular remodeling, and ischemic heart disease as well as their therapeutic relevance.


Assuntos
Anti-Inflamatórios , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Descoberta de Drogas , Prostaglandinas/fisiologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Prostaglandina-E Sintases/efeitos dos fármacos , Prostaglandinas/biossíntese , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Remodelação Vascular
7.
Cochrane Database Syst Rev ; 4: CD013581, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32297973

RESUMO

BACKGROUND: Acute low back pain (LBP) is a common health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are often used in the treatment of LBP, particularly in people with acute LBP. In 2008, a Cochrane Review was published about the efficacy of NSAIDs for LBP (acute, chronic, and sciatica), identifying a small but significant effect in favour of NSAIDs compared to placebo for short-term pain reduction and global improvement in participants with acute LBP. This is an update of the previous review, focusing on acute LBP. OBJECTIVES: To assess the effects of NSAIDs compared to placebo and other comparison treatments for acute LBP. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed, and two trials registers for randomised controlled trials (RCT) to 7 January 2020. We also screened the reference lists from relevant reviews and included studies. SELECTION CRITERIA: We included RCTs that assessed the use of one or more types of NSAIDs compared to placebo (the main comparison) or alternative treatments for acute LBP in adults (≥ 18 years); conducted in both primary and secondary care settings. We assessed the effects of treatment on pain reduction, disability, global improvement, adverse events, and return to work. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials to be included in this review, evaluated the risk of bias, and extracted the data. If appropriate, we performed a meta-analysis, using a random-effects model throughout, due to expected variability between studies. We assessed the quality of the evidence using the GRADE approach. We used standard methodological procedures recommended by Cochrane. MAIN RESULTS: We included 32 trials, with a total of 5356 participants (age range 16 to 78 years). Follow-up ranged from one day to six months. Studies were conducted across the globe, the majority taking place in Europe and North-America. Africa and the Eastern Mediterranean region were not represented. We considered seven studies at low risk of bias. Performance and attrition were the most common biases. There was often a lack of information on randomisation procedures and allocation concealment (selection bias); studies were prone to selective reporting bias, since most studies did not register their trials. Almost half of the studies were industry-funded. There is moderate quality evidence that NSAIDs are slightly more effective in short-term (≤ 3 weeks) reduction of pain intensity (visual analogue scale (VAS), 0 to 100) than placebo (mean difference (MD) -7.29 (95% confidence interval (CI) -10.98 to -3.61; 4 RCTs, N = 815). There is high quality evidence that NSAIDs are slightly more effective for short-term improvement in disability (Roland Morris Disability Questionnaire (RMDQ), 0 to 24) than placebo (MD -2.02, 95% CI -2.89 to -1.15; 2 RCTs, N = 471). The magnitude of these effects is small and probably not clinically relevant. There is low quality evidence that NSAIDs are slightly more effective for short-term global improvement than placebo (risk ratio (RR) 1.40, 95% CI 1.12 to 1.75; 5 RCTs, N = 1201), but there was substantial heterogeneity (I² 52%) between studies. There is very low quality evidence of no clear difference in the proportion of participants experiencing adverse events when using NSAIDs compared to placebo (RR 0.86, 95% CI 0.63 to 1.18; 6 RCTs, N = 1394). There is very low quality evidence of no clear difference between the proportion of participants who could return to work after seven days between those who used NSAIDs and those who used placebo (RR 1.48, 95% CI 0.98 to 2.23; 1 RCT, N = 266). There is low quality evidence of no clear difference in short-term reduction of pain intensity between those who took selective COX-2 inhibitor NSAIDs compared to non-selective NSAIDs (mean change from baseline -2.60, 95% CI -9.23 to 4.03; 2 RCTs, N = 437). There is moderate quality evidence of conflicting results for short-term disability improvement between groups (2 RCTs, N = 437). Low quality evidence from one trial (N = 333) reported no clear difference between groups in the proportion of participants experiencing global improvement. There is very low quality evidence of no clear difference in the proportion of participants experiencing adverse events between those who took COX-2 inhibitors and non-selective NSAIDs (RR 0.97, 95% CI 0.63 to 1.50; 2 RCTs, N = 444). No data were reported for return to work. AUTHORS' CONCLUSIONS: This updated Cochrane Review included 32 trials to evaluate the efficacy of NSAIDs in people with acute LBP. The quality of the evidence ranged from high to very low, thus further research is (very) likely to have an important impact on our confidence in the estimates of effect, and may change the estimates. NSAIDs seemed slightly more effective than placebo for short-term pain reduction (moderate certainty), disability (high certainty), and global improvement (low certainty), but the magnitude of the effects is small and probably not clinically relevant. There was no clear difference in short-term pain reduction (low certainty) when comparing selective COX-2 inhibitors to non-selective NSAIDs. We found very low evidence of no clear difference in the proportion of participants experiencing adverse events in both the comparison of NSAIDs versus placebo and selective COX-2 inhibitors versus non-selective NSAIDs. We were unable to draw conclusions about adverse events and the safety of NSAIDs for longer-term use, since we only included RCTs with a primary focus on short-term use of NSAIDs and a short follow-up. These are not optimal for answering questions about longer-term or rare adverse events.


Assuntos
Dor Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Lombar/tratamento farmacológico , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Avaliação da Deficiência , Humanos , Pessoa de Meia-Idade , Medição da Dor , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Life Sci ; 251: 117631, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251635

RESUMO

Initially, the selective COX-2 inhibitors were developed as safer alternatives to the conventional NSAIDs, but later on, most of them were withdrawn from the market due to the risk of heart attack and stroke. Celecoxib, the first selective COX-2 inhibitor, was approved by the Food and Drug Administration (FDA) in December 1998 and was taken back from the market in 2004. Since then, many coxibs have been discontinued one by one due to adverse cardiovascular events. United States (US), Australian and European authorities related to Therapeutic Goods Administration (TGA) implemented the requirements to carry the "Black box" warning on the labels of COX-2 drugs highlighting the risks of serious cardiovascular events. These facts encouraged the researchers to explore them well and find out the biochemical basis behind the cardiotoxicity. From the last few decades, the molecular mechanisms behind the coxibs have regained the attention, especially the specific structural features of the selective COX-2 inhibitors that are associated with cardiotoxicity. This review discusses the key structural features of the selective COX-2 inhibitors and underlying mechanisms that are responsible for the cardiotoxicity. This report also unfolds different strategies that have been reported in the last 10 years to combat the problem of selective COX-2 inhibitors mediated cardiotoxicity.


Assuntos
Cardiotoxicidade/etiologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Celecoxib/administração & dosagem , Celecoxib/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/química , Rotulagem de Medicamentos , Humanos
10.
J Orthop Surg Res ; 15(1): 39, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024535

RESUMO

BACKGROUND: Many selective cyclooxygenase (COX-2) inhibitors are currently used in clinical practice. COX-2 inhibitors have good anti-inflammatory, analgesic, antipyretic effects, and gastrointestinal safety. However, the analgesic effects and adverse reactions of COX-2 after total knee/hip arthroplasty (TKA/THA) are not fully known. OBJECTIVE: To evaluate the efficacy and safety of selective COX-2 inhibitors in postoperative pain management in patients receiving TKA/THA. METHODS: Randomized controlled trials (RCTs) were retrieved from medical literature databases. Risk ratios (RR) Std mean difference (SMD) and 95% confidence intervals (CI) were calculated to analyze the primary and safety endpoints. RESULTS: In total, 18 articles (23 trial comparisons) were retrieved comprising 3104 patients. Among them, 1910 patients (61.5%) were randomized to the experimental group whereas 1194 patients (38.5%) were randomized to the control group. The primary endpoints were the patients' VAS score at rest or on ambulation (within 3 days). We found that VAS score in patients that received selective COX-2 inhibitor was significantly lower compared to those of the control group. CONCLUSION: This meta-analysis shows that selective COX-2 inhibitor therapy is effective, safe, and reliable in relieving postoperative pain of THA/TKA.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Artroplastia de Quadril/tendências , Artroplastia do Joelho/tendências , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Humanos , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
11.
Int Arch Allergy Immunol ; 181(1): 24-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31752003

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most prevalent causes of drug hypersensitivity reactions (DHRs), yet the underlying processes are far from clear. Despite the established role of histamine in allergic reactions, its precise implication in DHRs is elusive. OBJECTIVES: This study aimed to explore the connection of basal blood histamine levels to the reported NSAID hypersensitivity. METHODS: Sixteen patients reporting hypersensitivity reactions to a single or multiple NSAIDs and/or paracetamol and 18 healthy volunteers serving as the normal control group enrolled in the study. The medical history was recorded and histamine was quantified spectrophotofluorometrically in whole peripheral blood and plasma. RESULTS: Compared to the normal group, plasma but not whole blood histamine levels were significantly higher in patients (p < 0.001), mainly in the subgroup reporting hypersensitivity to a single agent (p < 0.001). Plasma histamine levels were significantly correlated with the culprit drug selectivity for cyclooxygenase (COX) isozymes (p < 0.001), with higher levels being obtained in patients reporting reactions to COX-1 than to COX-2 selective inhibitors (p < 0.05). CONCLUSIONS: The findings provide first evidence connecting basal blood histamine levels to the reported NSAID-triggered DHRs. Prospective studies are expected to decipher the contribution of histamine-associated parameters to the mechanisms underlying DHRs.


Assuntos
Acetaminofen/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Hipersensibilidade a Drogas/imunologia , Histamina/sangue , Acetaminofen/imunologia , Acetaminofen/uso terapêutico , Adulto , Idoso , Alérgenos/imunologia , Anti-Inflamatórios não Esteroides/imunologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores/sangue , Inibidores de Ciclo-Oxigenase 2/imunologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
13.
JBJS Rev ; 7(12): e4, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31851037

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are being increasingly employed as a part of multimodal non-opioid strategies to treat postoperative pain. In the present study, we sought to review the effects of short-term NSAID use on musculoskeletal soft-tissue healing. METHODS: We performed a scoping review of all studies that included the use of NSAIDs and their effect on healing of soft tissues, which for the purpose of this review refers to non-osseous musculoskeletal tissue such as ligament, tendon, labrum, and meniscus. The inclusion criteria encompassed all studies (human, animal, and in vitro) that evaluated the effect of NSAIDs on soft-tissue healing. Subgroup analyses, wherever applicable, were conducted on the basis of the type of NSAID (cyclooxygenase [COX]-specific or nonspecific) and the type of study (human, animal, or in vitro). Relevant metadata from each study were abstracted, and descriptive statistics were used to summarize the results. RESULTS: A total of 44 studies met the inclusion criteria, including 3 human studies, 33 animal studies, and 8 in vitro studies. These studies included 4 different NSAIDs in the human subgroup, 16 different NSAIDs in the animal subgroup, and 7 different NSAIDs in the in vitro subgroup. The majority of reported studies (including 1 of 2 human studies, 10 of 14 animal studies, and 3 of 3 in vitro studies) demonstrated that COX-2-selective inhibitors had negative impact on soft-tissue healing. In contrast, the majority of human and animal studies (2 of 2 and 19 of 30, respectively) demonstrated that nonselective COX inhibitors had no negative effect on the healing of labrum, tendons, and ligaments. The majority of in vitro studies demonstrated that NSAIDs have a harmful effect on biological processes involved in tendon-healing and regeneration (tenocyte proliferation, collagen and glycosaminoglycan synthesis). CONCLUSIONS: Current limited evidence demonstrates that selective COX-2 inhibitors can negatively affect healing of musculoskeletal soft tissue after surgical repair. In contrast, the majority of studies demonstrate that nonselective COX inhibitors have no negative effect on musculoskeletal soft-tissue healing. Additional high-quality human clinical trials are necessary to provide more definitive conclusions.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Lesões dos Tecidos Moles/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Humanos , Período Pós-Operatório , Resultado do Tratamento
14.
Int J Clin Pharmacol Ther ; 57(11): 531-541, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397273

RESUMO

OBJECTIVE: Osteoarthritis is highly prevalent in older adults and often treated with nonsteroidal anti-inflammatory drugs (NSAIDs). COX-2-selective NSAIDs have been shown to offer better gastrointestinal (GI) safety benefits than non-selective NSAIDs (ns-NSAIDs). However, most COX-2-selective NSAIDs have not been comprehensively evaluated for use in combination with gastroprotective agents (GPAs). This study compared the risk of adverse GI events in patients treated with COX-2-selective NSAIDs and ns-NSAIDs alone, or in combination with GPAs. MATERIALS AND METHODS: We utilized National Health Insurance Claim Data collected from 2012 to 2015. Newly diagnosed patients with osteoarthritis (60 years or older) were included in this study. The study population was divided into two groups: 1) COX-2-selective NSAID treatment and 2) ns-NSAIDs treatment. Patients were followed-up for up to 6 months to determine whether GI events occurred. The Cox proportional hazards model was used to identify differences in risk. Subgroup analyses were conducted for monotherapies and combination treatments with GPAs. RESULTS: The number of subjects prescribed COX-2-selective NSAID and ns-NSAIDs were 20,868 (5.6%) and 353,494 (94.4%), respectively. After adjustment for confounding factors, COX-2-selective NSAID were safer than ns-NSAIDs (adjusted hazard ratio (aHR) = 0.80, 95% confidence interval (CI): 0.77 - 0.82). Use of GPAs with COX-2-selective NSAID was associated with a lower risk of GI events than use of ns-NSAIDs (aHR = 0.92, 95% CI: 0.87 - 0.97). CONCLUSION: Use of COX-2-selective NSAID was associated with a lower risk of GI adverse events than use of ns-NSAIDs as a monotherapy. Furthermore, COX-2-selective NSAID were safer than ns-NSAIDs in combination with GPAs.
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Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Gastroenteropatias/induzido quimicamente , Osteoartrite/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Humanos , Estudos Retrospectivos
16.
Int J Mol Sci ; 20(16)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405112

RESUMO

Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant efficacy, but also considerable toxicity. This study addresses the chemopreventive effect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16-/-, n = 10, parecoxib-treated); II (HPV16-/- n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/-, n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn't modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive effects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.


Assuntos
Anticarcinógenos/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Papillomavirus Humano 16/isolamento & purificação , Isoxazóis/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/virologia , Animais , Anticarcinógenos/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Feminino , Papillomavirus Humano 16/genética , Isoxazóis/efeitos adversos , Camundongos , Camundongos Transgênicos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Pele/efeitos dos fármacos , Pele/patologia , Pele/virologia , Neoplasias Cutâneas/patologia
17.
Cancer Sci ; 110(10): 3018-3026, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31361372

RESUMO

Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer-related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well-established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of CRC. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non-steroidal anti-inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first-line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel "post-aspirin" agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger CRC prevention, but also to improvement of other obesity-related diseases.


Assuntos
Antineoplásicos/uso terapêutico , Quimioprevenção/métodos , Neoplasias Colorretais/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Comitês Consultivos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/efeitos adversos , Cardiotoxicidade , Doenças Cardiovasculares/induzido quimicamente , Quimioprevenção/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Expert Opin Ther Pat ; 29(6): 407-427, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31132889

RESUMO

INTRODUCTION: COX-2 is a key enzyme in the process of prostaglandins (PGs) synthesis. The products of this enzyme could play a major role as the mediators of the inflammatory response and some other medical states such as cancer. The design and synthesis of novel selective COX-2 inhibitors have always been attractive to researchers. This review discusses the structures of novel COX-2 inhibitors synthesized during the last five years and describes their efficacy as anticancer agents. AREAS COVERED: It is well established that COX-2 is overexpressed in many different cancers and treatment with selective COX-2 inhibitors could relieve their symptoms and limit their adverse sequences. EXPERT OPINION: The diversity of selective COX-2 inhibitors is mainly related to the types of scaffolds. Monocyclic, bicyclic, tricyclic, and acyclic scaffolds with different pharmacological effects and toxicological profiles could be found in the family of selective COX-2 inhibitors. The great interest of the researchers in this field is due to the importance of selective COX-2 inhibitors as a relatively safe and effective set of compounds which could present different properties such as antirheumatic, anti-inflammatory, antiplatelet, anti-Alzheimer's disease, anti-Parkinson's disease, and anticancer.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Desenho de Fármacos , Humanos , Neoplasias/enzimologia , Patentes como Assunto
20.
Drugs Aging ; 36(Suppl 1): 25-44, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31073922

RESUMO

OBJECTIVE: Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. METHODS: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). RESULTS: Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09-1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03-1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08-1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01-2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80-1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22-2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21-2.29; 0%). CONCLUSIONS: In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.


Assuntos
Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Lactonas/efeitos adversos , Osteoartrite/tratamento farmacológico , Sulfonas/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Lactonas/administração & dosagem , Lactonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfonas/administração & dosagem , Sulfonas/uso terapêutico , Resultado do Tratamento
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