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1.
BMC Pulm Med ; 21(1): 268, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404358

RESUMO

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .


Assuntos
Asma , COVID-19 , Curcumina , Eosinófilos , Imunoglobulina E/sangue , Administração Oral , Adulto , Assistência Ambulatorial/métodos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Asma/sangue , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/fisiopatologia , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Ensaios Clínicos Fase II como Assunto , Curcumina/administração & dosagem , Curcumina/efeitos adversos , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Contagem de Leucócitos/métodos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
2.
Drug Saf ; 44(9): 929-938, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339037

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been discouraged for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, fearing that they could increase the risk of infection or the severity of SARS-CoV-2. METHODS: Original studies providing information on exposure to NSAIDs and coronavirus disease 2019 (COVID-19) outcomes were retrieved and were included in a descriptive analysis and a meta-analysis with Cochrane Revue Manager (REVMAN 5.4), using inverse variance odds ratio (OR) with random- or fixed-effects models. RESULTS: Of 92,853 papers mentioning COVID-19, 266 mentioned NSAIDs and 61 mentioned ibuprofen; 19 papers had analysable data. Three papers described NSAID exposure and the risk of SARS-CoV-2 positivity, five papers described the risk of hospital admission in positive patients, 10 papers described death, and six papers described severe composite outcomes. Five papers studied exposure to ibuprofen and death. Using random-effects models, there was no excess risk of SARS-CoV-2 positivity (OR 0.86, 95% confidence interval [CI] 0.71-1.05). In SARS-CoV-2-positive patients, exposure to NSAIDs was not associated with excess risk of hospital admission (OR 0.90, 95% CI 0.80-1.17), death (OR 0.88, 95% CI 0.80-0.98), or severe outcomes (OR 1.14, 95% CI 0.90-1.44). With ibuprofen, there was no increased risk of death (OR 0.94, 95% CI 0.78-1.13). Using a fixed-effect model did not modify the results, nor did the sensitivity analyses. CONCLUSION: The theoretical risks of NSAIDs or ibuprofen in SARS-CoV-2 infection are not confirmed by observational data.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Hospitalização/estatística & dados numéricos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Estudos Observacionais como Assunto , Razão de Chances , SARS-CoV-2 , Índice de Gravidade de Doença
3.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371956

RESUMO

We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5-20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1ß and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Fatores Imunológicos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Linhagem Celular , Sobrevivência Celular , Colágeno/análise , Citocinas/genética , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Derme/patologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Epiderme/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Imunomodulação , Tecido Linfoide/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Triterpenos Pentacíclicos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Molecules ; 26(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279377

RESUMO

Laser radiation has been shown to be a promising approach for in situ amorphization, i.e., drug amorphization inside the final dosage form. Upon exposure to laser radiation, elevated temperatures in the compacts are obtained. At temperatures above the glass transition temperature (Tg) of the polymer, the drug dissolves into the mobile polymer. Hence, the dissolution kinetics are dependent on the viscosity of the polymer, indirectly determined by the molecular weight (Mw) of the polymer, the solubility of the drug in the polymer, the particle size of the drug and the molecular size of the drug. Using compacts containing 30 wt% of the drug celecoxib (CCX), 69.25 wt% of three different Mw of polyvinylpyrrolidone (PVP: PVP12, PVP17 or PVP25), 0.25 wt% plasmonic nanoaggregates (PNs) and 0.5 wt% lubricant, the effect of the polymer Mw on the dissolution kinetics upon exposure to laser radiation was investigated. Furthermore, the effect of the model drug on the dissolution kinetics was investigated using compacts containing 30 wt% of three different drugs (CCX, indomethacin (IND) and naproxen (NAP)), 69.25 wt% PVP12, 0.25 wt% PN and 0.5 wt% lubricant. In perfect correlation to the Noyes-Whitney equation, this study showed that the use of PVP with the lowest viscosity, i.e., the lowest Mw (here PVP12), led to the fastest rate of amorphization compared to PVP17 and PVP25. Furthermore, NAP showed the fastest rate of amorphization, followed by IND and CCX in PVP12 due to its high solubility and small molecular size.


Assuntos
Anti-Inflamatórios não Esteroides/química , Celecoxib/química , Raios Infravermelhos , Nanopartículas/química , Povidona/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Celecoxib/administração & dosagem , Estabilidade de Medicamentos , Lasers , Viscosidade
7.
Isr Med Assoc J ; 23(7): 412-415, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34251122

RESUMO

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by different phenotypes in terms of joint involvement. The so-called oligoarticular pattern involves fewer than five active joints at a different time points. The evaluation of disease activity in this subset of patients is an unmet need due to the lack of specific indices able to capture modifications over time. OBJECTIVES: To evaluate the ability of musculoskeletal ultrasound to monitor the response to apremilast treatment in oligoarticular PsA patients. METHODS: We evaluated 24 oligoarticular patients (19 women, 5 men; median age 56 years, interquartile range (IQR) 19; median disease duration 5 years, IQR 5.75). All patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 (T3) weeks. Clinical assessment included evaluation of 66 swollen joints and patient global health assessment. All the patients underwent ultrasound assessment of the clinically involved joints. Synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0-3). The total inflammatory score was the sum of the scores. RESULTS: We found a reduction in the ultrasound inflammatory score at all time points, with a significant improvement at 6 and 12 weeks of treatment compared with baseline: T0 median 8.5 (IQR 5.0); T1 3.5 (3.0); T2 2.0 (3.5); P = 0.01. We observed a significant reduction of patient global health assessment after 24 weeks (T0 median 50 (32.5); T3 40 (57.5); P = 0.01). CONCLUSIONS: Musculoskeletal ultrasound could be useful in the assessment of treatment response in PsA patients with oligoarticular subset.


Assuntos
Artrite Psoriásica , Monitoramento de Medicamentos/métodos , Membrana Sinovial , Talidomida/análogos & derivados , Ultrassonografia/métodos , Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/fisiopatologia , Feminino , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Tamanho do Órgão , Gravidade do Paciente , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Líquido Sinovial/diagnóstico por imagem , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Talidomida/administração & dosagem
8.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200719

RESUMO

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.


Assuntos
Aminoácidos/química , Anti-Inflamatórios não Esteroides/farmacologia , Celulose/química , Ésteres/química , Ibuprofeno/farmacologia , Absorção Cutânea/efeitos dos fármacos , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Bactérias/metabolismo , Sistemas de Liberação de Medicamentos , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Suínos
9.
Biomed Pharmacother ; 139: 111710, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243616

RESUMO

PURPOSE: Postoperative pain is typically treated with multimodal analgesia, using systemic acetaminophen and/or nonsteroidal anti-inflammatory drugs in conjunction with opioids as required. The present study aimed to determine the safety and tolerability of repeated doses of an intravenous fixed-dose combination (FDC) of acetaminophen and ibuprofen. METHODS: This multicenter, open-label, single arm, multiple dose study was conducted at 4 centers across New Zealand and the United States between July 2019 and July 2020. Adults (>18 years) requiring multiple doses of parenteral nonopioid analgesics over multiple days following non-laparoscopic general, plastic or orthopedic surgery were eligible. The study drug (acetaminophen 1000 mg+ibuprofen 300 mg) was administered 6-hourly as a 5 min infusion for between 48 h and 5 days. Adverse event data was collected throughout the study, in addition to scheduled vital sign assessments, laboratory tests and electrocardiograms. Participants completed a global evaluation of the FDC at the end of the treatment period. FINDINGS: 232 participants received ≥ 1 dose of the FDC. Most were female (62.1%), White (56.5%) or Black or African American (39.2%), and had undergone orthopedic surgery (85.3%). There was a broad age range (19-87 years), with a mean age of 53.4 years, and 26.3% of participants aged ≥ 65 years. The FDC was safe when used for 48 h to 5 days. Treatment-emergent adverse events (TEAEs) affected 56.0% of participants, the most common were infusion site pain, nausea, infusion site extravasation, constipation, and headache. Minimal changes in vital signs were observed at scheduled timepoints. No clinically significant changes in electrocardiogram assessments occurred. Transient elevations in the hepatic enzymes ALT and AST to < 3 times the upper limit of normal (ULN) affected 10.5% and 9.6% of subjects, elevations to ≥ 3 times the ULN affected 2.6% and 2.2% of subjects, respectively. There were no apparent differences in the safety profile of the FDC in older participants. The FDC was well tolerated; most TEAEs were mild or moderate in severity. Five participants discontinued treatment due to TEAEs, none were considered treatment-related. The FDC was perceived well by study participants; the majority rated their experience as 'excellent' (40.1%) or 'very good' (35.3%). IMPLICATIONS: The safety profile was comparable to previous studies with no novel safety concerns. The FDC was safe, well tolerated, and perceived positively by participants treated for acute pain between 48 h and 5 days following orthopedic or plastic surgery, supporting a favorable risk benefit profile.


Assuntos
Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Ibuprofeno/administração & dosagem , Ibuprofeno/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Aguda/tratamento farmacológico , Administração Intravenosa/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Medição da Dor/métodos , Adulto Jovem
11.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066280

RESUMO

We previously designed a Carbopol gel formulation (N-IND/MEN) based on a combination of indomethacin solid nanoparticles (IND-NPs) and l-menthol, and we reported that the N-IND/MEN showed high transdermal penetration. However, the detailed mechanism for transdermal penetration of IND-NPs was not clearly defined. In this study, we investigated whether endocytosis in the skin tissue of rat and Göttingen minipig is related to the transdermal penetration of IND-NPs using pharmacological inhibitors of endocytosis. The pharmacological inhibitors used in this study are as follows: 54 µM nystatin, a caveolae-mediated endocytosis (CavME) inhibitor; 40 µM dynasore, a clathrin-mediated endocytosis (CME) inhibitor; and 2 µM rottlerin, a micropinocytosis (MP) inhibitor. The N-IND/MEN was prepared by a bead mill method, and the particle size of solid indomethacin was 79-216 nm. In both rat and Göttingen minipig skin, skin penetration of approximately 80% IND-NPs was limited by the stratum corneum (SC), although the penetration of SC was improved by the combination of l-menthol. On the other hand, the treatment of nystatin and dynasore decreased the transdermal penetration of indomethacin in rats and Göttingen minipigs treated with N-IND/MEN. Moreover, in addition to nystatin and dynasore, rottlerin attenuated the transdermal penetration of IND-NPs in the Göttingen minipigs' skin. In conclusion, we found that l-menthol enhanced the SC penetration of IND-NPs. In addition, this study suggests that the SC-passed IND-NPs are absorbed into the skin tissue by energy-dependent endocytosis (CavME, CME, and/or MP pathways) on the epidermis under the SC, resulting in an enhancement in transdermal penetration of IND-NPs. These findings provide significant information for the design of nanomedicines in transdermal formulations.


Assuntos
Endocitose , Indometacina/administração & dosagem , Mentol/administração & dosagem , Nanopartículas/administração & dosagem , Absorção Cutânea , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antipruriginosos/administração & dosagem , Composição de Medicamentos , Metabolismo Energético , Masculino , Nanopartículas/química , Ratos , Suínos , Porco Miniatura
12.
Eur Rev Med Pharmacol Sci ; 25(11): 4156-4162, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34156697

RESUMO

OBJECTIVE: Approximately 30% of patients with confirmed COVID-19 report persistent smell or taste disorders as long-term sequalae of infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory changes to the olfactory bulb, and treatments with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after infection. Our study investigated the efficacy of a supplement with Palmitoylethanolamide (PEA) and Luteolin to support recovery of olfaction in COVID-19 patients. PATIENTS AND METHODS: We conducted a randomized-controlled pilot study in outpatients with history of confirmed COVID-19 with post-infection olfactory impairment that persisted ≥ 90 days after SARS-CoV-2 negative testing. Patients were randomized to two times a day olfactory rehabilitation alone or weekly olfactory rehabilitation plus daily oral supplement with PEA and Luteolin. Subjects with preexisting olfactory disorders were excluded. Sniffin' Sticks assessments were performed at baseline and 30 days after treatment.  Data on gender, age, and time since infection were collected. Kruskal-Wallis (KW) test was used to compare variances of Sniff scores between groups over time, and Spearman's correlation coefficients were calculated to assess for correlations between Sniff Score and gender or duration of infection. RESULTS: Among 12 patients enrolled (n=7, supplement; n=5, controls), patients receiving supplement had greater improvement in olfactory threshold, discrimination, and identification score versus controls (p=0.01). Time since infection was negatively correlated with Sniff Score, and there was no correlation between gender. CONCLUSIONS: Treatment combining olfactory rehabilitation with oral supplementation with PEA and Luteolin was associated with improved recovery of olfactory function, most marked in those patients with longstanding olfactory dysfunction. Further studies are necessary to replicate these findings and to determine whether early intervention including olfactory rehabilitation and PEA+Luteolin oral supplement might prevent SARS-CoV-2 associated olfactory impairment.


Assuntos
Amidas/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Antivirais/administração & dosagem , COVID-19/tratamento farmacológico , Etanolaminas/administração & dosagem , Luteolina/administração & dosagem , Transtornos do Olfato/tratamento farmacológico , Ácidos Palmíticos/administração & dosagem , Adulto , COVID-19/complicações , COVID-19/diagnóstico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Projetos Piloto , Método Simples-Cego , Olfato/efeitos dos fármacos , Olfato/fisiologia
13.
Int J Nanomedicine ; 16: 3889-3905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135583

RESUMO

Introduction: Delayed wound healing represents a common health hazard. Traditional herbal products have been often utilized to promote wound contraction. The current study aimed at assessing the wound healing activity of Opuntia ficus-indica seed oil (OFI) and its self-nanoemulsifying drug delivery system (OFI-SNEDDS) formula in a rat model of full-thickness skin excision. Methods: Based on droplet size, an optimized OFI-SNEDDS formula was prepared and used for subsequent evaluation. Wound healing activity of OFI and OFI-SNEDDS was studied in vivo. Results: The optimized OFI-SNEDDS formula droplet size was 50.02 nm. The formula exhibited superior healing activities as compared to regular OFI seed oil-treated rats at day 14 of wounding. This effect was further confirmed by histopathological examinations of H&E and Masson's Trichrome-stained skin sections. Moreover, OFI-SNEDDS showed the highest antioxidant and anti-inflammatory activities as compared to OFI seed oil-treated animals. Both OFI and OFI-SNEDDS significantly enhanced hydroxyproline skin content and upregulated Col1A1 mRNA expression, accompanied by enhanced expression of transforming factor-beta (TGF-ß). Further, OFI-SNEDDS improved angiogenesis as evidenced by increased expression of vascular endothelial growth factor (VEGF). Conclusion: OFI possesses wound healing properties that are enhanced by self-emulsification of the oil into nano-droplets. The observed activity can be attributed, at least partly, to its anti-inflammatory, pro-collagen and angiogenic properties.


Assuntos
Emulsões/química , Opuntia/química , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacologia , Colágeno Tipo I/genética , Sistemas de Liberação de Medicamentos , Emulsões/farmacologia , Hidroxiprolina/metabolismo , Masculino , Óleos Vegetais/administração & dosagem , Ratos Wistar , Sementes/química , Pele/efeitos dos fármacos , Pele/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Cicatrização/genética
14.
Cochrane Database Syst Rev ; 5: CD013263, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33998669

RESUMO

BACKGROUND: Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES: To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA: Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period. Our secondary outcomes were time to and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related or opioid-related AEs. For subgroup analysis, we planned to analyze different doses of parenteral ketorolac separately and to analyze results based on the type of surgery performed. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 12 studies, involving 1905 participants undergoing various surgeries (pelvic/abdominal, dental, and orthopedic), with 17 to 83 participants receiving intravenous ketorolac in each study. Mean study population ages ranged from 22.5 years to 67.4 years. Most studies administered a dose of ketorolac of 30 mg; one study assessed 15 mg, and another administered 60 mg. Most studies had an unclear risk of bias for some domains, particularly allocation concealment and blinding, and a high risk of bias due to small sample size. The overall certainty of evidence for each outcome ranged from very low to moderate. Reasons for downgrading certainty included serious study limitations, inconsistency and imprecision. Ketorolac versus placebo Very low-certainty evidence from eight studies (658 participants) suggests that ketorolac results in a large increase in the number of participants achieving at least 50% pain relief over four hours compared to placebo, but the evidence is very uncertain (risk ratio (RR) 2.81, 95% confidence interval (CI) 1.80 to 4.37). The number needed to treat for one additional participant to benefit (NNTB) was 2.4 (95% CI 1.8 to 3.7). Low-certainty evidence from 10 studies (914 participants) demonstrates that ketorolac may result in a large increase in the number of participants achieving at least 50% pain relief over six hours compared to placebo (RR 3.26, 95% CI 1.93 to 5.51). The NNTB was 2.5 (95% CI 1.9 to 3.7). Among secondary outcomes, for time to rescue medication, moderate-certainty evidence comparing intravenous ketorolac versus placebo demonstrated a mean median of 271 minutes for ketorolac versus 104 minutes for placebo (6 studies, 633 participants). For the number of participants using rescue medication, very low-certainty evidence from five studies (417 participants) compared ketorolac with placebo. The RR was 0.60 (95% CI 0.36 to 1.00), that is, it did not demonstrate a difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with placebo (74% versus 65%; 8 studies, 810 participants; RR 1.09, 95% CI 1.00 to 1.19; number needed to treat for an additional harmful event (NNTH) 16.7, 95% CI 8.3 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from eight studies (703 participants) did not demonstrate a difference in rates between ketorolac and placebo (RR 0.62, 95% CI 0.13 to 3.03). Ketorolac versus NSAIDs  Ketorolac was compared to parecoxib in four studies and diclofenac in two studies. For our primary outcome, over both four and six hours there was no evidence of a difference between intravenous ketorolac and another NSAID (low-certainty and moderate-certainty evidence, respectively). Over four hours, four studies (337 participants) produced an RR of 1.04 (95% CI 0.89 to 1.21) and over six hours, six studies (603 participants) produced an RR of 1.06 (95% CI 0.95 to 1.19). For time to rescue medication, low-certainty evidence from four studies (427 participants) suggested that participants receiving ketorolac waited an extra 35 minutes (mean median 331 minutes versus 296 minutes). For the number of participants using rescue medication, very low-certainty evidence from three studies (260 participants) compared ketorolac with another NSAID. The RR was 0.90 (95% CI 0.58 to 1.40), that is, there may be little or no difference between groups.   Ketorolac probably results in a slight increase in total adverse event rates compared with another NSAID (76% versus 68%, 5 studies, 516 participants; RR 1.11, 95% CI 1.00 to 1.23; NNTH 12.5, 95% CI 6.7 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from five studies (530 participants) did not demonstrate a difference in rates between ketorolac and another NSAID (RR 3.18, 95% CI 0.13 to 76.99). Only one of the five studies reported a single serious AE. AUTHORS' CONCLUSIONS: The amount and certainty of evidence for the use of intravenous ketorolac as a treatment for postoperative pain varies across efficacy and safety outcomes and amongst comparators, from very low to moderate. The available evidence indicates that postoperative intravenous ketorolac administration may offer substantial pain relief for most patients, but further research may impact this estimate. Adverse events appear to occur at a slightly higher rate in comparison to placebo and to other NSAIDs. Insufficient information is available to assess whether intravenous ketorolac has a different rate of gastrointestinal or surgical-site bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was a lack of studies in cardiovascular surgeries and in elderly populations who may be at increased risk for adverse events.


Assuntos
Dor Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Cetorolaco/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Viés , Diclofenaco/administração & dosagem , Humanos , Injeções Intravenosas , Isoxazóis/administração & dosagem , Cetorolaco/efeitos adversos , Pessoa de Meia-Idade , Números Necessários para Tratar , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Adulto Jovem
16.
Biomed Pharmacother ; 139: 111608, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33932737

RESUMO

INTRODUCTION: Ketoprofen (K) was synthesized in 1968. K belongs to nonsteroidal anti-inflammatory drugs (NSAIDs) and has analgesic, anti-inflammatory and antipyretic properties. K is commonly used due to rapid absorption, simple metabolism, high antinociceptive activity and fast blood brain barrier crossing. However, this substance causes various side effects which are the major factors affecting its' popularity. Many researchers have modified this drug to discover an improved and safe NSAID. AIM: The aim of the review was to find in recent publications data bout future prospects of K of improved safety for the gastric mucosa after oral administration. METHOD: Systematic literature review was conducted in March 2021 (2015 onwards). We selected 22 articles from PubMed, Google Scholar, Medline Complete databases. RESULTS AND DISCUSSION: Many studies aimed at obtaining K with lower ulcerogenic properties. This article describes K with lysine, new K delivery systems, K in form of hydrogels, prodrugs and codrugs of K, K as ATB-352, K with zinc, K encapsulated as proliposomal powders and several substances that reduce the gastric side effects of K described after 2015. CONCLUSION: Our review confirms that modifications of K maintain its' desirable actions and decrease ulcer producing side effect. Some new forms of K were also found to have better activity profile compared to the parent drug.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Cetoprofeno/administração & dosagem , Úlcera Gástrica/prevenção & controle , Animais , Humanos
17.
Res Vet Sci ; 137: 235-242, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34049110

RESUMO

Osteoarthritis is treated with COX or fosfolipase A2 inhibitors such as carprofen, a propionic acid NSAID. The enhancement of its action over the articular cartilage is mandatory to facilitate its therapeutic application. Drug uptake into the cartilage requires high synovial fluid concentrations, anticipating its rapid distribution towards bloodstream. Thus, intraarticular administration improves local targeting of the drug, lining with the site of action. A pharmacokinetic study in rabbits has been performed to evaluate carprofen nanoparticles after intraarticular administration. Pharmacokinetic analysis of plasma profiles through a modelling approach, has demonstrated the rapid distribution of drug outside of synovial chamber but mainly remaining in plasma. The data modelling has demonstrated the existence of two release-absorption processes when the nanoparticles are administered in the synovial space. Additionally, results are predictive of the PK profile of some other species such as cat, dogs or humans.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Carbazóis/farmacocinética , Sistemas de Liberação de Medicamentos/veterinária , Injeções Intra-Articulares/veterinária , Nanopartículas , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Carbazóis/administração & dosagem , Cartilagem Articular , Masculino , Coelhos
18.
Pan Afr Med J ; 38: 170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995777

RESUMO

Introduction: currently, the non-steroid anti-inflammatory drugs constitute a veritable object of auto medication throughout the world. The goal of this study was to evaluate the endoscopic and clinical aspects of gastro-duodenal ulcer secondary to taking of non-steroid anti-inflammatory of various sources. Methods: this was a cross-sectional study which was conducted between July 2016 and December 2017. All adult patients admitted to hospital for clinical symptoms suggestive of gastroduodenal involvement after taking anti-inflammatory drugs and having undergone upper digestive endoscopy were included in this study. Data analysis was done with Epi-info version 7 Software. Results: a total of 114 patients were included, the mean age was 47.18±26 years with a male predominance (64.9%). Among the patients, only 1.75% had taken a non-steroid anti-inflammatory (NSAIDs) from pharmacy. The NSAIDs used were of different types: diclofenac, aceclofenac, aspirin and non-selective NSAIDs. For each drug used, more than half were derived from the streets. Clinically we noted: the dyspepsia (38.58%), hemorrhages (11.40%), the ulcerous syndrome (77.19%), haematemesis (19.29%), haematemesis associated with melena (37.71%), and the rectorrhagia in 6.14 of cases. The specific endoscopic lesions were bulbar ulcer (45.61%), gastric ulcers (20.17%), antral ulcerations (5.26%) and acute gastritis (9.64%), esophagitis (7.89%), esophageal varices (6.14%), and uncomplicated hiatal hernia in 7.01% of cases. Conclusion: the serious gastroduodenal lesions observed in this study and due to use of NSAIDs are mainly attributable to unauthorized molecules due to safety concerns. It would be necessary to conduct sensitization days at the community level and in each health facility.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Úlcera Duodenal/diagnóstico , Endoscopia Gastrointestinal , Úlcera Gástrica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Estudos Transversais , Úlcera Duodenal/induzido quimicamente , Úlcera Duodenal/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/diagnóstico , Úlcera Péptica/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Adulto Jovem
19.
BMC Infect Dis ; 21(1): 427, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962573

RESUMO

PURPOSE: Hyperinflammation in severe COVID-19 infection increases the risk of respiratory failure and one of the cogent reasons of mortality associated with COVID-19. Baricitinib, a janus kinases inhibitor, can potentially suppress inflammatory cascades in severe COVID-19 pneumonia. METHODS: The objective of this study was to compare the clinical outcomes of high dose of baricitinib with its usual dose in patients with severe COVID-19 pneumonia. This prospective cohort study was conducted on 238 adult patients with severe COVID-19 pneumonia. Eight milligram and 4 mg of baricitinib was given orally to 122 patients in the high dose (HD) group and 116 patients the usual dose (UD) group, respectively daily for 14 days, and clinical outcomes were compared among the groups. RESULTS: Blood oxygen saturation level was stabilized (≥94% on room air) earlier in the HD group compared to the UD group [5 (IQR: 4-5)/8 (IQR: 6-9), P < 0.05]. Patients in the HD group required intensive care unit (ICU) and intubation supports more in the UD group than that in patients of the HD group [17.2%/9%, P < 0.05; 11.2%/4.1%, P > 0.05; N = 116/122, respectively]. The 30-day mortality and 60-day rehospitalization rate were higher in the UD group than the HD group [6%/3.3%, P < 0.01; 11.9%/7.6%, P > 0.05; N = 116/122, respectively]. CONCLUSION: The daily high dose of baricitinib in severe COVID-19 results in early stabilization of the respiratory functions, declined requirements of critical care supports, reduced rehospitalization with mortality rate compared to its daily usual dose.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Azetidinas/administração & dosagem , COVID-19/tratamento farmacológico , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Administração Oral , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Azetidinas/uso terapêutico , Bangladesh , COVID-19/mortalidade , Comorbidade , Cuidados Críticos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos Prospectivos , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/virologia , Sulfonamidas/uso terapêutico , Resultado do Tratamento
20.
Paediatr Drugs ; 23(4): 361-372, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34046854

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used for pediatric pain management in the emergency setting and postoperatively. This narrative literature review evaluates pain relief, opioid requirements, and adverse effects associated with NSAID use. A PubMed search was conducted to identify randomized controlled trials evaluating the use of conventional systemic NSAIDs as pain management for children in the perioperative or emergency department (traumatic injury) setting. Trials of cyclooxygenase-2 inhibitors ("coxibs") were excluded. Search results included studies of ibuprofen (n = 12), ketoprofen (n = 5), ketorolac (n = 6), and diclofenac (n = 4). NSAIDs reduced the opioid requirement in 10 of 13 studies in which this outcome was measured. NSAID use did not compromise pain relief; NSAIDs provided improved or similar pain scores compared with opioids (or other control) in 24 of 27 studies. Adverse event frequencies were reported in 26 studies; adverse event frequencies with NSAIDs were lower than with opioids (or other control) in three of 26 studies, similar in 21 of 26 studies, and more frequent in two of 26 studies. Perioperative and emergency department use of NSAIDs may reduce opioid requirements while maintaining pain control, with similar or reduced frequencies of opioid-associated adverse events.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Serviço Hospitalar de Emergência , Manejo da Dor/métodos , Dor/tratamento farmacológico , Assistência Perioperatória/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Ibuprofeno/administração & dosagem , Ibuprofeno/efeitos adversos , Dor/diagnóstico , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico
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