RESUMEN
Prediction of performance of traditional, reformulated, and novel oral formulations in adults and pediatrics is of great importance. This study was conducted to assess solubility of celecoxib in age-appropriate fasted- and fed-state gastric and intestinal biorelevant media, classify celecoxib into biopharmaceutical classification system (BCS), and assess the effects of age-related developmental changes in the composition and volume of gastrointestinal fluids on the solubility and performance of oral formulations containing celecoxib. Solubility of celecoxib was assessed at 37°C in the pH range specified by the BCS-based criteria in 13 age-appropriate biorelevant media reflective of the gastric and proximal small intestinal environment in both fasted and fed states in adults and different pediatric subpopulations. A validated HPLC-UV method was used to quantify celecoxib. Experimental and computational molecular descriptors and in vivo pharmacokinetic data were used to assign the permeability class of celecoxib. Celecoxib belonged to BCS class 2. The pediatric to adult solubility ratios were outside the 80-125% boundaries in 3 and borderline in 1 biorelevant media. Significant age-related variability could be predicted for oral formulations containing celecoxib intended for pediatric use. Findings of this study indicated that the criteria used in the adult BCS might not be directly applied to pediatric subpopulations.
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Productos Biológicos/clasificación , Productos Biológicos/farmacocinética , Celecoxib/clasificación , Celecoxib/farmacocinética , Ayuno/metabolismo , Absorción Gastrointestinal/fisiología , Administración Oral , Adulto , Antiinflamatorios no Esteroideos/clasificación , Antiinflamatorios no Esteroideos/farmacocinética , Líquidos Corporales/química , Líquidos Corporales/metabolismo , Niño , Preescolar , Evaluación Preclínica de Medicamentos/métodos , Predicción , Absorción Gastrointestinal/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Permeabilidad , SolubilidadRESUMEN
INTRODUCTION: Ibuprofen is one of the widespread used non-steroidal anti-inflammatory drugs. Ibuprofen active ingredient is manufactured in many sites located all around the world. The aim of this paper was to classify the geographical source of ibuprofen active pharmaceutical ingredients (APIs) from the legal market, based on chemical characteristics and its impurity pattern and to define a geographical fingerprint. METHODS: To classify ibuprofen in different geographical groups, the chemometrics by principal component analysis (PCA) and Cluster analysis was applied to HPLC, 1H-NMR data of twenty-four samples of APIs from approved manufacturers located in different European and Asian countries. RESULTS: The PCA showed clearly two different geographical groups, based on particular patterns of European or Indian samples; the cluster analysis showed the similarity of group. CONCLUSION: The chemometric analysis is an important tool for tracking the geographical origin of APIs. This could be useful to supplement the quality control ensuring safety of the medicinal products in legal market and dealing with the evolving changes of the illegal market.
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Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/clasificación , Cromatografía Líquida de Alta Presión , Ibuprofeno/química , Ibuprofeno/clasificación , Espectroscopía de Protones por Resonancia Magnética , Análisis por Conglomerados , Industria Farmacéutica/legislación & jurisprudencia , Italia , Análisis de Componente PrincipalRESUMEN
PURPOSE: This study aimed to review previous articles and evaluate the influence of topical non-steroidal anti-inflammatory drugs (NSAIDs) on intraocular pressure (IOP) in glaucoma patients who were treated with prostaglandin analogues (PGs). METHOD: The presenting study was designed as a meta-analysis of previous research. Databases include PubMed, Web of science, Cochrane library, and Embase were searched with keywords of "intraocular pressure, prostaglandin analogues, NSAIDs, latanoprost, travoprost, bimatoprost, tafluprost, unoprostone, latanoprostene bunod, ketorolac, diclofenac, nepafenac, bromfenac, flurbiprofen". Inclusion criteria were: 1. Study population were glaucoma patients; 2. Comparison between PGs monotherapy and PGs in combination with topical NSAIDs; 3. Changes of IOP as final outcomes. Studies with non-randomized design, treatments combining other anti-glaucomatous drugs, or unavailable absolute IOP were excluded from the analysis. Estimated difference in IOP were calculated using STATA 14.0. RESULT: Seven studies were retrieved for this meta-analysis. Since there is a significant heterogeneity (I2 = 94%) in these studies, random-effect model was used to calculate pooled standardized mean differences (SMD). Our results showed a significantly favorable IOP lowering effect in glaucoma patients treated with combination of topical NSAIDs and PGEs (SMD: 1.3 and -0.03, 95% CI: 0.29 to 2.38 and -0.32 to 0.26, Z = 2.50 and 0.23, p = 0.013 and 0.820, respectively). CONCLUSION: Results of our meta-analysis suggested that topical NSAIDs may enhance the IOP lowering effect of topical PGs in glaucoma patients.
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Antiinflamatorios no Esteroideos/uso terapéutico , Glaucoma/tratamiento farmacológico , Presión Intraocular/efectos de los fármacos , Prostaglandinas Sintéticas/uso terapéutico , Administración Tópica , Antiinflamatorios no Esteroideos/clasificación , Glaucoma/patología , Humanos , Prostaglandinas Sintéticas/clasificación , Tonometría OcularRESUMEN
Owing to the efficacy in reducing pain and inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popularly used medicines confirming their position in the WHO's Model List of Essential Medicines. With escalating musculoskeletal complications, as evident from 2016 Global Burden of Disease data, NSAID usage is evidently unavoidable. Apart from analgesic, anti-inflammatory and antipyretic efficacies, NSAIDs are further documented to offer protection against diverse critical disorders including cancer and heart attacks. However, data from multiple placebo-controlled trials and meta-analyses studies alarmingly signify the adverse effects of NSAIDs in gastrointestinal, cardiovascular, hepatic, renal, cerebral and pulmonary complications. Although extensive research has elucidated the mechanisms underlying the clinical hazards of NSAIDs, no review has extensively collated the outcomes on various multiorgan toxicities of these drugs together. In this regard, the present review provides a comprehensive insight of the existing knowledge and recent developments on NSAID-induced organ damage. It precisely encompasses the current understanding of structure, classification and mode of action of NSAIDs while reiterating on the emerging instances of NSAID drug repurposing along with pharmacophore modification aimed at safer usage of NSAIDs where toxic effects are tamed without compromising the clinical benefits. The review does not intend to vilify these 'wonder drugs'; rather provides a careful understanding of their side-effects which would be beneficial in evaluating the risk-benefit threshold while rationally using NSAIDs at safer dose and duration.
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Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/farmacología , Insuficiencia Multiorgánica/inducido químicamente , Animales , Antiinflamatorios no Esteroideos/clasificación , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Inhibidores de la Ciclooxigenasa 2/clasificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Humanos , Insuficiencia Multiorgánica/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Muscleblind-like 1 (MBNL1) is a ubiquitously expressed RNA-binding protein, which is highly expressed in skeletal muscle. Abnormally expanded CUG-repeats in the DMPK gene cause myotonic dystrophy type 1 (DM1) by sequestration of MBNL1 to nuclear RNA foci and by upregulation of another RNA-binding protein, CUG-binding protein 1 (CUGBP1). We previously reported that a nonsteroidal anti-inflammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. NSAIDs inhibit cyclooxygenase (COX), which is comprised of COX-1 and COX-2 isoforms. In this study, we screened 29 NSAIDs in C2C12 myoblasts, and found that 13 NSAIDs enhanced Mbnl1 expression, where COX-1-selective NSAIDs upregulated Mbnl1 more than COX-2-selective NSAIDs. Consistently, knockdown of COX-1, but not of COX-2, upregulated MBNL1 expression in C2C12 myoblasts and myotubes, as well as in myotubes differentiated from DM1 patient-derived induced pluripotent stem cells (iPSCs). Luciferase assay showed that COX-1-knockdown augmented the MeR2 enhancer activity. Furthermore, bisulfite sequencing analysis demonstrated that COX-1-knockdown suppressed methylation of MeR2. These results suggest that COX-1 inhibition upregulates Mbnl1 transcription through demethylation of the MeR2 enhancer. Taken together, our study provides new insights into the transcriptional regulation of Mbnl1 by the COX-1-mediated pathway.
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Antiinflamatorios no Esteroideos/farmacología , Ciclooxigenasa 1/genética , Ciclooxigenasa 2/genética , Proteínas de Unión al ADN/genética , Proteínas de la Membrana/genética , Distrofia Miotónica/tratamiento farmacológico , Proteínas de Unión al ARN/genética , Animales , Antiinflamatorios no Esteroideos/clasificación , Proteínas CELF1/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/crecimiento & desarrollo , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Distrofia Miotónica/genética , Distrofia Miotónica/patología , Proteína Quinasa de Distrofia Miotónica/genética , Fenilbutazona/farmacologíaRESUMEN
The aim of the present study was to enhance the dissolution rate of an NSAID drug Ketoprofen by formulating it into solid dispersions with water soluble carrier Poloxamer 188 and Eudragit S 100. The solid dispersions of Ketoprofen with Poloxamer 188 were prepared at 1:1, 1:1.5 and 1:2 (Ketoprofen: Poloxamer 188) ratio by Solvent evaporation methods. The same concentration ratio was used for the preparation of solid dispersion with Eudragit S 100 by melting/fusion technique. Further, solid dispersions were investigated by solubility, ATR-FTIR, XRD, DSC, surface morphology, in-vitro dissolution and accelerated stability study. Results demonstrated that both Poloxamer 188 and Eudragit S 100 improve solubility of drugs by 810 folds. The result of ATR-FTIR study showed the slight shifting/broadening of principle peaks. In vitro dissolution studies showed that in the solid dispersion system containing Ketoprofen: Poloxamer 188 batch P2 (1:1.5) gives faster dissolution rate of Ketoprofen than the physical mixtures. The solid dispersion with Eudragit S 100, batch E1 (1:1) gives faster dissolution rate of Ketoprofen than the physical mixtures. In phase solubility study with Poloxamer 188 showed concentration dependent solubilization of drug but Eudragit S 100 produced opposite result. The effect of pH on solubility of Eudragit S 100 was carried out which showed solubility at pH 7.4. The dissolution profile of solid dispersion with Eudragit S 100 at pH 7.4 gives excellent result. The Accelerated stability of solid dispersions & its physical mixtures were studied at 400±2 °C/75 ± 5% RH for a period of 1 month. In these studies, Solid Dispersion batches produced an unstable formulation. The Ketoprofen solid dispersions with Poloxamer 188 and Eudragit S 100 could be introduced as a suitable form with improved solubility
Asunto(s)
Solubilidad , Cetoprofeno/análogos & derivados , Triaje/clasificación , Poloxámero/análogos & derivados , Técnicas In Vitro , Preparaciones Farmacéuticas/administración & dosificación , Antiinflamatorios no Esteroideos/clasificación , Espectroscopía Infrarroja por Transformada de Fourier , Disolución/análisis , Concentración de Iones de HidrógenoRESUMEN
INTRODUCTION: Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use. METHODS: The Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID). RESULTS: From a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided. CONCLUSION: Analgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved.
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Analgésicos Opioides/uso terapéutico , Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Utilización de Medicamentos/estadística & datos numéricos , Prescripciones/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Analgésicos/clasificación , Analgésicos Opioides/clasificación , Antiinflamatorios no Esteroideos/clasificación , Femenino , Médicos Generales/estadística & datos numéricos , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Italia , Masculino , Vigilancia de la Población/métodos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
Importance: Ovarian cancer is a highly fatal malignant neoplasm with few modifiable risk factors. Case-control studies have reported a modest reduced risk of ovarian cancer among women who frequently use aspirin or regularly use low-dose aspirin. Objective: To evaluate whether regular aspirin or nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use and patterns of use are associated with lower ovarian cancer risk. Design, Setting, and Participants: This cohort study analyzed NSAID use and ovarian cancer diagnosis data from 2 prospective cohorts, 93â¯664 women in the Nurses' Health Study (NHS), who were followed up from 1980 to 2014, and 111 834 in the Nurses' Health Study II (NHSII), who were followed up from 1989 to 2015. Follow-up was completed on June 30, 2014, for the NHS and June 30, 2015, for NHSII. Data were analyzed from June 13, 2016, to September 18, 2017. Exposures: For each analgesic type (aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen), timing, duration, frequency, and number of tablets used were evaluated; exposure information was updated every 2 to 4 years. Main Outcomes and Measures: Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of aspirin, nonaspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All statistical tests were 2-sided, with a significance level of .05. Results: In the NHS, the mean (SD) age at baseline (1980) was 45.9 (7.2) years, and 93% of participants identified as non-Hispanic white. In the NHSII, the mean age at baseline (1989) was 34.2 (4.7) years, and 92% identified as non-Hispanic white. Among the 205â¯498 women in both cohorts, there were 1054 cases of incident epithelial ovarian cancer. Significant associations between aspirin and ovarian cancer risk were not observed when current vs nonuse of any aspirin was evaluated regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). However, when low-dose (≤100-mg) and standard-dose (325-mg) aspirin were evaluated separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96), but no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49) was observed. Current use of nonaspirin NSAIDs was positively associated with risk of ovarian cancer compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and significant positive trends for duration of use (P = .02 for trend) and cumulative average tablets per week (P = .03 for trend) were observed. There were no clear associations for the use of acetaminophen. Conclusions and Relevance: These results appear to be consistent with case-control studies that show a reduced risk of ovarian cancer among regular users of low-dose aspirin. An increased risk of ovarian cancer with long-term high-quantity use of other analgesics, particularly nonaspirin NSAIDs, was observed, although this finding requires confirmation.
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Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Carcinoma Epitelial de Ovario/epidemiología , Neoplasias Ováricas/epidemiología , Adulto , Analgésicos/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/clasificación , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Enfermeras y Enfermeros/estadística & datos numéricos , Factores de RiesgoRESUMEN
AIMS: Although antinociception produced by non-steroidal anti-inflammatory drugs (NSAIDs) is partly attributed to nerve conduction inhibition, this has not been thoroughly examined yet. The aim of the present study was to reveal quantitatively how various types of NSAIDs affect compound action potentials (CAPs), a measure of nerve conduction. MAIN METHODS: CAPs were recorded from the frog sciatic nerve by using the air-gap method. KEY FINDINGS: Soaking the sciatic nerve with acetic acid-based NSAIDs (diclofenac and aceclofenac) reduced the peak amplitude of CAP in a concentration-dependent manner; their IC50 values were 0.94 and 0.47â¯mM, respectively. Other acetic acid-based NSAIDs (indomethacin, acemetacin and etodolac) also inhibited CAPs [the extent of inhibition: some 40% (1â¯mM), 40% (0.5â¯mM) and 15% (1â¯mM), respectively], except for sulindac and felbinac at 1â¯mM that had no effects on CAP peak amplitudes. A similar inhibition was produced by fenamic acid-based NSAIDs [tolfenamic acid (IC50â¯=â¯0.29â¯mM), meclofenamic acid (0.19â¯mM), flufenamic acid (0.22â¯mM) and mefenamic acid] which are similar in chemical structure to diclofenac and aceclofenac; their derivatives (2,6-dichlorodiphenylamine and N-phenylanthranilic acid) also inhibited. On the other hand, salicylic acid-based (aspirin), propionic acid-based (ketoprofen, naproxen, ibuprofen, loxoprofen and flurbiprofen) and enolic acid-based (meloxicam and piroxicam) NSAIDs had no effects on CAP peak amplitudes. SIGNIFICANCE: At least a part of antinociception produced by NSAIDs used as a dermatological drug to alleviate pain may be attributed to their inhibitory effects on nerve conduction, which depend on the chemical structures of NSAIDs.
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Potenciales de Acción/efectos de los fármacos , Antiinflamatorios no Esteroideos/clasificación , Antiinflamatorios no Esteroideos/farmacología , Fibras Nerviosas/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Potenciales de Acción/fisiología , Analgésicos/clasificación , Analgésicos/farmacología , Animales , Aspirina/clasificación , Aspirina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Indometacina/clasificación , Indometacina/farmacología , Masculino , Naproxeno/clasificación , Naproxeno/farmacología , Fibras Nerviosas/fisiología , Ranidae , Nervio Ciático/fisiologíaRESUMEN
OBJECTIVES: To explore the relative efficacy of oral pharmacologic interventions in the treatment of knee OA. METHODS: A systematic literature review was conducted using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases to identify trials conducted in patients with knee OA with a minimum 6 weeks of follow-up. The standardized mean differences of the change from baseline to week 6 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain between the treatment groups were estimated using Bayesian random-effects network meta-analyses. Subgroup analyses of baseline pain status (high, pain score ≥60 mm; low, pain score <60 mm) were performed. RESULTS: Of 4067 manuscripts, 44 were included in the evidence synthesis. Etoricoxib had the highest ranking for improving WOMAC pain (probability of being top ranked, p (best) = .43) followed by naproxen (p (best) = .12), acetaminophen (AAP) (p (best) = .04), and celecoxib (p (best) = .02). The top three ranked interventions were etoricoxib, celecoxib and aceclofenac in the higher pain group, and tramadol, celecoxib, and diclofenac in the lower pain group. CONCLUSION: In the overall analysis, etoricoxib, celecoxib, and aceclofenac had the highest rankings for improving WOMAC pain. The ability to improve knee OA symptoms may differ depending on baseline pain and radiologic features.
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Antiinflamatorios no Esteroideos , Articulación de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla , Antiinflamatorios no Esteroideos/clasificación , Antiinflamatorios no Esteroideos/farmacología , Humanos , Metaanálisis en Red , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/tratamiento farmacológico , Dimensión del Dolor/métodos , Resultado del TratamientoRESUMEN
Curcumin is poorly absorbed, which is interest in new preparations. However, little is known about variations in its pharmacokinetics and tissue bioavailability between formulations. In this randomized, crossover study we evaluated the relationship between steady-state plasma and rectal tissue curcuminoid concentrations using standard and phosphatidylcholine curcumin extracts. There was no difference in the geometric mean plasma AUCs when adjusted for the 10-fold difference in curcumin dose between the 2 formulations. Phosphatidylcholine curcumin extract yielded only 20% to 30% plasma demethoxycurcumin and bisdemethoxycurcumin conjugates compared to standard extract, yet yielded 20-fold greater hexahydrocurcumin. When adjusting for curcumin dose, tissue curcumin concentrations were 5-fold greater for the phosphatidylcholine extract. Improvements in curcuminoid absorption due to phosphatidylcholine are not uniform across the curcuminoids. Furthermore, curcuminoid exposures in the intestinal mucosa are most likely due to luminal exposure rather than to plasma disposition. Finally, once-daily dosing is sufficient to maintain detectable curcuminoids at steady state in both plasma and rectal tissues.
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Antiinflamatorios no Esteroideos/farmacocinética , Curcumina/farmacocinética , Recto/metabolismo , Adolescente , Adulto , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/clasificación , Área Bajo la Curva , Disponibilidad Biológica , Biotransformación , Estudios Cruzados , Curcumina/administración & dosificación , Curcumina/análogos & derivados , Curcumina/clasificación , Curcumina/metabolismo , Diarilheptanoides , Femenino , Glucurónidos , Voluntarios Sanos , Humanos , Absorción Intestinal , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, are among the most commonly used drugs worldwide. They account for a large number of adverse drug reactions (ADRs). The prevalence of NSAID-induced reactions is increasing. Distinguishing between a predicted side effect of a drug and a potentially life-threatening hypersensitivity reaction is essential to manage the affected patient. However, most clinicians find it difficult to diagnose these types of reactions despite published classification schemes. In this overview, we provide an in-depth review of NSAID classification, types of NSAID reactions, diagnostic tactics, and management strategies to provide the reader with a greater understanding of NSAID-induced reactions.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/terapia , Antiinflamatorios no Esteroideos/clasificación , Manejo de la Enfermedad , HumanosRESUMEN
La curcumina es una sustancia derivada de una planta llamada Curcuma longa. A esta sustancia se le han atribuido diversos efectos terapéuticos. En relación con la clínica dental, se ha observado que, además de ayudaren el control del dolor, ha sido efectiva contra la periodontitis, estomatitis y mucositis pediátrica. El control del dolor e inflamación son aspectos muy importantes para la mayoría de los tratamientos en odontología; la búsqueda de nuevas alternativas analgésicas y antiinflamatorias que, en comparación con las actuales, sean más eficientes, efectivas y tengan menos efectos colaterales es uno de los grandes retos de las ciencias biomédicas. La presente revisión muestra algunas evidencias científicas de los efectos de la curcumina como un antiinflamatorio y analgésico, con el propósito de sentar las bases para futuros estudios clínicos y de ciencia básica que aporten un mayor entendimiento de los procesos celulares, bioquímicos, moleculares, fisiológicos y farmacológicos de la curcumina como una sustancia potencialmente útilen el consultorio dental.
Curcumin is a substance derived from the plant Curcuma longa andone that has been attributed a range of therapeutic eff ects. In dentalpractice, curcumin has not only been found to help with pain control, buthas also been eff ective against periodontitis, stomatitis, and pediatricmucositis. Controlling pain and infl ammation are both very importantaspects of most dental treatments. The search for more effi cient andeff ective analgesic and anti-infl ammatory alternatives with fewerside eff ects compared to those currently used is one of the greatestchallenges for biomedical science. This review presents some of thescientifi c evidence of the eff ects of curcumin, both as an analgesic andan anti-infl ammatory agent, in order to establish the foundations forfurther clinical and basic science studies that will provide a greaterunderstanding of the cellular, biochemical, molecular, physiological,and pharmacological processes of curcumin as a potentially usefulsubstance in dental practice.
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Humanos , Analgésicos/clasificación , Antiinflamatorios no Esteroideos/clasificación , Curcumina/farmacología , Curcumina/uso terapéutico , Antineoplásicos/clasificación , Antineoplásicos/uso terapéutico , Antisépticos Bucales/clasificación , Antisépticos Bucales/uso terapéutico , Enfermedades Periodontales/tratamiento farmacológico , Estomatitis/tratamiento farmacológicoRESUMEN
OBJECTIVE: In inflammatory bowel disease (IBD), adherence to both medical treatment and other aspects of care has a substantial impact on the course of the disease. Most studies of medical adherence have reported that 30-45% of patients with IBD were non-adherent. Our study aimed to investigate the different aspects of adherence and to identify predictors of non-adherence, including the quality of care, for outpatients with IBD. MATERIALS AND METHODS: An anonymous electronic questionnaire was used to investigate different aspects of adherence, the quality of care, patient involvement and shared decision making among 377 IBD outpatients. RESULTS: Three hundred (80%) filled in the questionnaire. The overall adherence rate was 93%. Young age (< 35 years old) and smoking were significantly associated with non-adherence (prevalence odds ratio (POR) 2.98, 95% CI 1.04-8.52, p < 0.05 and POR 3.88, 95% CI 1.36-11.05, p < 0.05, respectively). The lowest medical adherence rates were found for 5-ASA and topical treatments among patients with inactive disease. A large majority of patients stated that treatment strategies were agreed upon as a shared decision between the patient and the health care professionals. CONCLUSIONS: Predictors for non-adherence were young age and smoking. High adherence rates could be explained by a high patient satisfaction and a high degree of shared decision making.
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Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Satisfacción del Paciente , Calidad de la Atención de Salud/normas , Adulto , Antiinflamatorios no Esteroideos/clasificación , Toma de Decisiones , Dinamarca , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Encuestas y Cuestionarios , Centros de Atención Terciaria , Adulto JovenRESUMEN
We have undertaken the metrological assessment of the method for the quantitative determination of a number of non-steroidal anti-inflammatory drugs (NSAID) including ibuprofen, ketorolac, diclofenac, indomethacin, naproxen, and ketoprofen with the use of gas chromatography mass spectrometry in the model blood samples in the framework of the screening survey of medicinal and narcotic substances. The method was evaluated in terms of the following characteristics: specificity, linearity, correctness, precision (reproducibility), and intra-laboratory precision. The proposed method can be applied for the quantitative evaluation of indomethacin, ketoprofen, and naproxen content as well as for the preliminary quantitative determination of ibuprofen and diclofenac in the framework of the chemico-toxicological and forensic chemical analysis. The method can be employed for the quantitative determination of ketorolac from such characteristics as «linearity¼ and «reproducibility¼.
Asunto(s)
Antiinflamatorios no Esteroideos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/análisis , Antiinflamatorios no Esteroideos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Toxicología Forense/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Reproducibilidad de los ResultadosRESUMEN
The composition of the gut microbiome with the use of non-steroidal anti-inflammatory drugs (NSAIDs) has not been fully characterized. Drug use within the past 30 days was ascertained in 155 adults, and stool specimens were submitted for analysis. Area under the receiver operating characteristic curve (AUC) was calculated in logit models to distinguish the relative abundance of operational taxonomic units (OTUs) by medication class. The type of medication had a greater influence on the gut microbiome than the number of medications. NSAIDs were particularly associated with distinct microbial populations. Four OTUs (Prevotella species, Bacteroides species, family Ruminococcaceae, and Barnesiella species) discriminated aspirin users from those using no medication (AUC = 0.96; 95% CI 0.84-1.00). The microbiome profile of celecoxib users was similar to that of ibuprofen users, with both showing enrichment of Acidaminococcaceae and Enterobacteriaceae. Bacteria from families Propionibacteriaceae, Pseudomonadaceae, Puniceicoccaceae and Rikenellaceae were more abundant in ibuprofen users than in controls or naproxen users. Bacteroides species and Erysipelotrichaceae species discriminated individuals using NSAIDs plus proton-pump inhibitors from those using NSAIDs alone (AUC = 0.96; 95% CI 0.87-1.00). Bacteroides species and a bacterium of family Ruminococcaceae discriminated individuals using NSAIDs in combination with antidepressants and laxatives from those using NSAIDs alone (AUC = 0.98; 95% CI 0.93-1.00). In conclusion, bacteria in the gastrointestinal tract reflect the combinations of medications that people ingest. The bacterial composition of the gut varied with the type of NSAID ingested.
Asunto(s)
Antiinflamatorios no Esteroideos/clasificación , Antiinflamatorios no Esteroideos/farmacología , Bacterias/aislamiento & purificación , Microbioma Gastrointestinal/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Bacterias/clasificación , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDS) are among the most common causes of drug hypersensitivity (HS) reactions. The diagnosis is based on a careful clinical history, and provocation tests are considered the gold standard for diagnosis. Skin tests have some value to study reactions to pyrazolones. Laboratory investigations are mostly used for research purposes. Different phenotypes have been described. OBJECTIVE AND METHODS: Our aim was to describe the most common clinical manifestations of NSAID HS in a large population of adult patients, the drugs involved, the association with previously described risk factors, and the outcome of diagnostic procedures. The classification of reactions proposed by the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group was adopted. RESULTS: Acetylsalicylic acid was the drug most often involved in reactions (34%), isolated cutaneous symptoms were the most reported (60%), and immediate reactions (58%) were the most common. There was an overall female predominance (64%) and 35% of the patients were atopic. HS to NSAIDs was confirmed in 21% of the patients. The most common phenotypes encountered among HS patients were NSAID-induced urticaria/angioedema and single-NSAID-induced urticaria/angioedema or anaphylaxis. Logistic regression analysis showed that gender and atopy were not significant risk factors for HS confirmation, but diagnosis depended on the number of previous reactions, the type of reaction, and the time interval between drug intake and reaction. CONCLUSION: Only 21% of suspected HS reactions were confirmed after diagnostic workup. Patients describing >1 previous reaction and suffering immediate reactions had a higher probability of a positive investigation.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/inmunología , Adolescente , Adulto , Anciano , Antiinflamatorios no Esteroideos/clasificación , Reacciones Cruzadas/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Pruebas Cutáneas , Factores de Tiempo , Adulto JovenRESUMEN
This study aimed to analyse UK pharmacovigilance data to quantify adverse events (AEs) associated with the non-steroidal anti-inflammatory drug (NSAID) molecules found in veterinary medicines authorised for use in dogs and cats. It was hypothesised that the frequency of AEs would be lower when associated with cyclo-oxygenase-2 selective (coxib), compared to non-selective (non-coxib) NSAIDs. The UK Veterinary Medicines Directorate (VMD) supplied frequencies of AEs derived from Periodic Safety Update Reports subdivided by formulation and species for each NSAID molecule. Frequencies of AEs were similar between species. The five most reported AEs were emesis, death, anorexia, lethargy, and diarrhoea. Reported frequency of emesis, renal insufficiency and death was higher with injectable compared to oral NSAIDs (P = 0.043). Reported frequency of emesis, lethargy and death was higher with coxib, compared to non-coxib NSAIDs (P = 0.029). Median (range) interval since authorisation was shorter for coxibs at 5 (2.5-9) years compared to non-coxibs at 15 (12-25) years. A negative correlation between time elapsed since authorisation and the frequency of AEs was identified (rs = -0.11 to -0.94). Higher frequency of reported AEs with injectable NSAIDs may be related to perioperative administration. The AE frequency associated with coxib and non-coxib NSAIDs may be confounded by changes in reporting habits over time. This study highlights the value of interrogating passive surveillance data to identify low frequency AEs and the need to facilitate improvement in recording and collecting AEs in small animal practice.