Removal of ibuprofen, naproxen and 17-ß-estradiol in water using L. octovalvis constructed wetlands.

This study was developed to evaluate the removal potential of ibuprofen, naproxen and 17-ß-estradiol in artificial wetlands constructed on a laboratory scale, using eight experimental devices planted with L. octovalvis species, tested with gravel substrate and without gravel substrate, which were fortified with synthetic mixtures at concentrations of 1, 2 and 5 mg/L of the three compounds, during a batch exposure time of nine days. The removal efficiency for 17-ß-estradiol was 94.5 ± 2.47%, followed by ibuprofen 94.03 ± 1.96% and naproxen 81.57 ± 8.74%, respectively. The treatment with the highest removal was the one performed without the presence of gravel substrate. The highest removal efficiency occurred from the third day of exposure for the three compounds, so it was established as the optimum residence time. The model that best explained the adsorption process of the three compounds studied, was the Langmuir isotherm. The observed results demonstrate that L. octovalvis can be used as a native species in artificial wetlands for the efficient removal of pharmaceutical compounds.

Through the use of a macrophyte plant native to the state of Morelos, an artificial wetland was built, which was capable of removing several drugs with tolerance to changes in concentration, which constitutes an economic and sustainable alternative that can be coupled to the treatment of wastewater contaminated with this type of compounds.

Priority list of pharmaceutical active compounds in aquatic environments of Mexico considering their occurrence, environmental and human health risks.

Pharmaceutical active compounds (PhACs) are detected pollutants in aquatic environments worldwide at concentrations ranging from ng L-1 to µg L-1. Currently, PhAC monitoring is poorly realized in Mexico. This study proposes a priority list of PhACs in Mexican aquatic environments, considering their occurrence and environmental and human health risks. Ecological risks were assessed as Risk Quotients (RQ) values using the PhAC concentrations detected in surface water, obtaining high risks (RQ > 1) against aquatic organisms, especially of naproxen, ibuprofen, diclofenac, acetaminophen, 17ß-estradiol, carbamazepine, ketoprofen, caffeine. In contrast, potential human health risks (RQH) were assessed on the Mexican population using the concentrations quantified in groundwater, demonstrating potential risks (RQH > 0.2) on the population, particularly of DCF and CBZ. Thus, a priority list of PhACs can be used as a reference for environmental monitoring in Mexican water supplies as well as PhACs monitoring in countries of the Caribbean region and Central America.

Photocatalytic Degradation of Naproxen: Intermediates and Total Reaction Mechanism.

Photochemical and photocatalytic oxidation of naproxen (NPX) with UV-A light and commercial TiO2 under constant flow of oxygen have been investigated. Adsorption experiments indicated that 90% of the solute remained in the solution. Combined chemical analysis of samples on the photochemical degradation indicated that NPX in an aqueous solution (20 ppm) is efficiently transformed into other species but only 18% of the reactant is mineralized into CO2 and water after three hours of reaction. Performing the photocatalytic oxidation in the presence of TiO2, more than 80% of the organic compounds are mineralized by reactive oxidation species (ROS) within four hours of reaction. Analysis of reaction mixtures by a combination of analytical techniques indicated that naproxen is transformed into several aromatic naphthalene derivatives. These latter compounds are eventually transformed into polyhydroxylated aromatic compounds that are strongly adsorbed onto the TiO2 surface and are quickly oxidized into low-molecular-weight acids by an electron transfer mechanism. Based on this and previous studies on NPX photocatalytic oxidation, a unified and complete degradation mechanism is presented.

Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

CYP2C9 Polymorphism Influence in PK/PD Model of Naproxen and 6-O-Desmethylnaproxen in Oral Fluid.

Polymorphisms in CYP2C9 can significantly interfere with the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen. The present research aimed to study the PK/PD parameters of naproxen and its metabolite, 6-O-desmethylnaproxen, associated with allelic variations of CYP2C9. In our study, a rapid, selective, and sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method was developed and validated for the determination of naproxen and its main metabolite, 6-O-desmethylnaproxen, in oral fluid. Naproxen and its main metabolite were separated using a Shim-Pack XR-ODS 75L × 2.0 column and C18 pre-column at 40 °C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v), with an injection flow of 0.3 mL/min. The total analytical run time was 3 min. The volunteers, previously genotyped for CYP2C9 (16 ancestral­CYP2C9 *1 and 12 with the presence of polymorphism­CYP2C9 *2 or *3), had their oral fluids collected sequentially before and after taking a naproxen tablet (500 mg) at the following times: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72 and 96 h. Significant differences in the PK parameters (* p < 0.05) of naproxen in the oral fluid were: Vd/F (L): 98.86 (55.58−322.07) and 380.22 (261.84−1097.99); Kel (1/h): 0.84 (0.69−1.34) and 1.86 (1.09−4.06), in ancestral and mutated CYP2C9 *2 and/or *3, respectively. For 6-O-desmethylnaproxen, no PK parameters were significantly different between groups. The analysis of prostaglandin E2 (PGE2) proved to be effective and sensitive for PD parameters analysis and showed higher levels in the mutated group (p < 0.05). Both naproxen and its main metabolite, 6-O-desmethylnaproxen, and PGE2 in oral fluid can be effectively quantified using LC-MS/MS after a 500 mg oral dose of naproxen. Our method proved to be effective and sensitive to determine the lower limit of quantification of naproxen and its metabolite, 6-O-desmethylnaproxen, in oral fluid (2.4 ng/mL). All validation data, such as accuracy, precision, and repeatability intra- and inter-assay, were less than 15%. Allelic variations of CYP2C9 may be considered relevant in the PK of naproxen and its main metabolite, 6-O-desmethylnaproxen.

Preparation, Characterization and Study of the Dissociation of Naproxen from Its Chitosan Salt.

Salts of naproxen (NAP) with chitosan (CTS) and reticulated chitosan (CEP) were prepared under optimized conditions to maximize the yield of reaction. The objective was to evaluate the dissociation in water, which can guide studies of release of the drug from biopolymeric salts in pharmaceutical applications. Higher salification was found after 24 h of reaction at 60 °C in a molar ratio 1:1.05 (CTS:NAP, mol/mol), resulting in a degree of substitution (DS) of 17% according to 13C NMR, after neutralization of the -NH2 group of the biopolymer by the carboxylic group of the drug. The presence of NAP salt is evidenced by FTIR bands related to the -NH3+ group at 856 cm-1, a decrease in crystallinity index in XRD diffractograms as well as changes in mass loss ratios (TG/DTG/DTA) and increased thermal stability of the salt regarding CTS itself. The CEPN crosslinked salt presented a DS = 3.6%, probably due to the shielding of the -NH2 groups. Dissociation studies revealed that at pH 2.00, dissociation occurred faster when compared to at pH 7.00 in the non-reticulated salt, while the opposite was observed for the reticulated one.

Application of biowaste generated by the production chain of pitaya fruit (Hylocereus undatus) as an efficient adsorbent for removal of naproxen in water.

Pharmaceutical compounds are a serious problem in the environment. They cause damage to the aquatic, animal, and human organisms and soon became considered emerging pollutants where their removal is extremely urgent. Among the techniques used, adsorption has been used with success, where several adsorbent materials, including those from residual biomass, have been used to remove these pollutants. In this study, the skins of the pitaya fruit (Hylocereus undatus) productive chain were carbonized with ZnCl2 to obtain activated carbon and later used in the adsorption of the drug naproxen (NPX) in a batch system. The Freundlich model demonstrated a better adjustment for the equilibrium isotherms. A high adsorption capacity for NPX (158.81 mg g-1) was obtained at 328 K, which can be attributed to the remarkable textural properties of the adsorbent, besides certain functional groups present on its surface. Thermodynamic studies confirmed the endothermic nature of the adsorption process (∆H0 = 0.2898 kJ mol-1). The linear driving force model (LDF) presented a good statistical adjustment to the experimental kinetic data. The application of the material in the treatment of simulated wastewater composed of various pharmaceutical drugs and salts was very promising, reaching 75.7% removal. Therefore, it can be inferred that the application of activated carbon derived from pitaya bark is highly promising in removing the NPX drug and treating synthetic mixtures containing other pharmaceutical substances.

Woody residues of the grape production chain as an alternative precursor of high porous activated carbon with remarkable performance for naproxen uptake from water.

Activated carbon prepared from grape branches was used as a remarkable adsorbent to uptake naproxen and treat a synthetic mixture from aqueous solutions. The material presented a highly porous texture, a surface area of 938 m2 g-1, and certain functional groups, which were key factors to uptake naproxen from effluents. The maximum adsorption capacity predicted by the Langmuir model for naproxen was 176 mg g-1. The thermodynamic study revealed that the adsorption process was endothermic and spontaneous. The linear driving force (LDF) model presented a good statistical adjustment to the experimental decay data. A suitable interaction pathway of naproxen adsorption onto activated carbon was proposed. The adsorbent material was highly efficient to treat a synthetic mixture containing several drugs and salts, reaching 95.63% removal. Last, it was found that the adsorbent can be regenerated up to 7 times using an HCl solution. Overall, the results proved that the activated carbon derived from grape branches could be an effective and sustainable adsorbent to treat wastewaters containing drugs.

Evaluation of the Antinociceptive, Antiallodynic, Antihyperalgesic and Anti-Inflammatory Effect of Polyalthic Acid.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug-drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56-320 mg/kg), antiallodynic (100-562 mg/kg), and antihyperalgesic and anti-inflammatory (10-178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.

Development and evaluation of naproxen-loaded sericin/alginate beads for delayed and extended drug release using different covalent crosslinking agents.

Different polymer matrix compositions based on sericin and alginate blend (using or not the covalent crosslinking agents dibasic sodium phosphate, polyvinyl alcohol and polyethylene glycol) were evaluated to entrap naproxen. Sericin has been shown to be essential for improving incorporation efficiency. Comparing the formulations with and without crosslinking agent, the best results were obtained for that composed only of sericin and alginate, with satisfactory values of entrapment efficiency (>80%) and drug loading capacity (>20%). In this case, delayed release (<10% in acid medium) and prolonged release (~360 min) were achieved, with a complex release mechanism involving swelling and polymer chain relaxation. The incorporation of the drug could be confirmed by the techniques of characterization of X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), as well as drug compatibility with the polymer matrix. In addition, particles of suitable size for multiparticulate systems were obtained and with higher thermal stability when compared to the pure drug.

A ingestão do anti-inflamatório não esteroide naproxeno afeta parâmetros neuromusculares e metabólicos? / Does the ingestion of naproxen affect neuromuscular and metabolic parameters?

O naproxeno, assim como outros anti-inflamatórios não esteroides (AINEs), está entre os medicamentos mais prescritos no mundo. O objetivo do presente estudo é analisar o efeito da ingestão de naproxeno em parâmetros neuromusculares e determinar seu efeito no dano muscular por meio do uso do marcador lactato. Metodologicamente, foi conduzido um estudo cruzado randomizado, duplo-cego e controlado por placebo em 11 homens treinados em resistência, que realizaram uma sessão de treinamento de força após ingerir 500 mg de naproxeno e outra sessão de treinamento após ingerir um placebo. Os participantes realizaram três séries de supino horizontal com uma carga de 90% da repetição máxima (1RM) até a falha concêntrica. As variáveis de resultado incluíram número de repetições, carga de trabalho e lactato. Os resultados mostraram que há uma correlação positiva e moderada entre as variáveis somatório de repetições e carga total e entre as variáveis lactato e carga total, no grupo naproxeno. No grupo placebo, a correlação positiva e moderada deu-se entre somatório de repetições e carga total. Na análise magnitude baseada nas interferências, as variáveis se mostraram possíveis para uma probabilidade positiva ou trivial e improvável para uma probabilidade negativa. Concluiu-se no presente estudo que o uso do naproxeno como recurso ergogênico no treinamento de força reduz a percepção de fadiga, mas não tem efeito direto no dano muscular, analisado a partir do marcador lactato, logo não interfere de maneira significativa nos parâmetros neuromusculares analisados.

Naproxen, as other non-steroidal anti-inflammatory drugs (NSAIDs), features among the most widely prescribed drugs in the world. The aim of this study is to analyze the effect of naproxen intake on neuromuscular parameters and determine its effect on muscle damage through the use of the lactate marker. In terms of methodology, a randomized, double-blind, placebo-controlled crossover study was conducted on 11 resistance-trained men who underwent a strength training session after taking 500 mg of naproxen and another training session after taking a placebo. The participants performed three sets of horizontal bench presses with a load of 90% maximum repetition (1RM) until concentric failure. Result variables included number of repetitions, workload and lactate. The results showed that there is a positive and moderate correlation between the sum of repetition and total load variables and between lactate and total load variables in the naproxen group. In the placebo group, a positive and moderate correlation was observed between sum of repetitions and total load. In the magnitude analysis, based on the interferences, the variables were shown to be possible for a positive or trivial probability and unlikely for a negative probability. It was concluded that the use of naproxen as an ergogenic resource in strength training reduces the perception of fatigue but has no direct effect on muscle damage when analyzed from the lactate marker, therefore it does not significantly interfere in the analyzed neuromuscular parameters.

Magnetic Solid-Phase Extraction Based on Poly 4-Vinyl Pyridine for HPLC-FLD Analysis of Naproxen in Urine Samples.

A magnetic solid phase extraction technique followed by liquid chromatography with a fluorescence detector for naproxen analysis in human urine samples was developed. The method includes the extraction of naproxen with a magnetic solid synthetized with magnetite and poly 4-vinylpriridine, followed by the magnetic separation of the solid phase and desorption of the analyte with methanol. Under optimal conditions, the linear range of the calibration curve was 0.05-0.60 µg L-1, with a limit of detection of 0.02 µg L-1. In all cases values of repeatability were lower than 5.0% with recoveries of 99.4 ± 1.3%. Precision and accuracy values are adequate for naproxen (Npx) analysis in urine samples.

Pharmacotherapy and inappropriate prescriptions in patients with psoriasis.

Background Psoriasis is a chronic inflammatory and systemic disease that primarily affects the skin, nails, and joints. Some medications have been linked to worsening clinical manifestations of cutaneous psoriasis. Objective To identify pharmacological treatments and drugs related to worsening dermatological lesions in patients with psoriasis. Setting Patients diagnosed with psoriasis or psoriatic arthritis between November 1, 2018, and October 30, 2019. Methods This was a cross-sectional study from a population database that identified the prescriptions of patients with psoriasis during 2019. All medications prescribed for the treatment of psoriasis and other comorbidities were investigated. Main outcome measure Potentially inappropriate medications. Results We identified 2088 patients with psoriasis, with a mean age of 53.6 ± 15.5 years, and 52.9% were men. A total of 92.6% received pharmacological treatment, and of these, topical corticosteroids were the most commonly used group (76.6%). A total of 55.3% of patients with cutaneous psoriasis received at least one drug associated with worsening dermatological lesions. The most frequent were naproxen (25.5%), diclofenac (14.7%), and dexamethasone (10.8%). Residing in Barranquilla (odds ratio 1.27, 95%confidence interval 1.009-1.607), having any chronic comorbidities (odds ratio 1.94, 95%confidence interval 1.566-2.402), and having a history of coronary heart disease (odds ratio 6.25, 95%confidence interval 1.895-20.645) increased the probability of receiving these prescriptions. Conclusions The pharmacological treatment of psoriasis was in accordance with the recommendations of the clinical practice guidelines, but the high proportion of potentially inappropriate prescriptions makes it necessary to promote educational and pharmacovigilance strategies that improve the formulation habits of the physicians involved in the treatment of these patients.

The association between nonsteroidal anti-inflammatory drugs and skin cancer: Different responses in American and European populations.

OBJECTIVE: To conduct a comprehensive systematic meta-analysis investigating the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and their subtypes with skin cancer (SC) and its subclasses (basal cell carcinoma BCC; squamous cell carcinoma SCC; melanoma; nonmelanoma skin cancer NMSC) in general, American and European populations. METHODS: PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure and ClinicalTrials.gov were searched up to 24 February 2019. Pooled effect sizes and 95% confidence intervals were used to estimate associations. RESULTS: Results based on 26 original studies including 223,619 cases and 1,398,507 controls showed both NSAIDs and nonselective Cyclooxygenase (COX) inhibitors to be statistically significantly associated with a reduced risk of SC, BCC, SCC and NMSC but not with melanoma. Conversely, no association was observed between selective Cyclooxygenase 2 (COX-2) inhibitors and SC or its subclasses. Further subgroup analysis showed that the results analyzed for American populations were almost the same as those for the general population. For European populations, neither NSAIDs nor its subtypes correlated significantly with susceptibility to SC or its subclasses. CONCLUSIONS: The use of NSAIDs might reduce the risk of SC, but many factors including study population, drug subtype, and disease subclass affect the significance of the association.

Utilization of naproxen by Amycolatopsis sp. Poz 14 and detection of the enzymes involved in the degradation metabolic pathway.

The pollution of aquatic environments by drugs is a problem for which scarce research has been conducted in regards of their removal. Amycolatopsis sp. Poz 14 presents the ability to biotransformation naphthalene at high efficiency, therefore, in this work this bacterium was proposed as an assimilator of naproxen and carbamazepine. Growth curves at different concentrations of naproxen and carbamazepine showed that Amycolatopsis sp. Poz 14 is able to utilize these drugs at a concentration of 50 mg L-1 as a source of carbon and energy. At higher concentrations, the bacterial growth was inhibited. The transformation kinetics of naproxen showed the total elimination of the compound in 18 days, but carbamazepine was only eliminated in 19.9%. The supplementation with cometabolites such as yeast extract and naphthalene (structure similar to naproxen) at 50 mg L-1, showed that the yeast extract shortened the naproxen elimination to 6 days and reached a higher global consumption rate compared to the naphthalene cometabolite. The biotransformation of carbamazepine was not improved by the addition of cometabolites. The partial sequencing of the genome of Amycolatopsis sp. Poz 14 detected genes encoding putative enzymes for the degradation of cyclic aromatic compounds and the activities of aromatic monooxygenase, catechol 1,2-dioxygenase and gentisate 1,2-dioxygenase exhibited their involving in the naproxen biodegradation. The HPLC-MS analysis detected the 5-methoxysalicylic acid at the end of the biotransformation kinetics. This work demonstrates that Amycolatopsis sp. Poz 14 utilizes naproxen and transforms it to 5-methoxysalicylic acid which is the initial compound for the catechol and gentisic acid metabolic pathway.

Efectividad Analgésica de Naproxeno Sódico y Etoricoxib Post Extracción Dental Simple: Ensayo Clínico Aleatorizado Paralelo / Analgesic Effectiveness of Sodium Naproxen and Etoricoxib Post Simple Dental Extraction: Parallel Randomized Clinical Trial

RESUMEN: El objetivo de este estudio fue comparar la efectividad analgésica de naproxeno sódico y etoricoxib post extracción dental simple. El presente ensayo clínico, aleatorizado paralelo y ciego simple, se desarrolló en la Clínica Odontológica de la Universidad Privada Antenor Orrego. Los pacientes, quienes requerían exodoncia simple por caries dental en molar mandibular, fueron distribuidos aleatoriamente en tres grupos de 17 participantes cada uno, donde recibieron naproxeno sódico, etoricoxib o ibuprofeno (grupo testigo), según los criterios establecidos. El procedimiento fue estandarizado, evaluándose la eficacia analgésica mediante la escala visual analógica (EVA) a las 1, 8, 24 y 48 horas, después del inicio de la medicación. El análisis estadístico se realizó mediante la prueba de Kruskal-Wallis, considerándose un nivel de significancia del 5 %. No se evidenció diferencia en la efectividad analgésica entre naproxeno sódico y etoricoxib, post extracción dental simple. Este hallazgo se observó a las 1 (p=0,602), 8 (p=0,884), 24 (p=0,338) y 48 horas (p=0,189). No existe diferencia en la efectividad analgésica entre naproxeno sódico y etoricoxib, post extracción dental simple.

ABSTRACT: The aim of the study was to compare the analgesic effectiveness of naproxen sodium and etoricoxib after simple dental extraction. This randomized parallel and single blind clinical trial, was developed in the Clínica Odontológica of the Universidad Privada Antenor Orrego. The patients, who required simple exodontia for dental caries in the mandibular molar, were randomized into three groups of 17 participants each, where they received naproxen sodium, etoricoxib or ibuprofen (control group), according to established criteria. The procedure was standardized, evaluating the analgesic efficacy by means of the analog visual scale at 1, 8, 24 and 48 hours, after the start of the medication. The statistical analysis was carried out using the Kruskal-Wallis test, considering a level of significance of 5 %. There was no difference in the analgesic effectiveness between naproxen sodium and etoricoxib, after simple dental extraction. This finding was observed at 1 (p = 0.602), 8 (p = 0.884), 24 (p = 0.338) and 48 hours (p = 0.189). There is no difference in the analgesic effectiveness between naproxen sodium and etoricoxib, after simple dental extraction.

Inhibition of key enzymes in the inflammatory pathway by hybrid molecules of terpenes and synthetic drugs: In vitro and in silico studies.

The aim of this work was to compare the anti-inflammatory activity of compounds prepared from terpenes and the synthetic drugs ibuprofen and naproxen. The anti-inflammatory activity of the hybrid compounds was compared with the activity of the parent compounds. This was accomplished using in vitro inhibition of lipoxygenases (LOX) and COX-2, and in silico docking studies in 15-LOX and COX-2. The synthesized hybrids showed an inhibition of COX-2 and LOX between 9.8%-57.4% and 0.0%-97.7%, respectively. None of the hybrids showed an improvement in the inhibitory effect toward these pro-inflammatory enzymes, compared to the parent terpenes and non-steroidal anti-inflammatory drugs. The docking studies allowed us to predict the potential binding modes of hybrids 6-15 within COX-2 and 15-LOX active sites. The relative affinity of the compounds inside the binding sites could be explained by forming non-covalent interactions with most important and known amino acids reported for those enzymes. A good correlation (r2  = 0.745) between docking energies and inhibition percentages against COX-2 was found. The high inhibition obtained for compound 10 against COX-2 was explained by hydrogen bond interactions at the enzyme binding site. New synthetic possibilities could be obtained from our in silico models, improving the potency of these hybrid compounds.

[Cardiovascular risk of non-steroidal anti-inflammatory drugs]. / Riesgo cardiovascular de los antiinflamatorios no esteroideos.

Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs. Both the analgesic and antiinflammatory effects, as well as the cardiovascular adverse effects, depend on the COX-2 inhibition. This paper reviews the available evidence of the increased risk of thrombotic events for both coxibs and traditional NSAID. The prothrombotic effect could be due to the inhibition of endothelial COX-2, with a decrease in production of prostacyclin and a relative increase in platelet thromboxane levels. Coxibs and diclofenac 150 mg/day seem to increase the risk of major vascular events by more than a third. Ibuprofen 2400 mg/day could slightly increase the risk of coronary events. Naproxen 1000 mg/day apparently does not increase the risk of vascular events. Besides ibuprofen and naproxen have the potential to decrease the cardioprotective effect of low doses of aspirin. Naproxen (= 1000 mg/day) and low doses of ibuprofen (= 1200 mg/day) are considered to have the most favorable thrombotic cardiovascular safety profiles of all NSAIDs. Therapeutic decisions should be based on an assessment of a person's individual risk factors, using the safest NSAIDs, at the lowest effective doses, for the shortest duration necessary to control symptoms, restricting their use in patients with increased cardiovascular risk.

Riesgo cardiovascular de los antiinflamatorios no esteroideos / Cardiovascular risk of non-steroidal anti-inflammatory drug

Los antiinflamatorios no esteroideos (AINEs) se encuentran entre los fármacos más utilizados en la práctica clínica. Actúan mediante el bloqueo de las enzimas ciclooxigenasas (COX), pero el grado de inhibición de COX-1 y COX-2 varía entre ellos. Se ha generalizado la clasificación entre COX-2 selectivos o coxibs, y los no selectivos o AINEs tradicionales. Tanto los efectos analgésico y antiinflamatorio como los efectos adversos cardiovasculares dependen de la inhibición de COX-2. Este trabajo revisa las evidencias disponibles del aumento del riesgo de eventos trombóticos tanto para los coxibs como para los AINEs tradicionales. El efecto protrombótico podría deberse a la inhibición de la COX-2 endotelial, con disminución de la prostaciclina y un incremento relativo de los niveles del tromboxano plaquetario. Los coxibs y el diclofenac, 150 mg/día, aumentarían el riesgo de eventos vasculares mayores en más de un tercio. El ibuprofeno 2400 mg/día aumentaría levemente el riesgo de eventos coronarios. El naproxeno 1000 mg/día no incrementaría el riesgo de eventos vasculares. Además, el ibuprofeno y el naproxeno tienen el potencial del disminuir el efecto cardioprotector de bajas dosis de aspirina. El naproxeno (≤ 1000 mg/día) y el ibuprofeno a bajas dosis (≤ 1200 mg/día) deberían considerarse los AINEs con el mejor perfil de seguridad cardiovascular. Las decisiones terapéuticas deben basarse en una adecuada evaluación del riesgo del paciente, utilizando los AINEs más seguros, a las menores dosis efectivas, por el menor tiempo posible que permita el control de los síntomas, restringiendo su utilización en enfermos con aumento del riesgo cardiovascular.

Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs. Both the analgesic and anti-inflammatory effects, as well as the cardiovascular adverse effects, depend on the COX-2 inhibition. This paper reviews the available evidence of the increased risk of thrombotic events for both coxibs and traditional NSAID. The prothrombotic effect could be due to the inhibition of endothelial COX-2, with a decrease in production of prostacyclin and a relative increase in platelet thromboxane levels. Coxibs and diclofenac 150 mg/day seem to increase the risk of major vascular events by more than a third. Ibuprofen 2400 mg/day could slightly increase the risk of coronary events. Naproxen 1000 mg/day apparently does not increase the risk of vascular events. Besides ibuprofen and naproxen have the potential to decrease the cardioprotective effect of low doses of aspirin. Naproxen (≤ 1000 mg/day) and low doses of ibuprofen (≤ 1200 mg/day) are considered to have the most favorable thrombotic cardiovascular safety profiles of all NSAIDs. Therapeutic decisions should be based on an assessment of a person´s individual risk factors, using the safest NSAIDs, at the lowest effective doses, for the shortest duration necessary to control symptoms, restricting their use in patients with increased cardiovascular risk.

Efficacy and safety of a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for pain relief in patients with osteoarticular diseases and dyspeptic symptoms.

PURPOSE: This study investigated the safety and efficacy of fixed-dose combination tablets of naproxen/esomeprazole magnesium and nimesulide/pantoprazole to determine if both regimens are equally suited to relieve pain in patients with osteoarticular diseases and dyspeptic symptoms. METHODS: Patients were randomly assigned to receive either nimesulide/pantoprazole (100 mg/20 mg) twice daily or naproxen/esomeprazole magnesium (500 mg/20 mg) twice daily for 14 days. The primary endpoint was defined as the mean change in modified Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Secondary endpoints were mean visual analog scale score of dyspeptic symptoms (nausea, abdominal discomfort/pain, epigastric burning, postprandial fullness), mean visual analog scale score of individual dyspeptic symptoms, and individual score of dyspeptic symptoms according to patient diary. This study is registered at ClinicalTrials.gov: NCT01670552. RESULTS: A total of 490 patients were enrolled and randomized, and 399 completed treatment (naproxen/esomeprazole, n=201; nimesulide/pantoprazole, n=198). The difference in mean change in the modified Western Ontario and McMaster Universities Osteoarthritis Index pain score after 7 days of treatment between the two treatment groups was 2.33 mm (95% CI, -1.22 to 5.89 mm). After 14 days of therapy, the difference was 0.45 mm (95% CI, -3.29 to 4.19 mm). The most common adverse events in the pooled group were abdominal discomfort, abdominal distention, dyspepsia, and nausea, but none of these was deemed to be clinically meaningful. CONCLUSION: The present study demonstrated noninferiority of a 14-day regimen with a fixed-dose combination of nimesulide/pantoprazole compared to naproxen/esomeprazole for the treatment of osteoarticular pain.