Nonselective Nonsteroidal Anti-inflammatory Drugs Research Articles

Prospective study of risk factors for community-acquired acute kidney injury

Background and hypothesisCauses and risk factors for community-acquired acute kidney injury (CA-AKI) have not been thoroughly studied. The aim of this study was to examine the risk factors for CA-AKI. MethodsIn this prospective study, we examined serum creatinine from all individuals visiting a university hospital's emergency department (ED) over an 11-month period for the presence of AKI defined according to the KDIGO criteria. Patients with AKI were invited to participate. Randomly selected controls (1:2) were paired according to age, sex, and date of admission. Participants answered questions about their medical history and medication use, including over-the-counter (OTC) drugs. Conditional logistic regression was used to identify factors associated with AKI. ResultsOf 602 AKI cases identified, 512 participated in the study. AKI cases were significantly more likely than controls to have used nonsteroidal anti-inflammatory drugs (NSAIDs) (26.0 % vs 18.0 %, p = 0,001) in the week preceding the ED visit, particularly OTC NSAIDs (23.3 % vs 15.9 %, p < 0.001). AKI was associated with a recent history of vomiting (OR 2.52 [95 %CI 1.87–3.39]), diarrhea (1.30 [1.00–1.70]) and urinary retention (1.92 [1.36–2.72]), use of non-selective NSAIDs (1.84, [1.37–2.48]), RAAS blockers (1.63 [1.21–2.19]), and diuretics (1.53 [1.13–2.08]), and a history of diabetes (1.42 [1.04–1.94]), CKD (1.36 [1.01–1.83]) and smoking (1.72 [1.24–2.37]). ConclusionsEvents in the setting of acute illness and medication use, including OTC NSAIDs, may play a greater role in the development of CA-AKI than comorbid conditions. Frequent use of OTC NSAIDs is a concern and should be addressed in view of serious adverse effects.

Survey of Usage and Awareness of Ibuprofen Among the Syrian Population

Ibuprofen is a non-selective NSAID. This drug inhibits both COX-1 and COX-2. It is commonly used to manage some conditions in Syria, especially pain. This research aimed to assess the awareness and use of ibuprofen among the Syrian population. A survey was conducted on social networking sites during January, February, and March 2024 to achieve this purpose. 217 responses were collected. Most participants were female (65%) and between 20 and 30 years old (83.9). Most participants had taken ibuprofen 80.9%. 45% use ibuprofen as a pain reliever. 74.4% responded that they can get ibuprofen from the pharmacy without a prescription. Half of the participants believe that the recommended dose of ibuprofen to relieve pain is 400 mg every 8 hours for an adult. Only 23.5% of participants had experienced side effects when taking ibuprofen, mainly stomach pain (55%). The first alternative drug to ibuprofen among participants was paracetamol 32%. The treatment plan of 69.8% of participants includes the combination of ibuprofen with paracetamol. The results of this survey demonstrated high consumption of Ibuprofen in Syria. Indeed, the surveyed Syrians had a good understanding of this medication.

Current challenges for therapy of comorbid patients: a new look at celecoxib. A review

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.

A Systematic Review and Meta-analysis of Selective Cyclooxygenase-2 Inhibitors and Non-selective Non-steroidal Anti-inflammatory Drugs for Acute Gout

Background The term “gout” refers to a broad clinical spectrum of diseases, including common and complex forms of arthritis, that affect multiple joints in a patient due to an elevated serum urate concentration. Purpose The study aims to compare the efficacy and safety of selective cyclooxygenase-2 (COX-2) inhibitors and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of acute gout, as well as to conduct a meta-analysis on safety. Methodology As of December 2021, the literature search was conducted using authorised electronic databases such as PubMed, Embase, Web of Science, and the Cochrane Library. Results There were seven investigations included in this study’s findings. Three COX-2 inhibitors, etoricoxib, celecoxib, and meloxicam, were reportedly compared to indomethacin or diclofenac. Four hours after the initial dose, 120 mg of etoricoxib reduces pain and inflammation by diminishing erythema. At higher dosages, celecoxib is more effective than at lower doses. Meloxicam has the same efficacy as NSAIDs. The subgroup analysis revealed that the risk of adverse events was 8.0% lower in the COX-2 inhibitors group than in the non-selective NSAIDs group (risk ratio = 0.92, 95% confidence interval = 0.60 to 0.40, p-value = 0.5). Conclusion Etoricoxib, a COX-2 inhibitor, has a more potent effect and may be more effective than non-selective NSAIDs. COX-2 inhibitors are more well tolerated and reduce the risk of adverse gastrointestinal events more effectively than non-selective NSAIDs. In the treatment of gout, non-selective NSAIDs may be a suitable alternative to COX-2 inhibitors.

Imrecoxib: Advances in Pharmacology and Therapeutics.

Imrecoxib, a cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug (NSAID), was discovered via the balanced inhibition strategy of COX-1/COX-2. It is indicated for the relief of painful symptoms of osteoarthritis. There have been some pharmacological and therapeutic advances since the approval of imrecoxib in 2011. However, an update review in this aspect is not yet available. Relevant literature until January 2024 was identified by search of PubMed, Web of science, Embase and CNKI. From the perspective of efficacy, imrecoxib provides relief of osteoarthritis symptoms, and potential off-label use for treatment of idiopathic pulmonary fibrosis, perioperative pain, hand-foot syndrome, axial spondyloarthritis, COVID-19, cartilage injury, and malignancies such as lung and colon cancer. From a safety point of view, imrecoxib showed adverse effects common to NSAIDs; however, it has lower incidence of new-onset hypertension than other types of selective COX-2 inhibitors, less gastrointestinal toxicities than non-selective NSAIDs, weaker risk of drug interaction than celecoxib, and more suitable for elderly patients due to balanced inhibition of COX-1/COX-2. From a pharmacoeconomic perspective, imrecoxib is more cost-effective than celecoxib and diclofenac for osteoarthritis patients. With the deepening of the disease pathophysiology study of osteoarthritis, new therapeutic schemes and pharmacological mechanisms are constantly discovered. In the field of osteoarthritis treatment, mechanisms other than the analgesic and anti-inflammatory effects of COX-2 inhibitors are also being explored. Taken together, imrecoxib is a moderate selective COX-2 inhibitor with some advantages, and there would be more clinical applications and research opportunities in the future.

Individual trombocity reactivity in hematuria associated with nephrolitiasis: the role of purinergic signalisation in the treatment of nesteroid protective preparations

Aim of the study was to establish the significance of TR-receptor, P2X1-receptor and P2Y-receptor synergism for the efficiency of TC aggregation in patients with different sensitivity to non-selective NSAIDs, which will allow us to approach an understanding the causes of the variability of hematuria associated with NLT. Material and methods. The study was prospective and included 60 patients with nephrolithiasis who were treated with high doses of NSAIDs for analgesia. The cohort of patients was divided into two groups: with effective (group 1. n=30) and ineffective (group 2. n=30) COX inhibition. The severity of hematuria was assessed during 7 days of drug therapy. The activity of TR receptors, purine P2X1- and P2Y- receptors of platelets (Tc) was analysed by turbidimetric method on ChronoLog analyser (USA). Agonists (ATP, ADP and Arachidonic acid) were used at EC50 and EC10 concentrations. Results. In the 1 group of patients, hyporeactivity of the TP receptor was established within 72 hours, which was restored to the level of normoreactivity on the 5th day of therapy. Optimal modulation of the compensatory reaction of Pl in response to hematuria was provided through the synergism of purine P2X1 and P2Y receptors. Optimal modulation of the compensatory reaction of Tc in response to hematuria was provided through the synergism of purine P2X1 and P2Y receptors. On the 7th day, a residual level of COX activity was reached, while intracellular signaling associated with stimulation of the TP receptor and purine P2 receptors did not provide the limitation of hematuria. In the 2 group, when patients were prescribed NSAIDs for 7 days, hyperreactivity of the TP receptor, P2 receptors and a stable level of microhematuria remained. In the case of COX resistance and increased production of TxA2, the maximum increase in proaggregant Tc activity was ensured through the stereotypical mechanism of intracellular signaling associated with stimulation of P2Y receptors (through Gi- and Gq- proteins) and the TP receptor (through Gq- and Gq12/13- proteins). Conclusion. Further study of the mechanisms of crosstalk signaling pathways with different COX activity will allow us to establish promising directions for pharmacological correction aimed at preventing hematuria and ensuring hemostasis in nephrolithiasis.

Ibuprofen delays ovulation by several hours: prospective controlled study in natural cycles with HCG-triggered ovulation

Research questionDoes ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DesignTwo-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3 × 400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. ResultsA total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). ConclusionsWomen trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study

BackgroundAging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. MethodsA case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1–7 days and 181–187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. ResultsThe study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70–4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47–5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15–26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82–66.64). ConclusionsNSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.

Indomethacin-omeprazole as therapeutic hybrids? Salt and co-amorphous systems enhancing physicochemical and pharmacological properties

Multidrug therapeutic hybrids constitute a promising proposal to overcome problems associated with traditional formulations containing physical mixtures of drugs, potentially improving pharmacological and pharmaceutical performance. Indomethacin (IND) is a non-selective non-steroidal anti-inflammatory drug (NSAIDs) that acts by inhibiting normal processes of homeostasis, causing a series of side effects, such as gastrointestinal symptoms. Proton pump inhibitors, such as omeprazole (OME), have been used to treat such gastrointestinal tract symptoms. In this work, two new multidrug therapeutic hybrids were prepared (an IND:OME salt and an IND:OME co-amorphous system) by ball mill grinding crystalline IND and OME under different conditions, i.e., liquid assisted grinding (LAG) with ethanol and dry grinding, respectively. The crystalline salt returned to a neutral state co-amorphous system when submitted to ball mill grinding in the absence of solvent (dry grinding), but the reverse process (LAG of the IND:OME co-amorphous system) showed partial decomposition of OME. The IND:OME co-amorphous system showed a higher physical stability than the neat IND and OME amorphous materials (with an amorphous stability longer than 100 days, compared to 4 and 16 h for the neat amorphous drugs, respectively, when stored at dry conditions at room temperature). Furthermore, OME presented a higher chemical stability in solution when dissolved from a salt form than from the pure crystalline form. The dissolution studies showed a dissolution enhancement for IND in both salt (1.8-fold after 8 h of dissolution) and co-amorphous (2.5-fold after 8 h of dissolution) forms. Anti-inflammatory activity using a mice paw oedema model showed an increase of the pharmacological response to IND at a lower dose (∼5mg/kg) for both IND:OME salt (2.8-fold) and IND:OME co-amorphous system (3.2-fold) after 6 h, when compared to the positive control group (IND, administered at 10 mg/kg). Additionally, the anti-inflammatory activity of both salt and co-amorphous form was faster than for the crystalline IND. Finally, an indomethacin-induced gastric ulceration assay in mice resulted in a higher mucosal protection at the same dose (40 mg/kg) for both IND:OME salt and IND:OME co-amorphous system when compared with crystalline OME.

NSAIDs between past and present; a long journey towards an ideal COX-2 inhibitor lead.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most abundantly used classes among therapeutic agents in medicine. NSAIDs inhibit the enzyme cyclooxygenase (COX), which is responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, non-selective NSAIDs are considered as a double-edged weapon since inhibition of COX-1 can lead to gastrointestinal side effects and kidney damage, whereas selective COX-2 inhibition provides anti-inflammatory effects without gastrointestinal toxicity. The detection of COX-2 role in inflammation process launched a new era in its management. Several trials have been established to proceed towards selectivity of well-defined anti-inflammatory members. COX-2 selective inhibitors are evidently safer on the gastrointestinal tract than non-selective NSAIDs. Nevertheless, their unexpected cardiovascular risks cannot be ignored. This review article highlights the latest trials aimed at developing new compounds with promising selective COX-2 activity.

Pain Management Strategies before Pan‐Retinal Photocoagulation for Diabetic Retinopathy: A Systematic Review

Purpose. This systematic review aims to consolidate key findings regarding the efficacy of pain relief medications administered prior to pan‐retinal photocoagulation (PRP) for diabetic retinopathy (DR). Methods. A comprehensive search of major databases from 1993 to 2023 was conducted. Clinical trials comparing pain relief drugs before PRP in patients diagnosed with DR requiring PRP treatment were eligible for inclusion. The assessment of pain scores involved the use of various scales, such as the visual analog scale (VAS), numerical rating scale (NRS), verbal rating scale (VRS), and other ordinal pain scales. In addition, laser parameters were taken into consideration during the analysis. Results. Twenty‐two clinical trials from initial 150 studies were included in the review. Nine studies evaluated the pain relief effects of nonsteroidal anti‐inflammatories NSAIDs (selective NSAID and nonselective NSAID), two studies compared the effects of opioids (conventional opioids and atypical opioids), and eleven studies investigated the effects of benzodiazepines, lidocaine, and other sedatives. Conclusion. This review synthesizes findings from multiple studies reporting pain as an adverse outcome of PRP in patients with advanced DR. Based on the evidence from reviewed clinical trials, the administration of lidocaine 2% via transconjunctival, retrobulbar, or peribulbar block along with specific NSAIDs, such as topical ketorolac administrated 24 hours before treatment or oral diclofenac potassium (50 mg) prior to PRP, demonstrated beneficial effects among patients with DR.

Regulation of platelet proaggregant activity in cyclooxygenase inhibition in patients with nephrolithiasis

Aim of the study was to establish the possibility of synergism between the TP receptor for TxA2 and purinergic P2 receptors during COX inhibition, and the effect of the resulting remodeling of signaling pathways on aggregometry parameters in patients with nephrolithiasis (NLT). Materials and Methods. The study was prospective and included 30 patients with imaging evidence of urinary tract calculi who were treated with high doses of non-selective NSAIDs for analgesia. The severity of hematuria was assessed at the time of hospitalization and during 7 days of lithokinetic therapy (LKT). Analysis of functional activity of TR-receptors, purine P2X1and P2Yreceptors of platelets (Tc) was performed by turbidimetric method on ChronoLog analyzer (USA). Agonists (ATP, ADP and Arachidonic acid) were used at concentrations of EC50 and EC10. Statistical analysis was performed using MedCalc package. Results. Two waves of COX activity decrease were revealed 24h and 72h after the beginning of NSAID administration. On the 5th day of LKT, the compensatory reaction of Tc was switched on, which was reproduced at restoration of normoreactivity of TR-receptor. Purine P2X1 – and P2Y-receptor synergism had a more pronounced inducing effect on aggregation parameters compared with the interaction between P2Y-receptor and TR-receptor or TR-receptor and P2X -receptor. On the 7th day, the residual level of COX activity was reached and hyporeactivity of TR-receptor was registered; at the same time the preserved level of TxA2 synthesis did not provide limitation of hematuria. Conclusion. Upon COX inhibition, potentiation of Tc proaggregant activity is reproduced by purine P2-receptor and TR-receptor interaction due to an increase in the rate of intracellular signalling (Slope) and the number of aggregates formed (AUC).

Comparison of different nonsteroidal anti-inflammatory drugs for cesarean section: a systematic review and network meta-analysis.

Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery. CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis. We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs. Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.

Co-administered oral anticoagulants with nonsteroidal anti-inflammatory drugs and the risk of bleeding: A systematic review and meta-analysis

BackgroundThe bleeding risk of individuals taking nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with oral anticoagulants (OACs) compared to OACs alone remains controversial. This meta-analysis aims to evaluate the bleeding risk of concomitant use of OACs and NSAIDs, and to make comparisons between different OACs types. MethodsPubMed, Embase, Cochrane Library and Web of Science were searched systematically until 11 August 2023 for studies reporting the bleeding risk of combined use of OACs and NSAIDs. Summary estimates with 95 % confidence interval (CI) were calculated by meta-analysis. Heterogeneity was assessed by I2 statistics. We performed subgroup analyses according to the types of NSAIDs, the types of OACs, the indication for therapy and the types of research. ResultsA total of 27 studies were included. Taking vitamin K antagonist (VKAs) concurrently with NSAIDs was associated with a higher risk of any bleeding [odds ratio (OR) = 1.55; 95 % CI, 1.21 to 2.00; P = 0.0007), gastrointestinal bleeding (OR = 2.66; 95 % CI, 1.96 to 3.62; P < 0.00001) as well as major bleeding (OR = 1.55; 95 % CI, 1.04 to 2.30; P = 0.03). Concomitant exposure to direct OACs (DOACs) and NSAIDs increased the risks of any bleeding (OR = 1.54; 95 % CI, 1.33 to 1.80; P < 0.00001) and gastrointestinal bleeding (OR = 2.18; 95 % CI, 1.02 to 4.69; P = 0.05), but was nonsignificant for major bleeding (OR = 1.42; 95 % CI, 0.84 to 2.40; P = 0.19). Without considering other confounding factors, concomitant exposure to DOACs and NSAIDs was associated with a lower risk of bleeding compared to VKAs plus NSAIDs (OR = 0.55; 95 % CI, 0.34 to 0.90; P = 0.02) in atrial fibrillation and venous thromboembolism patients. Subgroup analyses showed that compared to VKAs only, concurrent administration of VKAs and nonselective NSAIDs was associated with a heightened risk of bleeding (OR = 3.06; 95%CI, 1.99 to 4.71; P < 0.00001). However, inconsistent result was observed when it comes to selective NSAIDs (OR = 1.99; 95%CI, 0.87 to 4.51; P = 0.10). Compared to DOACs only, combined use of rivaroxaban and NSAIDs increased bleeding risk (OR = 1.61; 95 % CI, 1.21 to 2.14; P = 0.001), while dabigatran co-administered with NSAIDs showed no significant association with bleeding (OR = 1.40; 95 % CI, 0.80 to 2.44; P = 0.24). Regardless of indication, concomitant administration of NSAIDs and DOACs increased the risk of bleeding. ConclusionsCo-administered OACs with NSAIDs significantly increased the risk of any bleeding and gastrointestinal bleeding compared to OACs alone. Without considering other confounding factors, DOACs were associated with a lower risk of bleeding compared to VKAs in atrial fibrillation and venous thromboembolism patients.

Indomethacin Induces Spermidine/Spermine-N1-Acetyltransferase-1 via the Nucleolin-CDK1 Axis and Synergizes with the Polyamine Oxidase Inhibitor Methoctramine in Lung Cancer Cells.

Indomethacin is a non-selective NSAID used against pain and inflammation. Although cyclooxygenase (COX) inhibition is considered indomethacin's primary action mechanism, COX-independent ways are associated with beneficial effects in cancer. In colon cancer cells, the activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) is related to the increase in spermidine/spermine-N1-acetyltransferase-1 (SSAT-1), a key enzyme for polyamine degradation, and related to cell cycle arrest. Indomethacin increases the SSAT-1 levels in lung cancer cells; however, the mechanism relying on the SSAT-1 increase is unclear. Thus, we asked for the influence of the PPAR-γ on the SSAT-1 expression in two lung cancer cell lines: H1299 and A549. We found that the inhibition of PPAR-γ with GW9662 did not revert the increase in SSAT-1 induced by indomethacin. Because the mRNA of SSAT-1 suffers a pre-translation retention step by nucleolin, a nucleolar protein, we explored the relationship between indomethacin and the upstream translation regulators of SSAT-1. We found that indomethacin decreases the nucleolin levels and the cyclin-dependent kinase 1 (CDK1) levels, which phosphorylates nucleolin in mitosis. Overexpression of nucleolin partially reverts the effect of indomethacin over cell viability and SSAT-1 levels. On the other hand, Casein Kinase, known for phosphorylating nucleolin during interphase, is not modified by indomethacin. SSAT-1 exerts its antiproliferative effect by acetylating polyamines, a process reverted by the polyamine oxidase (PAOX). Recently, methoctramine was described as the most specific inhibitor of PAOX. Thus, we asked if methoctramine could increase the effect of indomethacin. We found that, when combined, indomethacin and methoctramine have a synergistic effect against NSCLC cells in vitro. These results suggest that indomethacin increases the SSAT-1 levels by reducing the CDK1-nucleolin regulatory axis, and the PAOX inhibition with methoctramine could improve the antiproliferative effect of indomethacin.

A Preliminary Study on the Relationship between Gastric Lesions and Anti-Inflammatory Drug Usage in Heavy Pigs.

Gastric lesions in pigs cause welfare and economic losses. Their prevalence in heavy pigs reared for premium products (e.g., Parma ham) requires further investigation. Stress, nutrition, and farm management are known risk factors, but the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are largely unknown. The aim of this study was to evaluate the prevalence of gastric lesions in Italian heavy pigs and their possible association with the use of anti-inflammatory drugs. A total of 9371 pig stomachs from 76 farms were evaluated. Among these, 20.3% showed no lesions, while 30.7%, 42.1%, and 6.8% were scored 1, 2 and 3, respectively. A tendency for an inverse relationship with farm size emerged. The use of steroids and NSAIDs was estimated by calculating a treatment incidence per 1000 (TI1000) in a subset of 36 farms. At least one prescription for NSAIDs and/or steroids was found in 80.6% of the farms (55.6% used NSAIDs and 63.9% used steroids). Median TI1000 was 0.07 (range: 0-30.1) and 0.18 (range: 0-6.2) for NSAIDs and steroids, respectively. Gastric scores were positively associated with NSAID use, but not with steroid use. Although the role of these drugs in gastric lesions needs to be further clarified, these findings suggest a cautious use of non-selective NSAIDs.

Selective COX-2 inhibitors after bariatric surgery: Celecoxib, etoricoxib and etodolac post-bariatric solubility/dissolution and pharmacokinetics

Anatomical/physiological gastrointestinal changes after bariatric surgery may influence the fate of orally administered drugs.Since non-selective NSAIDs are not well-tolerated post-surgery, selective cyclooxygenase-2 (COX-2) inhibitors may be important for these patients. In this work we investigated celecoxib, etoricoxib and etodolac, for impaired post-bariatric solubility/dissolution and absorption. Solubility was studied in-vitro, and ex-vivoin aspirated gastric contents from patients pre- vs. post-surgery. Dissolution was studied in conditions simulating pre- vs. post-surgery stomach. Finally, the experimental solubility data were used in physiologically-based biopharmaceutics model (PBBM) (GastroPlus®) to simulate pre- vs. post-surgery celecoxib/etoricoxib/etodolac pharmacokinetic (PK) profiles.For etoricoxib and etodolac (but not celecoxib), pH-dependent solubility was demonstrated: etoricoxib solubility decreased ∼1000-fold, and etodolac solubility increased 120-fold, as pH increased from 1 to 7, which was also confirmed ex-vivo. Hampered etoricoxib dissolution and improved etodolac dissolution post-surgery was revealed. Tablet crushing, clinically recommended after surgery, failed to improve post-bariatric dissolution. PBBM simulations revealed significantly impaired etoricoxib absorption post-surgery across all conditions; for instance, 79% lower Cmax and 53% decreased AUC was simulated post-gastric bypass procedure, after single 120 mg dose. Celecoxib and etodolac maintained unaffected absorption after bariatric surgery.This mechanistically-based analysis suggests to prefer the acidic drug etodolac or the neutral celecoxib as selective COX-2 inhibitors, over the basic drug etoricoxib, after bariatric surgery.

Pericardial diseases in pregnancy.

Pericardial effusion is the most common manifestation of pericardial diseases during pregnancy. This effusion is benign, mild, or moderate, well tolerated, and with spontaneous resolution after delivery; no specific treatment is required. Acute pericarditis is the second most common condition, usually requiring medical therapy during pregnancy. Cardiac tamponade and constrictive pericarditis are rare in pregnancy. Pre-pregnancy counselling is essential in women of childbearing age with recurrent pericarditis to plan pregnancy in a phase of disease quiescence and to review therapy. High-dose aspirin or non-selective nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can be used up to the 20th week of gestation. Low-dose prednisone (2.5 to 10 mg/day) can be administered throughout pregnancy. All of these medications, apart from high-dose aspirin, may be used during lactation. Colchicine is compatible with pregnancy and breastfeeding, and it can be continued throughout pregnancy in order to prevent recurrences. Appropriate follow-up with a multidisciplinary team with experience in the field is recommended throughout pregnancy to ensure good materno-fetal outcomes.

Postoperative pain assessment and management among nurses in selected hospitals in Benin City, Edo State, Nigeria

ABSTRACTObjective:This study was designed to determine the nurse assessment of postoperative pain and its management in selected hospitals, Benin City, Edo State, Nigeria.Materials and Methods:A descriptive cross-sectional survey was adopted. The target population consist of 222 purposely nurses who are in the cadre of nursing officer II to chief nursing officer who works in the various surgical wards/units of the selected health facilities. The data were collected from the participants using the pretested structured questionnaire developed by the researcher.Results:Results showed that 66.2% of nurses had a poor level of knowledge on postoperative pain assessment. The McGill Pain Questionnaire was the most used pain assessment tool with a mean score of 2.84 whereas the Dallas Pain Questionnaire was the least used with a mean score of 1.90. “Providing clean, calm, and well-ventilated ward environment” (3.69 ± 0.61) was the most used nonpharmacological method for postoperative pain management, followed by “distraction, relaxation, and guided imagery” (3.52 ± 0.50), “dressing, bandage, splint, and reinforce wound sites postoperatively” (3.39 ± 0.54), and “early ambulation/exercise” (3.20 ± 0.62). The most used pharmacological interventions were “acetaminophen” (3.63 ± 0.55), “topical anesthetic” (2.92 ± 0.62), “nonselective nonsteroidal anti-inflammatory drugs” (2.87 ± 0.43), and “mixed opioid agonist–antagonist” (2.56 ± 0.56).Conclusion:There is a poor level of knowledge on postoperative pain assessment among nurses in this study setting. It is, therefore, pertinent for hospitals to organize continuous in-service training for postoperative pain assessment and management, especially on nonpharmacological approaches among nurses.

Medicinal and toxicological investigation of some common NSAIDs; A computer-aided drug design approach

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment of pain, fever, and inflammation. Their consumption rises some crucial side effects like gastrointestinal, cardiovascular, and renal injury because of the non-selective reduction of prostaglandin synthesis, with differences in the extent of inhibition of the cyclooxygenase. Attempts have been taken for a comparative biochemical, medicinal, and toxicological investigation to raise awareness of the consumption of NSAIDs. In-silico methods were incorporated to investigate their physicochemical, spectral, medicinal, pharmacological, and toxicological properties. Molecular docking and non-bonding calculations were performed against the human prostaglandin synthase protein to reveal their binding affinity and interactions with the amino acid residues of the receptor protein. Further, molecular dynamics simulation was conducted to validate the binding mode and drug-protein stability at the inhibiting binding pocket. The physical and chemical analysis supports their geometries and spectral results confirming the presence of essential functional groups at the core structure. From ADMET and PASS prediction, all the drugs are non-carcinogenic (except IBP), and nonselective NSAIDs showed relatively higher adverse effects compared to selective agents. Based on the above studies, this report can be helpful to understand more deeply the medicinal, and toxicological effects of the reported NSAIDs.