Nonselective Nonsteroidal Anti-inflammatory Drugs Research Articles

Senescent preosteoclast secretome promotes metabolic syndrome associated osteoarthritis through cyclooxygenase 2.

Metabolic syndrome-associated osteoarthritis (MetS-OA) is a distinct osteoarthritis phenotype defined by the coexistence of MetS or its individual components. Despite the high prevalence of MetS-OA, its pathogenic mechanisms are unclear. The aim of this study was to determine the role of cellular senescence in the development of MetS-OA. Analysis of the human osteoarthritis initiative (OAI) dataset was conducted to investigate the MRI subchondral bone features of MetS-human OA participants. Joint phenotype and senescent cells were evaluated in two MetS-OA mouse models: high-fat diet (HFD)-challenged mice and STR/Ort mice. In addition, the molecular mechanisms by which preosteoclasts become senescent as well as how the senescent preosteoclasts impair subchondral bone microenvironment were characterized using in vitro preosteoclast culture system. Humans and mice with MetS are more likely to develop osteoarthritis-related subchondral bone alterations than those without MetS. MetS-OA mice exhibited a rapid increase in joint subchondral bone plate and trabecular thickness before articular cartilage degeneration. Subchondral preosteoclasts undergo senescence at the pre- or early-osteoarthritis stage and acquire a unique secretome to stimulate osteoblast differentiation and inhibit osteoclast differentiation. Antagonizing preosteoclast senescence markedly mitigates pathological subchondral alterations and osteoarthritis progression in MetS-OA mice. At the molecular level, preosteoclast secretome activates COX2-PGE2, resulting in stimulated differentiation of osteoblast progenitors for subchondral bone formation. Administration of a selective COX2 inhibitor attenuated subchondral bone alteration and osteoarthritis progression in MetS-OA mice. Longitudinal analyses of the human Osteoarthritis Initiative (OAI) cohort dataset also revealed that COX2 inhibitor use, relative to non-selective nonsteroidal antiinflammatory drug use, is associated with less progression of osteoarthritis and subchondral bone marrow lesion worsening in participants with MetS-OA. Our findings suggest a central role of a senescent preosteoclast secretome-COX2/PGE2 axis in the pathogenesis of MetS-OA, in which selective COX2 inhibitors may have disease-modifying potential. This work was supported by the National Institutes of Health grant R01AG068226 and R01AG072090 to MW, R01AR079620 to SD, and P01AG066603 to XC.

Mechanisms and Treatment of Delayed Onset Muscle Soreness in Athletes - A Review

Objective: The purpose of this study is to review mechanisms for Delayed Onset Muscle Soreness (DOMS) and the pharmacological treatment options with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Method: Our review of published research literature was based on an appropriate number of subjects included in the study with a statistical power of .80 or higher and an effect size of .30 or higher. In the case of review articles, two cited references from each article where significant data were used to establish the conclusion were examined for type II error using the criteria mentioned above. Our review also includes inflammation, tissue damage, and the treatment of DOMS with both selective and non-selective NSAIDs. Results: Frequently cited mechanisms of DOMS are "mechanical strain" and "metabolic overload" within the muscle structure. The inflammation associated with DOMS is caused by eccentric exercise-induced muscle damage. NSAIDs inhibit prostaglandin synthesis and/or block cyclooxygenase and there by reduce the pain and swelling associated with inflammation. There are both selective and non-selective NSAIDs, the former being the COX-2 inhibitors (e.g., celecoxib) and the later (e.g., ibuprofen, naproxen, and aspirin). Conclusion: For the treatment of DOMS, naproxen taken at anti­inflammation levels for at least 3 days shows the most consistent results for improving the recovery rate of affected muscle.

Effects of various analgesics on pain perception and rate of tooth movement: a randomized controlled clinical study

Background: Pain is one of the most reported side effects of orthodontic treatment despite the advanced technology in orthodontics. Many analgesics have been introduced to control orthodontic pain including acetaminophen and selective and nonselective nonsteroidal anti-inflammatory drugs. The great concern about these drugs is their adverse effect on rate of teeth movement. Aims: The purpose of this study was to evaluate and compare the effect of acetaminophen, ibuprofen and etoricoxib on pain perception and their influence on the rate of teeth movement during leveling and alignment stage. Methods: Forty patients were evenly and randomly distributed in a blinded way to one of four groups: placebo (starch capsules), acetaminophen 500mg thrice daily, ibuprofen 400mg thrice daily, and etoricoxib 60mg once daily. The drugs were given one hour before bonding and archwire placement and continued for three days. A visual analogue scale was used to express pain levels before and after archwire placement, on the first, second, third, and seventh day. Little’s irregularity index was measured before bonding and at every activation visit until the end of the alignment and leveling stage. Results: All three drugs showed a lower pain level than placebo at the bonding and first activation visits. Etoricoxib showed the least pain level among other drugs followed by ibuprofen. No statistically significant differences were found between the drug groups and the placebo at the second and third activation visits. No statistically significant differences were detected between the 4 experimental groups concerning the rate of teeth movement. Conclusions: The three drugs were only effective in controlling pain during the first two visits of orthodontic treatment; and etoricoxib 60mg/day was the best. All three drugs had no influence on rate of teeth movement when used in their least recommended dose.

NSAIDs in sciatica (NIS): study protocol for an investigator-initiated multicentre, randomized placebo-controlled trial of naproxen in patients with sciatica

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat sciatica, despite insufficient evidence from placebo-controlled trials. NSAIDs may cause serious side effects; hence, there is a strong need to clarify their potential beneficial effects in patients with sciatica.MethodsThis is a multicentre, randomized, placebo-controlled, parallel-group superiority trial. Participants will be recruited among sciatica patients referred to outpatient clinics at hospitals in Norway who have radiating pain below the knee with a severity score of ≥ 4 on a 0–10 numeric rating scale and clinical signs of nerve root or spinal nerve involvement. The intervention consists of oral naproxen 500 mg or placebo twice daily for 10 days. Participants will report the outcomes and adverse events daily using an electronic case report form. The primary endpoint is change in leg pain intensity from baseline to day 10 based on daily observations. The secondary outcomes are back pain intensity, disability, sciatica symptom severity, rescue medication (paracetamol) consumption, opioid use, ability to work or study, 30% and 50% improvement in leg pain, and global perceived change of sciatica/back problem. The outcomes will be analysed using mixed effects models for repeated measurements. The total duration of follow-up is 12 (± 2) days.DiscussionThis trial aims to evaluate the benefits of naproxen, a non-selective NSAID, in patients with sciatica. No important differences in efficacy have been demonstrated between different NSAIDs in the management of musculoskeletal disorders; hence, the results of this trial will likely be applicable to other NSAIDs.Trial registrationClinicalTrials.gov NCT03347929. Registered on November 20, 2017.

Risk of NSAID-associated anastomosis leakage after colorectal surgery: a large-scale retrospective study using propensity score matching.

NSAIDs are commonly used as opioid-sparing analgesics in colorectal surgery. Many efforts are made to elucidate the risk of NSAID-associated anastomotic leakage after colorectal surgery. However, these results still remain controversial. In this study, we applied large-scale retrospective analysis using propensity score matching to fully clarify the association between risk of anastomotic leakage and use of NSAID after colorectal surgery. All colorectal cancer patients receiving operation during February 2008 to August 2018 in our multi-institution medical organization research database were enrolled. It is worthy to mention that only patients requiring re-operation within 21days after colorectal surgery due to anastomotic leakage were counted as anastomosis leakage. Furthermore, a propensity score TriMatch analysis was performed to prevent from interference of confounding factors. A total of 10,584 patients were included in this study and divided into three groups, no NSAIDs group, non-selective NSAIDs group, and selective COX-2 inhibitors group, respectively. Before tri-matching analysis, significant differences in anastomotic leakage rate were observed. After propensity score matching analysis, the ratio of anastomotic leakage requiring re-operation occurred in 2.0%, 3.6%, and 2.0% in no NSAIDs, non-selective NSAIDs, and selective COX-2 inhibitors group, respectively. No significant difference was observed in these three groups. These results suggest that NSAIDs are not associated with incidence of anastomosis leakage following colorectal surgery. To our knowledge, it is the first study demonstrating that NSAIDs is not associated with incidence of anastomosis leakage following colorectal surgery using propensity score matching at a larger-scale retrospective study.

Selective COX-2 inhibitor continues to be a safe alternative in patients with nonselective NSAIDs hypersensitivity

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause different types of allergic and pseudo allergic reactions. This results in difficulties in clinical practice. Most cases of NSAID hypersensitivity are mediated by the inhibition of cyclooxygenase-1 enzyme (COX-1), which results in depletion of the protective prostaglandin E2, and promotes the unrestrained synthesis of inflammatory mediators from mast cells. Selective COX-2 inhibitors are considered safe alternatives in patients with NSAID allergy, although hypersensitivity reactions to COX-2 inhibitors have also been reported. Our study aimed to report the experience in Qatar for using COX2 inhibitors as an alternative treatment for nonselective NSAID allergy.Methods: Data of patients who underwent open challenge with a single dose of oral celecoxib 200 mg were retrieved from the procedure log of the Allergy and immunology Division in Hamad medical corporation, Doha, Qatar, from 2013 to 2022. The challenge was considered positive if the patient developed cutaneous or respiratory symptoms.Results: A total of 31 patients were identified; 4 with a history of celecoxib allergy. The remaining 27 (23 females and 4 males); with mean ( ± SD, range) age of 42 ( ± 12, 20–65) years had hypersensitivity to one (n = 11) or more than one (n = 16) nonselective NSAID, manifested as cutaneous, respiratory, or anaphylactic symptoms. Those 4 patients with celecoxib allergy were challenged and only one with a historical reaction of anaphylaxis developed anaphylaxis during the challenge. Celecoxib was well tolerated in all 27 patients with hypersensitivity reactions to nonselective NSAIDs. Also, patients were contacted by telephone call at 24 hours and after 1 week with no evidence of delayed reactions.Conclusions: Selective COX-2 and nonselective NSAIDs have similar overall efficacy as analgesic, anti-inflammatory, and antipyretic agents. Hypersensitivity reaction to COX-2 inhibitors has been reported; however, it is rare. So, it is safer to challenge the patients with COX-2 inhibitors before prescribing them as alternative medication in patients with Nonselective NSAID allergies. We plan to conduct a single-/double-blind placebo-controlled study for more patients, especially using graded challenges for high-risk profile candidates. Also, it may be of significance to test more than one type of selective COX-2 to avoid drug-specific reactions.

Meloxicam versus Celecoxib for Postoperative Analgesia after Total Knee Arthroplasty: Safety, Efficacy and Cost.

Introduction:Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2 inhibitors (e.g., celecoxib) are believed to have fewer gastrointestinal (GI) adverse effects than nonselective NSAIDS. Meloxicam is less selective for COX-2 than celecoxib is and partially inhibits COX-1 at higher doses. Nonetheless, some surgeons prefer using nonselective NSAIDs because of their lower expense.Methods:Four thousand nine hundred ninety-four patients who underwent TKA between January 2015 and February 2020 and took either celecoxib (n = 3,174), meloxicam 15 mg/d (n = 1,819), or meloxicam 7.5 mg/d (n = 451) were studied. Mutlimodal postoperative analgesia protocols were otherwise similar. GI bleeding and wound complication incidence were determined, as well as average 30-day prescription costs.Results:GI bleeding incidence was similar in the three cohorts (P = 0.4). The incidence of wound complications did not significantly differ between the groups: 0.06%, 0.07%, and 0.22% in the celecoxib, meloxicam 15 mg/d, and meloxicam 7.5 mg/d groups, respectively (P = 0.06). Subsituting meloxicam for celecoxib results in an average savings of $183 per prescription.Discussion:Meloxicam used at higher doses (15 mg/d) does not markedly increase the risk of GI or wound complications associated with COX-1 inhibition and is less costly for multimodal analgesia after TKA.

A Systematic Review on the Effect of Common Medications on Platelet Count and Function: Which Medications Should Be Stopped Before Getting a Platelet-Rich Plasma Injection?

Background:Platelet-rich plasma (PRP) exerts its effect through the release of growth factors and cytokines from the platelet concentrate. Certain medications may affect platelet count or function, resulting in decreased efficacy of PRP injections.Purpose:To systematically review the literature regarding common medications and their effects on platelets to establish guidelines for which medications should be stopped before obtaining a PRP injection.Study Design:Systematic review; Level of evidence, 2.Methods:This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for studies assessing the effect of common medications on platelet count or platelet function was performed of the PubMed, Cochrane Library, Web of Science, and OpenGrey databases. Inclusion criteria were as follows: drug studied was aspirin, acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), a statin, or gabapentin; human participants; and article in the English language. Risk of bias was assessed using the Cochrane Risk of Bias tool and the Risk of Bias in Non-randomised Studies—of Interventions tool.Results:A total of 1711 studies were identified through the initial search, with 20 studies meeting all inclusion criteria. No studies involving gabapentin met all inclusion criteria. Patients treated with aspirin (268 patients) or acetaminophen (13 patients) showed a significant decrease in platelet aggregation. Statin therapy (73 patients) did not result in a significant decrease in platelet aggregation. Patients who took NSAIDs (172 patients) demonstrated significantly decreased platelet aggregation only when treated with nonselective formulations. Those treated with cyclooxygenase (COX)-2–selective NSAIDs showed no significant difference in platelet aggregation. Treatment with aspirin, acetaminophen, statins, or NSAIDs did not lead to a significant decrease in platelet count.Conclusion:Aspirin, acetaminophen, and nonselective NSAIDs should be considered for suspension before a PRP injection because of their potential to diminish the effects of the injection. COX-2–selective NSAIDs and statins do not need to be withheld before a PRP injection.

Safety of Non-Steroidal Anti-Inflammatory Drugs in the Elderly: An Analysis of Published Literature and Reports Sent to the Portuguese Pharmacovigilance System.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently used agents to treat musculoskeletal disorders (principally by the elderly), thus raising the risk of adverse drug reactions (ADRs). This work aims to monitor NSAIDs safety profile in older people by using literature and pharmacovigilance data. Published clinical studies reporting the NSAIDs safety in elderly patients (age ≥ 65) were identified by a literature search and were then deeply analyzed. In addition, suspected ADRs reports submitted to the Portuguese Pharmacovigilance System (PPS) involving patients aged ≥65 with at least one NSAID as suspected drug were explored in detail. Most studies concluded that the risk of gastrointestinal, cardiovascular, and renal ADRs was significantly lower with cyclooxygenase-2 (COX-2)-selective NSAIDs use than with nonselective NSAIDs. The PPS data analysis showed that serious gastrointestinal ADRs occurred mostly in patients taking more than one NSAID and/or another concomitant drug that increases the incidence of these events, in the absence of gastroprotection. The results suggest that while NSAID toxicity is well understood, their safe use needs to be monitored in clinical practice. Furthermore, the pharmacovigilance data analyzed also showed that monitoring NSAIDs use in elderly remains essential to mitigate the associated risks, especially in those with comorbidities and under polytherapy.

Respiratory Syncytial Virus Infection Modeled in Aging Cotton Rats (Sigmodon hispidus) and Mice (Mus musculus).

Serious infection with respiratory syncytial virus (RSV) is associated with high risk in infants, children, and elderly. There is currently no approved vaccine against RSV infection, and the only available prevention is immunoprophylaxis utilized in high-risk infants, leaving the elderly without many options. In the elderly, the chronic low-grade inflammatory state of the body can play a significant role during infection. The cotton rat and mouse have emerged as the preferred small animal models to study RSV infection in the elderly. These animal models of aging have shown an age-dependent time course for clearance of virus correlating with a significantly diminished cytotoxic T lymphocyte and humoral immune response in old animals compared to adult animals. In addition, protection through vaccination is reduced in aging rodents. These results mirror the findings in humans. In mice and cotton rats, treatment with ibuprofen, a nonselective nonsteroidal anti-inflammatory drug (NSAID), to decrease the chronic low-grade inflammation of the elderly immune system has proven successful in restoring the function of cytotoxic lymphocytes. While more research is required, these treatment types promise a beneficial effect in addition to a putative vaccine. Choosing an appropriate animal model to study RSV infection in the aging immune system is essential to benefit the growing population of elderly in the world. This review focuses on the current research of RSV infection in the cotton rat and mouse as model systems for an aging immune system.

Formulation and Evaluation of Combined Dosage Form of Diclofenac Sodium (Mini Tablet) and Omeprazole Sodium in Capsule Devices

The work investigates the formulation and evaluation of combined dosage form of diclofenac sodium (mini tablet) and omeprazole sodium in capsule devices. The design of effective and safe drug delivery systems has become an integral part for the development and formulating of new medicines. So, research continuously keeps on searching for new ways to deliver drugs over a long period of time or for a well-controlled release profile, to minimizing the loss of drug, to reduce the side effect. The continuous release mini matrix tablet of diclofenac sodium prepared by wet granulation using HPMC, the patients at risk for ulcer disease who require treatment for arthritis receive nonsteroidal anti-inflammatory drugs (NSAIDs) that are selective for cyclooxygenase-2 or the combination of a nonselective NSAID with a proton-pump inhibitor. We assessed whether celecoxib would be similar to diclofenac plus omeprazole in reducing the risk of recurrent ulcer bleeding in patients at high risk for bleeding.

Impact of Preventive Strategies on Gastrointestinal Complications in Elderly Patients on Concomitant Use of Oral Anticoagulants and Nonsteroidal Anti-Inflammatory Drugs: A Nationwide Cohort Study.

Despite growing evidence showing an increased risk of concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and anticoagulants, few studies have investigated whether proton pump inhibitors can prevent gastrointestinal (GI) complications in patients receiving both NSAIDs and anticoagulants. We aimed to evaluate the risk of serious GI complications and the impact of GI preventive strategies on the concomitant use of NSAIDs and anticoagulants. Our nationwide cohort study using Korea's claims data included elderly patients (aged ≥65 years) who started anticoagulants and NSAIDs from 2016 to 2017. The outcome was serious GI complications defined as hospitalization or emergency department visits with GI bleeding or perforation. A Cox regression analysis was performed using time-dependent variables and propensity score matching. In total, 92,379 patients were identified. Compared with non-prophylaxis, proton pump inhibitors and selective cyclooxygenase-2 inhibitors were associated with a 64% [adjusted hazard ratio, 0.36 (95% confidence interval 0.25-0.53)] and 74% [adjusted hazard ratio, 0.26 (95% confidence interval 0.19-0.36)] lower risk of serious GI complications, respectively. Cyclooxygenase-2 inhibitor use was not different from the use of non-selective NSAIDs with proton pump inhibitors for the prevention of serious GI complications. H2-receptor antagonists did not reduce the risk of serious GI complications compared with non-prophylaxis during concomitant non-selective NSAID and anticoagulant therapy. Proton pump inhibitors or cyclooxygenase-2 inhibitors used as GI preventive strategies did not completely eliminate but lowered the risk of serious GI complications among elderly patients receiving both NSAIDs and anticoagulants.

Abstract P1-10-05: Evidence that body mass index modifies breast tissue collagen peptide response pattern to treatment with the non-steroidal anti-inflammatory drug sulindac

Abstract Background. In observational studies, regular use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with reduced breast cancer risk and disease recurrence with evidence that the benefit is greater in overweight/obese women. This parallels findings that obesity is associated with an increase in proinflammatory processes with possible effects on the breast stroma and extracellular matrix. Methods. To assess if body mass index (BMI kg/m2) alters breast tissue response to NSAIDs, we conducted exploratory analyses of change in breast tissue collagen-associated peptides following 6 months of treatment with the NSAID sulindac (150 mg bid) by BMI category: normal (18.5-24.9 n=6), overweight (25-29.9 n=14) and obese (≥30 n=11). Samples for this study were non-cancer core needle breast biopsies from postmenopausal women with a history of hormone receptor positive breast cancer enrolled to study sulindac effect on breast tissue biomarkers. At completion, 36 of 50 patients underwent baseline biopsy and 31 had sufficient tissue for paired analyses. Tissue collagen-associated peptides were studied using whole slide tissue imaging mass spectrometry proteomics. Individual peptide signals were normalized to total ion current and mean peak intensity per area across the entire biological specimen were used to generate a score per patient. Change in stroma peptides was evaluated by BMI status using the Wilcoxon matched pairs signed rank test. Unsupervised hierarchical clustering and heatmap visualization were used to assess differential expression of the peaks. Results. Approximately, 550 peptide peaks were found by targeted collagen tissue imaging proteomics. Striking differences in response to sulindac were observed by BMI. In overweight patients, 6 peptides related to COL1A1, COL6A1, COL6A3 and VIM on database matching differed significantly before and after sulindac treatment. Three were also altered in obese women. Two of the peptides overlapped 10 peptide changes identified in unstratified analyses reported in a separate submitted abstract on the main effect of sulindac on tissue collagen. Interestingly, these peptides were not altered in patients with normal BMI. In addition, on study 15 patients experienced a decrease in BMI and 12 experienced an increase. Two collagen peptides showed inverse relationships dependent on change in BMI status during the study. Conclusion. Six-month treatment with the non-selective NSAID sulindac was associated with changes in collagen-associated peptide differently by BMI status and by weight change. Our findings are most consistent with changes in post-translational hydroxylated proline modifications of collagen variation in the triple helical region. Ongoing work may provide insights on inflammation/adiposity-associated inflammation and effects on breast tissue collagen. Citation Format: Denys Rujchanarong, Peggi M. Angel, Alison Stopeck, Christina Preece, Pavani Chalasani, Patricia A. Thompson. Evidence that body mass index modifies breast tissue collagen peptide response pattern to treatment with the non-steroidal anti-inflammatory drug sulindac [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-10-05.

The rationality of recommendations of drugs for patients with cephalgia in simulated situations in the pharmacy

Relevance. According to statistics of the World Health Organization, at least half of the world’s adult population experienced headaches at least once a year. Patients suffering from headaches do not always have the opportunity to visit a doctor, therefore, an important role in helping these patients is assigned to pharmacists. Purpose. Based on the pharmacoepidemiological study to identify the features of providing pharmaceutical care to patients with headache in pharmacies in the issue of rationality of recommendations of pharmaceutical workers. Materials and methods. A pharmacoepidemiological study was conducted based on a survey of 153 pharmaceutical workers (Saratov) using a specially developed questionnaire that includes free-form questions with a simulated situation. The data was processed using Microsoft Excel 2010 and STATISTIKA 6.0. Results Of the groups recommended to visitors, INNs in the group «Nonsteroidal anti-inflammatory and antirheumatic drugs [M01A]» account for 45.0 % of all INNs, and the group «Analgesics [N02]» - 55.0 %. Ibuprofen (62.8 %) and the combination of drotaverine + caffeine + naproxen + paracetamol + phenylephrine (41.2 %) were noted as the most frequently recommended. A visit to a doctor was recommended by the majority of respondents (52.3 %, n=153) in the case of a patient with a headache accompanied by nausea and vomiting. Ibuprofen (90.8 %) or paracetamol (45.8 %), moreover in the form of suspension or suppositories, are the preferred recommendations for headache in children under 3 years of age (n=131). Paracetamol in combinations (69.2 %) prevails as the first recommendation for headache associated with acute respiratory viral infections (n??=146). Non-selective NSAIDs for a patient with gastrointestinal complications could be recommended by 43.4 % of specialists (n=113). The NSAID recommendation is the most frequent (51.8 %, n=110) in the case of an 80-year-old patient without concomitant diseases. Paracetamol (50.0 %) or ibuprofen (34.7 %) would be more often recommended by pharmaceutical workers for a pregnant woman with headache (n=98). In case of headache after trauma, 47.1 % recommend a visit to a doctor (n=153). Conclusion. The frequent recommendation of combined analgesics and their association with the development of drug-induced headaches indicates the need for careful recommendation of these drugs. Not always correct recommendations indicate the need to increase the level of professional knowledge, study clinical recommendations for the therapy and diagnosis of cephalgia, which can make it possible to make a rational choice of the drug, initially assume that the visitor has conditions that require a visit to a doctor, and ultimately improve the quality of pharmaceutical care.

Ефективність та доцільність застосування напроксену при різних клінічних ситуаціях

В оглядовій статті подано докази клінічної ефективності напроксену в лікуванні пацієнтів ревматологічного профілю. Сучасна концепція раціонального й безпечного застосування нестероїдних протизапальних препаратів (НПЗП) передбачає досягнення максимальної ефективності разом з максимальним зниженням ризику ускладнень, насамперед із боку серцево-судинної та гастроінтестинальної систем. За даними клінічних досліджень, серед усіх НПЗП найменший ризик кардіоваскулярних ускладнень відзначений у напроксену. Напроксен належить до групи неселективних НПЗП, активно використовується в клінічний практиці вже понад 40 років та завоював довіру лікарів як надійний анальгетик та протизапальний засіб. Терапевтичний потенціал напроксену доведений при різних клінічних ситуаціях — від гострих епізодів болю та запалення і до хронічного больового синдрому в ревматологічній практиці. У статті наведені та проаналізовані рандомізовані клінічні випробування, що підкреслюють клінічну ефективність та безпеку при застосуванні напроксену при гострому подагричному артриті, гострих травмах, остеоартриті, ревматоїдному артриті та спондилоартритах.

Racial and ethnic differences in the pharmacologic management of osteoarthritis: rapid systematic review.

Background:Racial and ethnic disparities in osteoarthritis (OA) patients’ disease experience may be related to marked differences in the utilization and prescription of pharmacologic treatments.Objectives:The main objective of this rapid systematic review was to evaluate studies that examined race/ethnic differences in the use of pharmacologic treatments for OA.Data sources and methods:A literature search (PubMed and Embase) was ran on 25 February 2022. Studies that evaluated race/ethnic differences in the use of OA pharmacologic treatments were included. Two reviewers independently screened titles and abstracts and abstracted data from full-text articles. Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.Results:The search yielded 3880 titles, and 17 studies were included in this review. African Americans and Hispanics were more likely than non-Hispanic Whites to use prescription non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for OA. However, compared to non-Hispanic Whites with OA, African Americans and Hispanics with OA were less likely to receive a prescription for cyclooxygenase-2-selective NSAIDs and less likely to report the use of joint health supplements (i.e. glucosamine and chondroitin sulfate). There were minimal/no significant race/ethnic differences in the patient-reported use of the following OA therapies: acetaminophen, opioids, and other complementary/alternative medicines (vitamins, minerals, and herbs). There were also no significant race differences in the receipt of intra-articular therapies (i.e. glucocorticoid or hyaluronic acid). However, there is limited evidence to suggest that African Americans may be less likely than Whites to receive opioids and intra-articular therapies in some OA patient populations.Conclusion:This systematic review provides an overview of the current pharmacologic options for OA, with a focus on race and ethnic differences in the use of such medical therapies.

Нестероидные противовоспалительные препараты: повреждающее действие на слизистую оболочку желудка и способы защиты от их ульцерогенного влияния

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for various diseases to relieve pain and reduce inflammation. However, the use of NSAIDs can lead to adverse side effects on the kidneys, heart, gastrointestinal tract (GIT) and the central nervous system, which complicates the use of NSAIDs in medicine. The review analyses literature on the anti-inflammatory action of NSAIDs and their adverse side effects. A special focus is given to the side effects of NSAIDs on the gastrointestinal tract. Taking NSAIDs can lead to pathological changes in the GIT: dyspeptic symptoms, gastropathy, gastrointestinal mucosal damage, including erosion and ulcers, which can be accompanied by serious complications such as gastrointestinal bleeding and perforations. The main mechanisms of the damaging effect of NSAIDs on the gastric mucosa include a slowdown in the blood flow rate in the stomach microvessels, which leads to an increase in their permeability, as well as an increase in gastric motility, a decrease in the secretion of mucus and bicarbonates in the stomach, a change in lipid peroxidation with the formation of free radicals that destroy the structure of cell membranes. Nonselective NSAIDs, including the well-known and popular indomethacin and aspirin, have a pronounced deleterious effect on the GIT. The selective NSAIDs are safer regarding the gastrointestinal side effects compared with nonselective ones, however, they can lead to serious cardiac problems. To mitigate the ulcerogenic effect of NSAIDs, antacids and proton pump inhibitors are used. They reduce the secretion of hydrochloric acid in the stomach. Another solution are drugs associated with membrane phospholipids. These drugs contain nitric oxide and hydrogen sulfide. Taking NSAIDs increases the level of glucocorticoid hormones in the blood, which compensate for the absence of prostaglandins and have a gastroprotective effect. Physical exercise stimulates the body’s natural defenses and protects the gastric mucosa from the negative effects of NSAIDs. In this regard, it is crucial for physiology to conduct more studies focusing on the mechanisms of NSAID-induced deleterious influence on the GIT, gastroprotective mechanisms and the development of evidence-based approaches to reduce the adverse effects of NSAIDs.

Análisis y evaluación del riesgo cardiovascular y gastrointestinal de los antiinflamatorios no esteroideos inhibidores selectivos y no selectivos de ciclooxigenasa

Introduction: the aim of this study is to review the current evidence on the clinical use of NSAIDs, coxibs and nonselective, and to evaluate its cardiovascular (CVR) and gastrointestinal risk (GIR) by means of a meta-analytic procedure. Materials and methods: cohort and case-control studies showing CVR and GIR associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Results: both coxibs (RR, 1.22 [95%CI, 1.17-1.28]) and nonselective NSAIDs (RR 1.18 [95%CI, 1.12-1.24]) were associated with an increased CVR. The coxibs CVR remained even for low-dose and low-baseline CVR subgroups. Analysis by drug disclosed that rofecoxib (RR 1.39 [95%CI, 1.31- 1.47]), along with diclofenac (RR, 1.34 [95%CI, 1.26-1.42]) and etoricoxib (RR 1.27 [95%CI, 1.12-1.43]) were the NSAIDs associated with the highest CVR. Gastrointestinal risk meta-analysis showed that coxibs were associated with a GIR increment [RR1.64 (95% CI 1.44-1.86)]. Analysis by drug disclosed that etoricoxib [RR 4.48 (95% CI 2.98-6.75)]presented the highest GIR followed by rofecoxib [RR 2.02 (95% CI 1.56-2.61)] and celecoxib [RR1.62 (95% CI 1.46-1.78)]. GIR was also high for <65 year-old and low-dose coxibs subgroups. Conclusion: according to our study the use of NSAIDs (coxibs and nonselective) are associated with a similar CVR increment, even for low-dose and low-baseline CVR subgroups. On the other hand, the use of coxibs is associated with a GIR increased, which would be high even for low-dose coxibs and <65-year-old subgroups. The risk would be higher for etoricoxib than for celecoxib and rofecoxib. Keywords: adverse drug reactions; nonsteroidal anti-inflammatory drugs; cardiovascular risk; meta-analysis; observational studies; cyclo-oxygenase 2 inhibitor; gastrointestinal events

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis.

To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.

Non-steroidal anti-inflammatory drugs for acute gout.

Non-steroidal anti-inflammatory drugs for acute gout.