Selective Nonsteroidal Anti-inflammatory Drugs Research Articles

Descriptive Analysis of Cross-Reactive Anaphylaxis as a Different Clinical Subtype of Nonsteroidal Anti-Inflammatory Drug (NSAID) Hypersensitivity

Introduction: The European Network of Drug Allergy and the European Academy of Allergy and Clinical Immunology have classified hypersensitivity reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs) into 5 phenotypes according to the pathophysiology, clinical manifestations, number of drugs involved, and the presence of underlying diseases. This classification does not include anaphylaxis as part of NSAID cross-reactivity. The objective of this study was to characterize a group of patients with anaphylactic NSAID cross-reactivity. Method: This was a retrospective, descriptive, observational study. Patients who developed anaphylaxis to one NSAID plus another acute reaction (anaphylactic or not) to at least one other NSAID of a different chemical group were included. Demographic and clinical characteristics and the diagnostic approach were studied. Results: A total of 38 patients were included, 28 (73.7%) of whom were women. The mean age was 40 ± 17.7 years. The main organs affected in the anaphylactic reaction were the skin and the respiratory system, occurring in 35 (92.1%) and 33 (86.8%) patients, respectively. Thirty-two (84.3%) patients presented with cutaneous and respiratory involvement simultaneously. The main anti-inflammatory agent involved in anaphylactic reactions was acetylsalicylic acid in 9 (23.7%) patients, followed by dipyrone in 8 (21.1%). The most frequent allergic comorbidity was rhinitis in 20 (52%) patients. Skin tests were performed in 15 (39.5%) patients, showing positivity in 12 (80%), mainly to mites. A total of 36 of 38 patients were challenged with alternative drugs, and 35 (97.2%) tolerated meloxicam and/or etoricoxib. Conclusion: In the present study, NSAID cross-anaphylaxis was more frequent in women, and acetylsalicylic acid and dipyrone were the main triggers. Rhinitis was the main allergic comorbidity, and there was a high incidence of atopy. The majority tolerated selective COX-2 NSAIDs.

Microsomal Prostaglandin E2 Synthase-1 Deletion Attenuates Isoproterenol-Induced Myocardial Fibrosis in Mice.

Deletion of microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibits inflammation and protects against atherosclerotic vascular diseases but displayed variable influence on pathologic cardiac remodeling. Overactivation of β-adrenergic receptors (β-ARs) causes heart dysfunction and cardiac remodeling, whereas the role of mPGES-1 in β-AR-induced cardiac remodeling is unknown. Here we addressed this question using mPGES-1 knockout mice, subjecting them to isoproterenol, a synthetic nonselective agonist for β-ARs, at 5 or 15 mg/kg per day to induce different degrees of cardiac remodeling in vivo. Cardiac structure and function were assessed by echocardiography 24 hours after the last of seven consecutive daily injections of isoproterenol, and cardiac fibrosis was examined by Masson trichrome stain in morphology and by real-time polymerase chain reaction for the expression of fibrosis-related genes. The results showed that deletion of mPGES-1 had no significant effect on isoproterenol-induced cardiac dysfunction or hypertrophy. However, the cardiac fibrosis was dramatically attenuated in the mPGES-1 knockout mice after either low-dose or high-dose isoproterenol exposure. Furthermore, in vitro study revealed that overexpression of mPGES-1 in cultured cardiac fibroblasts increased isoproterenol-induced fibrosis, whereas knocking down mPGES-1 in cardiac myocytes decreased the fibrogenesis of fibroblasts. In conclusion, mPGES-1 deletion protects against isoproterenol-induced cardiac fibrosis in mice, and targeting mPGES-1 may represent a novel strategy to attenuate pathologic cardiac fibrosis, induced by β-AR agonists. SIGNIFICANCE STATEMENT: Inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) are being developed as alternative analgesics that are less likely to elicit cardiovascular hazards than cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs. We have demonstrated that deletion of mPGES-1 protects inflammatory vascular diseases and promotes post-myocardial infarction survival. The role of mPGES-1 in β-adrenergic receptor-induced cardiomyopathy is unknown. Here we illustrated that deletion of mPGES-1 alleviated isoproterenol-induced cardiac fibrosis without deteriorating cardiac dysfunction. These results illustrated that targeting mPGES-1 may represent an efficacious approach to the treatment of inflammatory cardiovascular diseases.

Practice Advisory on the Appropriate Use of NSAIDs in Primary Care.

Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.

Pharmacological Management of Osteoarthritis With a Focus on Symptomatic Slow-Acting Drugs: Recommendations From Leading Russian Experts.

This article describes an updated stepwise algorithm for the pharmacological management of osteoarthritis (OA) to establish a treatment method for patients with OA. In step 1, background maintenance therapy includes symptomatic slow-acting drugs for OA, especially prescription crystalline glucosamine sulfate product, for which the high-quality evidence base of efficacy is unequivocal, or prescription chondroitin sulfate. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol only as rescue analgesia is given on top of the background therapy. Step 2: For patients with persistent OA symptoms, the use of oral NSAIDs is mandatory for maintaining supportive therapy with symptomatic slow-acting drugs for OA. It is recommended to properly stratify patients and carefully select oral NSAID therapy to maximize the benefit-to-risk ratio. Intra-articular hyaluronic acid and intra-articular corticosteroids are recommended as well in step 2 of the algorithm, especially for patients who do not respond to the previous therapies. Step 3: Duloxetine is considered along with the previous procedures, especially in patients with pain from central sensitization. Step 4: Total joint replacement is recommended for patients with severe symptoms and poor quality of life. The current guidelines and literature review provide evidence-based recommendations supported by clinical experience on how to organize the treatment process in patients with knee OA applicable in the Russian clinical practice. International evidence-based guidelines lack consensus on different treatments, including the use of prescription crystalline glucosamine sulfate, NSAIDs, and intra-articular hyaluronic acid. The content of this article needs a further discussion about the clinical evidence and harmonization of recommendations for knee OA management.

Safety of selective non-steroidal anti-inflammatory drugs: analysis of the last years data

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used pain relievers. However, their use often threatens with serious undesirable effects, associated mainly with damage to cardiovascular system (CVS), gastrointestinal tract, kidneys and liver. Contraindications to NSAIDs prescription are clearly regulated, algorithms for their personalized appointment are determined taking into account risk factors for cardiovascular and gastrointestinal adverse events. The severity of NSAIDs side effects is mainly due to the selectivity to cyclooxygenase-2 (COX-2), as well as the physicochemical properties of various drugs. Cardiovascular adverse events differ among various NSAIDs both within commonly used drugs and among COX-2 inhibitors. It is well known that NSAIDs selective for COX-2 are safer in terms of the effect on the gastrointestinal tract than non-selective drugs. A meta-analysis showed that relatively selective COX-2 inhibitors (meloxicam, etodolac) were associated with a comparable risk of developing symptomatic ulcers and ulcers identified by endoscopy, and safety and tolerability profiles of the drugs were similar.All NSAIDs are associated with cardiovascular toxicity, however, different drugs have significant risk differences. The mechanism of NSAIDs cardiovascular adverse effects is associated with an increase of blood pressure, sodium retention, vasoconstriction, platelet activation, and prothrombotic state. It has been shown that the risk of cardiovascular adverse events when taking COX-2 inhibitors (celecoxib, etoricoxib) significantly increases. According to a study of more than 8 million people, it was found that the risk of myocardial infarction was increased in patients taking ketorolac. Further, highest to lowest risk authors list indomethacin, etoricoxib, rofecoxib (not currently used), diclofenac, a fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen. When taking NSAIDs, the risk of heart failure decompensation increases, and it turned out to be the greatest for ketorolac, etoricoxib, and indomethacin. Meloxicam, aceclofenac, ketoprofen almost did not increase heart failure risk. It should be noted that when using the drugs (except for indomethacin and meloxicam), there is a tendency to increase the total cardiovascular and renal risks with increasing doses. Thus, it is obvious that a very careful approach is required when choosing NSAIDs. If there is an increased risk of gastrointestinal complications associated with NSAIDs, selective NSAIDs are preferred, with both coxibs and traditional selective NSAIDs showing the best safety profile in the studies. To minimize cardiovascular side effects specialists should consider the risk level of cardiovascular complications, as well as results of large clinical studies where particular NSAIDs are compared.

Non-steroidal anti-inflammatory drugs for acute low back pain.

Non-steroidal anti-inflammatory drugs for acute low back pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause male-biased sex differentiation in zebrafish

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used pharmaceuticals to treat pain, fever and inflammation. NSAIDs are also known to have many side effects including adverse effects on reproduction in both humans and animals. As NSAIDs usage is not regulated they are frequently detected at high concentrations in the environment. In order to understand the effect of NSAIDs on zebrafish sex differentiation, we used seven different NSAIDs which were either Cox-1 selective, Cox-1 biased, non-selective or COX-2 selective. We show that at higher concentration, NSAIDs are toxic to zebrafish embryo as they lead to mortality and hatching delay. Gene expression analysis following short term exposure of NSAIDs led to downregulation of female specific genes including zp2, vtg2 foxl2 and wnt4. Long term exposure of larvae to environmentally relevant concentrations of Cox-2 selective and non-selective NSAIDs resulted in male-biased sex ratio which confirmed the qRT-PCR analysis. However, the Cox-1 selective acetylsalicylic acid and the Cox-1 biased ketoprofen did not alter sex ratio. The observed male-biased sex ratio could also be due to induction of apoptosis process as the genes including p21 and casp8 were significantly upregulated following exposure to the Cox-2 selective and the non-selective NSAIDs. The present study indicates that NSAIDs alter sex differentiation in zebrafish, primarily through inhibition of Cox-2. This study clearly demonstrates that the use of NSAIDs and their release into the aquatic environment should be carefully monitored to avoid adverse effects to the aquatic organisms.

PHARMACOKINETICS OF ORAL MAVACOXIB IN CARIBBEAN FLAMINGOS (PHOENICOPTERUS RUBER RUBER).

Mavacoxib is a selective cyclooxygenase-2 nonsteroidal anti-inflammatory drug that has been used for management of osteoarthritis and other inflammatory conditions in dogs. The main advantage of mavacoxib over other nonsteroidal anti-inflammatory drugs is its longer plasma half-life, leading to decreased dosing frequency. This study determined the pharmacokinetics of mavacoxib in Caribbean flamingos (Phoenicopterus ruber ruber) after a single-dose oral administration of 6 mg/kg (n = 6). Plasma mavacoxib concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using noncompartmental methods. Mean peak plasma concentration (Cmax) was (mean; range) 2.97 (2.19--4.06) µg/ml; mean time to peak plasma concentration (Tmax) was 18.68 (4.00-48.00) hr; mean area under the curve (AUC) was 455 (292-637) hr * µg/ml; and mean terminal half-life (T1/2) was 74.47 (49.57-161.43) hr. Based on the results of this study, mavacoxib dosed at 6 mg/kg orally in Caribbean flamingos reaches plasma concentrations above the therapeutic concentration established for dogs, but further studies are needed to determine appropriate dosing recommendations in flamingos.

Thermodynamic Analysis of Etoricoxib in Amphiprotic and Amphiprotic: Aprotic Solvent Mixtures at Several Temperatures

The solubilities of etoricoxib (ETX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water–ethanol and ethanol–ethyl acetate mixtures at several temperatures (288.15–308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures; they showed a single maximum located at 30% ethanol–ethyl acetate (δ1 = 19.70 MPa1/2). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs energy of solution (ΔHS, ΔSS and $$\Delta G_{{{\text{hm}}}}^{{\text{S}}}$$, respectively). The apparent enthalpies of solution were nonlinear functions of the ethanol ratio in aqueous mixture. Non-linear enthalpy–entropy compensation analysis was observed indicating different dissolution mechanisms with the variation in mixture composition. The solubility enhancement is entropy driven in water-rich (0–40% v/v ethanol) and enthalpy controlled in ethanol-rich (40–100% ethanol) compositions, likely due to water structure loss around nonpolar moieties of the drug and in the ethanol rich mixtures it is the enthalpy, probably due to the better drug solvation.

Nonsteroidal anti-inflammatory drugs alleviate severity of post-endoscopic retrograde cholangiopancreatography pancreatitis by inhibiting inflammation and reducing apoptosis.

The prophylactic effect of nonselective nonsteroidal anti-inflammatory drugs on post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis has been observed for a long time. However, whether the selective nonsteroidal anti-inflammatory drugs possess similar abilities and the mechanisms by which nonsteroidal anti-inflammatory drugs work remain unclear. The present study aimed to determine the protective effects of nonsteroidal anti-inflammatory drugs on post-ERCP pancreatitis in a rat model and examine underlying mechanisms. Thirty-two female rats were equally and randomly divided into four groups: the sham group, post-ERCP pancreatitis model group, indomethacin-pretreated group, and parecoxib-pretreated group. Indomethacin or parecoxib was delivered 30min prior to surgery; 24h after post-ERCP pancreatitis establishment, the rats were sacrificed. Serum amylase and lipase activities, inflammatory cytokine release, pancreatic histopathological scores, neutrophil infiltration, and the expression pattern cyclooxygenase at the protein level and pancreatic apoptosis were quantified and analyzed. Both indomethacin and parecoxib inhibited the activities of serum amylase and lipase and reduced the severity of pancreatic histopathology. Mechanistically, both drugs decreased the expression level of cyclooxygenase 2; however, they had no influence on the cyclooxygenase 1 protein level. Moreover, they reduced inflammatory cytokine release, neutrophil infiltration into the pancreas, and NF-κB p65 activation. Notably, we found that apoptotic cells in the pancreas were remarkably diminished after the administration of both nonsteroidal anti-inflammatory drugs. Both selective and nonselective nonsteroidal anti-inflammatory drugs exert protective effects against post-ERCP pancreatitis by restraining inflammation and reducing acinar cell apoptosis through the inhibition of cyclooxygenase 2.

Clinical outcomes of non-variceal upper gastrointestinal bleeding and its relation to aspirin and anticoagulants.

BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a life-threatening emergency that requires an urgent management. Antiplatelet (e.g., aspirin) and anticoagulant drugs are widely chronically used in various cardiac and coronary artery diseases. These drugs increase the risk of NVUGIB as they may cause ulceration of the upper gastrointestinal (GI) mucosa directly or may cause bleeding or rebleeding. The management of NVUGIB is complicated as the risk between GI bleeding episodes and cardiovascular attacks needs to be well managed.
 AIM: The aim of this study is to determine the impact of antiplatelets (aspirin) and anticoagulants use on the morbidity, mortality, and clinical outcomes in patients presented with non-variceal GI bleeding.
 PATIENTS AND METHODS: A total of 105 patients presented with melena and/or hematemesis and diagnosed by upper GI endoscopy were enrolled in a prospective cohort study. Patients were sub-grouped according to their use of antiplatelets, anticoagulants, or none (controls). Patients were excluded if they had portal hypertension or nonsteroidal anti-inflammatory drugs (NSAIDs) use and divided into five groups: Group I – patients who had not taken anticoagulants and antiplatelet; Group II – patients on heparin, warfarin, and LMWH only; Group III – patients on aspirin only; Group IV – patients on clopidogrel and ticlopidine with or without aspirin; and Group V – patients on combined anticoagulants and antiplatelet. All patients were subjected to clinical, laboratory (complete blood count, liver function tests, renal function tests, prothrombin time, and partial thromboplastin time), and endoscopic investigations. Clinical details were reported including admission, blood transfusion, rebleeding, and mortality.
 RESULTS: Full medical history revealed that 43 patients were diabetic, 45 patients were cardiac, and 67 patients were hypertensive. Regarding the history of analgesic drug intake, 38 patients used NSAIDs and 29 of them used non-selective NSAIDs and 8 patients used selective NSAIDs. There were non-significant differences among the studied groups with NVUGIB regarding sex, hematemesis only presentation, melena only presentation, liver function tests, and endoscopic findings. On the other hand, there were statistically significant differences between the studied groups with NVGIB regarding increasing age, NSAIDs use whatever selective or non-selective, decrease level of HB, WBCs, serum albumin, bleeding profile, kidney function tests, clinical presentation in the form of hematemesis and melena, need for blood transfusion, history of associated diseases, especially being cardiac patients, rebleeding after 6 and 12 months, and mortality.
 CONCLUSION: Aspirin intake may be associated with less favorable clinical outcomes in patients with NVUGIB, while combined anticoagulants and antiplatelets seem to be associated with the worse outcomes.

Особенности применения нестероидных противовоспалительных препаратов у коморбидных пациентов. Как минимизировать риски НПВП-индуцированных осложнений со стороны желудочно-кишечного тракта?

Objective of the Review: to discuss the most common adverse events from the use of non-steroidal anti-inflammatory drugs (NSAID) for GIT: NSAID-induced esophago-, gastroduodeno- and enteropathy, possible management and the use of various therapies in order to minimize the risks of this pathology. Key Points. NSAIDs are efficient analgetics and anti-inflammatory products widely used in clinical setting. NSAIDs are prescribed mostly to patients with chronic joint and spine conditions. As a lot of patients who take NSAIDs are comorbid, they have frequent adverse reactions to drugs, including NSAIDs, and need stricter control if this is a therapy of choice. Selective NSAIDs (nimesulide) are characterised by good bioavailability; they are efficient pain killers, possess marked anti-inflammatory properties and are relatively safe, thus making it possible to minimise the rate of adverse reactions for GIT. Conclusion. It should be emphasised that the issue of NSAID-induced GIT disorders is still challenging and can be aggravated in comorbid patients. Of prime importance are timely prevention and diagnosis of NSAID-induced GIT disorders and sustainable and individuated NSAID prescription. Keywords: non-steroidal anti-inflammatory drugs, comorbidity, NSAID-induced gastroduodenopathy, NSAID-induced enteropathy, nimesulide, Nise

Upper gastrointestinal bleeding due to overdose of selective serotonin reuptake inhibitors and nonsteroidal anti-inflammatory drugs

Upper gastrointestinal bleeding due to overdose of selective serotonin reuptake inhibitors and nonsteroidal anti-inflammatory drugs

Development of dual–release pellets of the non-steroidal anti–inflammatory drug celecoxib

In the current study, once-a-day dual-release pellets of the selective non-steroidal anti-inflammatory drug celecoxib (200 mg) was developed to treat arthritis. Pellets were prepared where a 100 mg celecoxib, located in the outer layer, was released in an immediate-release (IR) pattern, whereas the remaining 100 mg celecoxib, located in the inner layer, was released in a sustained-release (SR) pattern. Pellets were subjected to four coating- and loading-stages using solid-dispersion and spray-drying including seal-coating, drug-loading, SR-coating, and IR-loading. Release studies were carried out using dissolution media with a pH range 1.2–12.0. The IR-stage showed a fast release rate, where 47.0% of celecoxib (equivalent to 94 mg) was released within the first hour. Whereas the SR-stage showed a sustained-release pattern up to 16 h. Celecoxib converted from crystalline to amorphous form during the development of pellets. This in turn improves the aqueous solubility and hence the dissolution of celecoxib. The results of stability studies showed that pellets were stable at 30 °C/65 %RH and 40 °C/75 %RH for 6 months. The present study demonstrated that celecoxib pellets can be an effective strategy for delivering the poorly-soluble drug celecoxib in a dual-release pattern.

Medication Use Quality and Safety in Older Adults: 2018 Update.

Improving the quality of medication use and medication safety is an important priority for prescribers who care for older adults. The objective of this article was to identify key articles from 2018 that address these issues. In addition, we selected four of these articles to annotate, critique, and discuss their broader implications for clinical practice. The first study highlights a cluster-randomized trial that utilized a pharmacist-led education-based intervention delivered to both patients and physicians to deprescribe four types of inappropriate medications (sedative-hypnotics, first-generation antihistamines, selective nonsteroidal anti-inflammatory drugs, and glyburide). The second study, a nested case-control study using data from within the UK Clinical Practice Research Datalink, examined the association between anticholinergic exposure, overall and by anticholinergic medication class, and dementia risk in 40 770 older adults. The third study, a longitudinal cohort study of 1028 Swedish older adults, examined the association between antihypertensive medications and incident dementia. The last study was a randomized, double-blind, placebo-controlled trial that investigated the effect of daily low-dose aspirin (100 mg) for primary prevention on cardiovascular events and major hemorrhage in 19 144 community-dwelling older adults. Collectively, this current article provides insight into the pertinent topics of medication use quality and safety in older adults and helps raise awareness about optimal prescribing in older adults. J Am Geriatr Soc 67:2458-2462, 2019.

Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage a wide variety of conditions in horses, including management of colic. Flunixin meglumine is by far the most commonly used drug in the control of colic pain and inflammation and has become a go-to for not only veterinarians but also horse-owners and nonmedical equine professionals. NSAID use, however, has always been controversial in critical cases due to a high risk of adverse effects associated with their potent cyclo-oxygenase (COX) inhibition. There are two important COX isoenzymes: COX-1 is generally beneficial for normal renal and gastrointestinal functions and COX-2 is associated with the pain and inflammation of disease. Newer selective NSAIDs can target COX-2-driven pathology while sparing important COX-1-driven physiology, which is of critical importance in horses with severe gastrointestinal disease. Emerging research suggests that firocoxib, a COX-2-selective NSAID labelled for use in horses, may be preferable for use in colic cases in spite of the decades-long dogma that flunixin saves lives.

Influence of Pain and Analgesia on Orthopedic and Wound-healing Models in Rats and Mice.

The surgical stress response and resulting physiologic changes can lead to postoperative complications and negatively impact animal welfare. Although appropriate pain management is crucial to reduce the pain and stress response to surgery, analgesic choice can significantly affect bone and wound healing. This review aims to summarize data from rat and mouse studies and to provide recommendations for integrating analgesia into orthopedic and wound healing models in these species. Data from other species, such as humans, rabbits and other rodents, is included, where available. From these data, we conclude that for orthopedic surgical models, opioids, local anesthetics and dissociative agents have minimal impact on fracture healing; cyclooxygenase 2 (COX2) selective nonsteroidal antiinflammatory drugs (NSAID) may be used in the shortterm; and steroids should be avoided. For wound healing models, short-term systemic or topical opioids have negligible impact on wound healing; NSAID or local anesthetics may be used short-term; and systemic steroids should be avoided. Alternative analgesics such as tramadol, gabapentin, ketamine, and acetaminophen warrant consideration and further evaluation for both orthopedic and wound healing models. In all cases, researchers and veterinarians should work together to determine the appropriate analgesic plan to minimize pain, as well as to minimize unwanted effects on the orthopedic and wound healing models themselves.

From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases

From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases Abstract. Inflammatory bowel diseases (IBD) are frequently accompanied by non-inflammatory joint pain and inflammatory spondyloarthritides. Spondyloarthritides can restrict joint function and typically manifest with inflammatory back pain with nightly pain and morning stiffness that improves upon exercising. In other patients, small or large peripheral joints are predominantly involved. Treatment comprises pain medication including COX-II selective non-steroidal anti-inflammatory drugs (NSAID), since non-selective NSAID can aggravate IBD. For axial manifestations, physiotherapy and tumor necrosis factor (TNF) inhibitors are effective, while for peripheral manifestations steroid injections, sulfasalazine and TNF inhibitors are useful. Osteopenia and osteoporosis may result from inflammation, malabsorption and/or steroids. Long-lasting disease activity or steroid treatment should prompt osteoporosis screening. Adequate calcium and vitamin D intake must be ensured and treatment with bisphosphonates evaluated.

Thermodynamic analysis of celecoxib in amphiprotic and amphiprotic-aprotic solvent mixtures at several temperatures

The solubilities of celecoxib (CLX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water-ethanol and ethanol-ethyl acetate mixtures at several temperatures (288.15-308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures, they showed a single maximum located at 50% ethanol-ethyl acetate (δ1 = 22.50 MPa1/2). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs free energy of solution (ΔHS,ΔSS and ΔGShm, respectively). The apparent enthalpies of the solution were a nonlinear function of the ethanol ratio in aqueous mixture. Non-linear enthalpy-entropy compensation analysis was observed indicating different dissolution mechanism with the variation in mixtures composition. The solubility enhancement is entropy driven at water-rich region (0-40% v/v ethanol) and enthalpy controlled at ethanol-rich region (40–100% v/v ethanol), likely due to water-structure loss around nonpolar moieties of the drug and for the ethanol-rich mixtures it is the enthalpy, probably due to the drug better solvation.

Recent advances of multimodal analgesia in spinal surgery

Optical postoperative analgesia can improve patient mobility, reduce the incidence of complications, and im-prove patient satisfaction, while reducing hospital stays and costs. Early postoperative analgesia mainly depends on the opioids. In recent years, multimodal analgesia (MMA) program has been developed rapidly, which can significantly reduce the use of opioids and related adverse reactions. MMA in spinal surgery mainly includes advanced analgesia, non-steroidal anti-inflammatory drugs, neuromodulation drugs, acetaminophen drugs, intrathecal block and local expanded anesthesia. Current studies show that selective non-steroidal anti-inflammatory drugs or short-term, low-dose non-selective non-steroidal anti-inflammatory drugs do not affect postoperative spinal fusion; Neuromodulators can alleviate pain and reduce opioid use, while without significant adverse effects; Acetaminophen is the basis for different analgesia regimens after spinal surgery; In addition, level I evidence suggests that intrathe-cal block after lumbar discectomy can improve short-term pain and neurological symptoms of patients; Some studies suggest that local expanded anesthesia can reduce the use of other analgesics after spinal surgery. A growing of evidence supports the use of ad-vanced MMA regimens to control postoperative pain in patients undergoing spinal surgery, but further high-quality studies are needed to determine the optimal agent, dose, and timing of the MMA regimen, and to further elucidate the impact on spinal surgery outcomes.