Conventional NSAIDs Research Articles

Physiology of Pain and its Management in Ayurveda w.s.r. to Jalaukavacarana

Pain is the most common symptom; it is universally accepted as a signal of disease that brings the patient to a physician’s attention. It is a sensation in which additional factors like mental or spiritual distress can cause the same overarching sensation as a physical damage. Anxiety is a common side effect of any pain, whether mild or severe. It interferes with the patient's daily routine. Patient gets apprehensive or concerned about getting pain relief. It is generally known that NSAIDs can have serious side effects, which are mostly attributed to their underlying mechanisms of action. NSAIDs like indomethacin, ibuprofen, diclofenac, naproxen, aspirin, causes damaging action upon the stomach and intestine due to their acidic nature. While the selective COX-2 inhibitors cause significant adverse effects in the renal and cardiovascular systems, possibly more serious than those caused by conventional NSAIDs. Leech therapy or Jalaukavacarana, universally accepted around the globe, is an integral part of Ayurvedic medicine especially Panchakarma. Although not directly indicated for pain-management in Ayurveda texts, various studies have identified the presence of analgesic enzymes in leech’s saliva that can be effective in pain management in musculoskeletal disorders. So purpose of this article is reduce the use of NSAIDS and avoid there adverse effect and use new emerging Ayurvedic methods.

The Efficacy of Corticosteroids in the Management of Tietze Syndrome: A Randomized Controlled Trial

Abstract Background So far there are no clinical trials in the literature discussing the methods of treatment of Tietze‟s syndrome. Particularly, conservative methods of treatment are used, which include pain management using analgesics and nonsteroidal anti-inflammatory drugs. Oral corticosteroids offer a safe and effective treatment modality that is proven to be useful in a significant number of chest wall syndromes such as Sternoclavicular arthritis, Painful xiphoid syndrome, Costovertebral arthritis, and Slipping rib syndrome as well as conditions arising from ligament and tendon diathesis. Objective To use oral Corticosteroids in management of patients with Tietze syndrome at Ain shams university hospitals‟ cardiothoracic department and measuring the outcome randomly compared with the conventional NSAIDs to achieve the best outcome and quality of life. Methods This study included 40 patients who were diagnosed clinically as Tietze Syndrome at Ain Shams University Hospitals-cardiothoracic department in the duration between August 2020 till March 2022 with age ranging from 14 to 45 years and were sorted randomly. Two groups of patients were chosen and matched randomly as „Control arm‟ and „Interventional arm‟. The control group received the conventional NSAIDs (in the form of 50 mg of diclofenac potassium as „cataflam‟ twice daily) and the Interventional group received oral corticosteroids (in the form of 20 mg of prednisolone as „solupred‟ twice daily). Results Our study suggested that in patients with moderate to severe chondritis diagnosed clinically as Tietze syndrome, a 3 week course of oral 40 mg prednisolone is superior to the conventional oral NSAIDs in alleviating pain and improving the quality of life which is evidenced by the decline in EQ-5D total score of patients receiving oral steroids at the end of the treatment course as well as during each week throughout the trial timeframe. A highly significant reduction in pain score demonstrated via NRS was evident in the steroid-treated group compared to the NSAIDs-treated group at the same time point. Conclusion Oral corticosteroids are effective and safe in non-responding, obstinate Tietze syndrome. The results were unexpectedly good, obtaining significant relief and an outstanding refinement in quality of life reported by patients receiving oral steoids. There is no widely accepted protocol for oral steroid usage in Tietze syndrome and similar chest wall pain syndromes. Some other studies propose surgery in such patients. We think that surgery is a troublesome intervention for the patient and his doctor as well.

Preparation and Evaluation of Aceclofenac microsphere containing Natural gum

Aceclofenac is an oxyacetic and non-steroidal anti-inflammatory drug which has a half-life of 4 h. Aceclofenac is used to reduce fever, inflammation of rheumatoid arthritis, traumatic pain etc. Aceclofenac has higher anti-inflammatory action than conventional NSAIDs. Development of aceclofenac microsphere is carried out to achieve sustained release of the drug after administration. The objective of this study was to find out the role of natural gum (Guar gum) for the preparation of microspheres. So, the amounts of natural gum were increased in various formulation at a successive rate. Aceclofenac microsphere is microencapsulated with guar gum and sodium alginate by Ionotropic gelation technique. There are various formulations of microspheres are developed. The prepared microspheres were spherical in shape, white in color and free flowing. Formulated microspheres were characterized for particle size, entrapment efficiency and in vitro drug release study. The aceclofenac microsphere showed particle size ranging from 330±10µm to 210±11µm 86.5% drug entrapment efficiency. The in vitro drug release is carried out up to 9 h in pH 6.8 phosphate buffer solution. F5 formulation showed maximum drug release of about 95.40% after 9 hour.

Isolation of alkaloidal and glycosidal fractions from leaves of Trigonella foenum-graecum L. cv. Desi indigenous to Pakistan for antiprostaglandin evaluation as substitute of nonsteroidal anti-inflammatory drugs

Ethnopharmacological relevanceTrigonella foenum graecum (fenugreek) has been in use for a long time as a traditional medicine and natural food additive. The reported gastro-protective property makes it unique among other herbs. Seeds and leaves have been shown to exert significant antiatherogenic, antidiabetic, antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and anti-inflammatory effects in several animal and human models. But its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs needs to be confirmed. Aim of the studyNonsteroidal anti-inflammatory drugs (NSAIDs) are in common use in treating inflammation associated with a variety of ailments, fever and pain such as menstrual cramps, back pain, arthritic pain and headaches. Their toxicity profile includes the risk of severe gastro-intestinal adverse events like increased bleeding tendency, ulceration, perforation, etc. Conventional NSAIDs have also been reported to reduce the glomerular filtration rate (GFR) by affecting afferent arterioles in nephrons. Exacerbated potassium levels were noted in patients using NSAIDs concomitantly with antihypertensive drugs belonging to the angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) classes. In this context, the need of the hour is to discover and isolate new compounds from the reported medicinal plants for evaluation of antiprostaglandin potential and safety profile in terms of the hepato-renal system. These compounds may be used as substitutes for NSAIDs in the future management of inflammation and pain with therapeutic equivalency and organ safety. In this scenario, the present study aimed to assess the antiprostaglandin potential of alkaloidal and glycosidal fractions from the leaves of Trigonella foenum-graecum L. cv. Desi variety, indigenous to Pakistan, in albino mice along with safety profile. The herb has been used as folk medicine since ancient times for treating inflammation and pain. Material and methodsAlkaloidal and glycosidal fractions were separated from a methanol extract of leaves of the fenugreek Desi variety. After separation of fractions, their subsiding effects on carrageenan-induced inflammation, air pouch exudate prostaglandin-E2 levels, Brewer's yeast induced pyrexia and acetic acid induced abdominal constrictions were assessed in adult male albino mice. The safety profile of fractions was assessed by measuring their effects on mice sera hepato-renal biomarkers. ResultAlkaloidal fraction of T. foenum Desi variety was found to be significantly effective in reducing inflammation, air pouch exudate PGE2 levels, fever (≤37 °C) and pain by inhibiting writhes (up to 96.58%) Gradual inhibition of paw edema was observed 1–6 h post-dose, with maximum reduction percentages of 62.82% and 62.57% for 100 mg and 200 mg, respectively. Both fractions did not disturb the normal physiology of the hepato-renal system by showing normal biomarker values. ConclusionIn summary, the results demonstrate the potent antiprostaglandin potential of the alkaloidal fraction of gastroprotective fenugreek “Desi” leaves with hepato-renal system safety and hence justify its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs.

The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses.

This review firstly examines the underlying pathophysiology of pain and inflammation associated with orthopedic disease and endotoxemia. Then, it reviews the clinical pharmacology (pharmacokinetics and pharmacodynamics) of both conventional and non-conventional NSAIDs in the adult horse, and finally provides an overview of different modalities to evaluate the therapeutic efficacy of NSAIDs in research.

The Cream which relieves the pain of Menstrual cramps without interfering with the Hormones or Period Cycle

Dysmenorrhea is a disease caused by an overproduction of cytokines and prostaglandins throughout the menstrual cycle. NSAIDs are commonly used to relieve pain, but they can cause nausea, vomiting, hormonal imbalance, infertility, and irregularities in the menstrual cycle if used for a longer interval. Menthol, Cinnamaldehyde, Quercetin, and trans-anethole are combined in a novel Topical formulation that has significant anti-inflammatory and anti-dysmenorrheal activities with fewer side effects, and the excipients added improve the permeability rate and pharmacological action. The formulation quickly penetrates the stratum corneum and operates on the uterus’ endometrial lining cells, blocking pro-inflammatory cytokines including LPS, TNF, IL1, IL6, COX-2, LOX, oxidative stress, and lowering antioxidant levels. Menthol in the formulation has cooling and anti-spasmodic properties, making it effective in the treatment of dysmenorrhea-related nausea, vomiting, and diarrhoea. Anethol regulates excessive contractions via modifying Ca2+ and K+ channels. Cinnamaldehyde and Quercetin decrease inflammation by inhibiting the release of key cytokines and pro-inflammatory mediators. The yield value, sensory testing, spreadibility, dynamic viscosity, pH, anti-microbial preservative concentration, microbiological limit, sterlity testing, skin permeation test, and assay testing will all be used to evaluate the formulation. The O/W cream that has been developed will be far more effective than conventional NSAIDs, will be simple to apply, and will not disturb the menstrual cycle.

Headache diagnoses in patients with orofacial pain at a specialized pain center

Background. Headache and orofacial pain (OFP) are widespread at specialized pain centers. However, reliable data on their prevalence and co-occurrence are lacking, and prevalence of OFP in headache patients seems to be underestimated. The aim of this study was to evaluate the types of headache in patients with OFP and types of OFP in patients with headache.Methods. We enrolled patients presenting with headache and/or OFP. Patients were examined by an experienced headache and pain specialist who questioned the patients about the presence of OFP. Depression was assessed with the Beck Depression Inventory (BDI-II), anxiety – with the Beck Anxiety Inventory (BAI). Bruxism was evaluated based on subject self-report.Results. We recruited 310 patients: 177 (57%) patients with headache, 28 (9%) patients with OFP and 105 (34%) patients presenting with both types of pain. The prevalence of OFP in headache patients was 37.2%. Migraine was the most prevalent type of headache, while painful temporomandibular disorder (TMD) – the most prevalent form of OFP. Patients with PFP presented with a high prevalence of sleep and awake bruxism.Conclusion. Migraine and pain-related TMD are the most prevalent diagnoses in a specialized pain center. OKI and OKI ACT are soluble forms of ketoprofen and reach peak concentration in 15 minutes. This enables faster onset of action compared to conventional NSAIDs and better tolerability. OKI and OKI ACT are recommended in the acute treatment of migraine with comorbid painful TMD.

Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window

Nepafenac is a highly effective NSAID used for treating postoperative ocular inflammation and pain after cataract surgery and its advantage over conventional topical NSAIDs has been proved many times. However, Nevanac® is a suspension eye drop, which clearly lacks patient compliance causing irritation, blurred vision, foreign body sensation along with problematic dosage due to its sticky, inhomogeneous consistence. In this study, nepafenac containing eye drops were prepared using hydroxypropyl-β-cyclodextrin to ensure complete dissolution of nepafenac, sodium hyaluronate to provide mucoadhesion and adequate viscosity and a preservative-free officinal formula, Oculogutta Carbomerae containing carbomer (just like Nevanac®), therefore providing a similar base for the new formulations. According to an experimental design, 11 formulations were tested in vitro including two reference formulations by measuring their viscosity, mucoadhesion, drug release and corneal permeability. Finally, two formulations were found promising and investigated further on porcine eyes ex vivo and corneal distribution of nepafenac was determined by RAMAN mapping. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose were ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.

Computational Design, Synthesis, and Pharmacological Evaluation of Naproxen-Guaiacol Chimera for Gastro-Sparing Anti-Inflammatory Response by Selective COX2 Inhibition.

The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.

Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis: 24-week data from the SIMPACT study.

ObjectivesThe aim of the SIMPACT study was to evaluate the efficacy and safety of MTX-free s.c. tocilizumab (TCZ) therapy in RA patients.MethodsSIMPACT was an open-label, non-controlled, non-randomized, non-interventional study, in which RA patients for whom the treating physicians ordered s.c. TCZ were observed during a 24-week treatment period in Hungarian centres. Although the use of MTX was avoided during the study period, other conventional synthetic DMARDs, oral CSs and NSAIDs were allowed. Study endpoints included the change in DAS28 and clinical activity index (CDAI) scores, the proportion of patients achieving remission in the whole population and in subgroups defined based on prior RA treatment history, and age, weight or biological sex post hoc. The extent of supplementary medication use was monitored.ResultsThree hundred and thirty-seven RA patients were enrolled in 18 study centres. TCZ therapy significantly decreased the disease activity measured by both DAS28 (P = 0.0001) and CDAI (P = 0.0001). Clinical response was more pronounced in biologic-naïve patients and was lower in patients >75 years of age. In the whole population, DAS28 ESR or CRP and CDAI remission rates were 70.10%, 78.95% and 33.59%, respectively. In patients <45 years of age, the CDAI remission rate doubled (67.86%). A significant decrease in the frequency of co-administered medication was reported, including oral CSs and DMARDs.ConclusionReal-world clinical evidence on s.c. TCZ reported here is in line with the efficacy outcomes of randomized clinical trials. Subgroup analysis revealed that TCZ was more effective in biologic-naïve patients and in those <75 years old.Trial registrationClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02402686.

ViphyllinTM, a Standardized Black Pepper Seed Extract Exerts Antinociceptive Effects in Murine Pain Models via Activation of Cannabinoid Receptor CB2, Peroxisome Proliferator-Activated Receptor-Alpha and TRPV1 Ion Channels.

PurposePlant-based natural products as anti-nociceptors have enormous potential as safer alternatives to conventional opiates and NSAIDS. Piper nigrum (black pepper) is one of the major culinary spices with medicinal attributes.MethodsIn the present study, the antinociceptive activity of a standardized black pepper seed extract (Viphyllin) containing not less than 30% β-caryophyllene (BCP) was evaluated using pain models in mice, namely acetic acid-induced writhing test, formalin-induced paw licking test, hot plate test and tail flick test. Further, the antagonists SR141716A (0.1 mg/kg i.p.), AM630 (5 mg/kg i.p.), capsazepine (0.1 mg/kg body weight i.p.), and GW6471 (1 mg/kg i.p.) were used to evaluate the involvement of cannabinoid receptors CB1 and CB2, TRPV1 ion channel and PPARα receptor, respectively. Molecular docking (AutoDock 4.2) was used to study the interaction of BCP with the agonist-binding sites of the selected pain receptors.ResultsViphyllin at 10 mg, 25 mg and 50 mg/kg (i.p.) significantly inhibited the writhings in mice as compared to untreated control group (p < 0.001). Further, Viphyllin at 50 mg/kg showed strong antinociceptive effect in formalin-induced paw licking test (p < 0.05). Pretreatment of mice with AM630 significantly reversed the antinociceptive activity of Viphyllin in both early and late phases of formalin test (p < 0.05). Administration of Viphyllin markedly increased the latency time of mice in hot plate test (p < 0.001). Further, Viphyllin markedly increased the latency time of tail flick compared to control group from 30 min to 90 min after treatment. AM630, Capsazepine, and GW6471 abolished the analgesic effect of Viphyllin. These findings clearly suggest the involvement of CB2 receptor, TRPV1 ion channel and PPARα receptor activation in Viphyllin-mediated antinociceptive activity. Docking score predictions further supported the possible involvement of BCP in the antinociceptive mechanism of Viphyllin.ConclusionIn conclusion, Viphyllin could be a natural pain-relieving agent involving safer pain signaling mechanisms, unlike conventional opiates and NSAIDs.

2,5-Disubstituted-4-Thiazolidinones: Synthesis, Anti-Inflammatory, Free Radical Scavenging Potentials and Structural Insights through Molecular Docking

The present work reports the synthesis and screening of fifteen 2,5-disubstituted-4- thiazolidinones with different substitutions at imino and varied arylidene groups. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti- inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group thereby ensuring possible freedom from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals as depicted by DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five and the toxicity behavior of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

Comparison of tissue pharmacokinetics of esflurbiprofen plaster with flurbiprofen tablets in patients with knee osteoarthritis: A multicenter randomized controlled trial.

This open‐label, multicenter, prospective, randomized controlled trial aimed to determine the effectiveness of esflurbiprofen plaster (SFPP) and flurbiprofen tablets (FPTs) on knee osteoarthritis in patients scheduled for total knee arthroplasty by comparing the transfer of esflurbiprofen and flurbiprofen to tissues and fluids. Thirty‐eight patients were randomly assigned in a 1:1 ratio to receive SFPP or FPT. Both groups were then divided into four subgroups, according to whether they received the final dose of SFPP or FPT at 2, 7, 12, or 24 h before planned surgery. The primary endpoints were the esflurbiprofen concentrations in synovium, synovial fluid, and plasma. Areas under concentration–time curves (AUC0–24 h) of esflurbiprofen were calculated for each group. Pain was assessed using a numeric rating scale (NRS) 7 days before and immediately before surgery. The AUC0–24 h in the synovium were 4401.24 and 4862.70 ng·h/g in the SFPP and FPT groups, respectively. Maximum esflurbiprofen concentrations were observed in the synovium, synovial fluids, and plasma after SFPP application for 12 h. The NRS results indicated a long‐lasting effect of SFPP. The AUC of the synovial esflurbiprofen concentration of SFPP indicated that the SFPP is transferred to the synovium and synovial fluid in high concentration. The efficient deep‐tissue transfer of esflurbiprofen suggests that its pharmacokinetic characteristics differ from those of conventional topical NSAIDs. This study was prospectively registered in the Japan Registry of Clinical Trials (registration number: jRCTs031180228).

Potent anti-inflammatory effects of an H2 S-releasing naproxen (ATB-346) in a human model of inflammation.

ATB-346 is a hydrogen sulfide-releasing non-steroidal anti-inflammatory drug (H2 S-NSAID) derived from naproxen, which in preclinical studies has been shown to have markedly reduced gastrointestinal adverse effects. However, its anti-inflammatory properties in humans compared to naproxen are yet to be confirmed. To test this, we used a dermal model of acute inflammation in healthy, human volunteers, triggered by ultraviolet-killed Escherichia coli. This robust model allows quantification of the cardinal signs of inflammation along with cellular and humoral factors accumulating within the inflamed skin. ATB-346 was non-inferior to naproxen in terms of its inhibition of cyclooxygenase activity as well as pain and tenderness. ATB-346 significantly inhibited neutrophil infiltration at the site of inflammation at 4h, compared to untreated controls. Subjects treated with ATB-346 also experienced significantly reduced pain and tenderness compared to healthy controls. Furthermore, both classical and intermediate monocyte subsets infiltrating the site of inflammation at 48h expressed significantly lower levels of CD14 compared to untreated controls, demonstrating a shift toward an anti-inflammatory phenotype. Collectively, we have shown for the first time in humans that ATB-346 is potently anti-inflammatory and propose that ATB-346 represents the next generation of H2 S-NSAIDs, as a viable alternative to conventional NSAIDs, with reduced adverse effects profile.

Risk factors for herpes zoster in patients with rheumatic diseases: a nationwide cohort study in Korea.

To determine the risk factors for herpes zoster (HZ) in patients with rheumatic diseases in Korea. We used the nationwide database of the Health Insurance Review & Assessment Service to analyse patients aged ≥20 years who had visited a hospital more than twice for rheumatic disease as a principal diagnosis from January 2009 to April 2013. HZ was identified using HZ-related Korean Standard Classification of Diseases 6 (KCD-6) codes and the prescription of antiviral agents. The relationship between demographics, comorbidities and medications and HZ risk was analysed by Cox proportional hazards models. HZ developed in 1869 patients. In Cox proportional hazards models, female sex but not age showed an increased adjusted hazard ratio (HR) for HZ. Comorbidities such as haematologic malignancies, hypertension, diabetes mellitus, and chronic lung and liver diseases led to an increased HR. HZ risk was higher in patients with SLE (HR: 4.29, 95% CI: 3.49, 5.27) and Behçet's syndrome (BS, HR: 4.54; 95% CI: 3.66, 5.64) than with RA. The use of conventional DMARDs, immunosuppressants, TNF inhibitors, glucocorticoids and NSAIDs increased the HR. Infliximab and glucocorticoids (equivalent prednisolone dose >15 mg/day) produced the highest HZ risk (HR: 2.91, 95% CI: 1.72, 4.89; HR: 2.85, 95% CI: 2.15, 3.77, respectively). Female sex, comorbidities and medications increased HZ risk in patients with rheumatic diseases and even young patients could develop HZ. Compared with RA, SLE and BS are stronger HZ risk factors. Patients with rheumatic diseases and these risk factors are potential target populations for HZ vaccination.

A randomized controlled trial comparing the efficacies of ketorolac and parecoxib for early pain management after total knee arthroplasty

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce pain after orthopedic surgery. Currently, selective COX-2 inhibitors can provide effective pain reduction with less platelet inhibition compared with conventional NSAIDs. We aimed to compare the analgesic effect and perioperative blood loss (PBL) after total knee arthroplasty (TKA) between ketorolac and parecoxib administration. MethodsWe conducted a prospective randomized controlled study of 100 unilateral TKAs. The ketorolac group of 50 patients received an intraoperative periarticular injection (PAI) with 100 mg of bupivacaine and 30 mg of ketorolac. Afterwards, 30 mg of ketorolac was intravenously injected every 12 h until 48 h. In the parecoxib group of 50 patients, 20 mg of parecoxib was added to PAI, and the first intravenous dose was 20 mg followed by 40 mg every 12 h. The primary outcomes were visual analog scales (VASs) of postoperative pain, amount of morphine consumption, PBL, and blood transfusion rate. ResultsThe ketorolac group had a significantly lower VAS pain score than the parecoxib group at 6 h after TKA (2.38 ± 2.52 vs. 4.12 ± 2.86, P < 0.01). Thereafter, the VAS of both groups and total morphine consumption at 24 and 48 h were comparable. The PBLs of the ketorolac and parecoxib groups were 529.72 ± 263.02 and 402.40 ± 191.47 ml, respectively (P = 0.01). However, the blood transfusion rates between groups were not different. ConclusionParecoxib provides comparable analgesic effects to ketorolac. Additionally, perioperative use of parecoxib is safe and is associated with significantly less blood loss after TKA.

In silico guided designing of 4-(1H-benzo[d]imidazol-2-yl)phenol-based mutual-prodrugs of NSAIDs: synthesis and biological evaluation

ABSTRACT The free COOH group of conventional NSAIDs is a structural feature for non-selective cyclooxygenase (COX) inhibition and the molecular cause of their gastrointestinal (GI) toxicity. In this context, an in house database of synthesizable ester prodrugs of some well-known NSAIDs was developed by combining their -COOH group with -OH of a newly identified antioxidant 4-(1H-benzo[d]imidazol-2-yl)phenol (BZ). The antioxidant potential of BZ was unveiled through in silico PASS prediction and in vitro/in vivo evaluation. The in house database of NSAIDs-BZ prodrugs was first subjected to screening with our previously reported pharmacophore models of hCES1 (AAHRR.430) and hCES2 (AHHR.21) for determining hydrolytic susceptibility. Biotransformation behaviour of screened prodrugs was then assessed by using QM/MM and sterimol parameterization, followed by ADMET calculations to predict the drug likeness. On the basis of in silico results, five prodrugs were duly synthesized and the best three were subject to the in vivo evaluation for their anti-inflammatory, analgesic, antioxidant activities, and ulcerogenic index. Among these prodrugs, BN2 and BN5 displayed better anti-inflammatory and analgesics potential in comparison to their parent drugs. All the prodrugs were found to be gastro sparing in the rat model and significantly improved the levels of oxidative stress biomarkers in both blood plasma as well as gastric homogenate.

Effectiveness Of Mesotherapy In Treatment Of Fibromyalgia Tender Points

Background: Fibromyalgia is the second most common disease encountered in rheumatology practice Aim: This study designed to assess the potential effect of mesotherapy in treatment of tender points in primary fibromyalgia (PFM) patients. Methods: Thirty PFM patients who fulfilled the American Colleague of Rheumatology 1990 criteria, joined this study. They were divided into 2 groups randomly according to the treatment program received; Injection mesotherapy group (Group I: No=15 patients) who received a mixture of 2 ml of Ketoprofen (100mg/2ml) added to 3 ml of Saline Solution, once cession per week for a total of 6 successive weeks and other 15 patients (Group II) who received Ketoprofen 100 mg Extended- Release capsules once daily for 2 successive weeks which represent the control group. Patients‟ pain severity, quality of life and depression were assessed using visual analogue scale (VAS), fibromyalgia impact questionnaire (FIQ) and the Hamilton Rating Scale (HDRS) respectively before treatment and after the 3rd & the 6th cession then data were recorded and compared. Results: We found significant improvements (p<0.001) tender point‟s number, VAS, FIQ and HDRS in the injection mesotherapy group compared to the control group with no major adverse effects were described. Conclusion: This study supports the hypothesis that injection mesotherapy could offer a great therapeutic advantage in treatment of fibromyalgia tender points especially in the presence of associated comorbidities where there is a high risk of drug interaction, polypharmacy, or when conventional (oral or parenteral) NSAIDs use is contraindicated.

A COMPARATIVE STUDY OF ANTI-NOCICEPTIVE ACTIVITY OF CURCUMA LONGA LINN. WITH THAT OF IBUPROFEN IN EXPERIMENTAL ANIMALS

Objective: The aim of the study is to evaluate and compare the analgesic activities of Curcuma longa Linn. in the experimental animals.&#x0D; Methods: The present study was conducted in the Department of Pharmacology, Gauhati Medical College and Hospital, after getting approval from the Institutional Animal Ethics Committee (No MC/68F/2009/MAR-19/02). Healthy rodents weighing between 150 and 200 g were selected and randomly divided into five groups, each group consisting of six animals. Tail-flick analgesiometer was used to assess the analgesic activity of C. longa Linn. and ibuprofen in the experimental animals. Appropriate statistical analyses like Student’s t-test were used to analyze the data.&#x0D; Results: The mean reaction time (s) was prolonged on gradually increasing the dose of C. longa Linn. from 200 to 400 mg/kg. At 400 mg/kg dose C. longa Linn. produced similar analgesic activity as compared to ibuprofen (30 mg/kg).&#x0D; Conclusion: From the study, it can be concluded that curcumin has the capacity to attenuate pain, and when administered in high doses, may produce similar activity as other conventional NSAID’s.

Ankylosing Spondylitis-A review on Drug Promotion through the Ages

The diagnosis of ankylosing spondylitis is often delayed due to ambiguous clinical manifestations and strict diagnostic criteria. However, imaging techniques such as magnetic resonance imaging have been found effective for the early diagnosis of nonradiographic sacroilitis. New tumor necrosis factor alpha (TNF-α) inhibitors have good efficacy for patients with persistently high disease activity despite conventional nonsteroidal anti-inflammatory drug treatment which are effective in low diseases cores. Thus, early diagnosis and aggressive treatments are essential for ankylosing spondylitis patients. Though the disease can be stayed with conventional DMARDs and NSAIDs in low score diseases, in high score diseases TNF-α inhibitors are more effective. In this review, we discuss new diagnostic criteria for ankylosing spondylitis, administration methods of TNF-α inhibitors, comparative review between conventional AS drugs and TNF-α inhibitors and the long-term follow-up results for patients treated with TNF-α inhibitors.