Non-steroidal Anti-inflammatory Drugs Nsaids Research Articles

Amide Codrug Approach: Synthesis and Biopharmaceutical Evaluation of Nonsteroidal Anti-Inflammatory Drug and Calcium Channel Blocker Conjugates

Background and Aim Geriatric patients often suffer from osteoarthritis and hypertension comorbidity. The codrugs approach was shown to be an effective strategy for targeting diseases synergistically hence improving the quality of life of patients. The present study aimed to synthesize various Nonsteroidal Anti-inflammatory Drugs NSAIDs and Calcium channel blocker CCB Co-drugs and biopharmaceutical study to eliminate the adverse gastrointestinal effects of the NSAIDs to treat comorbid conditions in geriatric patients with significant reduction of polypharmacy.Methods Various conjugates were synthesized by a one-pot amidation reaction of Amlodipine with various NSAIDs. Further characterization by melting point TLC Fourier transform infrared nuclear magnetic resonance and mass spectroscopy followed by solubility partition coefficient and hydrolysis study in SGF and SIF.Results The synthesized codrugs satisfied the structural criteria of the proposed plan. From the biopharmaceutical and hydrolysis study it was observed that the co-drugs underwent significant hydrolysis in SIF pH 7.4 and have showed delayed onset of action with respect to the standard drugs. The delayed onset may be due to the hydrolysis of amide linkage followed by the release of the prodrug which finally releases the active drug.Conclusion The findings illuminated the codrugs pros and cons aiding optimization and development. This research advances amide-based mutual prodrugs and their use in pharmaceutical research. The outcome of this exploration confirmed that the described co-drug can offer desirable safety and therapeutic benefits. Hence these conjugates could be considered for further development.

Clinical profile of patients with the first presentation as anterior nodular scleritis — a case series

Background: The aims of this study was to report the clinical profile of five patients with features of anterior nodular scleritis as initial presentation in residents of Western Maharashtra. Material and methods: A retrospective review of medical records was done from February 2019 to December 2019. Five new anterior nodular scleritis cases were reported at the tertiary-eye care centre within two months. The slit-lamp examination, anterior-segment photographs, and laboratory data were collected and analysed. Results: A majority of cases (4/5) were presented in females. Three patients had a unilateral presentation, while 2 — had bilateral involvement. The most common presenting symptom was ocular pain and redness. Corneal involvement was seen in 1 case. Two female patients were diagnosed with rheumatoid arthritis, one female had multinodular goitre, and the other two were idiopathic. Three patients responded very well to oral non-steroidal anti-inflammatory drugs NSAIDs), while the rest two were managed with steroids. No patient had to be started on immunosuppressives. All the cases showed complete resolution with the treatment provided. All these patients presented at our centre in the autumn season. All these patients presented at our center in the autumn season only and no new case of anterior scleritis reported before or after this season. Conclusion: Management of scleritis may need a multidisciplinary approach as it may be the only presentation of an underlying systemic disease. It is to be considered in the differentials of red eye that presents with a substantial amount of ocular pain or with the known systemic disorder that leads to scleritis development. Also, there could be a seasonal association of anterior-nodular scleritis like episcleritis.

Common Medicinal Plants Effective in Peptic Ulcer Treatment: A Nutritional Review

Plants have long been used as drugs for treatment of diseases. With the decrease in the efficacy of synthetic drugs medicinal plants have gained importance. Peptic ulcer is the common gastrointestinal disorder that is associated with increase rate of morbidity and mortality. It is a break or lesion in the lining of the stomach and duodenum characterized by severe pain and bleeding. It is caused by increase in aggressive factors and decrease in defensive factors, genetics, stress, diet, alcohol, Helicobacter pylori and Non-steroidal anti-inflammatory drugs NSAIDS. Its medications such as Histamine, proton pump inhibitor and rostaglandins pose side effects such as arrhythmias, constipation, headache, blurred vision and bleeding. Plants containing flavonoids and terpenes protects the stomach lining and scavenge free radicals. This article reviews the medicinal plants having phytochemicals possessing gastroprotective and antiulcer activity.

A Study of Prescribing Pattern of Non-Steroidal Anti-Inflammatory Drugsin the Department of Orthopaedics, KIMS Hospital and Research Centre,Bangalore

Background Non-Steroidal Anti-Inflammatory Drugs NSAIDs are the most commonly used drugs for the management of pain and inflammation with good efficacy.Objective To determine the prescribing patterns of NSAIDs to report and document the potential drug-drug interactions and adverse drug reactions associated with its usage.Methodology The present study was a cross-sectional observational and prospective study conducted over 200 patients. The patient details included socio-demographics like age gender chief complaint diagnosis and information on the drugs prescribed which included brand andor generic name dose dosing frequency formulation route of administration and duration of treatment.Results Among the subjects 32 were prescribed paracetamol 9 were prescribed diclofenac and 1 were prescribed aspirin and aceclofenac each. 34.5 were prescribed the combination of aceclofenac paracetamol 62.5 were prescribed two NSAIDs. 117 prescriptions showed no interactions with NSAIDs whereas 62 were found to have interactions among aceclofenac bromelain commonly.Conclusion The common NSAID prescribed was preferential COX-2 inhibitor and a majority of prescriptions were not found with any interactions with NSAIDs. The prescribing pattern in our department was found to be rational.

Role of Low Environmental Temperature in Peptic Ulcer Development

Peptic ulcers are described as acid-induced lesions found in the stomach and duodenum caused bythe imbalance between the defending factors of the mucosa and the attacking factors such ashydrochloric acid in gastric juice, with Helicobacter Pylori (H. Pylori) and Non-Steroidal Anti-Inflammatory Drugs NSAIDs. They exhibit seasonal patterns in their occurrence, with higheroccurrence in winter and spring and a low occurrence in summer. Temperature plays a major role intheir occurrence, some of which have resulted in increased morbidity in some number of diseases,such as gastrointestinal bleeding, caused by an increase in air pressure, dry air (relative humidity)occurring from cold air, and also its actions on the protective effect helicobacter pylori in the humanbody. Their actions excite the adrenal gland marrow and the sympathetic nerve, causing rapidsecretion of adrenaline and non-adrenaline, angiotensin II and endothelin, resulting in damage tothe mucosa epithelial, caused by the contraction effect of the adrenal agents on the duodenalmucosa and blood vessel. It causes low expression of Epidermal Growth Factor Receptor (EGFR),Epidermal Growth Factor (EGF), Heat Shock Protein (HSP) 70, Occludin, Nitric Oxide Synthase(NOS), in the gastric mucosa, in extremely cold temperature than those in extremely hottemperature, increasing the gastric acid secretion in extremely cold temperature than in extremelyhot temperature. Therefore, this review aims to give general insight into the role of low temperaturein peptic ulcer development and further consideration in the treatment of peptic ulcer diseases.

The use of faecal immunochemical testing in the decision-making process for the endoscopic investigation of iron deficiency anaemia.

Background Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia (IDA) in adult men and postmenopausal women. Gastroduodenal endoscopy (GDE) and colonoscopy are frequently recommended, despite uncertainty regarding the coexistence of lesions in the upper and lower GI tract. The faecal immunochemical test (FIT) measures the concentration of faecal haemoglobin (f-Hb) originating only from the colon or rectum. We aimed to assess whether the FIT was able to select the best endoscopic procedure for detecting the cause of IDA. Methods A prospective study of 120 men and postmenopausal women referred for a diagnostic study of IDA were evaluated with an FIT, GDE and colonoscopy. The endoscopic finding of a significant upper lesion (SUL) or a significant bowel lesion (SBL) was considered to be the cause of the IDA. Results The diagnoses were 35.0% SUL and 20.0% SBL, including 13.3% GI cancer. In the multivariate analysis, the concentration of blood haemoglobin (b-Hb) <9 g/dL (OR: 2.60; 95% CI 1.13-6.00; p = 0.025) and non-steroidal anti-inflammatory drugs NSAIDs (2.56; 1.13-5.88; p = 0.024) were associated with an SUL. Age (0.93; 0.88-0.99; p = 0.042) and f-Hb ≥ 15 μg Hb/g faeces (38.53; 8.60-172.50; p < 0.001) were associated with an SBL. A "FIT plus gastroscopy" strategy, in which colonoscopy is performed only when f-Hb ≥15 μg Hb/g faeces, would be able to detect 92.4% of lesions and be 100% accurate in the detection of cancer while avoiding 71.6% of colonoscopies. Conclusions The FIT is an accurate method for selecting the best endoscopy study for the evaluation of IDA. An FIT-based strategy is more cost-effective than the current bidirectional endoscopy-based strategy and could improve endoscopic resource allocation.

English

The use of herbal medicines or drugs without professional prescription is a recurrent practice in several regions of Brazil. This action generates risks to the user, such as intoxication, masking of disease symptoms and important pharmacological interactions. The objective of this study was to analyze the profile of phytotherapeutic and drug use, without professional prescription, among residents of the municipality of Santa Cruz, Rio Grande do Norte, Brazil. Thus, a field survey was carried out through the application of a semi-structured questionnaire in the Likert scale model to 180 residents. The majority were women (80%), the predominant marital status were married (56%) and 44% were 49 years of age or older. It was observed that the target population has a low level of knowledge about self-medication, besides a constant consumption of Non-steroidal anti-inflammatory drugs NSAIDs without prescription. In addition, respondents do not have the habit of questioning health professionals, increasing of the self-medication. Therefore, health education actions are necessary in order to clarify the population, the change of habits in this practice, in search of a better quality of life. Key words: Self-medication, medicinal plants, plant-drug interactions.

Predictive Factors Associated With Acute Ocular Involvement in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

To suggest an objective score for grading the acute ocular severity of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to determine predictive factors for severe acute ocular involvement such as ocular surface epithelial defect and/or pseudomembrane formation. Retrospective cohort study. The medical records of SJS (n = 87) and TEN (n = 48) patients between 2005 and 2007 were reviewed. An acute ocular severity score was determined on a scale from 0 to 3 (none, mild, severe, and very severe) according to the existence of hyperemia, corneal or conjunctival epithelial defect, and pseudomembrane formation. The associations between the severe acute ocular involvement and factors such as patient age, exposed drugs, systemic severity, and the prevalence of ocular sequelae were examined. The number of cases with score grade 0, 1, 2, and 3 was 19 (21.8%), 31 (35.6%), 22 (25.3%), and 15 (17.2%) in 87 SJS cases and 12 (25.0%), 11 (22.9%), 17 (35.4%), and 8 (16.7%) in 48 TEN cases. Multivariate logistic regression analysis revealed that patient age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; P = .007) and nonsteroidal anti-inflammatory drugs NSAIDs or cold remedies (OR, 2.58; 95% CI, 1.26-5.29; P = .010) were predictive factors for severe acute ocular involvement. The prevalence of visual disturbance and eye dryness increased according to the increase of acute ocular severity (P = .001 and P = .007 in SJS; P = .007 and P = .014 in TEN, respectively). At the onset of SJS/TEN, strict attention should be paid to ocular involvement in young patients and in patients exposed to NSAIDs or cold remedies.

Combined toxicity of penicillin and aspirin therapy may elicit bilateral vestibulopathy

Bilateral vestibulopathy (BV) indicates a peripheral failure of the estibulo-ocular reflex which normally stabilizes gaze during head ovements and locomotion. Accordingly, BV causes severe gait nsteadiness associated with oscillopsia, i.e. the illusion that the isual environment is moving during locomotion. Antibiotic therpy with aminoglycosides seems to be the most frequent cause of V (about 10–20%). Nevertheless the aetiology in about 50% of all atients with BV remains unknown. Here we report for the first ime of two patients who developed BV following combined treatent with penicillin and non-steroidal anti-inflammatory drugs NSAIDs) etoricoxib and aspirin, and we propose an interactive athomechanism.

Conservative Management of Hip Pain

Thomas H. Hudgins, MD, and Joseph T. Alleva, MD, MBA cetabular dysplasia and femoral acetabular impingement are thought to e precursors of osteoarthritis. Likewise, disruption of the joint integrity hrough labral tears may also lead to early osteoarthritis. The goal of a omprehensive nonoperative approach to these entities is to restore unction and manage pain. Physical therapy to implement a home xercise program is the cornerstone of conservative care. Strengthening nd flexibility exercises around the hip joint are emphasized. The patient s instructed on a program that addresses his or her biomechanical mbalances. Typically, the patient will have decreased motion in hip exion and hip internal rotation. Therefore, promoting flexibility with hip exor stretches and hip external rotator stretches, such as the piriformis tretch, are part of the program. Strengthening exercises are conducted hrough closed kinetic chain exercises, such as step-ups and lunges, to educe sheer stress on the hip joint and simulate everyday functional asks. After pain is reduced, the patient is advanced to the maintenance hase of rehabilitation with sports-specific training. Oral medications such as nonsteroidal anti-inflammatory drugs NSAIDs) are effective to reduce acute inflammation and provide pain elief. Cox 2 inhibitors are used in patients with risks of gastrointestinal leeding. Acetaminophen (1000 mg 3 times per day) has been shown to e as effective as NSAIDs for pain management while reducing risk of astrointestinal toxicity. Glucosamine–chondroitin has not shown any adiographic improvement of hip osteoarthritis, but may reduce pain. It hould be taken at dosages of 1500 mg daily for 3-6 months for an dequate trial and can be combined with methylsulfonylmethane or hondroitin for additive benefit. Injections have been shown to provide temporary relief and can provide stopgap measure for patients who are not surgical candidates because of omorbidities or are waiting for surgery. Two approaches are generally ccepted, an anterior approach and a lateral approach. The procedures

Selective determination of acidic pharmaceuticals in wastewater using molecularly imprinted solid-phase extraction

The determination of acidic pharmaceuticals, such as non-steroidal anti-inflammatory drugs NSAIDs and clofibric acid (metabolite of clofibrate), at low ng L −1 levels in wastewater requires highly selective and sensitive analytical procedures. The removal of matrix components during sample preparation results in significant benefits towards reducing the matrix effects during LC–MS analysis. Therefore this work describes a simple method to enrich and clean up NSAIDs and clofibric acid from sewage water using molecularly imprinted solid-phase extraction (MISPE). Final analysis was performed by liquid chromatography–tandem mass spectrometry. The performance of this method has been evaluated in fortified tap and sewage water in terms of recovery, precision, linearity, and method quantification limit. Recovery for all compounds ranged in all matrices between 84 and 116% with intra-day R.S.D. values below 11.5%. Matrix effect evaluation demonstrated that even complex sample matrixes, such as pond or sewage water did not showed significant ion suppression/enhancement compared to tap water. The performance of the method was further emphasized by the study of pond water, which receives treated water from a sewage treatment plant in south Sweden. Raw sewage and treated water were also tested. In those samples, all acidic pharmaceuticals were detected in concentration above method quantification limits ranging from 5.1 to 5153.0 ng L −1.

Effect of Nonsteroidal Anti-Inflammatory Drugs on the Cellular Membrane Fluidity

In this work, fluorescence measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to evaluate the effects of the interaction of nonsteroidal anti-inflammatory drugs--NSAIDs (meloxicam, lornoxicam, and nimesulide) with several membrane systems (liposomes with and without cholesterol, mouse splenocytes, mouse macrophages cell line--J774, human leukemia monocyte cell line--THP-1, and human granulocytes and mononuclear cells). DPH fluorescence quenching studies revealed that the NSAIDs studied were able to efficiently quench the probe located in membrane hydrocarbon region. Fluorescence anisotropy measurements were also made to investigate the effects on membrane fluidity resulting from the interaction between the drugs and membrane systems. All the anti-inflammatory drugs studied show an increase in the membrane fluidity in a concentration dependent manner. Results obtained provide an insight into NSAIDs capacity to be inserted in lipid bilayers and alter the lipid dynamics. The induced changes in lipid dynamics may modulate the activity of inflammatory enzymes or may be related with deleterious topical action of NSAIDs on gastric phospholipid fluidity.

Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition

Celecoxib carries a smaller cardiovascular risk for myocardial infarction and hypertension than other cyclooxygenase-2 (COX-2)-selective non-steroidal anti-inflammatory drugs NSAIDs ("coxibs") and may ameliorate endothelial dysfunction. We aimed to determine which mechanism possibly accounts for the beneficial effect by investigating its vascular action in different in vitro preparations in comparison with other coxibs and reference phosphodiesterase-5 (PDE5) inhibitors. To uncover potential effects on coronary flow, the effects of celecoxib in comparison with other NSAIDs and the PDE5 inhibitors, sildenafil and zaprinast, were investigated in guinea-pig Langendorff heart. This was supported by studies for vasorelaxation, interaction with the NO/cGMP pathway, and measurement of cyclic nucleotide amounts released from rat aortic rings, and inhibition of human PDE5 as well as PDE4 activity. Bolus injections of sildenafil, celecoxib, and zaprinast (at 100 nmol) into the Langendorff heart increased coronary flow by approximately 100, 65, and 25%, respectively, while rofecoxib, lumiracoxib, parecoxib, and diclofenac, except valdecoxib (>100 nmol), failed to increase coronary flow up to 300 nmol. In rat aorta, sildenafil, celecoxib and zaprinast caused endothelium-dependent relaxation with -log[EC(50)]M values of 8.90, 6.66 and 5.56, respectively; their rank order of potency corresponds to their coronary dilatory effect. Celecoxib-induced relaxation of aorta was attenuated by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) and by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 10(-5) M). In aortic rings, celecoxib (3x10(-5) M) caused a fivefold increase in the cGMP level and potentiated that induced by sodium nitroprusside (5x10(-7) M). Celecoxib and valdecoxib inhibited human PDE5A1 with an IC(50) of 1.6x10(-5) and 1x10(-4) M, respectively, whereas other coxibs were without inhibitory effect. Celecoxib caused coronary vasodilatation in guinea-pig hearts and relaxation of rat aorta and had a potentiating effect on the NO/cGMP signaling pathway in rat aorta through specific blockade of PDE5. These unexpected findings clearly support the notion that celecoxib possesses an as yet undisclosed molecule-specific property that possibly compensates a decrease of prostacyclin-dependent cAMP generation by concomitantly increasing cGMP levels resulting from inhibition of PDE5.

Use of transgenic mice in identifying chemopreventive agents

Cancer chemoprevention uses natural- or synthetic chemical compounds to reverse, suppress or to prevent one or more of the biological events leading to the development of cancer. Chemopreventive agents are classified as blocking or suppressing according to their action on either the initiation or promotion-progression phases in experimental models using carcinogen treated animals. Transgenic animal technology has resulted in a plethora of murine models for cancer research providing insight into the complex oncogenic events contributing to the loss of cell cycle control and tumourigenesis. Transgenic models also offer an important opportunity to identify and study both tumourigens and chemopreventive agents. However, so far chemoprevention has in such models only been investigated to a limited degree and primarily in models with inactivated tumour suppressor genes. Studies show that spontaneous tumour developing due to loss of p53 function may be offset by preventive measures. The preventive actions of retinoids and polyamine synthesis inhibitors have been studied in the PIM mouse susceptible to lymphoma development. Most chemopreventive studies have been performed on murine familial adenomatous polyposis (FAP) models, which carry one non-functional apc gene and develop multiple intestinal adenomas upon inactivation of the wild type allele. Particularly non-steroidal anti-inflammatory drugs NSAIDs, which block COX-2, but also food components such as n-3 fatty acids show promising chemopreventive effects in these models. Transgenic cancer models demonstrate a strong gene-environment interaction, which is promising for the development of chemopreventive strategies.

Rationale Verwendung nicht-steroidaler antiphlogistischer Analgetika (inklusive selektiver COX-2-Hemmer) in der Praxis

Non-steroidal antiinflammatory drugs NSAIDs exert their pharmacological and side effects by suppressing the activity of the enzyme cyclooxygenase (COX). The identification and molecular- biological characterization of an inducible COX isoform (COX-2) in inflammatory cells led to the hypothesis that a selective inhibition of COX-2 would result in relieve of inflammation and pain without causing the COX-1-dependent side effects. However, all currently available NSAIDs inhibit both COX-1 and COX-2 at therapeutic doses, although they vary in their relative potencies against the two isozymes. Whereas the mechanism-based side effect of NSAIDs (e.g., gastrointestinal and renal toxicity, platelet dysfunctions) are due to a suppression of COX-1-derived prostanoids, an inhibition of prostanoids produced by COX-2 can be ascribed to the antiinflammatory, analgesic and antipyretic effects of NSAIDs. Furthermore, evidence has increased during the last two decades that the pharmacokinetic profil of NSAIDs (i.e., rate of absorption, elimination half-life and oral bioavailability) contributes to either therapeutic effects as well as to the type and incidence of side effects. Thus, the pharmacokinetic behaviour should be considered for the optimal clinical use of these substances. In the present review, the different pharmacokinetics of NSAIDs, their side effects, and perspectives of a therapy with novel specific inhibitors of the COX-2 isozyme are discussed.

The Separation of the Enantiomers of a Variety of Non-Steroidal Anti-Inflammatory Drugs Nsaids) as Their Anilide Derivatives Using a Chiral Stationary Phase

Abstract Widespread demand for accurate determinations of the enantiomenc purity of pharmaceutical used in synthetic and pharmacological research has increased the need for reliable and efficacious methods for separating the stereoisomers of a variety of biologically active compounds. Here we present a procedure for the separation of the enantiomers of a number of non-steroidal anti-inflammatory drugs (NSAIDs), as their anilide derivatives, by HPLC using chiral stationary phases. The chromatographic conditions the chiral stationary phase, and the choice of the derivitizing amine can be altered to accomodate various requirements.