Side Effects Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Prevalence, awareness, and patterns of non-steroidal anti-inflammatory drug use among health science students in Palestine: a cross-sectional study

Despite the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs), many people lack sufficient awareness regarding their side effects and proper usage. Consequently, this study aimed to assess the knowledge, behavior, and usage patterns of NSAIDs among students enrolled in Palestinian health colleges. The study was conducted in December 2020 using a cross-sectional design, and a convenience sampling method was employed to enroll a total of 206 students. The questionnaire comprised seven sections, each containing approximately 5 to 10 closed-ended questions. Data were analyzed using version 21 of the Statistical Package for the Social Sciences (IBM-SPSS Statistics 21). The percentage of respondents who admitted that NSAIDs were used several times in the year was 35.9%. More than half of the students believed that NSAIDs were generally safe. Seventy-two percent of the students were aware that more than one type of NSAID at the same time increased the side effects. The median knowledge score of NSAID side effects was 9 [6.25–11] out of 13. The knowledge score increased significantly with age (p < 0.001), higher academic year (p < 0.001), and pharmacy and medicine specialties (p = 0.002). The college students surveyed in this study possess a general awareness of NSAIDs. Nonetheless, there remains a necessity to enhance their behavior and practices concerning the utilization of NSAIDs through the implementation of programmed educational strategies.

Synthesis and pharmacological characterization of new curcumin ester pro-drugs with enhanced anti-inflammatory, anti-ulcerogenic and improved tissue distribution

In this work, curcumin- Non steroidal anti-inflammatory drugs (NSAIDs) conjugates were synthesized by esterification of the phenolic group of curcumin with the acid group of NSAIDs using the Steglich esterification method to enhance the anti-inflammatory activity of curcumin and to reduce the gastrointestinal side effects of NSAIDs. A set of bis C-NSAIDs conjugates was prepared by direct coupling of curcumin with Aceclofenac and Diflunisal respectively in good yield and characterized by Fourier-transform infrared spectra (FTIR) and Proton Nuclear Magnetic Resonance Spectra (1HNMR). In vivo, studies were performed to evaluate the toxicity, anti-inflammatory activity, bio-distribution, and anti-ulcerogenic studies of selected conjugates using different animal models. In Vivo, studies reveal enhanced biological activity with better tissue distribution of conjugates than that of parent curcumin and it could be a curcumin-based therapeutic molecule that might be explored further for its efficacy in managing inflammatory diseases.

Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses.

Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses. PBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites. Non-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46-7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb. PBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation.

Pattern of use and awareness of side-effects of non-steroidal anti-inflammatory drugs in the Jordanian population

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly utilized to reduce pain, inflammation, and fever. This study aimed to assess patterns of use and awareness of NSAID-related side-effects in an adult Jordanian. And the associations with sociodemographic factors. Methods: This cross-sectional study among a representative sample of 604 adults >18 years. A validated, self-administered questionnaire was used to collect basic sociodemographic data from the participants, as well as information regarding NSAID use. Results: Most respondents were NSAID users (65.7%), female (53.4%) and under 50 years of age (74.5%). Overall, 42.6% had been prescribed NSAIDs by a physician. Male gender and smoking were negatively correlated with NSAIDs use (multivariable odds ratio [OR]: 0.5, 95% confidence interval [CI]: 0.4–0.8, p = 0.001 and OR: 0.6, 95% CI 0.4–0.8, p = 0.003). In contrast, the Ministry of Health Insurance was associated with NSAIDs use with OR: 1.6, 95% CI: 1.1–2.6, p = 0.03. Overall, 65.1% were aware of kidney NSAID-related side-effects and 22.4% were aware of the increased risk of asthma and allergy. Conclusion: Despite the high frequency of NSAID use in the Jordanian general population, there is limited knowledge of their side-effects as well as drug interactions. This is cause for concern, particularly as many participants reported having been prescribed NSAIDs by physicians without adequate patient safety education.

Characteristics of NSAIDs Prescription in Elderly Knee Osteoarthritis Patients

&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) as pharmacological therapy for OA was found to be imprecise. In 2018, the rationality of NSAIDs prescribed at Wolter Monginsidi Hospital, Manado showed as much as 100% proper indication, 77% proper dose, and 89% proper medication. This shows that the rationality of NSAIDs prescription is still irrational. Irrational prescribing has the potential to result in side effects or the incidence of drug-related problems&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To determine the characteristics and the rationality of NSAIDs prescriptions in elderly knee OA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This is a descriptive study of 108 medical records for the period January 2020-April 2021 at BS Clinic, Semarang, using purposive sampling method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;Results showed the characteristics of elderly knee OA patients at BS Clinic were 74.1% women, 47.2% belonging to obese group, and 41.7% experiencing severe pain. Patient’s age had a median value of 66 years. In the number of comorbidity, the median value was 1. The rationality of NSAIDs prescription was 95,4% proper diagnosis, 100% proper drug, 97.2% proper dose, and 99.1% proper indication with the incidence of side effects of NSAIDs prescribing was 1.9%.&lt;/p&gt;

Impact of OTC Purchase and Utilization of Pain Killers in Rheumatoid Arthritis

Pain may be alleviated externally using topical therapies. It's true that topical pain relievers are effective. A lot of the time they also cause a thermal or a thermal sensation on the skin. The lack of systemic absorption means that topical therapies are safer than oral drugs. There are a variety of over-the-counter (OTC) topical creams, sprays, and gel pain relievers available for the treatment of arthritis and other types of physical pain. Both nonsteroidal anti-inflammatory drugs (NSAIDs) and capsaicin, the chemical responsible for chilli peppers' spiciness, may be used. Yet, NSAIDs are not without hazards and adverse effects. Prostaglandins are involved in a variety of processes in addition to pain. Yet, since NSAIDs lower prostaglandins in the body, the stomach lining may become more susceptible to injury from acid. Causes of stomach distress, ulcers, and internal bleeding may result from this. Additional potential NSAID side effects include hives, wheezing, which may be harmful for those with asthma; changes in renal function; and a rash. This study takes an indepth look at the use of pain killers in rheumatoid arthritis.

General characteristics and features of the use of nonsteroidal anti-inflammatory drugs in the treatment of dorsopathies in clinical practice (literature review)

Back pain ranks first among all non-communicable diseases in terms of the number of years of life lost due to poor health. At the same time, the choice of tactics for the treatment of dorsopathies presents certain difficulties, in particular, the choice of a nonsteroidal anti-inflammatory drug (NSAID), which depends on a number of factors. NSAIDs are effectively used in the treatment of musculoskeletal pain, but they have side effects, which determines the individual characteristics of their use. The article presents an overview of scientific data published in the sources MEDLINE, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Clinical Trials.gov, services for the exchange of research information on the clinical practice of NSAID use. The general characteristics and side effects of NSAIDs in clinical practice are analyzed in order to choose an effective and safe trajectory of their use in the treatment of dorsopathies. In the acute period of dorsopathy, the therapeutic effect should be aimed primarily at reducing pain. At the same time, the use of NSAIDs is necessary and justified, should include a detailed assessment of side effects, duration of use, alternative trajectories of drug and non-drug treatment. Numerous side effects of NSAIDs from the gastrointestinal tract, liver, cardiovascular system, allergic reactions, congenital anomalies in the fetus when using NSAIDs during pregnancy and other undesirable consequences, make it necessary to take the maximum possible measures to minimize adverse reactions and long-term undesirable consequences for the patient. Combined therapeutic effects, including, along with the use of NSAIDs, physiotherapy, physical therapy, massage, reflexotherapy, optimization of motor activity, optimization of posture under static loads, the use of cognitive behavioral therapy methods, is optimal from the standpoint of risk stratification and the expected clinical effect in patients with dorsopathy.

Efficacy and Safety of Naproxen Gel in Musculoskeletal Pain Management: A Prospective Cohort Study

Introduction: Naproxen is effective for various musculoskeletal conditions and has a longer half-life, making it a favourable choice for sustained relief. Additionally, there is a potential unmet need for guidelines on the usage of topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Asia-Pacific region. A study on naproxen 10% gel aims to address this need and increase awareness of its therapeutic potential in the region. Aim: To assess the efficacy and safety of naproxen 10% gel in relieving pain associated with lower back, knee, cervical, synovitis, bursitis, muscle sprain, and tendinitis. Materials and Methods: This prospective, cohort, observational, open-label, single-arm, multicentric study was conducted at 458 centres in India, including Ahmedabad, Bengaluru, Chandigarh, Chennai, Delhi, Guwahati, Hyderabad, Indore, Jaipur, Kolkata, Lucknow, Meerut, Mumbai, Patna, and Pune, between February 2023 and May 2023. The data was collected from outpatient settings/clinics of orthopaedicians and clinicians who have been prescribing topical naproxen 10% gel to their patients. The study included patients aged 18 to 60 years of either sex who were suffering from back pain, muscle pain, sprains, frozen shoulder, arthritis, acute low back ache (non-specific), or pain. The data was captured during the scheduled follow-up visits planned by the treating clinician, with data recorded at 3, 5, 10, and 15 days. At the baseline visit, demographic details (age, sex, weight, height, body mass index, and symptoms), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale score, pain intensity on movement score, Visual Analogue Scale (VAS), and overall pain score were obtained. Results: Out of 10,587 patients, 10,265 completed the present study. The majority of patients had lower back pain (n=3386, 32.99%) and knee pain (n=3184, 31.02%). The average pain intensity on movement score of patients with bursitis significantly decreased from the baseline to 15 days {mean change {95% Confidence Interval (CI)}: 6.04 (5.89, 6.20); p&lt;0.001}. Post-naproxen treatment, the average pain intensity, WOMAC pain score, VAS, and overall pain score significantly decreased from baseline to day 15 in patients with knee pain and lower back pain. A significant improvement in WOMAC, WOMAC pain (5.42 vs 17.98), WOMAC stiffness (1.49 vs 5.75), and WOMAC physical function score (18.93 vs 56.21) at day 15 was observed in patients with a muscle sprain. Adverse Events (AE) were reported in 173 (1.69%) patients overall, with dryness (n=125) being the most common, followed by erythema (n=20) and pruritus (n=17). Conclusion: Naproxen 10% gel is an effective topical treatment for lower back pain, knee pain, cervical pain, synovitis, bursitis, muscle sprain, and tendinitis. It could prove helpful in patients where the side-effects of oral NSAIDs are to be avoided.

The Role of Probiotic Bacillus Spores and Amino Acids with Immunoglobulins on a Rat Enteropathy Model.

Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used drugs due to their anti-inflammatory, analgesic and antipyretic pharmacological effects. Gastrointestinal side effects are some of the most severe and frequent side effects of NSAIDs. These depend on the balance of the gut microbiome, the abundance of Gram-negative bacteria, and the amount of lipopolysaccharide released. Therefore, restoring or improving gut bacteria balance with probiotic supplements could prove to be an adjuvant therapy against mild NSAID-induced enteropathy. Twenty-five Wistar albino male rats were divided into five groups. The negative control group was administered carboxymethylcellulose and the positive control group diclofenac (DIC), 8 mg/kg for 7 days, which represented the enteropathy model. Treatment groups consisted of a combination of pro-biotic spores (MSB), amino acids and immunoglobulins supplement (MM), which were also administered for 7 days. We analyzed hepatic injury markers (AST, ALT) and creatinine, and inflammatory markers, IL-6, TNF-α, PGE2, iNOS, as well as total antioxidant capacity. The results obtained in the present study suggest that the modulation of the intestinal microbiota by administration of probiotics (Bacillus spores), alone or in combination with immunoglobulins and amino acids, represents an attractive therapy for the prevention of NSAID-induced enteropathy.

Поражение почек, ассоциированное с нестероидными противовоспалительными препаратами

The review is devoted to one of the important problems of the clinic of internal diseases - kidney damage associated with painkillers and main non-steroidal anti-inflammatory drugs (NSAIDs). Possible variants of acute and chronic kidney damage when taking NSAIDs are considered. Acute kidney injury is a serious side effect of NSAIDs associated with suppression of the vasodilatory effects of prostaglandins, decompensation of intrarenal hemodynamics, and an acute decrease in glomerular filtration rate levels. A high risk of acute kidney injury when taking NSAIDs is observed in elderly patients with concomitant diseases and polypharmacy, as well as with an initial impairment of renal function. Taking NSAIDs can cause the development of acute interstitial nephritis in combination with podocytopathy, which is manifested by high proteinuria and nephrotic syndrome in younger patients. The mechanisms and clinical manifestations of analgesic nephropathy - chronic kidney damage leading to progressive renal failure are considered separately. The cause of the development of analgesic nephropathy may be the long-term use of combined analgesic drugs, the so-called analgesic mixtures. The erased clinical picture and the mask of chronic pyelonephritis complicate the diagnosis of this disease. Specific for this pathology is renal papillary calcification on computed tomography in combination with a history of long-term analgesic abuse. Withdrawal of anesthetic drugs can slow down the progression of the disease and the development of end-stage chronic kidney disease. The possibility of the development and progression of chronic kidney disease associated with the certain classes of NSAIDs is discussed. An algorithm for treatment of chronic pain syndrome is presented, depending on the degree of risk of kidney damage.

Metabolomic Studies for Metabolic Alterations Induced by Non-Steroidal Anti-Inflammatory Drugs: Mini Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) are Food and Drug Administration (FDA) approved antipyretic, anti-inflammatory, and analgesic drugs to mitigate pain, however it is associated with gastrointestinal injury and cardiovascular disease in some individuals. Metabolomics has the potential to understand the interaction of host and the drugs, such as NSAIDs administration. This discipline has been used by many researchers to understand the serious side effects of NSAIDs. We highlighted (1) the potential of metabolomics in understanding the pathogenesis of adverse events due to NSAIDs administration; (2) choice of metabolomics techniques, bio sample handling; (3) review of metabolomics studies in the front of NSAIDs in different biofluids and tissues; (4) pathway analysis of the data presented in the published literature. In our analysis we find tricarboxylic acid cycle (TCA), “glycine serine and threonine metabolism,” “alanine, aspartate, and glutamate metabolism,” and fatty acid metabolism to be altered by the NSAIDs like ibuprofen, indomethacin, naproxen, aspirin, and celecoxib. In conclusion, metabolomics allows the use of biological samples to identify useful pathways involved in disease progression, and subsequently inform a greater understanding of the disease pathogenesis. A further in-depth investigation of the associated pathways mentioned above holds the potential for drug targets for side effects mitigation.

Design, Synthesis and Biological Evaluation of New N-Acyl Hydrazones with a Methyl Sulfonyl Moiety as Selective COX-2 Inhibitors.

The mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) is inhibition of specific prostaglandin (PG) synthesis by inhibition of cyclooxygenase (COX) enzymes. The two COX isoenzymes show 60 % similarity. It is known that the nonspecific side effects of conventional NSAIDs are physiologically caused by inhibition of the COX-1 enzyme. Therefore, the use of COX-2 selective inhibitors is seen to be a more beneficial approach in reducing these negative effects. However, some of the existing COX-2 selective inhibitors show cardiovascular side effects. Therefore, studies on the development of new selective COX-2 inhibitors remain necessary. It is important to develop new COX-2 inhibitors in the field of medicinal chemistry. Accordingly, novel N-acyl hydrazone derivatives were synthesized as new COX-2 inhibitors in this study. The hydrazone structure, also known for its COX activity, is important in terms of many biological activities and was preferred as the main structure in the design of these compounds. A methyl sulfonyl pharmacophore was added to the structure in order to increase the affinity for the polar side pocket present in the COX-2 enzyme. It is known that methyl sulfonyl groups are suitable for polar side pockets. The synthesis of the compounds (3a-3j) was characterized by spectroscopic methods. Evaluation of in vitro COX-1/COX-2 enzyme inhibition was performed by fluorometric method. According to the enzyme inhibition results, the obtained compounds displayed the predicted selectivity for COX-2 enzyme inhibition. Compound 3j showed important COX-2 inhibition with a value of IC50 =0.143 uM. Interaction modes between the COX-2 enzyme and compound 3j were investigated by docking studies.

A survey and optical microscopy in pilot comparative analysis of generic and original nimesulide granules

BackgroundSecondary to increased development of generic nonsteroidal anti-inflammatory drugs (NSAIDs), there is a lack of simple and inexpensive ways of pilot detection of differences between the batches of generic drugs and the original ones. ObjectivesTo determine the peculiarities of the use of generic NSAIDs in routine practice through a pilot survey of dentists and to conduct a pilot comparative analysis of generic and original NSAIDs containing nimesulide granules using optical microscopy. MethodsThe first part of the study included a pilot survey Convenience sampling of 192 dentists to study the use of generic NSAIDs in their routine practice. The second part included the use of a pilot optical microscopy of nimesulide particles isolated from four drugs: original drug (NA) and generic ones (NB, NC, ND). ResultsIn the questionnaires, dentists pointed to a 68.7% lower clinical efficacy and a 62.6% higher percentage of side effects of generic NSAIDs compared to the original ones. Based on the results of pilot optical microscopy, a statically significant difference in the size distribution of the drug substance particles in all generic nimesulide granules was determined as follows: NB (χ2: 15.15; p < 0.01); NC (χ2: 11.09; p < 0.05); ND (χ2: 1625.34; p < 0.001) compared with the original drug NA. ConclusionsA pilot survey of dentists showed that doctors noted the practical difference in the effects of the original and generic NSAIDs. A significant difference in the size of nimesulide particles and their distribution in generic drugs NB, NC, ND compared to the original NA suggests a possible difference in bioavailability and bioequivalence.

COMPARISON OF NONSTEROIDAL ANTI-INFLAMMATORY OF COX-1 AND COX-2 REGARDING SIDE EFFECTS IN THE ASTROINTESTINAL TRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat symptoms caused by rheumatoid arthritis due to their ability to inhibit prostaglandin synthesis by inhibiting cyclooxygenase (COX). The side effects of NSAIDs are also associated with inhibiting prostaglandin production. Consequently, their application is problematic. NSAID selective COX-2 inhibitors give minor gastrointestinal complications. Our study aims to compare nonsteroidal anti-inflammatory inhibitors of COX-1 and COX-2 regarding side effects in the gastrointestinal tract of patients with rheumatoid arthritis. Keywords: Nonsteroidal anti-infammatory drugs, rheumatoid arthtritis, COX-2, gastrointestinal tract, PPIs .

Применение нестероидных противовоспалительных препаратов при сердечно-сосудистых заболеваниях: проблемы и решения

Objective of the Review: To analyse the contemporary idea of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in cardiovascular comorbidities. Key Points. Adverse class-mediated side effects of NSAIDs complicate the use of these drugs in cardiovascular pathologies. Moderate Nimesulide selectivity is a cause of low risks of blood pressure destabilization, vascular catastrophes (acute myocardial infarction, stroke), other thrombotic complications recorded in clinical trials. Conclusion. These characteristics allow recommending Nimesulide in cardiovascular comorbidities, especially in situations where the use of other NSAIDs is limited due to side effects and contraindications. Keywords: nonsteroidal anti-inflammatory drugs, cyclooxygenase, comorbidity, cardiovascular diseases, Nimesulide, Nise.

A Descriptive Study of Pain Relief Practices Among Student-Athletes in Palestine: Focus on Non-Steroidal Anti-Inflammatory Drugs, and Complementary Medicine and Alternative Medicine Use.

Many athletes suffering from musculoskeletal pain and dysfunction will use some types of complementary and alternative medicine (CAM) or Non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, this study aimed to determine the prevalence, awareness, and behaviors related to NSAIDs and CAM use in Palestinian student-athletes. This was a cross-sectional study that involved 227 students from the Faculty of Sports at An-Najah National University. A self-administered questionnaire was designed in Arabic; it had six sections and a number of open-ended and closed-ended questions. SPSS version 21 was used to analyze the results. Descriptive statistics (i.e., frequencies, percentages) were used to describe the results including demographic characteristics. Overall, 79.3% of the student-athletes had used NSAIDs in the past and 89.0% had used CAM. The CAM methods used by participants were: herbals (57.3%), supplements (32.2%), cupping (11.9%), acupuncture (2.2%), massage (51.5%), yoga (4.0%), praying (18.1%) and ice packs (20.7%). The herbs commonly used by participants were: sage (20.7%), Menthol (21.1%), Aniseed (10.6%), Chamomile (4.0%), Cinnamon (1.3%), Turmeric (4.0%), Ginger (35.7%), and a mixture of herbs (18.5%); Regarding the perceived advantages of CAM use, 82.2% thought that CAM is beneficial for their health, 79.7% thought CAM is safe, 71.3% used it because of the successful experience of others, and 60.9% used it because it's more available than medical therapy. Among NSAIDs users, 17.2% reported recent use of over-the-counter (OTC) NSAIDs, and 33.9% of users used prescribed NSAIDs within the last three months for sport-related reasons. When asked to report any side-effect of NSAIDs they knew, only 22.6% were able to list at least one side-effect. This study shows a high prevalence of NSAIDs and CAM use among student-athletes in Palestine with a low level of knowledge and awareness of their side-effects. Therefore, education strategies that focus on enhancing and improving student-athletes' knowledge of the proper use and the possible side-effects of NSAIDs and CAM are needed.

Certain Indicators of Diclofenac Sodium Pharmacokinetics in Patients with Rheumatoid Arthritis Considering Comorbide States

Introduction: Much attention is paid to pharmacokinetic (FK) researches for studying the processes ofsupply, distribution, biotransformation and excretion of medications at the present time, as well as identifyinglinks between medical substances concentration and (or) its metabolites in biological fluids and tissues, andits pharmacological effect. In the treatment of rheumatoid arthritis (RA), non-steroidal anti-inflammatorydrugs (NSAID) are widely used for a symptom therapy, where Diclofenac Sodium (DS) is most commonlyprescribed. Duration of anti-inflammatory effect, effectiveness of NSAID in whole are directly dependent onthe level of effective concentration of medications and circulation duration in blood in free form.The Aim of the present research work is to study in a comparative aspect certain indicators of DiclofenacSodium pharmacokinetics in patients with rheumatoid arthritis with gastric microbiocenosis disorders(gastric dysbiosis) and without disorders (without dysbiosis).Materials and Method: 38 patients at the age from 18 to 60 years were examined, with I-II-III degree ofdisease activity. In addition to the general clinical examination, an immune-enzyme method and urease testwere carried out to determine Helicobacter Pylori and highly effective liquid chromatography to determineDiclofenac pharmacokinetics.Results: Conducted researches and analysis of their results indicate that in conditions of rheumatoid arthritis,particularly, in the presence of comorbid states, there is a decrease in the metabolism rate and an extension ofNSAID half-excretion period, which increases the risk of side effects, especially to the gastrointestinal tract,and significantly affects the disease course and the results of the treatment.Conclusion: In conditions of rheumatoid arthritis with comorbid states, there is more frequent occurrenceof the NSAID side effects. Research conducted and analysis of their results indicate that in conditionsof rheumatoid arthritis, particularly at comorbid states, there are reasonable changes in the NSAIDpharmacokinetics. The decreasing of metabolic rate and the extension of the NSAID half-excretion increasesthe risk of side effects, especially on the side of the GIT, which significantly affects the disease course andresults of the treatment. This circumstance dictates the need to take these results into account in the treatmentof the studied pathology and in the development of a personalized approach to the treatment of rheumatoidarthritis

Regulation of Autophagy by Non-Steroidal Anti-Inflammatory Drugs in Cancer.

Cancer is the leading cause of death, placing a substantial global health burden. The development of the most effective treatment regimen is the unmet clinical need for cancer. Inflammation plays a role in tumorigenesis and progression, and anti-inflammation may be a promising option for cancer management and prevention. Emerging studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) display anticarcinogenic and chemopreventive properties through the regulation of autophagy in certain types of cancer. In this review, we summarize the pharmacological functions and side effects of NSAIDs as chemotherapeutic agents, and focus on its mode of action on autophagy regulation, which increases our knowledge of NSAIDs and cancer-related inflammation, and contributes to a putative addition of NSAIDs in the chemoprevention and treatment of cancer.

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.

Study of Melatonin as Preventive Agent of Gastrointestinal Damage Induced by Sodium Diclofenac.

Safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) has been widely studied and both therapeutic and side effects at the gastric and cardiovascular level have been generally associated with the inhibitory effect of isoform 1 (COX-1) and 2 (COX-2) cyclooxygenase enzymes. Now there are evidences of the involvement of multiple cellular pathways in the NSAIDs-mediated-gastrointestinal (GI) damage related to enterocyte redox state. In a previous review we summarized the key role of melatonin (MLT), as an antioxidant, in the inhibition of inflammation pathways mediated by oxidative stress in several diseases, which makes us wonder if MLT could minimize GI NSAIDs side effects. So, the aim of this work is to study the effect of MLT as preventive agent of GI injury caused by NSAIDs. With this objective sodium diclofenac (SD) was administered alone and together with MLT in two experimental models, ex vivo studies in pig intestine, using Franz cells, and in vivo studies in mice where stomach and intestine were studied. The histological evaluation of pig intestine samples showed that SD induced the villi alteration, which was prevented by MLT. In vivo experiments showed that SD altered the mice stomach mucosa and induced tissue damage that was prevented by MLT. The evaluation by quantitative reverse transcription PCR (RT-qPCR) of two biochemical markers, COX-2 and iNOS, showed an increase of both molecules in less injured tissues, suggesting that MLT promotes tissue healing by improving redox state and by increasing iNOS/NO that under non-oxidative condition is responsible for the maintenance of GI-epithelium integrity, increasing blood flow and promoting angiogenesis and that in presence of MLT, COX-2 may be responsible for wound healing in enterocyte. Therefore, we found that MLT may be a preventive agent of GI damages induced by NSAIDs.