Influence of CYP2C9 and COX-2 Genetic Polymorphisms on Clinical Efficacy of Non-Steroidal Anti-Inflammatory Drugs in Treatment of Ankylosing Spondylitis

Objective: This study was conducted to investigate the correlation between serum levels of proinflammatory cytokines and the clinical efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with ankylosing spondylitis (AS). Methods: A total of 148 patients with AS were selected and received NSAID treatment. ELISA was used to assess cytokine levels, and patients were assigned into the following groups: positively effective; effective; moderately effective; and ineffective. Spearman and Pearson correlation analyses were used for correlation analysis. Results: The erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) levels, and immunoglobulin A (IgA) levels of the case group after NSAID treatment were markedly lower than those before NSAID treatment. After treatment, the levels of interleukin (IL)-6, IL-17, and tumor necrosis factor (TNF)-α were markedly reduced, while IL-10 levels increased in the positively effective, effective, and moderately effective groups, and IL-12 levels decreased in the positively effective and effective groups. In addition, the levels of IL-6 and TNF-α were correlated with a greater number in the efficacy indexes and clinical parameters, followed by IL-10 levels, while the levels of IL-17 and IL-12 had relatively weaker correlations with these indexes and parameters. Conclusion: NSAIDs could promote the clinical efficacy of treatment for ankylosing spondylitis by regulating serum levels of proinflammatory cytokines.

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The effectiveness of switching from an originator biological agent to its biosimilar, or vice versa, for ankylosing spondylitis in real clinical practice

Modern Rheumatology Journal ◽

10.14412/1996-7012-2020-4-157-160 ◽

2020 ◽

Vol 14 (4) ◽

pp. 157-160

Author(s):

K. V. Sakharova ◽

M. V. Podryadnova ◽

Sh. F. Erdes

Keyword(s):

Clinical Practice ◽

Ankylosing Spondylitis ◽

Clinical Efficacy ◽

Standard Therapy ◽

Biological Agent ◽

Biological Drugs ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Trade Names ◽

Real Clinical Practice

If standard therapy with nonsteroidal anti-inflammatory drugs is ineffective, biological drugs are usually prescribed for patients with active ankylosing spondylitis. These medicines are purchased in Russia not under their trade names, but under their international non-proprietary ones. This leads to the fact that either originator drugs or their biosimilars are purchased from time to time. For this reason, without a patient' and his/her attending physician's knowledge, the originator drug is switched to its biosimilar, or vice versa. The paper describes two cases of multiple switches from an originator drug to its biosimilars, or vice versa, which are not clinically indicated. The results of analyzing these cases confirm the opinion that biosimilars may have a significantly different clinical efficacy from their originator drugs.

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Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

Scientia Pharmaceutica ◽

10.3390/scipharm89020022 ◽

2021 ◽

Vol 89 (2) ◽

pp. 22

Author(s):

Mariia Mishchenko ◽

Sergiy Shtrygol’ ◽

Andrii Lozynskyi ◽

Semen Khomyak ◽

Volodymyr Novikov ◽

...

Keyword(s):

Drug Design ◽

Anticonvulsant Activity ◽

Inflammatory Activity ◽

Significant Protection ◽

Protection Level ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Target Agent

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters.

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The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

Current Medicinal Chemistry ◽

10.2174/0929867328666210910125229 ◽

2021 ◽

Vol 28 ◽

Author(s):

Josiane Viana Cruz ◽

Joaquín María Campos Rosa ◽

Njogu Mark Kimani ◽

Silvana Giuliatti ◽

Cleydson Breno Rodrigues dos Santos

Keyword(s):

Side Effects ◽

Inflammatory Diseases ◽

Structural Basis ◽

Potential Inhibitor ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

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Reducing pain in certain forms of obstetric pathology: nonsteroidal anti-inflammatory drugs (Сlinical lecture)

HEALTH OF WOMAN ◽

10.15574/hw.2017.122.9 ◽

2017 ◽

pp. 9-14

Author(s):

L. Nazarenko ◽

Keyword(s):

Preterm Birth ◽

Side Effects ◽

Key Words ◽

Clinical Efficacy ◽

Premature Birth ◽

Pain Syndrome ◽

Inflammatory Drug ◽

Threatened Abortion ◽

Inflammatory Drugs ◽

Anti Inflammatory

The article discusses the pathogenetic basis for the use of non-steroidal anti-inflammatory drugs (NSPVP) in obstetric practice for the treatment of pain syndrome in women with threatened abortion and pathological preliminary period. Provided with modern views on the mechanisms of analgesic clinical efficacy, side effects NSPVP. Provides information about the place of NSPVP during pregnancy, the risks to the fetus, the positive aspects in the conduct of women at risk of preterm birth, the pathological preliminary period. Key words: nonsteroidal anti-inflammatory drug, pain, premature birth, preliminary period.

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Nonsteroidal Anti-inflammatory Drugs and the COX-2 Inhibitors

Pain Review ◽

10.1016/b978-1-4160-5893-9.00343-9 ◽

2009 ◽

pp. 630-634

Author(s):

Steven D. Waldman

Keyword(s):

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

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COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

International Journal of Molecular Sciences ◽

10.3390/ijms21238917 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8917

Author(s):

Francesco Vieceli Dalla Sega ◽

Francesca Fortini ◽

Paolo Cimaglia ◽

Luisa Marracino ◽

Elisabetta Tonet ◽

...

Keyword(s):

Aortic Valve ◽

Clinical Analysis ◽

Dystrophic Calcification ◽

Calcific Aortic Valve Disease ◽

Aortic Valves ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Induced Apoptosis ◽

Human Aortic Valve

Calcific aortic valve disease (CAVD) is the result of maladaptive fibrocalcific processes leading to a progressive thickening and stiffening of aortic valve (AV) leaflets. CAVD is the most common cause of aortic stenosis (AS). At present, there is no effective pharmacotherapy in reducing CAVD progression; when CAVD becomes symptomatic it can only be treated with valve replacement. Inflammation has a key role in AV pathological remodeling; hence, anti-inflammatory therapy has been proposed as a strategy to prevent CAVD. Cyclooxygenase 2 (COX-2) is a key mediator of the inflammation and it is the target of widely used anti-inflammatory drugs. COX-2-inhibitor celecoxib was initially shown to reduce AV calcification in a murine model. However, in contrast to these findings, a recent retrospective clinical analysis found an association between AS and celecoxib use. In the present study, we investigated whether variations in COX-2 expression levels in human AVs may be linked to CAVD. We extracted total RNA from surgically explanted AVs from patients without CAVD or with CAVD. We found that COX-2 mRNA was higher in non-calcific AVs compared to calcific AVs (0.013 ± 0.002 vs. 0.006 ± 0.0004; p < 0.0001). Moreover, we isolated human aortic valve interstitial cells (AVICs) from AVs and found that COX-2 expression is decreased in AVICs from calcific valves compared to AVICs from non-calcific AVs. Furthermore, we observed that COX-2 inhibition with celecoxib induces AVICs trans-differentiation towards a myofibroblast phenotype, and increases the levels of TGF-β-induced apoptosis, both processes able to promote the formation of calcific nodules. We conclude that reduced COX-2 expression is a characteristic of human AVICs prone to calcification and that COX-2 inhibition may promote aortic valve calcification. Our findings support the notion that celecoxib may facilitate CAVD progression.

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Peran Kurkumin Sebagai Terapi Pada Osteoartritis

Journal of Health Science and Physiotherapy ◽

10.35893/jhsp.v2i1.36 ◽

2020 ◽

Vol 2 (1) ◽

pp. 106-110

Author(s):

Rilianda Abelira

Keyword(s):

Peptic Ulcer ◽

Side Effects ◽

Old Age ◽

Cyclooxygenase 2 ◽

Tnf Α ◽

The World ◽

Inflammatory Drugs ◽

Digestive Disorders ◽

Cox 2 ◽

Anti Inflammatory

Osteoartritis (OA) merupakan salah satu penyakit penyakit degeneratif atau geriatri yang disebabkan adanya inflamasi yang melibatkan kartilago, lapisan sendi, ligamen, dan tulang yang akibatnya dapat menyebabkan nyeri dan kekakuan pada sendi. Epidemiologi OA di didunia sekitar 15% dengan usia diatas 65-75 dan diperkirakan pada tahun 2020 penderita osteoarthritis akan meningkat 11,6 juta penderita. Kejadian OA di Indonesia dari tahun 1990 hingga 2010 telah mengalami peningkatan sebanyak 44,2% dan berdasarkan usia di Indonesia cukup tinggi dengan 65% pada usia tua (lansia) atau lebih dari 61 tahun. Pengobatan secara farmakologis untuk OA dengan menggunakan Obat Anti Inflamasi Non-Steroid (OAINS) salah satu contohnya adalah meloksikam. Namun, efek samping penggunaan OAINS dapat menimbulkan beberapa masalah seperti timbulnya ulkus peptikum dan gangguan pencernaan. Hal ini menyebabkan sedang dikembangkannya pengobatan herbal untuk OA yang harapannya dapat menjadi pengobatan utama dalam mengatasi OA dengan menggunakan kurkumin. Kurkumin berperan sebagai antiinflamasi dalam kunyit putih dengan menurunkan aktivitas cyclooxygenase 2(COX-2), lipoxygenase dan menghambat produksi sitokin seperti TNF-α, interleukin (IL). Osteoarthritis (OA) is a degenerative or geriatric disease that is caused by inflammation involving cartilages, joint lining, ligaments, and bones which can cause pain and stiffness in the joints. Epidemiology of OA in the world around 15% with ages above 65-75 and it is estimated in 2020, osteoarthritis will increase by 11.6 million. The incidence of OA in Indonesia from 1990 to 2010 has increased by 44.2% and by age in Indonesia is quite high with 65% in old age (elderly) or more than 61 years. Treatment for OA is using non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam. However, side effects of NSAID use can cause several problems such as the emergence of peptic ulcer and digestive disorders. This has led to the development of herbal treatments for OA which hopes to become the main treatment in overcoming OA by using curcumin. Curcumin acts as an anti-inflammatory in white turmeric by reducing the activity of cyclooxygenase 2 (COX-2), lipoxygenase and inhibiting the production of cytokines such as TNF-α, interleukin (IL).

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