Short-course high-dose ibuprofen causing both early and delayed jejunal perforations in a non-smoking man

Yehiyan, Aseef; Barman, Sowrav; Varia, Haren; Pettit, Stephen

doi:10.1136/bcr-2017-223644

Cited by 8 publications

(6 citation statements)

References 4 publications

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“…Despite the growing repository of newly synthesized NSAIDs, the development of new compounds is strictly required due to the side effects of the currently approved NSAIDs. For instance, even in short-term applications, a high dose of ibuprofen resulted in jejunal perforations [ 23 ]; naproxen affects bowel and jejunal integrity [ 24 ]. Within days of intake, diclofenac has been proven to raise the risk of heart attacks and strokes by 50% [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

2022

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The goal of achieving anti-inflammatory efficacy with the fewest possible adverse effects through selective COX-2 inhibition is still being investigated in order to develop drugs with safe profiles. This work shows the efficacy and safety profile of two novel benzimidazole piperidine and phenoxy pyridine derivatives in reaching this goal, which would be considered a major achievement in inflammatory therapy. The compounds were evaluated by virtual screening campaign, in vitro cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibition, in vivo carrageenan-induced rat paw edema assay, cytotoxicity against Raw264.7 cells, and histopathological examination of rat paw and stomach. Two new compounds, compound 1 ([(2-{[3-(4-methyl-1H-benzimidazol-2-yl)piperidin-1-yl]carbonyl}phenyl)amino]acetic acid) and compound 2 (ethyl 1-(5-cyano-2-hydroxyphenyl)-4-oxo-5-phenoxy-1,4-dihydropyridine-3-carboxylate) showed high selectivity against COX-2, favourable drug-likeness and ADME descriptors, a lack of cytotoxicity, relived paw edema, and inflammation without noticeable side effects on the stomach. These two compounds are promising new NSAIDs.

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Section: Discussionmentioning

confidence: 99%

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

2022

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“… 17 High-dose of ibuprofen caused jejunal perforations even in short-courses. 18 Another anti-inflammatory drug, naproxen, causes gastric antral ulcerations, and an increase of lipid peroxide levels, but the effect was reversed with curcumin. 19 Similarly perforated jejunal ulcers 20 and small bowel ulcerations 21 have been reported with the usage of NSAIDs.…”

Section: Current Targets and Their Limitationsmentioning

confidence: 99%

Overview on the Discovery and Development of Anti-Inflammatory Drugs: Should the Focus Be on Synthesis or Degradation of PGE2?

Mahesh¹,

Kumar²,

Reddanna³

2021

JIR

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Inflammation is a protective response that develops against tissue injury and infection. Chronic inflammation, on the other hand, is the key player in the pathogenesis of many inflammatory disorders including cancer. The cytokine storm, an inflammatory response flaring out of control, is mostly responsible for the mortality in COVID-19 patients. Anti-inflammatory drugs inhibit cyclooxygenases (COX), which are involved in the biosynthesis of prostaglandins that promote inflammation. The conventional non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastric and renal side-effects, as they inhibit both the constitutive COX-1 and the inducible COX-2. The majority of selective COX-2 inhibitors (COXIBs) are without gastric side-effects but are associated with cardiac side-effects on long-term use. The search for anti-inflammatory drugs without side-effects, therefore, has become a dream and ongoing effort of the Pharma companies. As PGE 2 is the key mediator of inflammatory disorders, coming up with a strategy to reduce the levels of PGE 2 alone without affecting other metabolites may form a better choice for the development of next generation anti-inflammatory drugs. In this direction the options being explored are on synthesis of PGE 2 -mPGES-1; PGE 2 degradation through a specific PG dehydrogenase, 15-PGDH, and by blocking its activity mediated through a specific PGE receptor, EP4. As leukotrienes formed via the 5-lipoxygenase (5-LOX) pathway also play an important role in the mediation of inflammation, efforts are also being made to target both COX and LOX pathways. This review focuses on addressing the following three points: 1) How NSAIDs and COXIBs are associated with gastric, renal and cardiac side-effects; 2) Should the focus be on the targets upstream or downstream of PGE 2 ; and 3) the status of alternative targets being explored for the discovery and development of anti-inflammatory drugs without side-effects.

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“…The symptoms include dysphagia, recurrent vomiting, weight loss, or blood in stools. Gastric mucosal damage leading to ulceration occurs due to stress, (Parmar et al, 1993) use of acetylsalicylic acid (ASA), NSAIDs (Yehiyan et al, 2017. Accordingly, diet therapy has played a key role in the prevention and treatment of Peptic ulcer with the main purpose of recovering and protecting the gastrointestinal lining, improving digestion, relieving pain, and contributing to a satisfactory nutritional status (Moayyedi et al, 2005) and (Reis, 2003).…”

Section: Nugrohoet Al (mentioning

confidence: 99%

A study to compare the effect of milk, licorice and tiger nut on stomach ulcer induced in rats

Ayat

Akram

2021

Egyptian Journal of Nutrition and Health

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Peptic ulcer is a disease affecting a large number of people, caused by various reasons including, NSAIDs and stress. Acute injury occurs more readily with aspirin. The extracts of milk,tigernut and licorice were evaluated for their activities against aspirin gastric ulcer induced in albino rats. Thirty male albino rats, with an average weight of 155-160g were used divided into five groups.6 rats each.All rats were fed basal diet and given free distilled water.Group (1) was left for the whole period of the study (29 days) as negative (-ve) control. Group (2) received 1 ml aspirin (acetyl salicylic acid) to induce gastric ulcer and left as positive control. The other 3 group received the same dose of aspirin; besides group 3 received milk, Group 4 received tiger nut, Group 5 received licorice as doses of 1 ml / rat each morning before breakfast, These 3 groups showed reduction of total area of the ulcer and accelerated healing. The result has shown an increase in final body weight gain of the rats, reduction of total area of the lesion and accelerated ulcer healing of rats treated with tiger nut,licorice and milk Also, reduced total cholesterol, LDL, triglycerides. while HDL was increased than the control

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Short-course high-dose ibuprofen causing both early and delayed jejunal perforations in a non-smoking man

Cited by 8 publications

References 4 publications

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

Drug Discovery of New Anti-Inflammatory Compounds by Targeting Cyclooxygenases

Overview on the Discovery and Development of Anti-Inflammatory Drugs: Should the Focus Be on Synthesis or Degradation of PGE2?

A study to compare the effect of milk, licorice and tiger nut on stomach ulcer induced in rats

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