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Ankle arthritis
Published in Maneesh Bhatia, Essentials of Foot and Ankle Surgery, 2021
C Senthil Kumar, Robert Clayton, Mansur Halai
Beyond over-the-counter analgesics, COX-2 inhibitors are available but remain controversial due to their side effects. Intra-articular corticosteroid injections are recommended by NICE, with short-term benefits being demonstrated up to 3 months. Many surgeons recommend the use of ultrasound guidance, or fluoroscopy with the use of a radio-opaque dye, so as to ensure accurate placement, of the injection. Although the risks are low, when consenting a patient for a steroid joint injection, the following risks should be mentioned: infection, failure to improve pain, the likelihood of benefit being short-lived, a transient worsening of symptoms and fat atrophy causing altered pigmentation of the skin.13 Although there is no concrete evidence, most surgeons recommend no more than three injections per year, leaving a ‘steroid holiday’ of 3 months before any planned operations.
Stomach and duodenum
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
This is caused by agents that disturb the gastric mucosal barrier; NSAIDs and alcohol are common causes. The NSAID-induced gastric lesion is associated with inhibition of the cyclo-oxygenase type 1 (COX-1) receptor enzyme, hence reducing the production of cytoprotective prostaglandins in the stomach. Many of the beneficial anti-inflammatory activities of NSAIDs are mediated by COX-2, and the use of specific COX-2 inhibitors reduces the incidence of these side effects. However, taken in the long term COX-2 inhibitors are associated with cardiovascular complications in common with many NSAIDs.
Ethical Considerations in the Management of Chronic Pain in Older Adults
Published in Michael E. Schatman, Ethical Issues in Chronic Pain Management, 2016
Two elements of this drama hold particular relevance to issues of beneficence in older adults. First, this age group is most vulnerable to the cardiac events that led to the class of drugs being withdrawn (violating the principle of nonmaleficence). Second, despite the increased risk of cardiovascular events for patients taking COX-2 inhibitors, many patients complained when they had to discontinue the medications. These patients were willing to trade the cardiac risks for the pain relief and increased quality of life provided to them by these medications. While their argument became academic when the FDA pulled the COX-2 inhibitors from the market, their dilemma exemplifies the risk/reward issues that can characterize treatment in this age group.
Novel N-methylsulfonyl-indole derivatives: biological activity and COX-2/5-LOX inhibitory effect with improved gastro protective profile and reduced cardio vascular risks
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
John N. Philoppes, Mohamed A. Abdelgawad, Mohammed A. S. Abourehab, Mohamed Sebak, Mostafa A. Darwish, Phoebe F. Lamie
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common method of treatment of inflammatory symptoms. They act through inhibition of biotransformation of arachidonic acid (AA), a membrane bound phospholipid, to prostaglandins (PGs), prostacyclines (PGI2) and thromboxane A2 (TXA2) by the action of cyclooxygenase (COX) enzymes (COX-1, 2, 3)5–7. COX-pathway inhibition leads to unwanted side effects such as ulcerogenicity, hepatic and renal toxicity, which have arisen due to COX-1 inhibitors and cardiovascular disorders caused by COX-2 inhibitors. Both NSAIDs that could inhibit both COX-1 and COX-2 enzymes, such as aspirin, phenazone and indomethacin, (Figure 1), as well as selective COX-2 inhibitors, especially like, roficoxib and valdecoxib, (Figure 1) can increase the cardiovascular risks specially in patients with pre-existing cardiovascular disease. This can be caused by the imbalance in PGI2 (potent vasodilator and antithrombotic)/TXA2 (prothrombotic) ratio. Consequently, most drugs have been used in a restricted manner or even withdrawn from the market8–10. This leads to a search for new compounds that act in another way to metabolise AA. Liopoxygenase (LOX) enzymes (5-, 8-, 12- and 15-LOX) convert AA to leucotrienes. 5-LOX is the one associated with inflammation, bronchoconstriction, allergy and asthma11–13.
Discovery of polymethoxyflavones as potential cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and phosphodiesterase 4B (PDE4B) inhibitors
Published in Journal of Receptors and Signal Transduction, 2022
Muhd Hanis Md Idris, Siti Norhidayah Mohd Amin, Siti Norhidayu Mohd Amin, Agustono Wibowo, Zainul Amiruddin Zakaria, Zurina Shaameri, Ahmad Sazali Hamzah, Manikandan Selvaraj, Lay Kek Teh, Mohd Zaki Salleh
Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors are the most widely used drug for reducing inflammation and pain. The drugs inhibit COX and stop arachidonic acid from transforming into prostaglandins, thromboxane, and prostacyclin. The traditional nonselective non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen are capable of inhibiting both COX-1 and COX-2 isoforms [5]. Nevertheless, adverse gastrointestinal events such as gastric mucosal damage and gastroduodenal ulcers have been reported due to the use of the non-steroidal anti-inflammatory drugs. More selective COX-2 inhibitors were developed to minimize the side effects but chronic use of some of these inhibitors still cause cardiovascular adverse effects and increase thrombotic risk due to blockage of prostaglandin I2 [6]. In addition, PDE4 inhibitors that are used for treating inflammation have been discontinued due to side effects such as emesis, mild to moderate nausea, headache, and diarrhea [7]. The only 5-LOX inhibiting drug, known as zileuton, was also withdrawn from the market due to its hepatotoxicity adverse effect [8].
Anti-tumor effect of M2000 (β-d -mannuronic acid) on the expression of inflammatory molecules in the prostate cancer cell
Published in Immunopharmacology and Immunotoxicology, 2021
Monireh Mohsenzadegan, Fatemeh Moghbeli, Abbas Mirshafiey, Mohammad M. Farajollahi
Cyclooxygenase-2 (COX-2) is a key enzyme that converts arachidonic acid to prostaglandins and other eicosanoids under inflammatory condition. COX-2 inhibitors are NSAIDs that could selectively inhibit the COX-2 enzyme. In addition, COX-2 is highly expressed in PCa. Treatment of human PCa cell lines with a selective COX-2 inhibitor could induce apoptosis both under in vitro and in vivo conditions [18]. Notably, other inflammatory factors involved in the progression of PCa are the matrix metalloproteinases (MMPs). Accordingly, MMPs, as a group of zinc-dependent endopeptidases, are involved in the degradation of the extracellular matrix. They play an important role in various pathological processes such as angiogenesis, tumor invasion, and metastasis by dissolving extracellular matrix. In addition, serum levels of MMP-2 and MMP-9 significantly increase in patients with PCa. Among patients with PCa, those with metastasis have significantly higher levels of MMP-2 and -9 compared to those patients with localized disease [19].