CoX-2 or prostaglandin GH synthetase-2 is an enzyme which has induction, especially in the inflamatory reactions. The inflamatory stimulations activate the CoX-2 of monocytes, macrophages, cells of synovial membrane to synthesize prostaglandin which induce the inflamatory reactions. The non- steroid anti- inflamatory drugs inhibit the CoX-2 so they have anti- inflamatory effects. However, they also inhibit CoX-1 which induce some side effects such as gastrointestinal and kidney accidents, haemorrhage and hypersensitivities. The selective CoX-2 inhibitors have some properties: long half elimination life, easier uptake by oral; the same pharmacokinetics in both elderly and children and uncommon side effects (0.1 -1% treated cases).
Anti-Inflammatory Agents, Non-Steroidal ; Pharmaceutical Preparations ; Cyclooxygenase 2 Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in the world. NSAID-induced lower gastrointestinal (GI) complications are increasing while upper GI complications are decreasing. Lower GI events accounted for 40% of all serious GI events in patients on NSAIDs. Capsule endoscopy and device assisted enteroscopy are available for detection of small intestinal lesions. Capsule endoscopy studies have demonstrated that NSAIDs use in healthy volunteers raised the incidence (55% to 75%) of intestinal damage. It appears that selective cyclooxygenase-2 inhibitors (coxibs) improved upper and lower GI safety based on results of clinical trials. Selective coxibs are still capable of triggering GI adverse events and cardiovascular toxicity issues were the main focus of concerns. Unfortunately, definite strategies are not available to prevent or heal NSAID-induced intestinal injuries. Thus, there is still a strong clinical need for effective drugs with improved safety profiles than the existing NSAIDs.
Anti-Inflammatory Agents, Non-Steroidal ; Capsule Endoscopy ; Cyclooxygenase 2 Inhibitors ; Humans ; Incidence ; Lower Gastrointestinal Tract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation. There are two kinds of NSAID classified according to the selectivity of COX-2 inhibition: non-selective NSAIDs and cyclooxygenase (COX)-2 inhibitors. Non-selective NSAIDs have a high incidence of gastrointestinal and bleeding-associated adverse events, while COX-2 inhibitors are safer in terms of these events. However, COX-2 inhibitors are thought to cause increased cardiovascular events. The COX-2 inhibitors rofecoxib and valdecoxib were withdrawn from the market over safety concerns. Three COX-2 inhibitors are now available in South Korea after the recent approval of etoricoxib and polmacoxib for osteoarthritis patients. After reviewing the history of and recent studies about the safety of COX-2 inhibitors, physicians should find new uses for old drugs.
Anti-Inflammatory Agents, Non-Steroidal ; Cyclooxygenase 2 Inhibitors* ; Cyclooxygenase Inhibitors ; Humans ; Incidence ; Inflammation ; Korea ; Osteoarthritis ; Prostaglandin-Endoperoxide Synthases

STUDY DESIGN: A cross-section observational study. OBJECTIVES: To evaluate the current prescription patterns of non-steroidal anti-inflammatory drugs (NSAIDs) and gastrointestinal (GI) risk assessment in patients with lumbar spine disease. SUMMARY OF LITERATURE REVIEW: NSAIDs are commonly prescribed medications for lumbar spine disease patients. Since the rate of GI complication varies for each patient, identification of individual GI risks is a prerequisite to prevent such a complication. There are few reports about the GI risks in patients with lumbar spine disease who take NSAIDs. MATERIALS AND METHODS: 2264 patients with lumbar degenerative spondylopathy who were taking NSAIDs were enrolled from May 2010 to September 2010. The Standardized Calculator of Risk for Event (SCORE) was used to measure patients' GI risk factors. NSAID prescription patterns and GI protective agents were also investigated. RESULTS: Being aged over 65 (1098 patients; 48.5%) and the presence of GI side-effects from NSAIDs (896 patients; 39.6%) were the most common risk factors. 31.9% and 5.8% percent of patients belonged to each of the high risk and the very high risk groups in GI risk factor analysis. The total prescription rate of gastroprotectants was 91.7% for all patients. However, the prescription rate of selective COX-2 inhibitors in the high risk group was low, and in 54.8% of patients who took COX-2 inhibitors there was GI discomfort. CONCLUSIONS: The prescription pattern of GI protective agents was not correlated with GI symptoms. Therefore, physicians should consider NSAID prescription based on the GI risk factors of individual patients.
Aged ; Anti-Inflammatory Agents, Non-Steroidal ; Cyclooxygenase 2 Inhibitors ; Humans ; Prescriptions ; Protective Agents ; Risk Assessment ; Risk Factors ; Spinal Diseases ; Spine

Serious concerns about the cardiovascular safety of rofecoxib had been present since the VIOXX(R) Gastrointestinal Outcomes Research (VIGOR) study first suggested that the drug may increase the risk of myocardial infarction. Subsequent data from major observational studies further implicated the association of rofecoxib with arterial thromboembolic disease. In September 2004, rofecoxib was withdrawn from the worldwide market based on the safety findings of the Adenomatous Polyp Prevention on VIOXX (APPROVe) study, which indicated an increase risk of myocardial infarction and stroke among subjects randomized to rofecoxib. In December 2004, the results of the Adenoma Prevention with Celecoxib (APC) study demonstrated a dose-related increase in the risk of cardiovascular events among patients randomized to celecoxib when compared with placebo. Two other large prospective prevention studies of celecoxib, the Prevention of Spontaneous Adenomatous Polyps (Pre SAP) trial and the Alzheimer's Disease Antiinflammatory Prevention Trial (ADAPT) did not show any sign of increased cardiovascular risk. None of the reported randomized trials studying any COX-2 selective imhibitor, thus far, has been specifically designed to examine cardiovascular outcomes. Hence, no cardiovascular hypotheses have yet been formally tested. Long-term and adequately powered prospective randomized clinical trials in relevant patient populations with clinically appropriate pre-specified cardiovascular end-points, ideally comparing COX-2 selective inhibitors with traditional NSAIDs, are required. Until these trials are completed, careful risk:benefit analysis of any putative increase in cardiovascular risk versus known gastrointestinal benefit for individual agents needs to be undertaken.
Adenoma ; Adenomatous Polyps ; Alzheimer Disease ; Anti-Inflammatory Agents, Non-Steroidal ; Cyclooxygenase 2 Inhibitors* ; Cyclooxygenase 2* ; Humans ; Myocardial Infarction ; Outcome Assessment (Health Care) ; Stroke ; Celecoxib

BACKGROUND: It is known that non-steroidal antiinflammatory drugs (NSAIDs) reduce the amount of proteinuria in nephrotic syndrome. It is based on the facts that the NSAIDs block the production of prostaglandins. Therefore selective cyclooxygenase-2 (COX-2) inhibitor may be expected to play a role in reduction of the proteinuria in nephrotic syndrome. METHODS: Twenty-seven Sprague-Dawley rats were divided into 3 groups. After 3 to 5 days of adaptation, we gave puromycin aminonucleoside to groups A and B via intraperitoneal route. The third group C was a normal control group. Selective COX-2 inhibitor was orally given to group A for 2 weeks. Each group was divided again into 3 subgroups by the day of experiment: 1, 14 and 21-day subgroups. We checked the changes in the serum and urine creatinine, albumin concentrations, creatinine clearances, the amount of proteinuria and the pathologic findings. The differences between groups were tested by 2-way ANOVA and Dunnett T-test, and the changes of proteinuria were tested by Repeated measures ANOVA. RESULTS: The changes of 24-hour urine protein excretion were significantly different between three groups (p<0.01). Protein excretion of group A was significantly decreased, especially between 14 and 21 days (p<0.05). The changes of creatinine clearance were significantly different between three groups (p<0.05), between 1 and 21 days (p<0.05). Electron microscopy showed morphological recovery of foot processes after administration of selective COX-2 inhibitor in PAN nephropathy rats (group A). CONCLUSION: It is suggested that selective COX- 2 inhibitors may be effective in reducing proteinuria and protecting the renal function in nephrotic syndrome.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Creatinine ; Cyclooxygenase 2* ; Cyclooxygenase Inhibitors ; Foot ; Microscopy, Electron ; Nephrotic Syndrome ; Prostaglandins ; Proteinuria ; Puromycin Aminonucleoside* ; Puromycin* ; Rats* ; Rats, Sprague-Dawley

PURPOSE: The purpose of this study was to determine the impact of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), statin, and cyclooxygenase 2 (COX-2) inhibitor on the development of kidney, prostate, and urothelial cancers by analyzing the Korean National Health Insurance Service–National Sample Cohort (NHIS-NSC) database. MATERIALS AND METHODS: Among a representative sample cohort of 1,025,340 participants in NHIS-NSC database in 2002, we extracted data of 799,850 individuals who visited the hospital more than once, and finally included 321,122 individuals aged 40 and older. Following a 1-year washout period between 2002 and 2003, we analyzed 143,870 (male), 320,861 and 320,613 individuals for evaluating the risk of prostate cancer, kidney cancer and urothelial cancer developments, respectively, during 10-year follow-up periods between 2004 and 2013. The medication group consisted of patients prescribed these drugs more than 60% of the time in 2003. To adjustfor various parameters of the patients, a multivariate Cox regression model was adopted. RESULTS: During 10-year follow-up periods between 2004 and 2013, 9,627 (6.7%), 1,107 (0.4%), and 2,121 (0.7%) patients were diagnosed with prostate cancer, kidney cancer, and urothelial cancer, respectively. Notably, multivariate analyses revealed that NSAIDs significantly increased the risk of prostate cancer (hazard ratio [HR], 1.35). Also, it was found that aspirin (HR, 1.28) and statin (HR, 1.55) elevated the risk of kidney cancer. No drugs were associated with the risk of urothelial cancer. CONCLUSION: In sum, our study provides the valuable information for the impact of aspirin, NSAID, statin, and COX-2 inhibitor on the risk of prostate, kidney, and urothelial cancer development and its survival outcomes.
Anti-Inflammatory Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Aspirin* ; Cohort Studies ; Cyclooxygenase 2 ; Follow-Up Studies* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Kidney ; Kidney Neoplasms ; Korea* ; Multivariate Analysis ; National Health Programs ; Prostate ; Prostatic Neoplasms

PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the conversion of arachidonic acid to prostaglandins, is believed to be an important enzyme related to colorectal cancer. A large number of studies have supported the concept that non-steroidal anti-inflammatory drugs (NSAIDs) targeting COX alter the biologic processes of colon carcinogenesis. Although COX-2 inhibitors generally reduce the growth rate of established tumors, tumor regression is rarely observed. Hence, it is reasonable that COX-2 inhibitors be given in conjunction with standard anti-cancer therapy in treating cancer. We investigated whether aspirin and meloxicam not only are cytotoxic but also potentiate the antitumor effect of 5-Fluorouracil (5-FU) against colon cancer cells. METHODS: Expressions of COX-1 and COX-2 were determined by using the reverse transcriptase-polymerase chain reaction (RT-PCR) & Western blotting assay in 9 colon cancer cell lines. The cytotoxicities of NSAIDs and/or 5-FU were determined by using a microculture tetrazolium dye (MTT) assay. RESULTS: COX-1 mRNA and protein, as well as COX-2 mRNA, were variably expressed in all the cell lines tested whereas COX-2 protein was expressed in HT-29 and to a lesser extent in HCT-8, but not in the other cell lines. We selected two representative cell lines, HT-29 expressing COX-2 protein and SNU-C1 not expressing it. The dose-dependent cytotoxicity was observed in both cell lines treated with aspirin and with meloxicam. A combination treatment of aspirin or meloxicam with 5-FU revealed some additive effect, rather than a synergistic effect, for both cells lines. This additive effect was remarkable even for low concentrations of the drugs. Furthermore, the additive effect was highest when the combination was adminstered sequentially, 5-FU followed by aspirin or meloxicam, in both cell lines. CONCLUSIONS: These results suggest that a combination therapy using NSAIDs and 5-FU might be useful in the treatment of colon cancer cells not expressing COX-2, as well as in colon cancer cells expressing COX-2.
Anti-Inflammatory Agents, Non-Steroidal* ; Arachidonic Acid ; Aspirin ; Blotting, Western ; Carcinogenesis ; Cell Line ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; Cyclooxygenase 2 Inhibitors ; Fluorouracil* ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins ; RNA, Messenger

OBJECTIVETo evaluate the clinical efficiency of selective cyclo-oxygenase-2 (COX-2) inhibitor compared to traditional nonselective NSAIDs for the prevention of heterotopic ossification (HO) after total hip arthroplasty (THA).

METHODSBy searching Medline, Embase, CENTRAL (Cochrane Central Register of Controlled Trials) and Science Citation Index et al, only randomised controlled studies of selective COX-2 inhibitors VS nonselective COX-1 and COX-2 inhibitors for the prevention of HO after THA were included. The quality assessment of included studies was evaluated according to the standard of the Cochrane Collaboration, and the data were analysised by statistic software Stata 10.0. The HO incidence of both groups in different degrees was compared.

RESULTSFour eligible randomised controlled trials of totally 808 patients were included. Meta-analysis results showed that no statistically significant difference was found in overall incidence of HO (RR = 1.08, 95% CI: 0.71-1.64,P = 0.73), incidence of moderate severe HO (Brooker II and III) (RR = 0.83, 95% CI: 0.48-1.42, P = 0.49) and any grade of Brooker classification between two groups. In all included studies, 16 patients receiving nonselective COX inhibitor (4.4%) discontinued treatment because of gastrointestinal toxicity,whereas 10 patients in the selective COX-2 inhibitor group (2.7%) discontinued for gastrointestinal side effects.

CONCLUSIONThe selective COX-2 inhibitors are as equally effective as nonselective NSAIDs for the prevention of HO after THA. Considering the side effects of nonselective NSAIDs, selective COX-2 inhibitors were recommend for the prevention of HO after THA.

Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; therapeutic use ; Arthroplasty, Replacement, Hip ; adverse effects ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Cyclooxygenase Inhibitors ; adverse effects ; therapeutic use ; Humans ; Ossification, Heterotopic ; prevention & control ; Randomized Controlled Trials as Topic

Colon cancer is one of the major leading causes of cancer-related deaths in the Western countries. In Korea, the incidence of colon cancer is increasing due to changes in environment and lifestyle such as diet. Chemoprevention strategy using non-steroidal anti-inflammatory drugs (NSAIDs) has been under intensive clinical and epidemiological research as these drugs suppress colorectal cancer. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. Among these PGs, prostaglandin E2 (PGE2) can promote tumor growth by binding its receptors and activating signal pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Therefore, COX inhibition is promising approach for chemoprevention of colorectal cancer. However, the prolonged use of COX-2 inhibitors is associated with unacceptable cardiovascular side effects. Thus, new targets involved in PGs metabolism are under investigation. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key metabolic enzyme of PGE2, was up-regulated in normal colonic epithelium, but decreased in colon cancer. Recent findings suggest that 15-PGDH is involved in the neoplastic progression of initiated colonic epithelial cells. Also, new players related with PGs metabolism including prostaglandin transporter (PGT) and microsomal prostaglandin E synthase (mPGES) were reported to play a role in colorectal cancer development. This review presents current knowledge about the role of prostaglandins and associated proteins in colorectal cancer development and progression.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Colonic Neoplasms/drug therapy/*etiology/prevention & control ; Cyclooxygenase 2/metabolism ; Cyclooxygenase Inhibitors/pharmacology/therapeutic use ; Humans ; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/metabolism ; Prostaglandins/metabolism/*physiology