Effect of Structural Modification of Enol−Carboxamide-Type Nonsteroidal Antiinflammatory Drugs on COX-2/COX-1 Selectivity

1997 ◽  
Vol 40 (6) ◽  
pp. 980-989 ◽  
Author(s):  
Edward S. Lazer ◽  
Clara K. Miao ◽  
Charles L. Cywin ◽  
Ronald Sorcek ◽  
Hin-Chor Wong ◽  
...  
Keyword(s):  
Structural Modification ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Cox 2 ◽  
Cox 1

scholarly journals Malignant Transformation and Antineoplastic Actions of Nonsteroidal Antiinflammatory Drugs (Nsaids) on Cyclooxygenase-Null Embryo Fibroblasts

1999 ◽  
Vol 190 (4) ◽  
pp. 451-460 ◽  
Author(s):  
Xinping Zhang ◽  
Scott G. Morham ◽  
Robert Langenbach ◽  
Donald A. Young
Keyword(s):  
Soft Agar ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Transformed Cells ◽  
Dependent Manner ◽  
Antiinflammatory Drugs ◽  
Cyclooxygenase 1 ◽  
The Status ◽  
Cox 2 ◽  
Transgenic Embryos ◽  
Cox 1

In this study, we use primary embryonic fibroblasts derived from cyclooxygenase-deficient transgenic embryos to further investigate the role of the two cyclooxygenases, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), in the process of neoplastic transformation. Cells with either, neither, or both of the cyclooxygenases were transformed by Ha-ras and/or SV40. Our results show that when a cyclooxygenase enzyme is present, the transformed cells have marked increases in COX-2 and/or COX-1 expression. Nevertheless, each type of cell, deficient in either or both cyclooxygenases, can be readily transformed at almost equal efficiency. Different nonsteroidal antiinflammatory drugs (NSAIDs) were used to examine their possible antineoplastic effects on the transformed cells, which have various levels of expression of COX-1 or COX-2. Our results show that NSAIDs suppress the colony formation in soft agar in a dosage-dependent manner in the absence of the cyclooxygenase(s). Thymidine incorporation and apoptosis analyses further demonstrate that the NSAIDs are effective in the cyclooxygenase-null cells. Our findings with cyclooxygenase knockout cells confirm recent reports that some of the antiproliferative and antineoplastic effects of NSAIDs are independent of the inhibition of either COX-1 or COX-2. They also show that transformation is independent of the status of cyclooxygenase expression, suggesting that the involvement of the cyclooxygenases in tumorigenesis may occur at later steps.

scholarly journals Factors Associated with Celecoxib and Rofecoxib Utilization

2005 ◽  
Vol 39 (4) ◽  
pp. 597-602 ◽  
Author(s):  
Nigel SB Rawson ◽  
Parivash Nourjah ◽  
Stella C Grosser ◽  
David J Graham
Keyword(s):  
Cardiovascular Disease ◽  
Disease Burden ◽  
Multiple Logistic Regression Analysis ◽  
Underlying Disease ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonselective Nsaid ◽  
Antiinflammatory Drugs ◽  
The Past ◽  
Increased Risk ◽  
Cox 2

BACKGROUND: The cyclooxygenase-2 (COX-2) selective nonsteroidal antiinflammatory drugs (NSAIDs) celecoxib and rofecoxib (before its removal) are marketed as having fewer gastrointestinal (GI)-related complications than nonselective NSAIDs. However, adverse reaction data suggest that the use of COX-2 selective NSAIDs is associated with clinically significant GI events. OBJECTIVE: To assess whether patients receiving celecoxib and rofecoxib have a greater underlying disease burden than patients prescribed nonselective NSAIDs. METHODS: The study population consisted of members of 11 health plans, aged >34 years, with a pharmacy claim for celecoxib or rofecoxib or a nonselective NSAID dispensed between February 1, 1999, and July 31, 2001, who had been continuously enrolled for >364 days before the dispensing date. Celecoxib and rofecoxib patients were randomly selected without replacement from a pool of eligible users in each of the 30 months. Nonselective NSAID users were randomly chosen without replacement within each month on a 2:1 ratio to cases; they could be chosen in more than one month. Univariate analyses comparing 9000 cases and 18 000 controls were performed, followed by a multiple logistic regression analysis conditioned on time. RESULTS: Increasing age, treatment by a rheumatologist or an orthopedic specialist, treatment with a high number of different medications in the past year, treatment with oral corticosteroids in the past year, and having had a previous GI bleed increased the likelihood of receiving celecoxib or rofecoxib, whereas treatment with a high number of nonselective NSAID prescriptions in the past year decreased it. Treatment with a high number of different medications was a predictor of increased prevalence of underlying diabetes mellitus and cardiovascular disease. CONCLUSIONS: Patients having a greater underlying disease burden were more likely to receive COX-2 selective NSAIDs than nonselective ones. Paradoxically, patients at higher risk for cardiovascular disease were channeled toward treatment with COX-2 selective NSAIDs, many of which may confer an increased risk of acute myocardial infarction and other adverse cardiovascular outcomes.

Angioedema Associated with Aspirin and Rofecoxib

2005 ◽  
Vol 39 (5) ◽  
pp. 944-948 ◽  
Author(s):  
Leisa L Marshall
Keyword(s):  
White Woman ◽  
Skin Testing ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Aspirin Therapy ◽  
Probability Scale ◽  
Antiinflammatory Drugs ◽  
Case Summary ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Auto Injector

OBJECTIVE: To report the probable association of angioedema with aspirin therapy and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib. CASE SUMMARY: A 44-year-old white woman, previously tolerant to aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs), developed angioedema of the lips after ingesting two 325-mg aspirin tablets during one day. The reaction occurred 3 hours after taking the second aspirin and resolved within 3 hours. Two weeks later, the patient took a 25-mg rofecoxib tablet for a sore throat, and she developed angioedema 51/2 hours later. Although the woman took 50 mg of diphenhydramine, the swelling did not subside. She repeated the diphenhydramine dose in the evening and, by noon the next day, 261/2 hours after the angioedema began, it was resolved. The patient's internist prescribed an epinephrine auto-injector and advised her to consult an allergist. With skin testing and oral rechallenge with aspirin, but not rofecoxib, the allergist determined the cause of the reactions to be aspirin-induced angioedema and selective COX-2 inhibitor intolerance. The Naranjo probability scale indicated that aspirin was a highly probable cause and rofecoxib was a probable cause of this patient's angioedema. DISCUSSION: Aspirin-induced angioedema and NSAID intolerance have been well documented. There are reports of both tolerance and intolerance to selective COX-2 inhibitors in patients with documented allergy-like reactions to aspirin and NSAIDs. CONCLUSIONS: Patients with aspirin and NSAID intolerance may develop intolerance to COX-2 inhibitors, especially with repeated exposure.

Blood Pressure in Native Americans Switched from Celecoxib to Rofecoxib

2005 ◽  
Vol 39 (5) ◽  
pp. 797-802 ◽  
Author(s):  
Jefferson Fredy ◽  
Daniel A Diggins ◽  
Gregory B Morrill
Keyword(s):  
Blood Pressure ◽  
Native American ◽  
Native Americans ◽  
Index Date ◽  
Medical Center ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Cardiovascular Safety ◽  
Antiinflammatory Drugs ◽  
The Mean ◽  
Cox 2

BACKGROUND: Nonsteroidal antiinflammatory drugs have been associated with exacerbation of hypertension. Differing effects on blood pressure (BP) have been reported in studies comparing celecoxib and rofecoxib. Concern regarding the cardiovascular safety of the cyclooxygenase-2 (COX-2) inhibitor class has intensified since the removal of rofecoxib from the market. OBJECTIVE: To evaluate the effect of a formulary change from celecoxib to rofecoxib on the BP of Native American patients at an Indian Health Service medical center. METHODS: Medical records of patients switched from celecoxib to rofecoxib were retrospectively reviewed. BP during the respective treatments was compared as follows: measurements recorded while taking celecoxib within 6 months before the index date and while taking rofecoxib from 1 week after the index date through 6 months of treatment were averaged. Differences in systolic and diastolic BP before and after the therapy change were evaluated using a paired Student's t-test. Subgroup analysis was performed for patients with preexisting hypertension. RESULTS: During rofecoxib therapy, the mean systolic BP was 2.9 mm Hg higher (p = 0.015) and the mean diastolic BP was 1.5 mm Hg higher (p = 0.042) than during celecoxib therapy. Among hypertensive patients, the respective mean systolic and diastolic BPs were 4.8 mm Hg (p = 0.009) and 2.0 mm Hg (p = 0.063) higher while taking rofecoxib. CONCLUSIONS: Switching patients from celecoxib to rofecoxib resulted in an increase in BP, with a larger difference observed in patients with hypertension. Future studies assessing the cardiovascular safety of currently marketed and investigational COX-2 inhibitors should evaluate the possible contribution of BP effects of these agents to overall risk.

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