Spontaneous Reports of Hypertension Leading to Hospitalisation in Association with Rofecoxib, Celecoxib, Nabumetone and Oxaprozin

Brinker, Allen; Goldkind, Lawrence; Bonnel, Renan A.; Beitz, Julie

doi:10.2165/00002512-200421070-00005

Cited by 23 publications

(16 citation statements)

References 16 publications

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“…Celecoxib reduced polyp burden in patients with familial adenomatous polyposis by about 30% in a 6-month randomized controlled clinical trial and was approved by the FDA for use in the prevention of colorectal polyps in these patients [10]. While the reduced gastrointestinal toxicity of COX-2-selective inhibitors favors their use, recent findings suggest that certain COX-2 inhibitors, like rofecoxib and possibly valdecoxib, increase the relative risk of cardiovascular morbidity in some persons [11, 12]. …”

Section: Role Of Nsaids and The Chemoprevention Of Crcmentioning

confidence: 99%

Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E<sub>2</sub>

Backlund¹,

Mann²,

DuBois³

2005

Oncology

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Carcinoma of the colon or rectum represents one of the most common malignancies worldwide with a higher prevalence in industrialized regions. Epidemiologic studies of individuals taking non-steroidal anti-inflammatory drugs (NSAIDs) have shown a significant reduction in colorectal cancer (CRC) mortality compared to those individuals not receiving these agents. NSAIDs inhibit the enzymatic activity of both isoforms of cyclooxygenase (COX-1 and COX-2), while COX-2-selective inhibitors have shown some efficacy in reducing polyp formation. COX-2-derived bioactive lipids, including the primary prostaglandin (PG) generated in colorectal tumors, PGE₂, are known to stimulate cell migration, proliferation and tumor-associated neovascularization while inhibiting cell death. Here we briefly review the role of NSAIDs in preventing CRC, as well as the proposed mechanism by which a COX-2-derived PG, PGE₂, promotes colon cancer.

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Section: Role Of Nsaids and The Chemoprevention Of Crcmentioning

confidence: 99%

Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E<sub>2</sub>

Backlund¹,

Mann²,

DuBois³

2005

Oncology

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“…Graham and coworkers showed in a nested case-control study that the relative risk for serious coronary heart disease is 1.5 to 3 times higher in patients on rofecoxib versus celecoxib users. Arterial hypertension is more frequently observed in patients taking rofecoxib compared to celecoxib [15][16][17][18]. Finally, although Solomon et al showed that celecoxib increased the incidence of cardiovascular fatalities, the overall mortality was identical with both placebo and celecoxib [4].…”

Section: Introductionmentioning

confidence: 99%

Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition

Klein¹,

Eltze²,

Grebe³

et al. 2007

Cardiovascular Research

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Objective: Celecoxib carries a smaller cardiovascular risk for myocardial infarction and hypertension than other cyclooxygenase-2 (COX-2)-selective non-steroidal anti-inflammatory drugs NSAIDs ("coxibs") and may ameliorate endothelial dysfunction. We aimed to determine which mechanism possibly accounts for the beneficial effect by investigating its vascular action in different in vitro preparations in comparison with other coxibs and reference phosphodiesterase-5 (PDE5) inhibitors. Methods: To uncover potential effects on coronary flow, the effects of celecoxib in comparison with other NSAIDs and the PDE5 inhibitors, sildenafil and zaprinast, were investigated in guinea-pig Langendorff heart. This was supported by studies for vasorelaxation, interaction with the NO/cGMP pathway, and measurement of cyclic nucleotide amounts released from rat aortic rings, and inhibition of human PDE5 as well as PDE4 activity. Results: Bolus injections of sildenafil, celecoxib, and zaprinast (at 100 nmol) into the Langendorff heart increased coronary flow by approximately 100, 65, and 25%, respectively, while rofecoxib, lumiracoxib, parecoxib, and diclofenac, except valdecoxib (N 100 nmol), failed to increase coronary flow up to 300 nmol. In rat aorta, sildenafil, celecoxib and zaprinast caused endothelium-dependent relaxation with − log [EC 50 ]M values of 8.90, 6.66 and 5.56, respectively; their rank order of potency corresponds to their coronary dilatory effect. Celecoxib-induced relaxation of aorta was attenuated by the nitric oxide (NO) synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME, 10 − 4 M) and by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, 10 − 5 M). In aortic rings, celecoxib (3 × 10 − 5 M) caused a fivefold increase in the cGMP level and potentiated that induced by sodium nitroprusside (5 × 10 − 7 M). Celecoxib and valdecoxib inhibited human PDE5A1 with an IC 50 of 1.6 × 10 − 5 and 1 × 10 − 4 M, respectively, whereas other coxibs were without inhibitory effect. Conclusion: Celecoxib caused coronary vasodilatation in guinea-pig hearts and relaxation of rat aorta and had a potentiating effect on the NO/cGMP signaling pathway in rat aorta through specific blockade of PDE5. These unexpected findings clearly support the notion that celecoxib possesses an as yet undisclosed molecule-specific property that possibly compensates a decrease of prostacyclin-dependent cAMP generation by concomitantly increasing cGMP levels resulting from inhibition of PDE5.

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“…However, rofecoxib differs in the following ways: 1) a significantly greater frequency and higher odds of CV events (Mamdani et al, 2004;Solomon et al, 2004a;Graham et al, 2005;Kimmel et al, 2005); 2) a shorter period and a lower dose (even at the clinical dose) leading to the incidence of CV events; and 3) an earlier onset and a greater hypertensive effect correlating closely with CV risk (Brinker et al, 2004;Solomon et al, 2004b;Wolfe et al, 2004;Fredy et al, 2005). Therefore, it is suggested that rofecoxib could have distinctive mechanisms or more potent toxic activity leading to CV risks, in comparison with other selective COX-2 inhibitors or nonselective NSAIDs.…”

Section: Introductionmentioning

confidence: 99%

COVALENT BINDING OF RADIOACTIVITY FROM [¹⁴C]ROFECOXIB, BUT NOT [¹⁴C]CELECOXIB OR [¹⁴C]CS-706, TO THE ARTERIAL ELASTIN OF RATS

Oitate

Hirota²,

Koyama³

et al. 2006

Drug Metab Dispos

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ABSTRACT:Rofecoxib is a cyclooxygenase-2 (COX-2) inhibitor that has been withdrawn from the market because of an increased risk of cardiovascular (CV) events. With a special focus on the arteries, the distribution profiles of radioactivity in rats orally administered Rofecoxib (VIOXX) is a potent and highly selective cyclooxygenase-2 (COX-2) inhibitor that has been widely used as a nonsteroidal anti-inflammatory drug (NSAID). However, this drug was withdrawn from the worldwide market because of an increased risk of cardiovascular (CV) events found in the Adenomatous Polyp Prevention on VIOXX (APPROVe) trial, which was conducted for the prevention of the recurrence of colorectal polyps and included 2600 patients with no history of CV disease before enrollment (Merck, 2004). The study had originally been intended to last for 3 years but was halted in midcourse because of the increased CV risks among patients in the group that was taking 25 mg of rofecoxib, in which the incidence of risk was more than twice that in the group taking the placebo.In the last few years, it has been reported that other selective COX-2 inhibitors (e.g., etoricoxib, parecoxib/valdecoxib, and celecoxib) and nonselective NSAIDs (e.g., naproxen) may also have a potential for increased CV risk (Bombardier et al., 2000;Ott et al., 2003; FDA, 2004; FDA Advisory Committee.com, 2004; NIH, 2004;Aldington et al., 2005;Krotz et al., 2005;Nussmeier et al., 2005). However, rofecoxib differs in the following ways: 1) a significantly greater frequency and higher odds of CV events (Mamdani et al., 2004;Solomon et al., 2004a;Graham et al., 2005;Kimmel et al., 2005); 2) a shorter period and a lower dose (even at the clinical dose) leading to the incidence of CV events; and 3) an earlier onset and a greater hypertensive effect correlating closely with CV risk (Brinker et al., 2004;Solomon et al., 2004b;Wolfe et al., 2004;Fredy et al., 2005). Therefore, it is suggested that rofecoxib could have distinctive mechanisms or more potent toxic activity leading to CV risks, in comparison with other selective COX-2 inhibitors or nonselective NSAIDs. Consequently, it is vital to investigate rofecoxib by comparing it with other selective COX-2 inhibitors to clarify its relevance to increased CV events.Several hypotheses have been proposed to explain the mechanism for the increased risk of CV events with rofecoxib. McAdam et al. (1999) suggested the endothelial prostacyclin (PGI 2 )/thromboxane A 2 (TxA 2 ) imbalance theory, whereby the CV complications caused by selective COX-2 inhibitors might be partially due to an imbalance of the concentration ratio of two prostanoids with major CV actions: PGI 2 , a vasodilator and inhibitor of platelet aggregation, and TxA 2 , a vasoconstrictor and promotor of platelet aggregation. That is, selective COX-2 inhibitors diminish the production of PGI 2 in the endothelium, but not TxA 2 in the platelets, so that the relative concentration of TxA 2 increases around the affected area, which might increase the risks. Walter et al. (200...

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Spontaneous Reports of Hypertension Leading to Hospitalisation in Association with Rofecoxib, Celecoxib, Nabumetone and Oxaprozin

Cited by 23 publications

References 16 publications

Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E<sub>2</sub>

Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E<sub>2</sub>

Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition

COVALENT BINDING OF RADIOACTIVITY FROM [¹⁴C]ROFECOXIB, BUT NOT [¹⁴C]CELECOXIB OR [¹⁴C]CS-706, TO THE ARTERIAL ELASTIN OF RATS

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Spontaneous Reports of Hypertension Leading to Hospitalisation in Association with Rofecoxib, Celecoxib, Nabumetone and Oxaprozin

Cited by 23 publications

References 16 publications

Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E<sub>2</sub>

Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E<sub>2</sub>

Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition

COVALENT BINDING OF RADIOACTIVITY FROM [14C]ROFECOXIB, BUT NOT [14C]CELECOXIB OR [14C]CS-706, TO THE ARTERIAL ELASTIN OF RATS

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COVALENT BINDING OF RADIOACTIVITY FROM [¹⁴C]ROFECOXIB, BUT NOT [¹⁴C]CELECOXIB OR [¹⁴C]CS-706, TO THE ARTERIAL ELASTIN OF RATS