Parecoxib Sodium, a Parenteral Cyclooxygenase 2 Selective Inhibitor, Improves Morphine Analgesia and Is Opioid-sparing following Total Hip Arthroplasty

Malan, T. Philip; Marsh, Greg D.; Hakki, Sam; Grossman, Evie H.; Traylor, Louise; Hubbard, Richard C.

doi:10.1097/00000542-200304000-00023

Cited by 140 publications

(107 citation statements)

References 28 publications

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“…Furthermore, coadministration of celecoxib with morphine provides analgesia even after 14 days of treatment, suggesting that celecoxib may have a salutary effect on opioid analgesia. Cyclooxygenase-2 inhibition may at least partly explain the clinical improvements in postoperative pain control that have been seen with a combination of opioids and COX-2 inhibitors and/or NSAIDs (Kroin et al, 2002;Malan et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia

et al. 2007

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Morphine and its congener opioids are the main therapy for severe pain in cancer. However, chronic morphine treatment stimulates angiogenesis and tumour growth in mice. We examined if celecoxib (a cyclooxygenase-2 (COX-2) inhibitor) prevents morphineinduced tumour growth without compromising analgesia. The effect of chronic treatment with celecoxib (by gavage) and/or morphine (subcutaneously), or PBS on tumour prostaglandin E 2 (PGE 2 ), COX-2, angiogenesis, tumour growth, metastasis, pain behaviour and survival was determined in a highly invasive SCK breast cancer model in A/J mice. Two weeks of chronic morphine treatment at clinically relevant doses stimulates COX-2 and PGE 2 (4.5-fold compared to vehicle alone) and angiogenesis in breast tumours in mice. This is accompanied by increased tumour weight (B35%) and increased metastasis and reduced survival. Coadministration of celecoxib prevents these morphine-induced effects. In addition, morphine and celecoxib together provided better analgesia than either agent alone. Celecoxib prevents morphine-induced stimulation of COX-2, PGE 2 , angiogenesis, tumour growth, metastasis and mortality without compromising analgesia in a murine breast cancer model. In fact, the combination provided significantly better analgesia than with morphine or celecoxib alone. Clinical trials of this combination for analgesia in chronic and severe pain in cancer are warranted.

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Section: Discussionmentioning

confidence: 99%

COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia

et al. 2007

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“…Parecoxib is the parenteral prodrug of the selective COX-2 inhibitor valdecoxib and is widely used outside of the United States for acute and perioperative pain. 65 A placebo-controlled randomized study of intravenous parecoxib sodium (3 days) followed by oral valdecoxib (7 days) in 1671 patients who had undergone coronary artery bypass graft surgery 6 showed that patients receiving these agents had a postoperative CV event rate of 2% compared with a rate of 0.5% in patients receiving placebo. Of interest was the finding that 35% of the events in the active treatment group were observed in a 30-day period that followed discontinuation of the parecoxib and valdecoxib.…”

Section: Use Of Parenteral Cox-2 Inhibitors In the Perioperative Periodmentioning

confidence: 99%

Cardiovascular Effects of the Cyclooxygenase Inhibitors

White

2007

Hypertension

106

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C yclooxyenase (COX)-2 selective inhibitors were developed to create a new class of nonsteroidal antiinflammatory drugs (NSAIDs) with properties similar to those of nonselective NSAIDS but without their potential COX-1-mediated gastrointestinal toxicities. 1,2 Studies of the various COX-2 selective inhibitors have shown that they are in fact associated with a significantly lower risk of upper and lower gastrointestinal complications than traditional NSAIDs, except in patients who are taking concomitant low-doses of aspirin.Recent evidence also suggests that some doses of the COX-2 selective inhibitors, and perhaps some traditional NSAIDs as well, are associated with an increased risk of adverse cardiovascular (CV) events. Reports of a higher incidence of myocardial infarction (MI) among patients with arthritis taking high doses of the COX-2 selective inhibitor rofecoxib compared with those taking the NSAID naproxen 2-4 have had heightened concerns since 2001 regarding selective COX-2 inhibitor safety. In addition, in early 2005, elevated CV event rates were reported in patients with spontaneous adenomatous polyps who were taking high doses of celecoxib compared with placebo 5 and in patients who received parenteral parecoxib followed by oral valdecoxib versus placebo immediately after coronary artery bypass graft surgery. 6 This article represents a compilation of the data concerning the effects of both nonselective and selective NSAIDs on blood pressure (BP), particularly in patients with hypertension and/or on antihypertensive agents. Subsequently, the impact that the COX inhibitors have on CV events from several recent clinical trials for the treatment of arthritis or for cancer prevention, as well as from selected large observational studies, is discussed. CV Pharmacology of COX InhibitionCOXs participate in numerous physiological functions and human pathological disorders. The COX-1 isoform is constitutively expressed in most tissues where it regulates the synthesis of prostaglandins. COX-1 is the only form of the enzyme in mature platelets and is also expressed in the vascular endothelium, the gastrointestinal epithelium, brain, spinal cord, and kidney. The COX-2 isoform plays an important role in induction of inflammation in response to injury, as well as later repair of inflammation. It is noteworthy that COX-2 may be induced by bacterial endotoxins, cytokines, and growth factors and is expressed in atherosclerotic plaques, during angiogenesis, during wound healing, and in a variety of epithelial cell cancers. [7][8][9] In addition, COX-2 is constitutively expressed in the macula densa and renal medullary interstitium. 10,11 As discussed below, one result of COX-2 inhibition is a reduction in natriuresis and the development of hypertension in susceptible populations. The COX isoenzymes are similar in structure, but the substrate-binding channel of COX-2 contains a side pocket that is absent in COX-1. This structural difference has allowed for the design and development of COX inhibitors with side chains ...

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“…Most of previous study of parecoxib were on the orthopedic surgery and showed that intravenous parecoxib did reduce the pain score postoperatively (13,14 (15) first carried out a study to find out the effect of parecoxib combined with thoracic paravertebral ropivacaine infusion in thoracotomy. Patients receiving parecoxib (40 mg intravenously used 20 min before extubation and 12 hrs after the procedure) had less pain at rest and during movement compared with those with placebo at 12, 24, and 48 hours after surgery.…”

Section: Discussionmentioning

confidence: 99%

Effect of parecoxib combined with thoracic epidural analgesia on pain after thoracotomy

Ling¹,

Fang²,

Zhang³

et al. 2016

J. Thorac. Dis.

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Background: Thoracotomy results in severe postoperative pain potentially leading to chronic pain. We investigated the potential benefits of intravenous parecoxib on postoperative analgesia combined with thoracic epidural analgesia (TEA).Methods: Eighty-six patients undergoing thoracic surgery were randomized into two groups. Patientcontrolled epidural analgesia (PCEA) was used until chest tubes were removed. Patients received parecoxib (group P) or placebo (group C) intravenously just 0.5 h before the operation and every 12 h after operation for 3 days. The intensity of pain was measured by using a visual analogue scale (VAS) and recorded at 2, 4, 8, 24, 48, 72 h after operation. The valid number of PCA, the side effects and the overall satisfaction to analgesic therapy in 72 h were recorded. Venous blood samples were taken before operation, the 1 st and 3 rd day after operation for plasma cortisol, adrenocorticotropic hormone (ACTH), interleukin-6 and tumor necrosis factor-α level. The occurrence of residual pain was recorded using telephone questionnaire 2 and 12 months after surgery.Results: Postoperative pain scores at rest and on coughing were significantly lower with the less valid count of PCA and greater patient satisfaction in group P (P<0.01). Adverse effect and the days fit for discharge were comparable between two groups. The cortisol levels in placebo group were higher than parecoxib group at T2. The level of ACTH both decreased in two groups after operation but it was significantly lower in group P than that in group C. There were no changes in plasma IL-6 and TNF-α levels before and after analgesia at T 1 and T 2 (P>0.05). The occurrence of residual pain were 25% and 51.2% separately in group P and C 3 months postoperatively (P<0.05).Conclusions: Intravenous parecoxib in multimodal analgesia improves postoperative analgesia provided by TEA, relieves stress response after thoracotomy, and may restrain the development of chronic pain.

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Parecoxib Sodium, a Parenteral Cyclooxygenase 2 Selective Inhibitor, Improves Morphine Analgesia and Is Opioid-sparing following Total Hip Arthroplasty

Abstract: Administration of parecoxib sodium with PCA morphine resulted in significantly improved postoperative analgesic management as defined by reduction in opioid requirement, lower pain scores, reduced time on PCA morphine, and higher Global Evaluation ratings.

Cited by 140 publications

References 28 publications

COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia

COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia

Cardiovascular Effects of the Cyclooxygenase Inhibitors

Effect of parecoxib combined with thoracic epidural analgesia on pain after thoracotomy

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