Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

COX-2 selective inhibitors provide analgesia and blunt inflammation while also sparing the gastrointestinal tract from classic NSAID toxicity. Therapeutic effects are thought to result from inhibition of the inflammatory COX-2 isoform. Organ sparing is considered the result of preservation of homeostatic COX-1 enzyme function. Similar roles of the COX isoforms in the kidney would reduce NSAID-associated nephrotoxicity. However, human kidney tissue expresses COX-2 enzyme, suggesting a role for this isoform in maintenance of physiological renal processes. Available clinical data on the renal effects of COX-2 selective inhibitors in humans also demonstrate nephrotoxic potential.
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PMID:COX-2 selective inhibitors: analysis of the renal effects. 1290 60

This article reviews the gastrointestinal manifestations of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and the improved gastrointestinal safety profile of cyclooxygenase selective (COX)-2 inhibitors. By inhibiting the COX enzyme, NSAIDs provide effective analgesia and suppress inflammation in a variety of conditions. Most NSAIDs (nonselective or traditional) not only inhibit prostaglandins at sites of inflammation but also inhibit prostaglandins that have important normal functions in other parts of the body. This may be harmful when normal gastrointestinal mucosal function is impaired and mucosal damage occurs. Although such damage is often trivial and usually not symptomatic, gastrointestinal ulceration may produce pain and, more ominously, lead to bleeding, perforation, or obstruction. A new approach to the gastrointestinal complications of NSAIDs became feasible with the discovery of two isoforms of COX, COX-1 and COX-2, with COX-1 expressed mainly in the gastrointestinal tract. The development of NSAIDs that preferentially inhibit COX-2 offers the promise of relieving pain and inflammation without the side effects attendant to COX-1 blockade. In prospective studies evaluating gastrointestinal ulceration with COX-2-specific NSAIDs, rates of endoscopic ulceration have been equivalent to those with placebo and much lower than those with nonselective NSAIDs. In the recently released studies of gastrointestinal outcomes (perforated, painful, or bleeding ulcers), incidence of clinically relevant ulceration with COX-2 NSAIDs is much lower than that of traditional NSAIDs.
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PMID:The role of cyclooxygenase selective inhibitors in the gastrointestinal tract. 1460 52

The newer COX-2 drugs are safer analgesics than the older NSAIDs. At the usual dose used in osteoarthritis, they have less analgesic effect than the older NSAIDs. The non-narcotic analgesics such as acetaminophen, salicylate, NSAIDs, and the newer COX-2 drugs seem to have distinctly different mechanisms of action. In limited clinical trials, some of these drugs in combination give additive analgesia. Consideration should be given to using these drugs in combination, after suitable clinical trials, to enhance the efficacy of this category of analgesics.
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PMID:A comparison of the newer COX-2 drugs and older nonnarcotic oral analgesics. 1462 37

Parecoxib, a prodrug of valdecoxib, a selective COX-2 inhibitor, has been recently introduced for the treatment of moderate to severe postoperative pain. This prospective, open, multicentric study enrolled 260 patients undergoing orthopaedic, gynaecological, dental and general surgery. Postoperatively, patients were treated with parecoxib, 40 mg IM/IV. There was a statistically significant decrease in the mean pain intensity score (p<0.05). At the end of 24 hours, 89.6% of total cases had a very good to total relief of pain. The mean duration of analgesia was 19.26 hours and mean time of onset of analgesia was 16.25 minutes ranging from 11-20 minutes. The laboratory values were within normal limits. The drug was well tolerated. There was no report of any hypersensitivity reaction. This study suggests that parecoxib, in a dose of 40 mg IM/IV, is an effective and safe option for the management of postoperative pain.
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PMID:Efficacy and safety of the first parenteral selective COX-2 inhibitor, parecoxib sodium, in adult patients with postoperative pain. 1474 83

Postoperative pain management is critical for optimal care of orthopedic surgery patients. Opioids, administered intramuscularly, as epidurals, or IV as patient-controlled analgesia, are effective for severe pain. Adjunctive therapy and preemptive analgesia such as nerve blocks, and methods of delivery such as infusion pumps, may be used after total knee arthroplasty and anterior cruciate ligament (ACL) reconstruction. Oral opioids are effective for moderate to severe pain, and tramadol, with efficacy comparable to morphine but with fewer severe side effects, is selected for moderate to moderately severe pain. Opioid-sparing NSAIDs, such as ketorolac, and COX-2-specific NSAIDS have use in pain management of hip, knee, and ACL procedures. An individualized regimen of appropriate analgesics, combined with nonpharmacologic treatments such as physical therapy or cryotherapy and patient education, can aid orthopedic surgery patients' recovery.
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PMID:Analgesics for orthopedic postoperative pain. 1507 60

This randomised, double-blind, placebo-controlled, parallel-group study compared the efficacy and tolerability of lumiracoxib (a novel COX-2 selective inhibitor) with rofecoxib, celecoxib and placebo in patients with moderate-to-severe post-operative dental pain. Following third molar extraction, patients received single oral doses of lumiracoxib 400 mg, rofecoxib 50 mg, celecoxib 200 mg or placebo (n = 355). Additional patients from a similar study, assigned to lumiracoxib, rofecoxib or placebo (n = 155), were included for analysis of the primary variable, Summed Pain Intensity Difference over the first 8 h post dose (SPID-8). For SPID-8, lumiracoxib was superior to rofecoxib (p < 0.05), celecoxib (p < 0.001) and placebo (p < 0.001). Lumiracoxib demonstrated the fastest onset of analgesia and the longest time to rescue medication use. Patient global evaluation of lumiracoxib was comparable to rofecoxib and superior to celecoxib and placebo. All treatments were well tolerated. Lumiracoxib 400 mg provides rapid, effective and sustained relief of post-operative dental pain, comparable or superior to rofecoxib.
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PMID:Analgesic efficacy of a single dose of lumiracoxib compared with rofecoxib, celecoxib and placebo in the treatment of post-operative dental pain. 1511 90

Valdecoxib is an orally administered, highly selective cyclo-oxygenase (COX)-2 inhibitor with anti-inflammatory and analgesic properties. In well designed trials, valdecoxib demonstrated efficacy versus placebo in patients with osteoarthritis (OA), rheumatoid arthritis (RA), primary dysmenorrhoea and postoperative pain. Initial results in patients with migraine headache were promising. The efficacy of valdecoxib appears dose dependent up to 40 mg/day. Valdecoxib 10 mg/day was as effective as naproxen and rofecoxib in improving signs and symptoms of OA. The American College of Rheumatology 20% response rate was similar in recipients of valdecoxib, naproxen and diclofenac in patients with RA. In patients with dysmenorrhoea, valdecoxib 20 or 40 mg up to twice daily provided as effective pain relief as naproxen sodium 550 mg twice daily. In acute post-surgical pain, single-dose valdecoxib 40 mg had a rapid onset of action, provided similar analgesia to oxycodone 10 mg plus paracetamol (acetaminophen) 1000 mg and provided a longer time to rescue medication than rofecoxib or oxycodone/paracetamol after oral surgery. Pre-emptive administration of valdecoxib 10-80 mg was particularly effective in dental pain. Valdecoxib had opioid-sparing effects after hip or knee arthroplasty and reduced pain after laparoscopic cholecystectomy. Valdecoxib is generally well tolerated. The incidence of gastroduodenal ulcers was generally lower than with nonselective NSAIDs (i.e. NSAIDs not specifically developed as selective COX-2 inhibitors). With concomitant aspirin, the ulcer rate in valdecoxib recipients increased significantly, but was still lower than that in recipients of aspirin plus nonselective NSAIDs. In conclusion, valdecoxib, a COX-2-selective inhibitor, is as efficacious in pain relief as nonselective NSAIDs, with better gastrointestinal tolerability. It was as effective in RA, OA and primary dysmenorrhoea (the approved indications) as nonselective NSAIDs and as effective as rofecoxib in RA flare. In acute post-surgical pain, valdecoxib provided similar pain relief to oxycodone/paracetamol, had a long duration of action, a rapid onset of analgesia and was opioid-sparing. Valdecoxib provides a valuable alternative in the treatment of chronic arthritis pain and acute pain.
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PMID:Valdecoxib: a review of its use in the management of osteoarthritis, rheumatoid arthritis, dysmenorrhoea and acute pain. 1516 29

Several lines of evidence have accumulated that release of excitatory amino acids, nitric oxide and prostaglandin E2 (PGE2) play a critical role in the development of peripheral tactile and thermal hypersensitivity in chronic inflammatory pain models. Synthesis of PGE2 is controlled by cyclooxygenase (COX), either the COX-1 or COX-2 isoform. COX-2 plays a central role in the inflammatory reactions. The relationship between central sensitization of a complete Freund's adjuvant (CFA) induced inflammation and expressions of COX-2 were assessed in a rat model of CFA injection induced inflammation. Moreover, the time course of analgesia and spinal COX-2 expression following intrathecal (IT) injection with a nonspecific COX inhibitor (ketorolac) and COX-2 inhibitor (celecoxib) were determined using Western blot and immunohistochemistry. COX-2 protein was slightly increased in the lumbosacral spinal cord at 24 h following subcutaneous injection of CFA in the plantar surface of the left hindpaw (p > 0.05). COX-1 was not detected in normal and CFA injection rats. Surprisingly, IT ketorolac or celecoxib significantly increased spinal COX-2 levels at 1 h post-IT injection (p < 0.05) both in inflamed and non-inflamed rats. Then, spinal COX-2 levels declined at 3 and 6 h post-IT injection. These results provide strong in vivo evidence that COX-2 activity but not level may play a central role in the Freund's adjuvant-induced inflammation. However, spinal COX-2 level was upregulated following IT ketorolac and celecoxib injection. These data implies that suppression of PGE2 activity may induce the expression of spinal COX-2 in Freund's adjuvant-induced pain model. Our study concludes that IT administration of COX-2 inhibitor or nonspecific COX inhibitor is associated with significant short-term increase in spinal COX-2 expression.
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PMID:Nonsteroidal anti-inflammatory drugs increase expression of inducible COX-2 isoform of cyclooxygenase in spinal cord of rats with adjuvant induced inflammation. 1519 28

Successful ambulatory surgery is dependent on analgesia that is effective, has minimal adverse effects, and can be safely managed by the patient at home after discharge. A number of studies have identified that the provision of effective postoperative analgesia is inadequate for a significant proportion of patients. The following discussion details the current available analgesic options for ambulatory surgery patients and the rationale for their use. Preemptive analgesia should be given to all patients unless there are specific contraindications. Consideration should be given to the use of long-acting oral COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) and long-acting oral opioids to treat postoperative pain. A standardized multimodal postdischarge analgesic regimen tailored to the patient's expected postoperative pain levels should be prescribed. Patient follow-up by telephone questionnaire will confirm those surgical procedures that result in mild or moderate-to-severe postoperative pain and the effectiveness of treatment plans.
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PMID:Pain management in ambulatory surgery. 1519 76

Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used analgesics in the management of acute and chronic pain. Combined use of NSAIDs and opioids has been indicated for achieving better analgesia with reduced side effects. The present study was aimed at evaluating the combination of different NSAIDs, which inhibit cyclooxygenase (COX) enzymes and tramadol against acetic acid-induced writhing in mice. The expected beneficial effect of combination regimen was analyzed by isobolographic analysis. The oral and intrathecally administered tramadol, a mu-opioid and naproxen, a nonselective COX inhibitor produced dose-dependent antinociception, however, rofecoxib, a selective COX-2 inhibitor lacked analgesic efficacy in writhing test. Isobolographic analysis showed synergistic or supra-additive interactions for the combinations of naproxen and tramadol after oral and intrathecal administration. However, similar interaction was not observed when tramadol was combined with rofecoxib. Pretreatment with naloxone partially reversed the antinociceptive effect of tramadol per se and its combination with naproxen without modifying the per se effect of NSAID. The results demonstrated marked synergistic interaction between naproxen and tramadol and such interaction involved opioid as well as non-opioid mechanisms of tramadol and inhibition of COX-1 but not COX-2 by naproxen.
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PMID:Isobolographic analysis of interaction between cyclooxygenase inhibitors and tramadol in acetic acid-induced writhing in mice. 1527 89


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