Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific inhibitors of cyclooxygenase-2 were introduced into widespread clinical use in 1999. Since that time, celecoxib and rofecoxib have become two of the most commonly prescribed medications in the United States. Clinical trials using these medications for arthritis and pain have uniformly demonstrated efficacy superior to that of placebo and similar to that of nonsteroidal anti-inflammatory drugs. However, controversy surrounding the proper place of cyclooxygenase-2 inhibitors in the hierarchy of treatment for arthritis continues, based primarily on their higher cost compared with that of acetaminophen and nonsteroidal anti-inflammatory drugs. A decreased risk of gastrointestinal toxicity remains the primary justification for using the more expensive cyclooxygenase-2 inhibitors in preference to nonsteroidal anti-inflammatory drugs. The renal and cardiovascular effects of rofecoxib and celecoxib have been investigated in relation to nonsteroidal anti-inflammatory drugs and to one another. The data with respect to alteration in renal function, lower extremity edema, and hypertension indicates that cyclooxygenase-2 inhibitors affect the kidney in a manner similar to that of nonsteroidal anti-inflammatory drugs. The data comparing the cyclooxygenase-2 inhibitors is difficult to interpret because it is not clear that comparable doses have been used in clinical trials. The potential thrombogenic risk of cyclooxygenase-2 inhibitors remains controversial, and conflicting data exist. It remains important to increase our understanding of the place of these agents in clinical practice from the perspective of efficacy, toxicity, and cost.
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PMID:Specific cyclooxygenase-2 inhibitors: what have we learned since they came into widespread clinical use? 1198 17

The American College of Rheumatology (ACR) recently provided an update to the guidelines published in 1995 on the management of osteoarthritis (OA) of the knee and hip. Members of the Ad Hoc Committee on OA Guidelines followed an evidence-based medicine approach to revise the guidelines by reviewing an extensive literature search of the Cochrane and Medline databases and published abstracts, and discussing evidence with expert rheumatologists. The goal of the guidelines is to provide recommendations to control patients' OA pain, improve function and health-related quality of life, and avoid therapeutic toxicity. As in the original guidelines, nonpharmacologic interventions involving patient education and physical measures are recommended following initial diagnosis of OA. The pharmacologic algorithm was updated to include currently available therapeutic agents. Acetaminophen remains first-line therapy because of its cost, efficacy, and safety profiles. Cyclooxygenase-2-selective inhibitors (coxibs) have been included as an alternative to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at risk for upper gastrointestinal adverse events. Tramadol is an available alternative for patients who have a contraindication to coxibs or nonselective NSAIDs or for those who have not responded to previous oral therapy. Intra-articular injections or topical therapy may be used as monotherapy, or as an adjunct to oral analgesia. Surgical treatment of OA remains a last resort for patients who have failed to respond to nonpharmacologic and pharmacologic treatment approaches, and have progressive limitation in their activities of daily living. Several therapies for the prevention or treatment of OA are currently under investigation, including nutritional supplements, such as glucosamine and chondroitin, disease-modifying OA drugs, and devices, such as acupuncture and electromagnetic therapy. It is anticipated that the guidelines for the management of OA will continue to evolve as new therapies become available.
J Pain Symptom Manage 2002 Apr
PMID:Update of ACR guidelines for osteoarthritis: role of the coxibs. 1199 47

Cyclooxygenase-2 (COX-2) is the enzyme that normally synthesizes prostaglandins during an inflammatory response. Many primary and metastatic cancers express COX-2, and its presence is correlated with tumor angiogenesis, more invasive tumor phenotype, resistance to apoptosis, and systemic immunosuppression. The expression of COX-2 is associated with a worse prognosis. Inhibition of prostaglandin synthesis may be beneficial in human malignancy. Regular consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of, and mortality rate resulting from, a number of types of gastrointestinal cancers. Premalignant colonic lesions regress following the administration of nonspecific COX inhibitors, such as sulindac (Clinoril). Advanced solid tumor patients treated with indomethacin (Indocin) survive twice as long as do such patients who receive supportive care alone. The U.S. Food and Drug Administration has approved specific COX-2 inhibitors for the treatment of arthritis, pain, and familial adenomatous polyposis. Preclinical studies show that these drugs block angiogenesis, suppress solid tumor metastases, and slow the growth of implanted gastrointestinal cancer cell lines. The COX-2 inhibitors have safely and effectively been combined with chemotherapeutic agents in experimental studies. Ongoing clinical trials are currently assessing the potential therapeutic role of COX-2 inhibitors in both prevention and treatment of a diverse range of human cancers.
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PMID:Celecoxib with chemotherapy in colorectal cancer. 1201 63

This study compared the efficacy and safety of the cyclooxygenase-2 specific inhibitor celecoxib with the conventional non-steroidal anti-inflammatory drug diclofenac in the symptomatic treatment of viral pharyngitis. Adult patients from 27 study centers in Latin America were treated with oral doses of celecoxib 200 mg once daily or 200 mg twice daily, or diclofenac 75 mg twice daily for 5 days in a double-blind, randomized study. The primary efficacy assessment was 'Throat Pain on Swallowing' on day 3. In addition, secondary quality-of-life assessments were performed on days 3 and 5. All adverse events and treatment-emergent signs and symptoms were recorded. Data from 313 patients were evaluable for efficacy (105 celecoxib 200 mg once daily, 107 celecoxib 200 mg twice daily, 101 diclofenac 75 mg twice daily). The upper 95% confidence limits for the visual analog scale of 'Throat Pain on Swallowing' on day 3 for celecoxib 200 mg once daily relative to diclofenac 75 mg twice daily, and celecoxib 200 mg twice daily relative to diclofenac 75 mg twice daily were 9.26 and 7.83, respectively. All secondary efficacy and quality-of-life measures were clinically similar for the three treatment groups, and no statistically significant differences were detected. The incidences of treatment-emergent adverse events and withdrawals due to adverse events were similar for all groups, but numerically higher among patients taking diclofenac than celecoxib. More patients in the diclofenac group reported gastrointestinal complaints (7.3%) compared with those in the celecoxib groups (4.3% in the celecoxib 200 mg once-daily group and 3.4% in the celecoxib 200 mg twice-daily group). In conclusion, 5 days of treatment with celecoxib 200 mg once daily is as effective as diclofenac 75 mg twice daily in the symptomatic treatment of viral pharyngitis. Celecoxib 200 mg once daily is also as effective as celecoxib 200 mg twice daily in this condition.
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PMID:Efficacy of celecoxib in treating symptoms of viral pharyngitis: a double-blind, randomized study of celecoxib versus diclofenac. 1202 27

Significant selective cyclooxygenase-2 (COX-2) inhibitory activities were observed for two new 1,4-naphthoquinone sodium salts, sodium 3-hydroxide-2[[sodium 3-hydroxide-1,4-dioxo(2-naphthyl)]ethyl]naphthalene-1,4-dione (impatienolate) (1) and sodium 2-hydroxide-3-(2-hydroxyethyl)naphthalene-1,4-dione (balsaminolate) (2), which were isolated from the corolla of Impatiens balsamina L. (Balsaminaceae). Their structures were elucidated by spectral techniques. Our results offer evidence supporting the use of I. balsamina L. to treat articular rheumatism, pain, and swelling.
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PMID:Cyclooxygenase-2 inhibitory 1,4-naphthoquinones from Impatiens balsamina L. 1203 10

Scheduled preoperative and postoperative analgesia should be offered in a multimodal management model. By a combined drug synergy effect, the central nervous system, afferent pathways, and peripheral wound site are modified collectively. In an ongoing effort to improve perioperative pain management, we retrospectively compared the results of a previously reported pain management protocol with 2 more recent groups of patients managed with modified pain protocols. In the earlier control protocol, epidural anesthesia was discontinued on arrival to the postanesthesia care unit, and regularly scheduled oral opioids and intravenous hydromorphone for breakthrough pain were initiated. The first more recent group used epidural anesthesia, and the second group used spinal anesthesia. Both protocols featured the use of cyclooxygenase-2-inhibiting anti-inflammatory medication administered for 2 weeks preoperatively and continued for 10 days postoperatively and patient-controlled analgesia for 24 hours followed by scheduled oral opioids.
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PMID:Pain management for joint arthroplasty: preemptive analgesia. 1206 23

Patellar tendinosis is characterized by longstanding localized and activity-related pain, swelling and tenderness on palpation, and characteristic features on magnetic resonance imaging and ultrasonography and during surgical excision. Histologic examination of tendinosis tissues shows disrupted collagen matrix, increased cellularity, and increased proteoglycan stainability, but lack of inflammatory cell infiltration despite the clinical signs resembling inflammation. Disturbances in inflammatory response may be associated with the development of tendinosis. Expression of cyclooxygenase-2 and transforming growth factor-beta1 were detected in tendinosis, and the in vitro production of prostaglandin E2 by tendinosis and healthy tendon fibroblast cultures also was observed. Eleven patients with patellar tendinosis and 12 control subjects with healthy patellar tendons, but deficient anterior cruciate ligaments, were included in the current study. The percentages of immunopositive cells in tendinosis samples for cyclooxygenase-2 and transforming growth factor-beta1 were 66.75 and 56.40, respectively, which were significantly higher than those of the control subjects (25.15 and 23.06 respectively). Tendinosis fibroblast culture also produced more prostaglandin E2 and active transforming growth factor-beta1. These findings indicate the involvement of prostaglandins and cytokines that may explain the clinical symptoms and nonhealing features of tendinosis.
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PMID:Increased expression of transforming growth factor-beta1 in patellar tendinosis. 1207 60

Anti-inflammatory agents have been used for centuries, but only in the last few decades has medical science gained insight into the complex biologic roles of the primary mediators of inflammation, the eicosanoids and their derivatives. Detailed understanding of the prostaglandins and leukotrienes provides a framework for the treatment of pain, inflammation, and fever with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), but these agents have exacted a substantial side effect burden. The discovery of cyclooxygenase-2 (COX-2) has guided development of rationally designed therapeutic agents that have the benefits of older NSAIDs with reduced gastrointestinal toxicity. Elucidation of the structure of COX isoenzymes has been key in the development of coxibs, the COX-2-selective subset of NSAIDs. Methods to determine the degree of COX-2 selectivity have been refined and are indispensable for comparing the relative selectivity of these agents. This review summarizes some of the key aspects of COX biochemistry, structure, and function and the evolution of understanding the mechanism of action of COX-2-selective inhibitors. The clinical relevance of COX-1 compared with COX-2 inhibition is discussed to provide a framework upon which clinicians can better appreciate current and future therapeutic applications of coxibs.
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PMID:Cyclooxygenase-2-selective inhibitors: translating pharmacology into clinical utility. 1208 89

Docetaxel is a new taxoid widely used in chemotherapy for advanced breast cancer and other solid malignancies. Painful nail changes with onycholysis occur in about 40% of docetaxel-treated patients as a prominent adverse effect. We report a patient with a complete peripheral palsy of the right arm due to advanced breast cancer with diffuse tumor infiltration of the brachial plexus. Treatment with docetaxel led to onycholysis at all extremities except the paretic hand. Sensory and motoric innervation measured by nerve conduction studies showed a complete loss of large nerve fiber function of the right arm. Function of deep mechanosensitive A beta-fibers (quantitative vibrametry) was severely decreased, but not absent. Sympathetic reflexes (induced by deep inspiration and measured with laser Doppler flowmetry) were absent on the right side and skin temperature was decreased consistent with a complete sympathetic denervation. Small afferent fibers investigated by quantitative thermotesting revealed a total loss of thermal and pain sensation. Furthermore, iontophoresis of histamine failed to induce any axon reflex-vasodilatation indicating a complete peripheral degeneration of small fiber afferents. In summary, a severe denervation of small and large fibers of the right upper limb was revealed. These results indicate that integrity of peripheral nerves seems to be a substantial factor for docetaxel-mediated nail changes. The role of an inflammatory process in onycholysis maintained by postganglionic sympathetic terminals and nociceptive C-fiber afferents is discussed. In accordance with this hypothesis, a cyclooxygenase-2 inhibitor improved nail alterations of the non-paretic limbs.
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PMID:Docetaxel-induced nail changes--a neurogenic mechanism: a case report. 1216 89

Valdecoxib is a potent and specific inhibitor of cyclooxygenase-2, which is used for the treatment of rheumatoid arthritis, osteoarthritis, and the dysmenorrhea pain. Eight male human subjects each received a single 50-mg oral dose of [(14)C]valdecoxib. Urine, feces, and blood samples were collected after administration of the radioactive dose. Most of the radioactivity in plasma was associated with valdecoxib and the hydroxylated metabolite of valdecoxib (M1). The estimated terminal half-life for valdecoxib was about 7 h. About 76.1% of the radioactive dose was recovered in urine and 18% of the radioactive dose was recovered in feces. Valdecoxib was extensively metabolized in human, and nine phase I metabolites were identified. The primary oxidative metabolic pathways of valdecoxib involved hydroxylation at either the methyl group to form M1 or N-hydroxylation at the sulfonamide moiety to form M2. Further oxidation of M1 led to the formation of several other phase I metabolites. Oxidative breakdown of the N-hydroxy sulfonamide function group in M2 led to the formation of corresponding sulfinic acid and sulfonic acid metabolites. The O-glucuronide conjugate of M1 and N-glucuronide conjugate of valdecoxib were the major urinary metabolites, which accounted for 23.3 and 19.5% of the total administered dose, respectively. The remaining urinary metabolites were glucuronide conjugates of other phase I metabolites. Only 3% of the administered dose was recovered in urine as unchanged parent, suggesting that renal clearance is insignificant for valdecoxib. Absorption of valdecoxib was excellent since the recovery of unchanged valdecoxib in feces was <1% of the administered dose.
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PMID:Disposition of a specific cyclooxygenase-2 inhibitor, valdecoxib, in human. 1216 67


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