UMLS:C0184567 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0184567 (acute pain)
3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lumiracoxib (Prexige) is a selective cyclo-oxygenase (COX)-2 inhibitor developed for the treatment of osteoarthritis, rheumatoid arthritis and acute pain. Lumiracoxib possesses a carboxylic acid group that makes it weakly acidic (acid dissociation constant [pKa] 4.7), distinguishing it from other selective COX-2 inhibitors. Lumiracoxib has good oral bioavailability (74%). It is rapidly absorbed, reaching maximum plasma concentrations 2 hours after dosing, and is highly plasma protein bound. Lumiracoxib has a short elimination half-life from plasma (mean 4 hours) and demonstrates dose-proportional plasma pharmacokinetics with no accumulation during multiple dosing. In patients with rheumatoid arthritis, peak lumiracoxib synovial fluid concentrations occur 3-4 hours later than in plasma and exceed plasma concentrations from 5 hours after dosing to the end of the 24-hour dosing interval. These data suggest that lumiracoxib may be associated with reduced systemic exposure, while still reaching sites where COX-2 inhibition is required for pain relief. Lumiracoxib is metabolised extensively prior to excretion, with only a small amount excreted unchanged in urine or faeces. Lumiracoxib and its metabolites are excreted via renal and faecal routes in approximately equal amounts. The major metabolic pathways identified involve oxidation of the 5-methyl group of lumiracoxib and/or hydroxylation of its dihaloaromatic ring. Major metabolites of lumiracoxib in plasma are the 5-carboxy, 4'-hydroxy and 4'-hydroxy-5-carboxy derivatives, of which only the 4'-hydroxy derivative is active and COX-2 selective. In vitro, the major oxidative pathways are catalysed primarily by cytochrome P450 (CYP) 2C9 with very minor contribution from CYP1A2 and CYP2C19. However, in patients genotyped as poor CYP2C9 metabolisers, exposure to lumiracoxib (area under the plasma concentration-time curve) is not significantly increased compared with control subjects, indicating no requirement for adjustment of lumiracoxib dose in these subjects. Lumiracoxib is selective for COX-2 compared with COX-1 in the human whole blood assay with a ratio of 515 : 1 in healthy subjects and in patients with osteoarthritis or rheumatoid arthritis. COX-2 selectivity was confirmed by a lack of inhibition of arachidonic acid and collagen-induced platelet aggregation. COX-2 selectivity of lumiracoxib is associated with a reduced incidence of gastroduodenal erosions compared with naproxen and a lack of effect on both small and large bowel permeability. Lumiracoxib does not exhibit any clinically meaningful interactions with a range of commonly used medications including aspirin (acetylsalicylic acid), fluconazole, an ethinylestradiol- and levonorgestrel-containing oral contraceptive, omeprazole, the antacid Maalox, methotrexate and warfarin (although, as in common practice, routine monitoring of coagulation is recommended when lumiracoxib is co-administered with warfarin). As such, dose adjustments are not required when co-administering these agents with lumiracoxib. In addition, moderate hepatic impairment and mild to moderate renal impairment do not appear to influence lumiracoxib exposure.
...
PMID:Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. 1637 23

The inhibition of prostaglandin (PG) synthesis is at the center of current anti-inflammatory therapies. Because cyclooxygenase-2 (COX-2) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of multiple PGs, there is currently a strong focus on characterizing the role of the different PGs in the inflammation process and development of arthritis. Evidence to date suggests that both PGE(2) and PGI(2) act as mediators of pain and inflammation. Most of the data indicating a role for PGI(2) in this context have been generated in animal models of acute pain. Herein, we describe the role of PGI(2) in models of osteoarthritis (OA) and rheumatoid arthritis using a highly selective PGI(2) receptor (IP, Ptgir) antagonist and IP receptor-deficient mice. In the rat OA model using monoiodoacetate injection into the knee joint, the IP antagonist reduced pain with an efficacy approaching that of the NSAID diclofenac. In a chronic model of inflammatory arthritis, collagen-antibody induced arthritis model in mice, IP receptor-deficient mice displayed a 91% reduction in arthritis score. Interestingly, pretreatment with the IP [N-[4-(imidazolidin-2-ylideneamino)-benzyl]-4-methoxy-benzamide] antagonist in this model also caused a significant reduction of the symptoms, whereas administration of the compound after the initiation of arthritis had no detectable effect. Our data indicate that, in addition to its role in acute inflammation, PGI(2) is involved in the development of chronic inflammation. The results also suggest that the inhibition of PGI(2) synthesis by NSAIDs and COX-2 inhibitors, in addition to that of PGE(2), contributes to their efficacy in treating the signs of arthritis.
...
PMID:Prostacyclin antagonism reduces pain and inflammation in rodent models of hyperalgesia and chronic arthritis. 1697 87

This review summarizes the principal therapeutic responses to the preferential COX-2 NSAID, nimesulide, in treating musculo-skeletal joint symptoms and various acute and chronic pain conditions and the mode of action in relation to therapy in these states. In extensive studies in laboratory animal models and clinical trails in patients nimesulide has been found to have potent analgesic, anti-inflammatory and anti-pyretic activities. It is approved for use in over 50 countries worldwide (including those in the EU, South and Central America, China, India and some other South-East Asia) for the treatment of acute pain, the symptomatic treatment of painful osteoarthritis and primary dysmenorrhoea. Its mode of action in these states is related to the preferential inhibition of the production of cyclo-oxygenase-2 (COX-2) and other inflammatory mediators whose production is controlled by stimulation of cyclic-3 ,5'-adenosine monophosphate (cAMP); this means that nimesulide is a multi-factorial drug in controlling inflammation and pain. The adverse reaction profile of nimesulide is, in general, like that of other NSAIDs. It does, however, have relatively low occurrence of gastro-intestinal (GI) side effects which is related to its low propensity to inhibit the physiologically important COX-1 in the GI mucosa and important physicochemical properties (high pKa of 6.5 and lipophilicity) as well as inhibiting of mast cell derived histamine and acid secretion in the stomach. In contrast with the coxibs, nimesulide has not been found to have appreciable cardiovascular toxicity.
...
PMID:Current status of the therapeutic uses and actions of the preferential cyclo-oxygenase-2 NSAID, nimesulide. 1698 92

In the 20-50-year age group, hip pain usually indicates dysplasia. Chronic mechanical pain is the usual pattern, although acute pain caused by avulsion or degeneration of the labrum may occur. The morphological characteristics of the dysplastic hip should be evaluated, and the link between the dysplasia and the osteoarthritis should be confirmed. Three factors indicate a favorable prognosis: joint space preservation, age younger than 40 years, and correctable femoral and acetabular abnormalities. Reconstruction is highly desirable, as it delays the need for joint replacement by 20 years. After 15 years, good outcomes are seen in 87% of patients after shelf arthroplasty and 85% after femoral varus osteotomy with or without shelf arthroplasty. Chiari acetabular osteotomy can be performed in patients with osteoarthritis but is followed by prolonged limping. Periacetabular osteotomy should be reserved for patients with moderate dysplasia and no evidence of osteoarthritis. Shelf arthroplasty and femoral osteotomy require 5-8 months off work (compared to 5 months after hip replacement surgery) but subsequently permits a far more active lifestyle. Hip replacement, which is required 20 years or more after biologic reconstruction, carries the same prognosis as first-line hip replacement (good results in 80% of patients after 15 years). Acute sharp pain related to anterior hip derangement also occurs in primary femoroacetabular impingement (FAI). The most common pattern is cam impingement, which is due to a decrease in head-neck offset and manifests as pain during flexion and adduction of the hip. Cam impingement can be corrected by anterolateral osteoplasty, which is often performed arthroscopically. Pincer-type impingement is contact between the anterior acetabular rim and the femoral neck due to retroversion of the proximal acetabulum. The imaging study strategy is discussed. Coxometry, computed tomography, and arthrography can be used. Primary FAI, which occurs as a result of geometric abnormalities, should be distinguished from secondary impingement. Causes of secondary impingement include exaggerated lumbar lordosis with pelvic tilt and to hip osteophytosis (sports or posterior hip osteoarthritis). Osteoplasty is rarely appropriate in patients with secondary impingement. The features of acute anterior hip derangement are now better defined. They can be used to guide palliative treatment, which is effective, in the medium term at least. Experience acquired over the last two decades has established the efficacy of surgery for hip dysplasia.
...
PMID:Hip pain from impingement and dysplasia in patients aged 20-50 years. Workup and role for reconstruction. 1713 20

Lumiracoxib is a selective cyclooxygenase (COX)-2 inhibitor that possesses a carboxylic acid group that makes it weakly acidic. It has good oral bioavailability; maximum plasma concentrations are reached two hours after oral administration. Despite its short elimination half-life of four hours from the plasma, the drug is distributed to inflamed tissues and is retained for up to 24 hours. This unique property suggests that lumiracoxib, while having reduced systemic exposure, can still reach sites where COX-2 inhibition is required for pain relief. Lumiracoxib is metabolized extensively with only a small amount excreted in the urine. Selectivity for COX-2 is high compared to all other similar agents. It is indicated for the relief of pain in osteoarthritis, rheumatoid arthritis, acute pain and primary dysmenorrhea. Lumiracoxib has been found to be effective at doses of 100-400 mg once a day for chronic pain and 400 mg/day for acute pain. Large clinical trials where lumiracoxib was administered to patients with osteoarthritis have demonstrated that this drug is equally effective as other COX-2 inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs). In comparison to NSAIDs, patients taking lumiracoxib experience significantly fewer adverse events and greater tolerability. It has also been shown to be effective in acute pain states, like the dental pain model and postoperative pain after orthopedic surgery. A large clinical study (TARGET) has demonstrated the gastrointestinal safety of lumiracoxib over one year. The study also showed that there was no increase in cardiovascular events in non-high-risk patients. However, a black box warning similar to those accompanying other COX-2 inhibitors has been placed by regulatory agencies that have approved this drug for clinical use. When lumiracoxib is coadministered with warfarin or aspirin, no dosage adjustment is required.
...
PMID:Lumiracoxib. 1738 Feb 11

A survey was conducted in 2000 into the use of analgesic drugs by veterinarians in South Africa. This survey was repeated in 2005 to establish whether the use of analgesic drugs has increased and which analgesic drugs are being used for acute pain and osteoarthritis. The number of sterilisations performed and the number of new cases of osteoarthritis in dogs and cats was estimated. It is estimated that approximately 260000 cats are operated on each year in South Africa and that 150000 cats are sterilised. Five hundred thousand dogs undergo surgery, of which 242000 are sterilised. It appears that the number of surgical procedures performed in South Africa has decreased. The estimated death rate following anaesthesia has remained unchanged at 1:1004. Overall, the use of analgesics by South African veterinarians has increased significantly. Fifty-six per cent of cats and 74% of dogs were given peri-operative analgesics but this increased to 94% and 84% after including pre-anaesthetic medications with analgesic properties. The use of opioids (morphine and buprenorphine) and propofol has increased significantly. Approximately 253000 dogs and 33000 cats with osteoarthritis are seen by veterinarians in South Africa annually. The recognition by veterinarians of osteoarthritis in cats appears to be poor and is in need of attention. Carprofen and glucosamine/chondroitin are the most commonly used agents for the treatment of osteoarthritis. Details of the drugs used by veterinarians are given. Knowledge of analgesic drugs has increased significantly over the last 5 years. Continuing education is thought to have played an important role in the changes reported in this study.
...
PMID:Anaesthesia and analgesia for dogs and cats in South Africa undergoing sterilisation and with osteoarthritis--an update from 2000. 1745 51

Lumiracoxib is a highly selective COX-2 inhibitor with a novel chemical structure and a relatively short plasma half-life. It has been approved in > 40 countries for the symptomatic treatment of osteoarthritis and/or acute pain related to primary dysmenorrhoea and dental or orthopaedic surgery. In these conditions, lumiracoxib has proved to be as effective as standard doses of conventional NSAIDs and other COX-2 selective inhibitors (coxibs). According to the Therapeutic Arthritis Research Gastrointestinal Trial, which enrolled 18,325 patients with osteoarthritis, lumiracoxib 400 mg/day (four times its recommended dosage) was associated with a significant decrease in the risk of ulcer complications compared with naproxen 1000 mg/day and ibuprofen 2400 mg/day, at least in the population not taking low-dose aspirin. The atherothrombotic potential of NSAIDs, especially coxibs, has been much debated. In this respect, available data do not suggest that lumiracoxib may be associated with an increased hazard of cardiovascular events compared with non-selective NSAIDs. Finally, lumiracoxib may be an effective and safe drug provided both physicians and patients will comply with its approved indications and contraindications.
...
PMID:Lumiracoxib in the management of osteoarthritis and acute pain. 1766 36

Etodolac is a non-steroidal anti-inflammatory drug with analgesic properties. Its primary anti-inflammatory mechanism of action is through a selective effect on cyclo-oxygenase-2 (COX-2). It is rapidly absorbed after oral administration, and maximum plasma concentration (C(max)) is reached in 1-2 h, with an elimination half-life (t1/2 ) of 6-8 h.Etodolac has been widely applied in the treatment of inflammatory arthritides such as rheumatoid arthritis, ankylosing spondylitis and gout and in osteoarthritis and has been shown to be efficacious and well tolerated.However, etodolac has other applications which rely primarily on its efficacy as an analgesic. In particular, etodolac has been evaluated in the treatment of a variety of different pain states. Etodolac has been observed to be efficacious in the treatment of acute pain following dental extraction, orthopaedic and urological surgery, and episiotomy, as well as in the treatment of pain due to acute sports injuries, primary dysmenorrhoea, tendonitis, bursitis, periarthritis, radiculalgia and low back pain.These studies indicate that etodolac is a multipurpose analgesic with many clinical applications in addition to its use in the treatment of inflammatory and degenerative forms of arthritis.
...
PMID:Etodolac in the management of pain: a clinical review of a multipurpose analgesic. 1769 63

Celecoxib, a selective COX-2 inhibitor, primarily used in treatment of osteoarthritis, rheumatoid arthritis and acute pain was encapsulated in microparticles composed of various polyesters, polymethacrylates or cellulose derivatives used alone or blended. The influence of polymers on microparticle mean diameter, encapsulation efficiency and in vitro and in vivo celecoxib release was investigated. Microparticles were in the size range 11-37 microm. Encapsulation efficiency was optimal due to poor aqueous solubility of celecoxib. Considering in vitro release, microparticles could be divided into drug delivery systems with fast and slow release profiles. Microparticles prepared with poly-epsilon-caprolactone, Eudragit RS and low viscosity ethylcellulose, together with physical mixture of celecoxib with lactose and Celebrex, were tested in vivo. Relative bioavailability of celecoxib was below 20% in all cases and was probably the consequence of a slow in vivo release of celecoxib from microparticles or low wettability in the case of Celebrex and physical mixture.
...
PMID:Influence of polymers on the bioavailability of microencapsulated celecoxib. 1776 56

Celecoxib (Celebrex), the first cyclo-oxygenase (COX) 2-selective inhibitor (coxib) to be introduced into clinical practice, has been available for almost a decade. It is approved in one or more countries worldwide for the relief of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (in patients aged > or =2 years) and ankylosing spondylitis (AS), the management of acute pain in adults, the treatment of primary dysmenorrhoea and the reduction in the number of adenomatous colorectal polyps in familial adenomatous polyposis. Celecoxib remains an effective and useful altenative to nonselective NSAIDs in the treatment of acute or chronic musculoskeletal pain. In the latter setting, it offers the prospect of improved gastrointestinal (GI) tolerability and, in patients not taking aspirin for cardioprophylaxis, a GI safety advantage. Currently available evidence of an increase in cardiovascular (CV) risk with celecoxib is inconsistent; any increase in risk is likely to be small and similar to that with nonselective NSAIDs. As with all NSAIDs, the potential GI, CV and renal risks of celecoxib must be weighed against the potential benefits in each individual; it is a rational choice for patients at low CV risk who require NSAID therapy, especially those at increased risk of NSAID-induced GI toxicity, but also those unresponsive to, or intolerant of, other NSAIDs. If selected, celecoxib, like all NSAIDs, should be used at the lowest effective dose for the shortest possible duration.
...
PMID:Celecoxib: a review of its use in the management of arthritis and acute pain. 1798 59

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>