Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective COX-2 inhibitors (coxibs) are approved for the relief of acute pain and symptoms of chronic inflammatory conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). They have similar pharmacological properties but a slightly improved gastrointestinal (GI) safety profile if compared to traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, long-term use of coxibs can be associated with an increased risk for cardiovascular (CV) adverse events (AEs). For this reason, two coxibs were withdrawn from the market. Currently celecoxib, etoricoxib, and lumiracoxib are used. These three coxibs differ in their chemical structure and selectivity for COX-2, which might explain some of their pharmacological features. Following oral administration, the less lipophilic celecoxib has a lower bioavailability (20-40%) than the other two coxibs (74-100%). All are eliminated by hepatic metabolism involving mainly CYP2C9 (celecoxib, lumiracoxib) and CYP3A4 (etoricoxib). Elimination half-life varies from 5 to 8 h (lumiracoxib), 11 to 16 h (celecoxib) and 19 to 32 h (etoricoxib). In patients with liver disease, plasma levels of celecoxib and etoricoxib are increased about two-fold. Clinical efficacies of the coxibs are comparable to tNSAIDs. There is an ongoing discussion about whether the slightly better GI tolerability (which is lost if acetylsalicylic acid is coadministered) of the coxibs is offset by their elevated risks for CV AEs (also seen with tNSAIDs other than naproxen), which apparently increase with dose and duration of exposure. In addition, the higher costs for coxibs (if compared to tNSAIDs, even when a "gastroprotective" proton pump inhibitor is coadministered) should be taken into consideration, if a coxib will be selected for certain patients with a high risk for GI complications. For such treatment, the lowest effective dose should be used for a limited time. Monitoring of kidney function and blood pressure appears advisable. It is hoped that further controlled studies can better define the therapeutic place of the coxibs.
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PMID:Clinical use and pharmacological properties of selective COX-2 inhibitors. 1799 57

(1) Paracetamol is the first-choice analgesic for joint pain. Nonsteroidal antiinflammatory drugs (NSAIDs), especially ibuprofen, are second-line options. Cox-2 inhibitors are no more effective than traditional NSAIDs and have no tangible advantages in terms of gastrointestinal tolerability. In contrast, they expose patients to an increased risk of cardiovascular adverse effects. (2) Etoricoxib is marketed in some European countries to relieve symptoms of osteoarthritis, rheumatoid arthritis, and gout attacks. (3) Many clinical trials have tested etoricoxib in these indications, as well as in ankylosing spondylitis, low back pain, and various types of acute pain. Etoricoxib was no more effective than other NSAIDs such as ibuprofen, naproxen or diclofenac in these situations. (4) Comparative trials showed a higher overall mortality rate with etoricoxib than with naproxen. A combined analysis of long-term comparative trials including 5441 patients, mainly versus naproxen, showed that etoricoxib does not reduce the risk of perforation, ulcer or severe gastrointestinal haemorrhage. Similarly, it does not reduce the risk of mild gastrointestinal events in at-risk patients: those with a history of gastrointestinal disorders, aspirin use, etc. (5) Three trials including a total of 34 701 patients (MEDAL programme) compared cardiovascular thrombotic events associated with etoricoxib and diclofenac. Overall, the cardiovascular risks appear to be similar but the thrombotic risk may be slightly higher with diclofenac than with other conventional NSAIDs. (6) Etoricoxib provoked arterial hypertension, oedema and heart failure during clinical trials. Serious skin reactions were reported both during clinical trials and after marketing, but their precise incidence is not known. Etoricoxib is partly metabolised by the cytochrome P450 isoenzyme CYP 3A4 and increases the bioavailability of ethinylestradiol. (7) When a NSAID is considered, drugs with which we have the most experience should be chosen, such as ibuprofen, and used at the lowest acceptable dose regimen (daily dose and length of treatment). Etoricoxib should be avoided.
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PMID:Etoricoxib: new drug. Avoid using cox-2 inhibitors for pain. 1808 59

Osteoarthritis (OA) is the leading cause of knee morbidity. Age and overweight are the main risk factors for development of knee OA. The majority of patients respond to conservative treatment. For those who don't, surgical treatment is the only alternative. Arthroscopic surgery for the osteoarthritic knee is a well known procedure. Recently, numerous publications addressed the advantages of arthroscopic treatment for this indication. Some of the publications concluded that arthroscopic treatment for knee OA equals placebo. Others found temporary relief of symptoms. Among special subgroup of patients, in which acute pain exacerbation, mechanical block or early OA, utilizing arthroscopic techniques revealed satisfactory results. In this review, we discuss the indications and contraindications for arthroscopic treatment of the osteoarthritic knee according to the latest literature.
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PMID:[Arthroscopic treatment for osteoarthritic knee]. 1868 16

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver.
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PMID:Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis. 1872 96

The effects of an analgesic treatment (lidocaine patches) on brain activity in chronic low back pain (CBP) and in knee osteoarthritis (OA) were investigated using serial fMRI (contrasting fMRI between before and after two weeks of treatment). Prior to treatment brain activity was distinct between the two groups: CBP spontaneous pain was associated mainly with activity in medial prefrontal cortex, while OA painful mechanical knee stimulation was associated with bilateral activity in the thalamus, secondary somatosensory, insular, and cingulate cortices, and unilateral activity in the putamen and amygdala. After 5% lidocaine patches were applied to the painful body part for two weeks, CBP patients exhibited a significant decrease in clinical pain measures, while in OA clinical questionnaire based outcomes showed no treatment effect but stimulus evoked pain showed a borderline decrease. The lidocaine treatment resulted in significantly decreased brain activity in both patient groups with distinct brain regions responding in each group, and sub-regions within these areas were correlated with pain ratings specifically for each group (medial prefrontal cortex in CBP and thalamus in OA). We conclude that the two chronic pain conditions involve distinct brain regions, with OA pain engaging many brain regions commonly observed in acute pain. Moreover, lidocaine patch treatment modulates distinct brain circuitry in each condition, yet in OA we observe divergent results with fMRI and with questionnaire based instruments.
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PMID:A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis. 1895 May 28

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat rheumatoid arthritis, osteoarthritis, acute pain, and fever. However, NSAIDs have side effects that include gastric erosions, ulceration, bleeding, and perforation, etc. Selective cyclooxygenase (COX)-2 inhibitors have been developed to avoid the adverse drug reaction of traditional NSAIDs. The COX-2 inhibitors have a different mechanism of action from nonselective COX inhibitors. In this study, pattern recognition analysis of the (1)H nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by NSAIDs in rats. Urine was collected for 5 h after administering the following NSAIDs at high doses: celecoxib (133 mg kg(-1), p.o.), a COX-2-selective inhibitor; and indomethacin (25 mg kg(-1), p.o.) or ibuprofen (800 mg kg(-1), p.o.), nonselective COX inhibitors. The urine was analyzed using 600 M (1)H NMR for spectral binning and targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin and ibuprofen caused severe gastric damage, but no lesions were observed in the celecoxib-treated rats. The (1)H NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to NSAIDs using partial least-squares discrimination analysis (PLS-DA). There were different clusterings of (1)H NMR spectra according to the gastric damage scores in global profiling. In targeted profiling, a few endogenous metabolites of allantoin, taurine, and dimethylamine were selected as putative biomarkers for the gastric damage induced by NSAIDs. The results of global and targeted profilings suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a current metabolomics study. In addition, the putative biomarkers might also be useful for predicting the risk of adverse effects caused by NSAIDs.
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PMID:Pattern recognition analysis for the prediction of adverse effects by nonsteroidal anti-inflammatory drugs using 1H NMR-based metabolomics in rats. 1946 90

Tapentadol is a novel, centrally acting analgesic with two mechanisms of action: micro-opioid receptor agonism and norepinephrine reuptake inhibition. It has demonstrated broad analgesic efficacy across multiple pain models. This article reviews the clinical development of tapentadol immediate release (IR), including results from Phase II and III clinical trials that evaluated the efficacy and safety of tapentadol IR in patients with moderate-to-severe acute pain. In clinical studies in patients with moderate-to-severe acute postoperative pain, osteoarthritis pain and/or low back pain, tapentadol IR 50, 75 or 100 mg every 4 - 6 h has demonstrated analgesic efficacy similar to that observed with the micro-opioid receptor agonist oxycodone HCl IR 10 or 15 mg every 4 - 6 h. However, at doses providing comparable analgesic efficacy, tapentadol IR has been associated with significantly lower incidences of nausea and/or vomiting and constipation, and a significantly lower rate of treatment discontinuation compared with oxycodone IR. The observed efficacy across different pain models and favorable gastrointestinal tolerability profile associated with tapentadol IR indicate that this novel analgesic is an attractive treatment option for the relief of moderate-to-severe acute pain.
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PMID:Tapentadol immediate release for the relief of moderate-to-severe acute pain. 1979 98

Celecoxib is intended for acute pain, menstrual cramps, pain, and inflammation of osteoarthritis and rheumatoid arthritis. The aim of this study was to evaluate the effects of celecoxib (10 and 50 mg/kg/day) treatment on rats orally for 28 days. We examined effects on some biochemical parameters and kidney and liver tissues of celecoxib-treated Wistar albino male rats. At the end of the study, hepatic and renal function tests were performed and liver and kidney of rats were microscopically examined to detect systemic toxicity of celecoxib. Celecoxib-treated rats had statistically significant decreases of cholesterol, total bilirubin, total protein, urea, globulin, blood urea nitrogen, phosphorus, and calcium. Serum gamma glutamyl transferase levels increased in 10- and 50-mg/kg/day celecoxib-treated rats. Histological examinations showed mononuclear cell infiltration, hyperplasia, and cellular degeneration in liver and tubular damage and mononuclear cell infiltration in kidney. We suggest that high doses of celecoxib may cause changes in liver and kidney histopathology, liver function, and in some biochemical parameters.
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PMID:Pathological and biochemical effects of therapeutic and supratherapeutic doses of celecoxib in Wistar albino male rats. 2012 24

Lumiracoxib Prexige, Novartis AG) is a highly selective inhibitor of cyclooxygenase-2 that has been approved in 22 countries including the UK for analgesic therapy in chronic and acute pain. For patients with osteoarthritis, the recommended initial dose is 100 or 200 mg once daily, in one or two divided doses. In patients with primary dysmenorrhea, or following dental or orthopedic surgery with moderate-to-severe acute pain, the recommended dose is 400 mg once daily. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) tested the efficacy and gastrointestinal safety of the drug against two traditional nonselective nonsteroidal anti-inflammatory drugs, naproxen and ibuprofen. The results from this trial demonstrated that lumiracoxib reduces gastrointestinal ulcer complication rates by 66% overall and 79% among nonaspirin users in a population without gastroprotection. Lumiracoxib was not associated with a statistically significant difference in cardiovascular morbidity and mortality compared with nonselective nonsteroidal anti-inflammatory drugs. However, in view of the ongoing debate about the safety of cyclooxygenase-2 inhibitors, the use of this drug class should be limited to patients with increased risk of gastrointestinal complications until results of randomized trials in cardiovascular high-risk populations are published.
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PMID:Lumiracoxib, a highly selective COX-2 inhibitor. 2047 53

Lumiracoxib is a selective cyclooxygenase-2 inhibitor developed for the symptomatic treatment of osteoarthritis and acute pain. Concerns over hepatotoxicity have contributed to the withdrawal or non-approval of lumiracoxib in most major drug markets worldwide. We performed a case-control genome-wide association study on 41 lumiracoxib-treated patients with liver injury (cases) and 176 matched lumiracoxib-treated patients without liver injury (controls). Several SNPs from the MHC class II region showed strong evidence of association (the top SNP was rs9270986 with P = 2.8 x 10(-10)). These findings were replicated in an independent set of 98 lumiracoxib-treated cases and 405 matched lumiracoxib-treated controls (top SNP rs3129900, P = 4.4 x 10(-12)). Fine mapping identified a strong association to a common HLA haplotype (HLA-DRB1*1501-HLA-DQB1*0602-HLA-DRB5*0101-HLA-DQA1*0102, most significant allele P = 6.8 x 10(-25), allelic odds ratio = 5.0, 95% CI 3.6-7.0). These results offer the potential to improve the safety profile of lumiracoxib by identifying individuals at elevated risk for liver injury and excluding them from lumiracoxib treatment.
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PMID:A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. 2125 84


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