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Nature Communications Dec 2021Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates...
Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identify that the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent plant immune response. TNX treatment decreases NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. A cysteine labeling assay reveals that cysteine residues in NPR1 can be oxidized in vitro, leading to disulfide-bridged oligomerization of NPR1, but not in vivo regardless of SA or TNX treatment. Therefore, this study indicates that oxicam inhibits NPR1-mediated SA signaling without affecting the redox status of NPR1.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arabidopsis; Arabidopsis Proteins; Gene Expression Regulation, Plant; Meloxicam; Piroxicam; Salicylic Acid
PubMed: 34911942
DOI: 10.1038/s41467-021-27489-w -
Chemical & Pharmaceutical Bulletin Jan 2003Two simple and accurate methods are described for the determination of piroxicam and tenoxicam in their pharmaceutical preparations. The spectrophotometric method...
Two simple and accurate methods are described for the determination of piroxicam and tenoxicam in their pharmaceutical preparations. The spectrophotometric method involves the oxidation of these drugs with potassium iodate in acid medium with the liberation of iodine and subsequent extraction with cyclohexane followed by measuring the absorbance at lambda=522 nm. Beer's law is obeyed in the concentration range of 0.05-1.1 and 0.05-0.6 mg x ml(-1) for piroxicam and tenoxicam, respectively. The apparent molar absorptivities of the resulting coloured products are found to be 2.7 x 10(3) and 2.5 x 10(3) l mol(-1) x cm(-1), whereas Sandell sensitivities are 0.012 and 0.013 g x cm(-2) for piroxicam and tenoxicam, respectively. The potentiometric method involves the direct titration of both drugs with N-bromosuccinimide in acid medium and the end point is determined potentiometrically using platinum indicator electrode. Piroxicam and tenoxicam can be determined quantitatively in the concentration range of 0.33-3.37 and 0.33-4.08 mg x ml(-1) for tenoxicam and piroxicam, respectively. The standard deviation and relative standard deviation values are found to be ranged from 0.05-0.07 and 0.37-0.98% and 0.025-0.078 and 0.25-1.2% for tenoxicam and piroxicam, respectively. The two methods are accurate within +/-1.0%. Optimum conditions affecting both methods are studied. The proposed methods are applied for the determination of the drugs in pure form and in commercial pharmaceutical preparations.
Topics: Pharmaceutical Preparations; Piroxicam; Potentiometry; Spectrophotometry
PubMed: 12520119
DOI: 10.1248/cpb.51.6 -
The Journal of Headache and Pain Nov 2023Medication overuse headache (MOH) is a secondary headache that accompanies chronic migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used...
OBJECTIVE
Medication overuse headache (MOH) is a secondary headache that accompanies chronic migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used analgesics worldwide and they are known to induce leaky gut. In this study, we aimed to investigate whether NSAID induced MOH is associated with altered circulating lipopolysaccharide binding protein (LBP) levels and inflammatory molecules.
MATERIALS AND METHODS
Piroxicam (10 mg/kg/day, po) for 5 weeks was used to induce MOH in female Sprague Dawley rats. Pain behavior was evaluated by periorbital withdrawal thresholds, head-face grooming, freezing, and head shake behavior. Serum samples and brain tissues were collected to measure circulating LBP, tight junction protein occludin, adherens junction protein vascular endothelial (VE)-cadherin, calcitonin gene-related peptide (CGRP), IL-6 levels and brain high mobility group box-1 (HMGB1) and IL-17 levels.
RESULTS
Chronic piroxicam exposure resulted in decreased periorbital mechanical withdrawal thresholds, increased head-face grooming, freezing, and head shake behavior compared to vehicle administration. Serum LBP, CGRP, IL-6, IL-17, occludin, VE-cadherin levels and brain IL-17 and HMGB1 levels were significantly higher in piroxicam group compared to controls. Serum LBP was positively correlated with occludin (r = 0.611), VE-cadherin (r = 0.588), CGRP (r = 0.706), HMGB1 (r = 0.618) and head shakes (r = 0.921), and negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.740).
CONCLUSION
Elevated serum LBP, VE-cadherin and occludin levels indicating disrupted intestinal barrier function and leakage of LPS into the systemic circulation were shown in female rats with MOH. LPS induced low-grade inflammation and elevated nociceptive and/or pro-inflammatory molecules such as HMGB1, IL-6, IL-17 and CGRP may play a role in the development and maintenance of MOH. Interference with leaky gut and pro-inflammatory nociceptive molecules could also be a target for sustained management of MOH.
Topics: Rats; Female; Animals; Lipopolysaccharides; Calcitonin Gene-Related Peptide; HMGB1 Protein; Interleukin-17; Rats, Sprague-Dawley; Piroxicam; Occludin; Interleukin-6; Headache Disorders, Secondary; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37940864
DOI: 10.1186/s10194-023-01672-4 -
European Endodontic Journal Oct 2022The objective of this study was to compare the effectiveness of premedication drugs including single dose Piroxicam and Prednisolone in regard to post endodontic pain at... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The objective of this study was to compare the effectiveness of premedication drugs including single dose Piroxicam and Prednisolone in regard to post endodontic pain at different time intervals (24, 48, 72 and 96 hours) after single visit root canal treatment.
METHODS
This randomized clinical trial (registration no. NCT04124822) was performed in operative dentistry department of a private clinical institute. One hundred twenty patients identified with symptomatic irreversible pulpitis were included in the study. The pain intensity levels were marked through the use of visual analog scale (VAS) before the commencement of treatment. The participants were randomly allocated in three groups, Group I (n=40) received no medication (control), Group II (n=40) received Piroxicam (20 mg) and Group III (n=40) received Prednisolone (20 mg). The drugs were administered thirty minutes before the endodontic procedure was initiated. Root canal treatmentwas carried out followed by placement of provisional restoration in a single appointment. The patients were instructed to continue marking their pain intensity levels after 24, 48, 72 and 96 hours using VAS. All patients were called for follow up after 4 days for clinical evaluation and the placement of permanent restoration. The effectiveness of each drug over different time interval was studied employing ANOVA test. The significance level was set at P≤0.05.
RESULTS
The results of the present study revealed that a higher percentage of patients in all 3 groups, reported no post-operative pain at all evaluated time durations (24, 48, 72, and 96 hours). However, the long term effectiveness (96 hours) of both drugs to reduce post-endodontic pain was observed to be statistically insignificant. There was no significant difference in demographic data in terms of age (P=0.14), gender (P=0.12), whilst tooth type (P≤0.05) showed statistically significant value.
CONCLUSION
Pre-medication with either single dose piroxicam or prednisolone was able to prevent post-endodontic pain in patients with symptomatic irreversible pulpitis.
Topics: Dental Pulp Cavity; Humans; Pain, Postoperative; Piroxicam; Prednisolone; Premedication; Pulpitis
PubMed: 36217645
DOI: 10.14744/eej.2022.24119 -
The Cochrane Database of Systematic... Jul 2015Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.
OBJECTIVES
To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults.
SEARCH METHODS
We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in-house database to January 2015. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers' websites.
SELECTION CRITERIA
We included randomised, placebo-controlled studies (parallel-group or cross-over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).
MAIN RESULTS
We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast-acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of treatment. Other participants were either in studies not reporting outcomes we could analyse, or were given one of several active comparators in single studies.For the IHS-preferred outcome of being pain free at 2 hours the NNT for ibuprofen 400 mg (all formulations) compared with placebo was 14 (95% confidence interval (CI), 8.4 to 47) in four studies, with no significant difference from placebo at 1 hour (moderate quality evidence). The NNT was 5.9 (4.2 to 9.5) for the global evaluation of 'very good' or 'excellent' in three studies (moderate quality evidence). No study reported the number of participants experiencing no worse than mild pain at 1 or 2 hours. The use of rescue medication was lower with ibuprofen 400 mg than with placebo, with the number needed to treat to prevent one event (NNTp) of 8.9 (5.6 to 21) in two studies (low quality evidence).Adverse events were not different between ibuprofen 400 mg and placebo; RR 1.1 (0.64 to 1.7) (high-quality evidence). No serious adverse events were reported.
AUTHORS' CONCLUSIONS
Ibuprofen 400 mg provides an important benefit in terms of being pain free at 2 hours for a small number of people with frequent episodic tension-type headache who have an acute headache with moderate or severe initial pain. There is no information about the lesser benefit of no worse than mild pain at 2 hours.
Topics: Acetaminophen; Administration, Oral; Adult; Analgesics, Non-Narcotic; Cyclooxygenase Inhibitors; Diclofenac; Humans; Ibuprofen; Ketoprofen; Naproxen; Numbers Needed To Treat; Pain Measurement; Piroxicam; Randomized Controlled Trials as Topic; Tension-Type Headache; Time Factors
PubMed: 26230487
DOI: 10.1002/14651858.CD011474.pub2 -
Journal of Translational Medicine May 2008Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently...
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cisplatin; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Enzyme Activation; Humans; Mesothelioma; Piroxicam
PubMed: 18498639
DOI: 10.1186/1479-5876-6-27 -
The Cochrane Database of Systematic... May 2012Decompression illness (DCI) is due to bubble formation in the blood or tissues following the breathing of compressed gas. Clinically, DCI may range from a trivial... (Review)
Review
BACKGROUND
Decompression illness (DCI) is due to bubble formation in the blood or tissues following the breathing of compressed gas. Clinically, DCI may range from a trivial illness to loss of consciousness, death or paralysis. Recompression is the universally accepted standard treatment of DCI. When recompression is delayed, a number of strategies have been suggested in order to improve the outcome.
OBJECTIVES
To examine the effectiveness and safety of both recompression and adjunctive therapies in the treatment of DCI.
SEARCH METHODS
In our previous update we searched until October 2009. In this version we searched CENTRAL (The Cochrane Library, October 2011); MEDLINE (1966 to October 2011); CINAHL (1982 to October 2011); EMBASE (1980 to October 2011); the Database of Randomised Controlled Trials in Hyperbaric Medicine (October 2011); and handsearched journals and texts.
SELECTION CRITERIA
We included randomized controlled trials that compared the effect of any recompression schedule or adjunctive therapy with a standard recompression schedule. We did not apply language restrictions.
DATA COLLECTION AND ANALYSIS
Three authors extracted the data independently. We assessed each trial for internal validity and resolved differences by discussion. Data were entered into RevMan 5.1.
MAIN RESULTS
Two randomized controlled trials enrolling a total of 268 patients satisfied the inclusion criteria. The risk of bias for Drewry 1994 was unclear as this study was presented as an abstract, while Bennett 2003 was rated as at low risk. Pooling of data was not possible. In one study there was no evidence of improved effectiveness with the addition of a non-steroidal anti-inflammatory drug (tenoxicam) to routine recompression therapy (at six weeks: relative risk (RR) 1.04, 95% confidence interval (CI) 0.90 to 1.20, P = 0.58) but there was a reduction in the number of compressions required when tenoxicam was added from three to two (P = 0.01, 95% CI 0 to 1). In the other study, the odds of multiple recompressions were lower with a helium and oxygen (heliox) table compared to an oxygen treatment table (RR 0.56, 95% CI 0.31 to 1.00, P = 0.05).
AUTHORS' CONCLUSIONS
Recompression therapy is standard for the treatment of DCI, but there is no randomized controlled trial evidence for its use. Both the addition of a non-steroidal anti-inflammatory drug (NSAID) and the use of heliox may reduce the number of recompressions required, but neither improve the odds of recovery. The application of either of these strategies may be justified. The modest number of patients studied demands a cautious interpretation. Benefits may be largely economic and an economic analysis should be undertaken. There is a case for large randomized trials of high methodological rigour in order to define any benefit from the use of different breathing gases and pressure profiles during recompression therapy.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Decompression Sickness; Humans; Hyperbaric Oxygenation; Piroxicam; Randomized Controlled Trials as Topic; Retreatment
PubMed: 22592704
DOI: 10.1002/14651858.CD005277.pub3 -
Avicenna Journal of Phytomedicine Nov 2014The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative...
OBJECTIVE
The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative stress and gastro-toxicity in Wistar rats.
MATERIALS AND METHODS
Thirty healthy male and female Albino Wistar rats (190-220 g) were grouped into six (n = 5) with designated treatments including: Normal saline, piroxicam (20 mg/kg), extract (200 and 400 mg/kg) alone and both doses of the extract co-administered with piroxicam. The drugs were administered orally to all the rats for fourteen consecutive days and on the fifteenth day, they were euthanized with chloroform inhalation. Blood samples and the stomachs were isolated for evaluation of the oxidative stress biomarkers and gastro integrity, respectively.
RESULTS
The results of the study revealed that the levels of oxidative stress markers didn't differ significantly between the groups receiving the extract alone, the extract in combination or piroxicam alone. Gross and histological observations of the stomach showed gastric mucosal changes and mild atrophic lesions in the piroxicam group only.
CONCLUSION
This study illustrates the interaction of Khaya senegalensis and piroxicam results in the gastro-protective beneficial effects. The extract's outcome on various prostaglandin levels and synthesis is being considered towards possible elucidation regarding the exact mechanism of cytoprotection.
PubMed: 25386401
DOI: No ID Found -
AAPS PharmSciTech 2009We have recently demonstrated that coprecipitation of cimetidine (C) and piroxicam (P) at a mole ratio of 1:1 results in the transformation of the crystalline forms of...
We have recently demonstrated that coprecipitation of cimetidine (C) and piroxicam (P) at a mole ratio of 1:1 results in the transformation of the crystalline forms of both drugs to an amorphous state. In this study, coprecipitates and physical mixtures of cimetidine and piroxicam were further investigated at C/P mole ratios of 1:10, 1:5, 1:4, 1:2, 10:1, 20:1, 30:1, 40:1, and 52.5:1, the latter being the composition of a clinically used dosage. The physicochemical properties of these samples were examined using X-ray diffraction and Fourier transform infrared spectroscopy. Additionally, dissolution of piroxicam in the samples at C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 was investigated at pH 1.2 and pH 4. In coprecipitates with C/P mole ratios of 10:1, 20:1, 30:1, and 40:1, crystalline forms of both drugs were transformed to amorphous states. A mixture of an amorphous state and cimetidine crystalline form A was observed for the coprecipitate with a C/P mole ratio of 52.5:1. For the coprecipitates with C/P mole ratios of 1:2, 1:4, 1:5, and 1:10, cimetidine form A was transformed to form C, whereas piroxicam form II was modified to form I. It is interesting that small molecules, instead of polymers or solvents, can cause such crystal structure transformations. The dissolution of piroxicam at pH 4 is lower than that at pH 1.2. Additionally, the coprecipitates and physical mixtures with C/P mole ratios of 10:1, 20:1, 30:1, 40:1, and 52.5:1 demonstrate substantially higher dissolution of piroxicam compared to that of drug alone.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cimetidine; Drug Combinations; Histamine H2 Antagonists; Hydrogen-Ion Concentration; Piroxicam; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 19521782
DOI: 10.1208/s12249-009-9263-9 -
British Journal of Clinical Pharmacology Jun 19961. An open-label study was performed to assess the effect of piroxicam on the pharmacokinetics of acenocoumarol enantiomers. 2. Eight healthy male volunteers received an...
1. An open-label study was performed to assess the effect of piroxicam on the pharmacokinetics of acenocoumarol enantiomers. 2. Eight healthy male volunteers received an oral dose of 4 mg rac-acenocoumarol on days 1 and 8, plus 40 mg piroxicam orally 2 h before the anticoagulant on day 8. R- and S-acenocoumarol, piroxicam and their metabolites were measured in plasma over a 24 h interval. 3. The pharmacokinetics of R-acenocoumarol were markedly modified by piroxicam: Cmax+28.0% (s.d.23.8), P < 0.05; AUC(0, 24 h)+47.2% (21.5), P < 0.005; and t1/2 +38.0% (34.5), P < 0.01. A concomitant decrease of CL/F was observed: -30.8% (10.0), P < 0.0001. A similar, but statistically non-significant trend, was observed on the S-enantiomer: Cmax: +9.5% (s.d.36.6), AUC(0, 24 h): + 15.4% (23.4), t1/2: +19.9% (42.0), and CL/F: -9.8% (20.5). V/F remained unchanged for both enantiomers. 4. Piroxicam plasma AUC(0, 24 h) correlated closely with R- and S-acenocoumarol AUCs on day 1 (r = 0.901, P < 0.005 and r = 0.797, P < 0.05, respectively), as well as with the difference of AUC between days 1 and 8 for R-acenocoumarol (r = 0.903, P < 0.001) and S-acenocoumarol (r = 0.711, P < 0.05). 5. Piroxicam markedly reduced acenocoumarol enantiomer clearance, with a greater effect on the more active R-isomer. This interaction, which occurs in addition to the well documented pharmacodynamic one (effect on platelets), is expected to result in increased anticoagulant effect.
Topics: Acenocoumarol; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Drug Interactions; Humans; Male; Piroxicam; Stereoisomerism
PubMed: 8799517
DOI: 10.1046/j.1365-2125.1996.03558.x