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)

Ro 15-8081, a substituted cyclohexanol hydrochloride, inhibits the re-uptake of norepinephrine and of serotonin. Its antinociceptive properties have been demonstrated in animals and then confirmed in humans after single-dose administration. The objective was to determine the analgesic efficacy and the safety of Ro 15-8081 in osteoarthritis of the hip and knee (femoro-tibial location) after multiple-dose application. The design for studying dosage employed 5 parallel groups in an international multicenter, double-blind, randomized trial having a duration of 2 weeks. Drugs studied were: 20 mg Ro 15-8081 (divided into 2 doses), 50 mg Ro 15-8081 (divided into 2 doses), 100 mg Ro 15-8081 (divided into 2 doses), placebo twice daily or 20 mg/day piroxicam (piroxicam in the morning and placebo in the evening). Piroxicam was used as a reference drug in order to validate clinical testing. Assessment criteria were pain (100-mm VAS) and function (Lequesne's index). A responder (main assessment criterion) was defined as a patient exhibiting a reduction of at least 30% of pain (VAS) during the study (intention-to-treat analysis). A total of 522 patients were enrolled in the study. A clear beneficial effect of piroxicam was observed when compared with placebo (70% and 48% of responders in piroxicam and placebo groups respectively; P < 0.0001). Multigroup comparison showed a statistically significant difference between Ro 15-8081 groups and the placebo group regarding mean change in pain between D1 and Dend and the rate of VAS responders. Comparison (Dunnett's t or chi 2 tests) between each individual Ro 15-8081 and the placebo group reached statistical significance for the 100 mg Ro 15-8081 group (mean change in pain between D1 and Dend: P = 0.05; percentage of responders: P = 0.0008) but no statistically significant difference for the other dosages of Ro 15-8081. Fifty-three patients withdrew from the study because of adverse events and/or inefficacy, mainly in 50 and 100 mg Ro 15-8081 groups and in a dose-related manner. The adverse events which appeared to be drug related were mainly dryness of the mouth, insomnia, headache, constipation, nausea, dizziness, nervousness, palpitation. This study suggests that 100 mg Ro 15-8081 per day divided into 2 doses has (1) an analgesic effect in hip or knee osteoarthritis and (2) poor acceptability in the conditions of the study regimen application.
Pain 1996 Jan
PMID:Ro 15-8081 in osteoarthritis of hip and knee: a double-blind placebo-controlled multicentre dose-ranging study on analgesia. 886 51

The study of comparison of the clinical responses of acute hemorrhagic conjunctivitis to antibiotic eye drops alone and combined with topical piroxicam was analyzed. Seventy-five patients (146 eyes) with viral conjunctivitis were randomly assigned to receive topical antibiotic (35 cases) or antibiotic combined with piroxicam eye drops (40 cases). The patients were examined under slit lamp biomicroscope every other day for the first week, then twice a week until recovery. There was no statistically significant difference between groups in mean age, sex, bilaterality, history of contact, systemic involvement, mean incubation period, mean onset and mean follow-up time. Mean recovery time in the piroxicam group (4.9 days) was less than for the control group (P = 0.003). Foreign body sensation, pain and tearing in the piroxicam group recovered significantly faster than in the control group. Complete recovery of all symptoms and signs in piroxicam treated eyes (61%) was significantly more common than with antibiotic only (29%) in spite of more drug induced burning. Piroxicam eye drops may have beneficial effects for acute hemorrhagic conjunctivitis to relieve discomfort, pain, and accelerate recovery.
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PMID:Topical piroxicam and conjunctivitis. 917 71

The objective of this study is to evaluate and compare the analgesic efficacy of Piroxicam Fast Dissolving Dosage Formulation (FDDF) administered sublingually either preoperatively or postoperatively with that of aspirin and placebo. Hundred patients, undergoing surgical removal of mandibular third molars were given sublingually either piroxicam FDDF 40 mg or placebo or aspirin 500 mg according to a double blind experimental model. Pain scores and pain relief was recorded hourly for six hours following the operation. Rescue analgesics used during the trial and overall assessment of the drug were recorded at the end of six hours. Scores were evaluated statistically by student t test. Piroxicam FDDF was significantly (p < 0.05) more effective than aspirin and placebo for all variables, and less rescue analgesics were required in patients receiving piroxicam preoperatively. It was concluded that single doses of piroxicam FDDF administered sublingually either preoperatively or postoperatively appeared to be effective analgesic for the control of pain after third molar surgery with no side effects.
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PMID:Postoperative pain control by single doses of piroxicam administered sublingually and aspirin. 956 95

A telephone audit was carried out on patients 24 hours after day case surgery. An initial audit shortly after the day case opened indicated pain scores and nausea that were considered unacceptable. Some 8.6% of patients called their family doctor (GP) to visit their home in the post-operative period. Pre-operative Piroxicam 20 mg was then initiated (in most patients) to reduce the pain scores, which it did. Only one patient in 111 (0.9%) called their GP out, but nausea scores remained unchanged. Methods to reduce this index are suggested.
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PMID:An audit of post-operative pain and nausea in day case surgery. 964 83

The possible role of spinal prostanoids in the tactile allodynia and thermal hyperalgesia associated with an experimental model of neuropathic pain was investigated. Neuropathic pain was induced by tight ligation of the L5 and L6 spinal nerves. Tactile allodynia was assessed 7 days after the surgery by measuring hindpaw withdrawal threshold to probing with von Frey filaments. Thermal hyperalgesia and nociception were determined by the 52 degrees C warm-water tail-flick test and by applying radiant heat to the plantar aspect of the hindpaw ipsilateral to the ligation. Minimal antiallodynic effect was produced by intrathecal (i.th.) administration of ketorolac or morphine up to the highest testable dose (100 microg) or by the (R)- or (S)-enantiomers of ketorolac (up to 6 microg) when administered alone. However, i.th. administration of a fixed ratio (1:1) of morphine plus racemic ketorolac or of morphine plus the (S)-enantiomer of ketorolac (S-ketorolac) produced a dose- and time-related antiallodynic effect: ED50 114 +/- 35.9 microg (total dose) for morphine plus ketorolac and 70.5 +/- 21.0 microg (total dose) for morphine plus S-ketorolac. The combination of i.th. morphine plus the (R)-enantiomer of ketorolac (R-ketorolac) (up to 200 microg total dose) was without effect. Similar antiallodynic activity was obtained for the co-administration of i.th. morphine and intravenous (i.v.) racemic ketorolac. In order to investigate the role of cyclooxygenase (COX) isozymes, relatively selective COX1 (piroxicam) and COX2 N-[2-cyclohexyloxy-4-nitrophenyl] metanesulfonamide (NS-398) inhibitors were administered i.th. (60 microg) alone or together with i.th. morphine. Piroxicam, NS-398, morphine and vehicle (90% DMSO) were without significant antiallodynic effect when administered alone, but moderate antiallodynic effects were produced by i.th. administration of fixed ratio (1:1) combinations of morphine with 60 microg each (highest soluble dose) of piroxicam (%MPE = 40.8 +/- 10.2) or NS-398 (%MPE = 32.4 +/- 9.5). Further, the combined i.th. administration of morphine, piroxicam and NS-398 in fixed 1:1:1 ratio (60 microg each) resulted in a supraadditive antiallodynic effect (%MPE = 70.4 +/- 10.8). Finally, morphine, but not ketorolac, given i.th. produced dose-dependent anti nociception in either the tail-flick or the paw-flick tests. However, there was no synergy between morphine and ketorolac against thermal nociception in either of the tests. These findings suggest that spinal prostanoids produced via both COX1 and COX2 pathways may play a role in neuropathic pain states and suggest the clinical utility of opioid plus COX-inhibitor combination therapy.
Pain 1999 Jul
PMID:Synergistic antiallodynic effects of spinal morphine with ketorolac and selective COX1- and COX2-inhibitors in nerve-injured rats. 1042 61

In 1997, we described a new automated method of scoring the pain behaviors in the formalin test. The algic behavior was automatically measured with the help of a video-analysis system. The time during which the animal grooms, licks, or bites itself was used as the parameter of pain. In the present study, we tested various analgesics to realize a pharmacological validation of the system. The effect of opiate analgesic (morphine, i.v.), nonsteroidal anti-inflammatory drugs (paracetamol, i.v., piroxicam, i.v., indomethacin, i.v.), antidepressant drugs (clomipramine, desipramine, nortryptyline, and paroxetine, i.p.), and serotonin (i.t.) were analyzed. A dose of 1.25 mg/kg of morphine induced a decrease in the scores of phases 1 and 2. Naloxone (0.25 mg/kg) reversed the effect of morphine (2.5 mg/kg). A 20-mg/kg dose of indomethacin induced a decrease in the second phase, and paracetamol induced a decrease in both phases (analgesic doses were 400 mg/kg and 200 mg/kg for first and second phases, respectively). Piroxicam had no effect on the pain scores. Clomipramine, desipramine, and paroxetine at a dose of 5 mg/kg induced a significant decrease in the second phase. Nortriptyline had no effect on the pain scores. A dose of 75 microg of serotonin induced a decrease in both phases 1 and 2. This study demonstrated that this system shows a good pharmacological sensitivity, although it is lower than that of manual assessment.
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PMID:Pharmacological validation of an automated method of pain scoring in the formalin test in rats. 1096 14

Piroxicam (Feldene) is indicated for osteoarthritis and rheumatoid arthritis but not analgesia due to its delayed onset of pain relief. Piroxicam-beta-cyclodextrin (PBCD) was developed for pain indication by virtue of the increased absorption rate of piroxicam. Forty-eight patients received a single dose of PBCD or Feldene (10, 20, and 40 mg) in a randomized study, and piroxicam plasma concentration and pain relief were measured. The purpose of the study was to investigate the PK-PD relationship of piroxicam, determine the optimal dose, and evaluate the effect of increased absorption rate on analgesic effect of piroxicam for the pain model studied. The pharmacokinetic data were best described by a two-compartment model with first-order absorption. The absorption rate of PBCD (5/h) was faster than Feldene (1.41/h). Pain relief was found to be increasing with drug concentration in a hypothetical effect compartment (Emax model). The estimated half-life of the equilibration between plasma and effect site was about 2.34 hours. Monte Carlo simulation showed that the time when at least 50% of the patients have a 75% probability of achieving meaningful pain relief (pain intensity difference (PID > or = 1) for PBCD and Feldene at a dose of 20 mg was about 0.5 and 1.5 hours, respectively. PBCD demonstrated an advantage with an onset of pain relief 1 hour earlier than Feldene.
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PMID:Comparative population pharmacokinetic-pharmacodynamic analysis for piroxicam-beta-cyclodextrin and piroxicam. 1107 11

Membrane fusion is an important event in many biological processes and is characterized by several intermediate steps of which content mixing between the two fusing vesicles signals the completion of the process. Fusion induced solely by small drug molecules is not a common event. Non Steroidal Anti-Inflammatory Drugs (NSAIDs), that control pain and inflammation, are also capable of exhibiting diverse functions. In this study we present a new function of NSAIDs belonging to the oxicam group, as membrane fusogenic agents. Small Unilamellar Vesicles (SUVs) formed by the phospholipid, dimyristoylphosphatidylcholine (DMPC), were used as model membranes. Fluorescence assays using terbium/dipicolinic acid (Tb/DPA) were used to monitor content mixing and corresponding leakage in presence of the drugs. Transmission Electron Microscope (TEM) was also used to image fusion bodies in drug treated vesicles as compared to the untreated ones. The results show that the three oxicam NSAIDs viz. Meloxicam, Piroxicam and Tenoxicam can induce fusion of DMPC vesicles and lead the fusion process to completion at a very low drug to lipid ratio (D/L) of 0.045. The oxicam drugs exhibit differential fusogenic behavior as reflected in the kinetics of content mixing and leakage, both of which can be described by a single exponential rate equation. Moreover, not all NSAIDs can induce membrane fusion. Indomethacin, an acetic acid group NSAID and ibuprofen, a propionic acid group NSAID, did not induce fusion of vesicles. This new property of NSAIDs has important applications in biochemical processes.
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PMID:Membrane fusion: a new function of non steroidal anti-inflammatory drugs. 1861 19

The aim of this study was to compare the efficacy of topical piroxicam and EMLA cream on pain control and subsequent inflammation in neodymium:yttrium-aluminum-garnet (Nd:YAG) 1,064 nm laser hair removal in female volunteers. Fifty female volunteers were enrolled in this prospective, randomized, double-blind, clinical study over a 6-month period. Patients were randomly assigned to receive topical piroxicam as group Piroxicam or EMLA cream as group EMLA. Topical analgesics were applied to the treatment sites for 60 min. The pain scores [on a visual analog scale (VAS)] and side effects were recorded before the hair removal, during the hair removal, at the end of the hair removal, and 1 h, 2 h and 24 h after the hair removal. Patients' characteristics and the treatment settings of the Nd:YAG 1,064 nm laser were similar in the two groups. The pain scores (VAS) were similar, and satisfaction was high in both groups after the hair removal. The number of blanching and erythema episodes were significantly higher in group E than in group P (P < 0.001). Inflammatory side effects were less frequent in group P than in group E after the procedure (P < 0.001). This study showed that topical piroxicam and EMLA provided adequate and similar pain relief after Nd:YAG 1,064 nm laser hair removal in female volunteers. Topical piroxicam was associated with fewer inflammatory side effects than was EMLA cream, because of its anti-inflammatory effect after the procedure.
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PMID:A clinical comparison of topical piroxicam and EMLA cream for pain relief and inflammation in laser hair removal. 1871 27

Piroxicam is a non-steroidal anti-inflammatory drug that is characterised by low solubility and high permeability. In order to improve the drug dissolution rate, the co-grinding method was used as an approach to prepare piroxicam co-ground in the carriers such as glucosamine hydrochloride. As, this amino sugar (glucosamine HCl) has been shown to decrease pain and improve mobility in osteoarthritis in joints, therefore, the incorporation of glucosamine in piroxicam formulations would be expected to offer additional benefits to patients. The effect of the order of grinding on the dissolution of piroxicam was also investigated. Co-ground drug and glucosamine were prepared in different ratios using a ball mill. The samples were then subjected to different grinding times. In order to investigate the effect of the grinding process on the dissolution behaviour of piroxicam, the drug was ground separately in the absence of glucosamine. Mixtures of ground piroxicam and unground D-glucosamine HCl were prepared. Physical mixtures of piroxicam and glucosamine were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FTIR, SEM, XRPD and DSC. These results showed that the presence of glucosamine HCl can increase dissolution rate of piroxicam compared to pure piroxicam. Generally, all dissolution profiles showed the fastest dissolution rate when ground piroxicam was mixed with unground glucosamine. This was closely followed by the co-grinding of piroxicam with glucosamine where lower grinding times showed the fastest dissolution. The solid state studies showed that the grinding of piroxicam for longer times had no effect on polymorphic form of piroxicam, whereas mixtures of piroxicam-glucosamine ground for longer times (60 min) converted piroxicam polymorph II to polymorph I.
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PMID:Effect of glucosamine HCl on dissolution and solid state behaviours of piroxicam upon milling. 2320 37


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