Nimesulide Group Research Articles

Etodolac, a selective cyclooxygenase-2 inhibitor, inhibits liver metastasis of colorectal cancer cells via the suppression of MMP-9 activity

Synchronous or metachronous liver metastasis occurs in approximately 15% of colorectal cancer patients and is an important negative prognostic factor. We therefore need an effective therapy to prevent metastasis. It has become apparent that cyclooxygenase (COX)-2 plays an important role in cancer growth, invasion and metastasis and that there is potential for chemoprevention via inhibition of these processes. We injected colon 26, a colorectal cancer cell line, in CDF1 mouse spleen and, from the following day, two kinds of COX-2 inhibitor (etodolac and nimesulide) were administered orally. Two weeks later, the animals were sacrificed, the liver was excised, and we counted the number of metastatic nodules on the liver surface. In addition, COX-2 mRNA, matrix metalloproteinase (MMP)-9 mRNA, and tissue inhibitor of MMP (TIMP)-1 mRNA of cancer tissue were measured by means of real-time RT-PCR. The number of metastatic nodules on the liver surface was significantly lower in the etodolac-treated group than in controls (p=0.001), but no significant difference was noted in the nimesulide-treated group. The expression of COX-2 mRNA was also significantly lower in the etodolac-treated group than in controls (p=0.04), but not in the nimesulide-treated group. In addition, the expression of MMP-9 mRNA was significantly lower in the etodolac group than in controls (p=0.02), but not in the nimesulide group. Among the groups, there were no significant differences in TIMP-1 mRNA. Expression of COX-2 mRNA and MMP-9 mRNA correlated significantly (r=0.78, p=0.001), but there was no correlation between either COX-2 mRNA and TIMP-1 mRNA expression or between MMP-9 mRNA and TIMP-1 mRNA expression. These findings indicate that the selective COX-2 inhibitor, etodolac, suppresses liver metastasis by reducing MMP-9 activity.

Double blind clinical trail comparing the safety and efficacy of nimesulide (100g) and diclofenac in osteoarthrosis of the hip and knee joints

Osteoarthritis of the hip or knees is a very disabling condition in both Caucasians and Africans. A lot of medical drugs have been in use with their corresponding side effects, hence the search for newer drugs with fewer side effects. A double blind clinical trial comparing the safety and efficacy of nimesulide and diclofenac was carried out in the University College Hospital Ibadan. All patients referred to the outpatients department of the orthopaedic division with osteoarthritis of the hips and knees who met the criteria for inclusion in the study were used for the study. There were a total number of sixty-seven (67) patients. 70.6% of the nimesulide patients had only mild pain in the involved joint on completion of the eight weeks trial compared to 50% of the diclofenac group. A significant proportion of the patients in the diclofenac group (50% vs 17.6%) had break through pain that warranted the use of at least two tablets of 500mg of paracetamol per week in contrast to the nimesulide group. There was a statistically significant difference in the frequency of side effects between the patients in the diclofenac group and the nimesulide group (p<0.05). Nimesulide was found to be more effective in relieving pain in osteoarthritis of the hip and knees and with less side effects than diclofenac.

The effect of selective cyclooxygenase-2 inhibitor nimesulide on breast cancer induced by dimethylbenzoic acid in rats

To study the effect of nimesulide (NIM) on the tumorigenesis of mammary tumors induced by dimethylbenzoic acid (DMBA), and to investigate possible mechanisms of NIM against tumors. The studied rats were randomly divided into four groups: experimental control group, NIM group, diet and drug of NIM control group. The incidence of mammary tumor was observed. RT-PCR, Western blot were used to detect 8 cancerous tissues in every group, randomly. The expressions of cylooxygenase-2 (COX-2) were assessed by immunohistochemistry. The levels of prostaglandin E(2) (PGE(2)) in blood plasma and tumor tissues were determined by means of radio-immunity assay. The apoptosis index and the proliferation index were evaluated by TUNEL assay, immunohistochemical staining for proliferating cell nuclear antigen (PCNA), respectively. The incidence of mammary tumor was 69.2% in experimental control group, 40.3% in NIM group. There was obviously decreased incidence in NIM group; The expressions of COX-2 mRNA and protein were significantly down-regulated in NIM group compared with experimental control group. The increased levels of PGE(2) synthesis in blood plasma and tumor tissues were significantly decreased by administering NIM (P < 0.05). The apoptosis index was obviously higher, the proliferation index was markedly less in NIM group than experimental control group. Nimesulide could inhibit the tumorigenesis and development of DMBA-induced mammary tumors by inhibition of proliferation and induction of apoptosis. COX-2 and COX-2-mediated PGE(2) synthesis may play an important role in rat DMBA-induced breast cancer.

Effectiveness and tolerability of once-daily nimesulide versus ibuprofen in pain management after surgical extraction of an impacted third molar: A 24-hour, double-blind, randomized, double-dummy, parallel-group study

Nimesulide is a nonsteroidal, anti-inflammatory drug that hasbeen used for a wide range of acute and chronic pain. A once-daily formulation of nimesulide is now commercially available, but its effectiveness in pain management after dental surgery has not been assessed. The aim of this study was to assess the analgesic effectiveness and tolerability of oral treatment with once-daily nimesulide versus ibuprofen q6h over 24 hours in patients with postoperative pain associated with surgical extraction of an impacted third molar. This 24-hour, double-blind, randomized, double-dummy, parallel-groupstudy was conducted at a private practice in Caracas, Venezuela. Patients aged between 12 and 60 years with moderate to severe pain after extraction of an impacted third molar were enrolled. Patients were randomized to receive a single dose of nimesulide (300-mg tablet) or ibuprofen (400-mg tablets) q6h for 24 hours. For double-dummy design, patients in the nimesulide group also received ibuprofen placebo tablets, to be taken q6h for 24 hours, and patients in the ibuprofen group received a nimesulide placebo tablet. The primary end points were pain intensity (PI) and pain relief scores over 24 hours. Secondary end points included total pain relief, PI difference (PID), sum of PID (SPID), time to first measurable change in PI (ie, PID ≥ 10 mm), and use of rescue medication (acetaminophen). Patients also rated the treatment's effectiveness as very poor to very good on questioning by the study investigator. Spontaneously reported adverse effects (AEs) were recorded. Eighty-six patients were enrolled (56 females, 30 males), with 43 patientsper treatment group (mean age: nimesulide group, 25.2 years; ibuprofen group, 24.2 years). The baseline characteristics were statistically similar between the 2 groups. Compared with baseline, mean PI scores were significantly lower in both treatment groups at all time points throughout the study (P < 0.001). Mean PI scores were significantly lower in the nimesulide group compared with the ibuprofen group at 15 and 45 minutes and 1 hour after study drug administration ( P ≤ 0.049). Time to first measurable change in PI was within the first 15 minutes in 22 patients (52%) in the nimesulide group and in 14 patients (33%) in the ibuprofen group ( P = 0.03). Analgesia lasted 24 hours with nimesulide and ibuprofen (PI scores at 24 hours, 9.4 and 3.6, respectively). The mean PR score was significantly lower in the nimesulide group compared with the ibuprofen group at 1 hour after study drug administration ( P = 0.049). Compared with baseline, PID and SPID were significantly higher in both treatment groups throughout the study ( P < 0.001). Significantly more patients in the nimesulide group than in the ibuprofen group reported that treatment provided effective pain relief (82% vs 73%; P = 0.013). No AEs were reported in either treatment group throughout the study. Use of rescue medication was statistically similar between the nimesulide and ibuprofen groups (38% and 31%, respectively). In this study of patients with moderate to severe pain afterextraction of impacted third molars, nimesulide and ibuprofen provided effective 24-hour relief. However, the results suggest that the analgesic effect of nimesulide had a faster onset (<15 minutes) and was stronger (based on patient opinion) than that of ibuprofen. Both study drugs were well tolerated.

Effectiveness and tolerability of once-daily nimesulide versus ibuprofen in pain management after surgical extraction of an impacted third molar: A 24-hour, double-blind, randomized, double-dummy, parallel-group study

Background: Nimesulide is a nonsteroidal, anti-inflammatory drug that hasbeen used for a wide range of acute and chronic pain. A once-daily formulation of nimesulide is now commercially available, but its effectiveness in pain management after dental surgery has not been assessed. Objective: The aim of this study was to assess the analgesic effectiveness and tolerability of oral treatment with once-daily nimesulide versus ibuprofen q6h over 24 hours in patients with postoperative pain associated with surgical extraction of an impacted third molar. Methods: This 24-hour, double-blind, randomized, double-dummy, parallel-groupstudy was conducted at a private practice in Caracas, Venezuela. Patients aged between 12 and 60 years with moderate to severe pain after extraction of an impacted third molar were enrolled. Patients were randomized to receive a single dose of nimesulide (300-mg tablet) or ibuprofen (400-mg tablets) q6h for 24 hours. For double-dummy design, patients in the nimesulide group also received ibuprofen placebo tablets, to be taken q6h for 24 hours, and patients in the ibuprofen group received a nimesulide placebo tablet. The primary end points were pain intensity (PI) and pain relief scores over 24 hours. Secondary end points included total pain relief, PI difference (PID), sum of PID (SPID), time to first measurable change in PI (ie, PID ≥ 10 mm), and use of rescue medication (acetaminophen). Patients also rated the treatment's effectiveness as very poor to very good on questioning by the study investigator. Spontaneously reported adverse effects (AEs) were recorded. Results: Eighty-six patients were enrolled (56 females, 30 males), with 43 patientsper treatment group (mean age: nimesulide group, 25.2 years; ibuprofen group, 24.2 years). The baseline characteristics were statistically similar between the 2 groups. Compared with baseline, mean PI scores were significantly lower in both treatment groups at all time points throughout the study (P < 0.001). Mean PI scores were significantly lower in the nimesulide group compared with the ibuprofen group at 15 and 45 minutes and 1 hour after study drug administration ( P ≤ 0.049). Time to first measurable change in PI was within the first 15 minutes in 22 patients (52%) in the nimesulide group and in 14 patients (33%) in the ibuprofen group ( P = 0.03). Analgesia lasted 24 hours with nimesulide and ibuprofen (PI scores at 24 hours, 9.4 and 3.6, respectively). The mean PR score was significantly lower in the nimesulide group compared with the ibuprofen group at 1 hour after study drug administration ( P = 0.049). Compared with baseline, PID and SPID were significantly higher in both treatment groups throughout the study ( P < 0.001). Significantly more patients in the nimesulide group than in the ibuprofen group reported that treatment provided effective pain relief (82% vs 73%; P = 0.013). No AEs were reported in either treatment group throughout the study. Use of rescue medication was statistically similar between the nimesulide and ibuprofen groups (38% and 31%, respectively). Conclusions: In this study of patients with moderate to severe pain afterextraction of impacted third molars, nimesulide and ibuprofen provided effective 24-hour relief. However, the results suggest that the analgesic effect of nimesulide had a faster onset (<15 minutes) and was stronger (based on patient opinion) than that of ibuprofen. Both study drugs were well tolerated.

Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a selective cyclooxygenase-2 inhibitor

The chemopreventive efficacies of raloxifene and nimesulide, an anti-estrogen but with anti-androgen action and a cyclooxygenase-2 (COX-2) selective inhibitor, respectively, were evaluated in probasin/SV40 T antigen (Tag) transgenic (TG) rats. The treatment groups were placebo, nimesulide (400 p.p.m. in basal diet p.o.), raloxifene (slow-release pellets implanted s.c., 5 mg/kg/day), raloxifene (5 mg/kg/day) plus nimesulide (400 p.p.m.), and raloxifene (10 mg/kg/day) plus nimesulide (400 p.p.m.). Animals were killed at 17 weeks of age, and prostate tissues were harvested and weighed by lobes. Tissues were evaluated by histology, immunohistochemistry, and western blot analyses and blood was collected to measure the testosterone levels. All the animals in the placebo group had tumors in each lobe compared with only 43% each in the dorsolateral (DLP) and anterior prostate (AP) of the animals treated with raloxifene (10 mg/kg/day) plus nimesulide. The total prostate weights and adenocarcinoma portions were significantly reduced in the three raloxifene-treated groups, whereas atrophic glands were increased. There were no significant differences between the nimesulide alone and placebo groups or between the raloxifene (5 mg/kg/day) alone and raloxifene (5 mg/kg/day) plus nimesulide group, suggesting a lack of cancer preventive effects of the COX-2 inhibitor in this animal model. PCNA positive rates in ventral prostate (VP) and DLP, and androgen receptor (AR) levels in VP were significantly reduced in the three raloxifene-treated groups. Furthermore, circulating testosterone was decreased after raloxifene (10 mg/kg/day) plus nimesulide treatment. These results demonstrate that raloxifene, but not nimesulide, inhibits prostate carcinogenesis in SV40 Tag TG rats associated with a decline in circulating testosterone levels and a loss of AR expression, as well as an inhibition of cell proliferation.

How important is the role of the physician in the correct use of a drug? An observational cohort study in general practice

The correct use of a drug is determined by several important factors. The most significant of these is a correct diagnosis for the choice of the appropriate therapeutic approach, followed by the physician's awareness of each drug's product characteristics--such as indications, contraindications and warnings--and by a careful evaluation of the patient in order to consider possible risk factors, concomitant pathologies and treatments. An adequate knowledge of pharmacological therapy and of the patient's history and disease states could in fact prevent most of the adverse drug reactions attributable to an inappropriate prescription. It is clear that the physician's role in the correct use of a drug is extremely important. Observational studies and surveys evaluating doctors' prescribing habits could be a very useful instrument in identifying medication prescribing errors and the consequent occurrence of adverse events. An open-label, multicentre, observational cohort study, recently performed in Ireland and involving more than 9000 patients, investigated the use of non-steroidal anti-inflammatory drugs (NSAIDs) in general practice, and in particular the use of diclofenac, nimesulide and ibuprofen. These three drugs were shown to be the NSAIDs most frequently prescribed (80% of total prescriptions) by general practitioners in Ireland. The study was designed and powered to detect differences in the general safety profile of the three NSAIDs and to test prescribing physicians' compliance with each drug's Summary of Product Characteristics (SmPC). The study was performed as closely as possible to the normal prescribing habits of the participating physicians. The three drugs were shown to be well tolerated. In the nimesulide group, the percentage of patients who experienced treatment-related adverse events was lower than that of the diclofenac group and similar to that observed with the use of ibuprofen. A more favourable gastrointestinal safety profile was evident for nimesulide in comparison to diclofenac. The data showed that the study physicians prescribed the drugs with a good degree of compliance (84% of prescriptions) with the information reported in each of the SmPCs. This supported the fact that the adverse events were markedly limited.

Comparative Effect of Nimesulide and??Ibuprofen on the Urinary Levels of??Collagen Type II C-Telopeptide Degradation Products and on the Serum Levels of Hyaluronan and Matrix Metalloproteinases-3 and -13 in??Patients with Flare-Up of Osteoarthritis

Because in vitro studies have shown that nimesulide not only preferentially inhibits COX-2 but also reduces the action/release of pro-inflammatory cytokines, down-regulates the synthesis and/or activity of collagenase(s), and releases reactive oxygen species and other toxic substances from neutrophils, this study investigated whether nimesulide and ibuprofen could affect levels of biochemical markers of joint inflammation and collagen catabolism in patients with flare-up of knee or hip osteoarthritis. Ninety patients were included in this randomised, prospective, single- blind study. They received either nimesulide (n = 45) or ibuprofen (n = 45) for a 4-week treatment period. The following parameters were analysed by ELISA: urinary levels of C-terminal cross-linking telopeptide of type II collagen (CTX-II), a marker of type II collagen breakdown; serum levels of hyaluronan (HA), a marker of synovial inflammation and hyperplasia; and circulating levels of stromelysin-1 (matrix metalloproteinase-3 [MMP-3]), collagenase-1 (MMP-1) and collagenase-3 (MMP-13). Statistical analysis used was ANOVA. At the end of the treatment period, nimesulide but not ibuprofen markedly reduced the urinary levels of CTX-II (p < 0.001) and the serum levels of HA (p < 0.05), two markers known to prognosticate poor outcome of the osteoarthritis disease process. Nimesulide also reduced the serum levels of both MMP-3 (p < 0.05) and MMP-13 (p < 0.001). Furthermore, in the nimesulide group, the decrease in levels of CTX-II correlated significantly with the decrease in levels of HA and MMP-13. Although nonsteroidal anti-inflammatory drugs are effective in improving pain and disability in OA patients, to date it has been unclear to what extent these drugs could affect joint metabolism and hence joint structure. Patients with flare-up of their osteoarthritis disease process exhibit enhanced levels of markers of joint inflammation and cartilage collagen breakdown, which were markedly decreased by nimesulide but not by ibuprofen.

TREATMENT OF DE QUERVAIN DISEASE WITH TRIAMCINOLONE INJECTION WITH OR WITHOUT NIMESULIDE

There is uncertainty as to whether supplemental oral nonsteroidal anti-inflammatory medication improves the effectiveness of steroid injections in the treatment of de Quervain disease. We tested the hypothesis that there are no significant differences in the success rates when this condition is treated with triamcinolone injection with or without supplemental oral nimesulide. In a randomized, double-blind trial, 160 patients with de Quervain disease received an injection of 10 mg of triamcinolone acetonide and either 200 mg of oral nimesulide for seven days (eighty patients) or placebo tablets for seven days (eighty patients). An independent, blinded evaluator assessed the primary outcomes (tenderness, pain, and the result on the Finkelstein test) at three weeks after injection. Adverse reactions were assessed, and probabilities of recurrence for both groups were compared. Factors possibly predictive of disease recurrence were also assessed. The success rate after one injection was 67% in the nimesulide group and 68% in the placebo group. The overall success rates after single or multiple injections with a mean follow-up of 13.6 months were 95% for both groups. No significant differences were noted with respect to the success rates (p = 0.69) or pain scores after treatment (p = 0.11). The most common adverse reactions to triamcinolone injection and nimesulide were pain after injection and dyspepsia, respectively. The symptoms of de Quervain disease recurred in 33% of the patients in the nimesulide group and in 37% of those in the placebo group. The median time of recurrence was at the fifth month in the nimesulide group and at the fourth month in the placebo group. The recurrence of symptoms was significantly (p = 0.01) related to the presence of crepitation (relative risk, 2.13; 95% confidence interval, 1.19 to 3.80). Supplemental oral administration of the nonsteroidal anti-inflammatory drug nimesulide does not improve the effectiveness of a single injection of triamcinolone acetonide in the treatment of de Quervain disease. Patients with crepitation in the first dorsal compartment during thumb extension or abduction are at increased risk for recurrence of this disease. Therapeutic study, Level I-1b (randomized controlled trial [no significant difference but narrow confidence intervals]).

Spinal Prostaglandin Formation and Pain Perception Following Thoracotomy: A Role for Cyclooxygenase-2

Prostaglandins (PGs) generated in the spinal cord may play a major role in pain perception. Consequently, the suppression of spinal cyclooxygenase (COX) and PG formation may contribute to the analgesic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in pain following surgery. Which isoform of COX is responsible for postsurgical pain and, consequently, should be targeted, is unclear. Prospective randomized blinded study. University teaching hospital. Thirty patients undergoing thoracotomy for lobectomy were recruited. Patients were randomized to receive the COX-2 selective inhibitor nimesulide, 100 mg orally twice daily, or ibuprofen (nonselective), 400 mg orally three times daily, in an open-label study. In addition, there was a randomized control group that received no NSAIDs. Cerebrospinal fluid (CSF) was analyzed for 6-keto-PGF(1)alpha, the principle metabolite of prostacyclin. COX-1 and COX-2 activity was determined by measuring serum thromboxane (TX) B(2) and endotoxin-induced PGE(2) generation in whole blood. Pain perception was measured by visual analog scores, and blinded assessment of opioid analgesic requirements and expiratory peak flow measurements were performed. At the doses used, nimesulide was selective for COX-2, while ibuprofen was nonselective based on serum TXB(2) levels. The mean (+/- SEM) levels of 6-keto-PGF(1)alpha in CSF increased following surgery from 32 +/- 4.9 to 127 +/- 29 pg/mL (p < 0.001), and this was suppressed by nimesulide (49 +/- 9.3 pg/mL; p = 0.0025) but not by ibuprofen (122 +/- 35 pg/mL). Pain scores (p < 0.001), morphine requirement (p = 0.0175), and the fall in peak expiratory flow rate (p < 0.001) were significantly lower in the nimesulide group. Increases in spinal PG synthesis after thoracotomy are repressed by a selective COX-2 inhibitor. This suggests that the inducible COX-2 mediates central PG synthesis, which may be important in the generation of pain, as the use of nimesulide also resulted in significant decreases in postoperative pain perception.

The effects of nimesulide combined with cisplatin on lung cancer.

To study the effects of cyclooxygenase 2 selective inhibitor Nimesulide (NIM) combined with Cisplatin (DDP) on human lung cancer and the possible mechanisms, the proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT reduction assay and flow cytometry respectively. The inhibitory effect on neoplasia in vivo was tested on nude mice subcutaneously implanted tumor. Our results showed that NIM and DDP could inhibit A549 cell proliferation in a concentration-dependent pattern; this action was enhanced when NIM (25 micromol/L) was given in combination with DDP and they worked in a synergistic or additive pattern as DDP concentration > or = 1 microg/ml. NIM and DDP could induce A549 cells apoptosis and the action was augmented when used in combination (P<0.01). NIM and DDP could inhibit the growth of subcutaneously implanted tumors on nude mice (P<0.05, P<0.01) and the inhibitory rate of NIM combined with DDP was significantly higher than that of NIM or DDP group (P<0.01, P<0.01). It is concluded that combined use of NIM and DDP has significant synergistic antitumor effects on lung cancer cell line A549 and in animals in vivo. The synergy may be achieved by growth inhibition and apoptosis induction.

The Analgesic Efficacy of Nimesulide After Third Molar Surgery: a Randomised Cross-over Prospective Study

Objective: To determine the efficacy of nimesulide in comparison to paracetamol for the relief of pain after third molar surgery.Patients and Methods: Twenty nine patients undergoing third molar surgery using local anaesthesia on 2 separate occasions were randomised to receive either nimesulide 200 mg or paracetamol 1000 mg as a single dose after surgery. Rescue medication consisting of paracetamol 1000 mg was given in case of inadequate pain relief with the test medication. Pain intensity and pain relief measures were recorded using a visual analogue scale and phrased categorical scales. The observation period was 6 hours after the cessation of local anaesthetic effects.Results: Twenty nine measurements were available for paracetamol and 27 for nimesulide. Rescue medication was used for 31% of patients in the paracetamol group and 7% in the nimesulide group. There was 50% greater decrease of pain, 27% greater peak of pain relief, and 44% greater total pain relief among patients in the nimesulide group.Conclusion: Nimesulide 200 mg resulted in significantly better pain relief than paracetamol 1000 mg in similar circumstances.

A cyclooxygenase-2 inhibitor, nimesulide, inhibits postinitiation phase of N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters.

The modification effects of nimesulide, a cyclooxygenase (COX)-2 inhibitor, administration during the postinitiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Male Syrian hamsters were given 4 weekly s.c. injections of BOP at a dose of 10 mg/kg and thereafter administered 0, 100 or 400 ppm nimesulide in the diet for 36 weeks. Additional groups of hamsters were fed 400 ppm nimesulide without prior BOP initiation or nontreated. At week 40, all surviving animals were killed and development of neoplastic and preneoplastic lesions was assessed histopathologically. The incidence of pancreatic adenocarcinomas was significantly (p < 0.05) decreased in the BOP/400 ppm nimesulide group compared to the BOP alone group. The multiplicity of total lesions of pancreatic adenocarcinoma plus atypical hyperplasia was also significantly (p < 0.05) lowered. Immunohistochemically, COX-2 was clearly expressed in pancreatic and lung tumor cells, whereas expression was not remarkably affected by the 400 ppm nimesulide treatment. Proliferating cell nuclear antigen labeling indices of pancreatic ducts were significantly (p < 0.01) reduced by nimesulide. The incidence and multiplicity of neoplastic lesions in other organs did not significantly differ among the BOP-treated groups, though only the multiplicity of lung tumors showed a tendency to decrease. No neoplastic lesions were detected in animals receiving nimesulide alone. Our results clearly indicate that nimesulide protects against BOP-induced pancreatic tumors in hamsters.

Nimesulide versus Ibuprofen for Postoperative Tonsillectomy Pain

Nonsteroidal anti-inflammatory drugs are effective analgesics but their use during tonsillectomy is controversial because of the risk of postoperative bleeding. The aim of this study was to compare the analgesic efficacy and safety of nimesulide, a preferential cyclo-oxygenase type-2 inhibitor, with ibuprofen in the treatment of pain after tonsillectomy. A prospective, double-blind, randomised clinical trial. A total of 80 consenting generally healthy patients, aged 14-58 years, undergoing tonsillectomy were randomly assigned to receive either nimesulide 100mg or ibuprofen 800mg orally 60 minutes before surgery. Subsequent doses of the same study medication were administered at 12-hour intervals for the first 7 days, and thereafter when needed. During the first 24 postoperative hours in hospital oxycodone was used for rescue analgesia, and after discharge patients were allowed to use a paracetamol-codeine combination for breakthrough pain. Recovery was recorded up to 3 weeks after surgery. The need for rescue analgesia during the first 24 hours was similar in the two study groups; 0-7 doses (mean +/- SD 3.3 +/- 1.7 doses) in the nimesulide group and 0-11 doses (3.3 +/- 2.4 doses) in the ibuprofen group. After discharge significant differences were found between the two study groups in favour of the nimesulide-treated patients. Cessation of significant pain while swallowing occurred after 3-19 (10.9 +/- 3.8) days in the nimesulide group versus 7-20 (12.9 +/- 3.3) days in the ibuprofen group (p = 0.041), and return to normal daily activities occurred after 3-21 (10.3 +/- 4.9) days in the nimesulide group versus after 3-19 (12.7 +/- 4.2) days in the ibuprofen group (p = 0.048). At 3 weeks, six of 33 patients in the nimesulide group versus 15 of 37 patients in the ibuprofen group had pain during swallowing (p = 0.049). One patient (3%) in the nimesulide group and five patients (12%) [p = 0.22] in the ibuprofen group needed electrocautery to stop postoperative bleeding. Oral nimesulide was as effective as ibuprofen in pain management after tonsillectomy, and nimesulide improved the recovery after discharge.

Intramuscular Dipyrone versus Oral???Ibuprofen or Nimesulide for???Reduction of Fever in the Outpatient Setting

To compare the effectiveness and rate of temperature reduction of three antipyretic medications in febrile children. A single-dose, randomised, prospective, modified double-blind, parallel clinical trial. The paediatric emergency department of a university hospital that has 13 000 annual visits. 252 otherwise healthy children aged 6 months to 14 years with acute, intercurrent, febrile illness. Enrolled children were assigned to receive a single dose of oral ibuprofen 10 mg/kg, oral nimesulide 2.5 mg/kg, or parenteral dipyrone 10 mg/kg. Axillary temperature was measured at the time of antipyretic administration and at 30, 45, 60 and 120 minutes thereafter. All three medications were effective in reducing the axillary temperature during the 2-hour testing period. The rates of axillary temperature change between the three medications were significantly different for the ibuprofen and dipyrone groups (p = 0.023). In addition, the axillary temperature in the dipyrone group was significantly lower than that in the ibuprofen group (p = 0.036) at 120 minutes. There was no significant difference in antipyretic effect between the nimesulide group and the other two groups during the testing period. Within each group the difference between initial temperature and the temperature at the end of the testing period was statistically significant (p = 0.036) for the dipyrone group only. All three antipyretic medications were effective in reducing the axillary temperature in febrile children. Although administration of intramuscular dipyrone seemed to be more effective than ibuprofen, this relationship was not significant when nimesulide was considered. In addition, in view of its known side effects and the problems associated with intramuscular administration in children, the preference for orally administered nimesulide or ibuprofen over dipyrone in the setting of the emergency department seems more logical provided that the child accepts oral therapy.

Prevention of postoperative adhesion formation in rat uterine horn model by nimesulide: a selective COX-2 inhibitor.

Pelvic surgery is one of the main causes of intraperitoneal (i.p.) adhesions that create various medical problems including pelvic pain, bowel obstructions and female infertility. A rat model was used to investigate the efficacy of nimesulide, a selective cyclooxygenase-2 inhibitor, in the prevention of adhesion formation. Fifty Wistar-Albino rats underwent bilateral uterine horn injury with a unipolar cautery. Study groups were as follows: (i) control group, no adjuvant therapy; (ii) i.p. Ringer's lactate group, 2 ml Ringer's lactate solution was instilled i.p.; (iii) i.p. Ringer's lactate plus nimesulide group, 1 ml Ringer's lactate plus 1 ml nimesulide (0.5 mg/ml) were given i.p.; (iv) intramuscular (i.m.) nimesulide group, 1 ml i.m. nimesulide (0.5 mg/ml) was given preoperatively for 5 days; and (v) i.p. nimesulide group, 1 ml nimesulide (0.5 mg/ml) was instilled i.p. At the end of the study all animals were killed, and a standard adhesion scoring system was applied by a blinded examiner. The mean adhesion extent in study groups was as follows: 1.33 +/- 0.76 in control group, 1.40 +/- 0.90 in i.p. Ringer's lactate group, 0.75 +/- 0.70 in i.p. Ringer's lactate plus nimesulide group, 0.25 +/- 0.44 in i.m. nimesulide group and 0.31 +/- 0.70 in i.p. nimesulide group. The mean +/- SD adhesion severities of control, i.p. Ringer's lactate, i.p. Ringer's lactate plus nimesulide, i.m. nimesulide, and i.p. nimesulide groups were 0.58 +/- 0.35, 0.30 +/- 0.41, 0.27 +/- 0.3, 0.12 +/- 0.28 and 0.15 +/- 0.35 respectively. The lowest adhesions were found in the groups treated with nimesulide i.m. and nimesulide i.p. ( P < 0.05). This study showed that preoperative i.m. or postoperative i.p. administration of nimesulide to the site of injury reduced the formation of postoperative adhesions in a rat uterine horn model.

Eficácia e tolerabilidade da nimesulida versus celecoxib na osteoartrite

O objetivo do estudo foi comparar a eficácia e a tolerabilidade da nimesulida versus o celecoxib no tratamento da osteoartrite. A casuística envolveu 57 pacientes com idade entre 40 e 80 anos, que foram randomizados em dois grupos, recebendo as medicações do estudo durante 30 dias de forma simples-cega na dosagem de um comprimido de 100mg de nimesulida duas vezes ao dia e uma cápsula de 100mg de celecoxib duas vezes ao dia. Após a inclusão no estudo na visita basal, foram realizadas três visitas com intervalo de dez dias entre elas. Os aspectos analisados foram: dor em repouso, dor em movimento e dor noturna, através de uma escala analógica da dor, duração da rigidez matinal, capacidade funcional (HAQ), classe funcional ACR-1991 e o índice de gravidade para osteoartrite de joelhos em todas as visitas. Foi também avaliado o tempo para andar 15 metros naqueles pacientes com acometimento de joelhos ou quadril. A avaliação da eficácia e tolerabilidade foi realizada pelo investigador e pelo paciente nas três visitas após o início do tratamento. Os eventos adversos foram registrados durante todo o período do estudo. Houve diminuição significativa e semelhante nas médias da escala para dor ao movimento e dor em repouso para ambos medicamentos em todas as visitas. Houve diminuição da dor noturna ao longo do tratamento no grupo celecoxib e a partir da visita 3 no grupo nimesulida, e ao final do estudo, as médias dos dois grupos foram semelhantes ( p = 0,152). As médias da duração da rigidez matinal diminuíram significativamente no grupo tratado com nimesulida durante todo o seguimento, e no grupo celecoxib a partir da visita 3, sendo semelhantes ao final do estudo ( p= 0,993). O tempo médio para andar 15 metros diminuiu significativamente no grupo nimesulida na visita 4 (p &lt; 0,001*), e todas as médias deste intervalo de tempo foram menores do que no grupo celecoxib a partir da segunda visita. Houve diminuição significativa nas médias de capacidade funcional ( escala HAQ) no grupo nimesulida durante todo o período do estudo, enquanto que no grupo celecoxib, apenas na visita 4, onde as médias foram semelhantes ( p=0,517). No grupo nimesulida o índice de gravidade de Lequesne e Samson (1991) para osteoartrite de joelhos diminuiu significativamente a partir da visita 3, o que não ocorreu no grupo celecoxib. Os dois grupos tiveram evolução semelhante quanto à classificação funcional ACR-1991 durante o período do estudo. Ambos grupos foram semelhantes na avaliação da eficácia e da tolerabilidade segundo o paciente, e da eficácia segundo o médico. Durante o período do estudo, 21% dos pacientes do grupo nimesulida e 25% do grupo celecoxib apresentaram eventos adversos. Em conclusão, a nimesulida demonstrou eficácia e tolerabilidade semelhante ao celecoxib no tratamento da osteoartrite. A dor noturna diminuiu mais precocemente no grupo celecoxib; nos parâmetros rigidez matinal, capacidade funcional e o índice de gravidade para a osteoartrite de joelho constatou-se uma resposta mais rápida nos pacientes tratados com a nimesulida.