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Anaesthesia Dec 1994Ketorolac, ketoprofen and nefopam are often used in the treatment of postoperative pain. While nefopam is a non-narcotic, non-opioid central analgesic agent, ketorolac... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Ketorolac, ketoprofen and nefopam are often used in the treatment of postoperative pain. While nefopam is a non-narcotic, non-opioid central analgesic agent, ketorolac and ketoprofen are non-steroidal anti-inflammatory drugs, which, due to their prostaglandin-synthetase inhibiting activity, have antiplatelet effects. In this study we investigated the effect of ketorolac, ketoprofen and nefopam on platelet function by performing bleeding time and in vitro platelet aggregation in 30 healthy volunteers (10 for each treatment) before and 3 h after drug administration. Nefopam did not affect bleeding time and platelet aggregation, while ketorolac and ketoprofen significantly prolonged bleeding time without significantly inhibiting platelet aggregation in response to adenosine diphosphate. The prolongation of bleeding time observed after ketorolac and ketoprofen may have clinical relevance and suggests that nefopam could be more safely administered for the treatment of postoperative pain, especially in patients with haemostatic defects or after high bleeding risk surgery.
Topics: Bleeding Time; Blood Platelets; Cells, Cultured; Female; Humans; Ketoprofen; Ketorolac; Nefopam; Platelet Aggregation; Platelet Aggregation Inhibitors; Tolmetin
PubMed: 7864317
DOI: 10.1111/j.1365-2044.1994.tb04352.x -
Anaesthesia Jul 1997Nonsteroidal anti-inflammatory drugs are effective in the management of mild to moderate postoperative pain in children. They can decrease or even eliminate the need for... (Review)
Review
Nonsteroidal anti-inflammatory drugs are effective in the management of mild to moderate postoperative pain in children. They can decrease or even eliminate the need for opioid analgesics, thus reducing or eliminating opioid-induced side-effects. The increasing peri-operative use of nonsteroidal anti-inflammatory drugs in children has, however, raised concerns about complications secondary to impaired haemostasis. To examine the extent of this unwanted side-effect, this paper reviews the published literature on analgesic efficacy and bleeding following the peri-operative use of nonsteroidal anti-inflammatory drugs in children. The reviewed literature confirms that haemorrhagic events in the postoperative period occur, but results remain inconclusive regarding the association between peri-operative use of nonsteroidal anti-inflammatory drugs and disordered haemostasis. In order to maximise the benefit of nonsteroidal anti-inflammatory drugs in children, the risks must be recognised and patients, clinical indications, the individual drug, timing and route of administration must be selected carefully. Nonsteroidal anti-inflammatory drugs appear to play a valuable role in the further improvement of postoperative pain management in children.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Diclofenac; Drug Administration Schedule; Humans; Ibuprofen; Infant; Ketorolac; Pain, Postoperative; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Tolmetin
PubMed: 9244028
DOI: 10.1111/j.1365-2044.1997.130-az0126.x -
Reproductive Biology and Endocrinology... Oct 2003Turkey reproduction is by artificial insemination using pooled semen so there is interest in storing semen. Fertilizing capacity declines after six hours storage,...
BACKGROUND
Turkey reproduction is by artificial insemination using pooled semen so there is interest in storing semen. Fertilizing capacity declines after six hours storage, possibly due to poor sperm mobility. Prostaglandins (PG) affect mammalian sperm motility, but avian sperm has not been widely studied. For this study, levels of PG E1, E2, and F2 alpha in turkey seminal plasma and sperm extract, and effects of cyclooxygenase (COX) inhibitors on sperm mobility were determined.
METHODS
Seminal Plasma and sperm extract PG E1, E2, and F2 alpha, from 1.0 mL pooled semen, were measured by ELISA. In Trial 1, PG were determined from 122 wk old toms (n = 4). Trial 2 used 36 wk old toms (n = 7). For Trial 3, PGE2 only was measured from 48 wk (n = 6) and 154 wk old toms (n = 3). The effects of non-specific COX inhibitors indomethacin, diclofenac, tolmetin, or aspirin (n = 10), or specific COX-1 or COX-2 inhibitors (n = 3) on sperm mobility were measured (Accudenz swim-down test).
RESULTS
Seminal plasma PG (pg/mL) in Trials 1 and 2, respectively, were 185.2 +/- 88.4 and 187.2 +/- 33.7 for PGE1; 141.4 +/- 43.1 and 100.4 +/- 14.6 for PGF2 alpha; and 431.0 +/- 155.1 for PGE2 (Trial 1 only). Sperm extract PG (pg/10 billion cells) in Trials 1 and 2, respectively, were 215.1 +/- 38.1 and 208.9 +/- 41.5 for PGE1; 133.7 +/- 51.7 and 49.8 +/- 8.3 for PGF2 alpha; and 52.3 +/- 8.6 for PGE2 (Trial 1 only). In Trial 3, seminal plasma PGE2 (pg/mL) in older versus younger males was 1097.9 +/- 99.3 versus 853.2 +/- 144.6 and sperm extract PGE2 (pg/10 billion cells) was 208.0 +/- 56.1 versus 102.4 +/- 14.8. Cyclooxygenase inhibitors (0.001 to 10 mM) decreased sperm mobility: indomethacin 15 to 100%; diclofenac 4 to 100%; tolmetin 27 to 74%; aspirin (tested at 0.01 to 15 mM) 22 to 42%; resveratrol (COX-1) and NS-398 (COX-2), both tested at 0.1 to 10 mM, 38 to 98% and 44 to 85%, respectively.
CONCLUSION
These results indicate that PG are present in turkey seminal plasma and sperm, and COX inhibitors decrease turkey sperm mobility.
Topics: Alprostadil; Animals; Aspirin; Cell Membrane; Cryopreservation; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Diclofenac; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Indomethacin; Isoenzymes; Male; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Resveratrol; Semen; Semen Preservation; Sperm Motility; Spermatozoa; Stilbenes; Sulfonamides; Tolmetin; Turkeys
PubMed: 14613550
DOI: 10.1186/1477-7827-1-74 -
A simple method to evaluate reactivity of acylglucuronides optimized for early stage drug discovery.Biological & Pharmaceutical Bulletin 2013Drugs containing the carboxylic functional group can be metabolized to form acylglucuronides believed to cause idiosyncratic drug toxicity when the acylglucuronide is...
Drugs containing the carboxylic functional group can be metabolized to form acylglucuronides believed to cause idiosyncratic drug toxicity when the acylglucuronide is unstable. Recent studies have shown that the half-life of an acylglucuronide in phosphate buffer is the best means for classifying acylglucuronides into safe, warning, and withdrawn drugs. However, it is difficult to halt the late stage development of new chemical entities due to the instability of their acylglucuronides. We report an optimized in vitro method for determining the half-lives of acylglucuronides in simple phosphate buffer without the need for authentic standards. The experiment was divided into two incubations. In the first incubation, acylglucuronide was synthesized by human liver microsomes, and in the second incubation, the degradation rate of acylglucuronide in phosphate buffer was determined. The degradation rate constants of acylglucuronides were determined from changes in the LC-MS/MS peak area and the half-lives were calculated. We evaluated the half-lives of 10 drugs: 3 safe drugs (telmisartan, gemfibrozil and flufenamic acid) and 7 withdrawn or warning drugs (zomepirac, diclofenac, furosemide, ibuprofen, S-naproxen, probenecid and tolmetin). The half-lives of the 3 safe drugs were 10.6 h or longer, whereas the half-lives of the 7 withdrawn or warning drugs were 4.0 h or shorter. Although authentic acylglucuronide standards were not used, we obtained half-lives of acylglucuronides in phosphate buffer similar to those reported previously. Using this method, the risk of reactivity caused by acylglucuronides can be evaluated in the early stages of drug discovery.
Topics: Chromatography, High Pressure Liquid; Drug Discovery; Glucuronides; Half-Life; Humans; Microsomes, Liver; Pharmaceutical Preparations; Phosphates; Potassium Compounds; Tandem Mass Spectrometry
PubMed: 23832447
DOI: 10.1248/bpb.b13-00329 -
Academic Emergency Medicine : Official... Jan 1997To evaluate ketorolac for pain relief and an opioid-sparing effect in children with forearm fractures necessitating reduction. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVES
To evaluate ketorolac for pain relief and an opioid-sparing effect in children with forearm fractures necessitating reduction.
METHODS
A prospective, randomized, double-blind study was conducted at an urban children's hospital ED. A convenience sample of children aged 3-18 years with isolated forearm fractures was studied. None received prior pain medication. A 10-point visual analog scale (VAS) was used to assess pain at the time of study entry and prior to sedation/analgesia. The Children's Hospital of Eastern Ontario's Pain Score (CHEOPS), a 13-point behavioral score, was used to assess pain during sedation. Patients received either IV ketorolac (K), 1 mg/kg, or saline (S) after entry into the study. After a minimum of 20 minutes, pain was reassessed and supplemental analgesia/sedation administered. A standard dose of midazolam, 0.1 mg/kg to a maximum of 6 mg, was given to all patients, and fentanyl was titrated at 1-microgram/kg increments based on patient need. Once the patient was comfortable, reduction was performed and a reduction CHEOPS score assigned.
RESULTS
For the 34 study children (17 K, 17 S), there was no difference in sex or mean age between the groups. Mean total doses of fentanyl were 2.26 micrograms/kg in the K group and 2.85 micrograms/kg in the S group (p = 0.07). The median changes in VAS score before and after receiving the study drug were -1.13 K and -0.18 S (p = 0.06). The median CHEOPS score was 10 for both groups. Seven of the 17 patients in the S group required the maximum fentanyl dose (4 micrograms/kg), compared with 2 of 17 in the K group (p = p.06).
CONCLUSIONS
Although ketorolac seems to add to patient comfort in children with forearm fractures, it does not have a significant opioid-sparing effect. Ketorolac showed a trend toward pain relief, but statistical significance was not reached.
Topics: Adolescent; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Double-Blind Method; Evaluation Studies as Topic; Female; Forearm Injuries; Fractures, Bone; Humans; Ketorolac; Male; Pain Measurement; Prospective Studies; Tolmetin; Treatment Outcome
PubMed: 9110007
DOI: 10.1111/j.1553-2712.1997.tb03638.x -
PloS One 2012Aldo-keto reductase 1C3 (AKR1C3) catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also...
Aldo-keto reductase 1C3 (AKR1C3) catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also over-expressed in prostate and breast cancer and its expression is correlated with the aggressiveness of the disease. The steroid products of AKR1C3 catalysis are important in proliferative signalling of hormone-responsive cells, while the prostanoid products promote prostaglandin-dependent proliferative pathways. In these ways, AKR1C3 contributes to tumour development and maintenance, and suggest that inhibition of AKR1C3 activity is an attractive target for the development of new anti-cancer therapies. Non-steroidal anti-inflammatory drugs (NSAIDs) are one well-known class of compounds that inhibits AKR1C3, yet crystal structures have only been determined for this enzyme with flufenamic acid, indomethacin, and closely related analogues bound. While the flufenamic acid and indomethacin structures have been used to design novel inhibitors, they provide only limited coverage of the NSAIDs that inhibit AKR1C3 and that may be used for the development of new AKR1C3 targeted drugs. To understand how other NSAIDs bind to AKR1C3, we have determined ten crystal structures of AKR1C3 complexes that cover three different classes of NSAID, N-phenylanthranilic acids (meclofenamic acid, mefenamic acid), arylpropionic acids (flurbiprofen, ibuprofen, naproxen), and indomethacin analogues (indomethacin, sulindac, zomepirac). The N-phenylanthranilic and arylpropionic acids bind to common sites including the enzyme catalytic centre and a constitutive active site pocket, with the arylpropionic acids probing the constitutive pocket more effectively. By contrast, indomethacin and the indomethacin analogues sulindac and zomepirac, display three distinctly different binding modes that explain their relative inhibition of the AKR1C family members. This new data from ten crystal structures greatly broadens the base of structures available for future structure-guided drug discovery efforts.
Topics: 3-Hydroxysteroid Dehydrogenases; Aldo-Keto Reductase Family 1 Member C3; Anti-Inflammatory Agents, Non-Steroidal; Flufenamic Acid; Flurbiprofen; Hydroxyprostaglandin Dehydrogenases; Ibuprofen; Indomethacin; Meclofenamic Acid; Mefenamic Acid; Naproxen; Sulindac; Tolmetin
PubMed: 22937138
DOI: 10.1371/journal.pone.0043965 -
British Journal of Anaesthesia Jul 1992We have compared the postoperative morphine requirements and analgesic efficacy of four doses of i.m. ketorolac 30 mg administered 6-hourly with placebo in a... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
We have compared the postoperative morphine requirements and analgesic efficacy of four doses of i.m. ketorolac 30 mg administered 6-hourly with placebo in a double-blind study of patients undergoing major or minor orthopaedic surgery. During the 24-h postoperative study period which began at the end of surgery, patients were prescribed i.m. morphine 10 mg as required 2-hourly and assessments were made of pain at 4 and 24 h. After major surgery, the median morphine consumption over 24 h was 10 mg in patients who received ketorolac, compared with 30 mg in those who received placebo (P = 0.008). Visual analogue pain scores and verbal pain assessments were better than placebo at 4 h (P = 0.028 and P = 0.008, respectively), but were not statistically different between the groups at 24 h. Overall assessment of pain was similar in both groups who had undergone major surgery. In the minor surgery groups, median morphine consumption was 0 mg in patients who received ketorolac, compared with 10 mg in those given placebo (ns). Visual analogue pain scores at 24 h after surgery were significantly less in patients who had received ketorolac compared with placebo (P = 0.046) and the overall assessment of pain relief was better in the ketorolac group (P = 0.0007). Mandatory administration of ketorolac appeared to be of benefit in both major and minor orthopaedic surgery, although the principal effects were reduction in requirement for supplementary morphine for major surgery and better overall analgesia for minor surgery.
Topics: Adolescent; Adult; Aged; Analgesia; Analgesics; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Injections, Intramuscular; Ketorolac Tromethamine; Male; Middle Aged; Minor Surgical Procedures; Morphine; Orthopedics; Pain, Postoperative; Tolmetin; Tromethamine
PubMed: 1303630
DOI: 10.1093/bja/69.1.19 -
World Journal of Clinical Cases Apr 2024Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been...
BACKGROUND
Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been developed.
AIM
To perform a systematic review and network meta-analysis to determine the optimal instructions.
METHODS
We searched for randomized controlled trials (RCTs) from PubMed, EMBASE, Google Scholar, CNKI, and Wanfang without restriction for publication date or language at August, 2023. Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis. The surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatments. value less than 0.05 was identified as statistically significant.
RESULTS
We included 8 RCTs (1127 patients) comparing 8 different instructions including meloxicam (0.125 qd and 0.250 qd), Celecoxib (3 mg/kg bid and 6 mg/kg bid), piroxicam, Naproxen (5.0 mg/kg/d, 7.5 mg/kg/d and 12.5 mg/kg/d), inuprofen (30-40 mg/kg/d), Aspirin (60-80 mg/kg/d, 75 mg/kg/d, and 55 mg/kg/d), Tolmetin (15 mg/kg/d), Rofecoxib, and placebo. There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response. The SUCRA shows that celecoxib (6 mg/kg bid) ranked first (SUCRA, 88.9%), rofecoxib ranked second (SUCRA, 68.1%), Celecoxib (3 mg/kg bid) ranked third (SUCRA, 51.0%). There were no significant differences between any two NSAIDs regarding adverse events. The SUCRA shows that placebo ranked first (SUCRA, 88.2%), piroxicam ranked second (SUCRA, 60.5%), rofecoxib (0.6 mg/kg qd) ranked third (SUCRA, 56.1%), meloxicam (0.125 mg/kg qd) ranked fourth (SUCRA, 56.1%), and rofecoxib (0.3 mg/kg qd) ranked fifth (SUCRA, 56.1%).
CONCLUSION
In summary, celecoxib (6 mg/kg bid) was found to be the most effective NSAID for treating JIA. Rofecoxib, piroxicam, and meloxicam may be safer options, but further research is needed to confirm these findings in larger trials with higher quality studies.
PubMed: 38680254
DOI: 10.12998/wjcc.v12.i12.2056 -
Anesthesiology Feb 1997
Review
Topics: Aged; Anesthesia, Spinal; Anti-Inflammatory Agents, Non-Steroidal; Female; Hematoma; Humans; Ketorolac; Paresis; Spinal Diseases; Tolmetin
PubMed: 9054268
DOI: 10.1097/00000542-199702000-00025 -
Folia Histochemica Et Cytobiologica Jan 2010Unusual expression of interleukin-1alpha, -1beta and -6 was previously found in the epiphyseal cartilage of rat fetuses prenatally exposed to various non-steroidal...
Unusual expression of interleukin-1alpha, -1beta and -6 was previously found in the epiphyseal cartilage of rat fetuses prenatally exposed to various non-steroidal anti-inflammatory drugs (NSAID, i.e., ibuprofen, piroxicam, tolmetin) and selective cyclooxygenase-2 inhibitor (DFU). The aim of the present study was to evaluate the role of placenta in such phenomenon. Morphology of the organ, thickness of basal and labyrinth layer, immunoexpression of COX isoenzymes were examined, and confronted with maternal biochemical data and fetal developmental parameters. Higher maternal urea level, as well as lower placental weight and labyrinth thickness were found in the group of fetuses who revealed expression of genes coded the selected interleukins, when compared with the xenobiotic-exposed pups without the selected genes expression and untreated control. A significant correlation between placental weight and maternal total protein or urea level was revealed. Histological changes like inflammatory infiltration and calcification were observed sporadically. Location and intensity of COX-1 staining was similar in all cases. However, more intense COX-2 staining for majority of cells of the basal zone and in dispersed giant cells of the labyrinth was found in inflamed organs. It could be concluded that abnormal expression of the selected interleukins is associated with low placental weight and decrease of its thickness, especially labyrinth zone, as well as with high maternal urea level.
Topics: Animals; Cartilage; Cyclooxygenase 1; Cyclooxygenase 2; Female; Fetus; Gene Expression Regulation, Developmental; Immunohistochemistry; Interleukin-1; Interleukin-6; Neutrophils; Organ Size; Placenta; Pregnancy; Rats; Rats, Wistar
PubMed: 20529813
DOI: 10.2478/v10042-008-0097-1