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Drugs May 2015Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the... (Review)
Review
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. This review illustrates how pharmaceutical technology has been used to modify the pharmacokinetic properties of diclofenac, leading to the creation of novel drug products with improved clinical utility.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Cyclooxygenase Inhibitors; Delayed-Action Preparations; Diclofenac; Dose-Response Relationship, Drug; Humans; Technology, Pharmaceutical
PubMed: 25963327
DOI: 10.1007/s40265-015-0392-z -
La Clinica Terapeutica 2019Post-Endoscopic Retrograde Cholangio-Pancreatography pancreatitis (PEP) is a relevant (1-4%) complication of biliopancreatic operative endoscopy. Rectal nonsteroidal... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Post-Endoscopic Retrograde Cholangio-Pancreatography pancreatitis (PEP) is a relevant (1-4%) complication of biliopancreatic operative endoscopy. Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac) have shown promising prophylactic activity in PEP. The aim of our prospective study is to report whether prophylactic oral versus rectal suppository versus intramuscular diclofenac versus placebo are able to reduce the incidence and the severity of ERCP-induced pancreatitis.
MATERIALS AND METHODS
In this randomized, double-blinded, prospective study, 100 patients (49 male, 51 female), similar with regard to indication for ERCP, were enrolled between January 2016 and November 2017 to undergo ERCP in the Section of General and Thoracic Surgery of University Hospital of Palermo. They were randomized into five groups, respectively 20 patients with placebo by mouth; 20 patients with 50 mg diclofenac sodium enteric-coated capsules by mouth; 20 with 100 mg rectal suppository diclofenac, 20 with 75 mg/3 ml intramuscular diclofenac sodium, 20 with 75 mg/3 ml intramuscular diclofenac sodium and 20 with 75 mg/3 ml intravenous diclofenac. All drugs were administered 30 to 90 minutes before ERCP. All clinical data were collected one day before and 2, 12 and 24 hour after ERCP.
RESULT
Data were prospectively collected and to demonstrate the preventive effect of rectal diclofenac on PEP, a two-by-two table and chi-square test with Yates correction were used: the incidence of PEP was significantly lower (p < 0.001) in the rectal diclofenac group respect to other groups and, in the same way, the incidence of post-ERCP pain was significantly lower in the rectal diclofenac group than in the other groups (p = 0.001) and patients discharge was consequently earlier (p < 0.01).
CONCLUSION
100 mg dose rectal diclofenac administered 30-60 minutes before ERCP can effectively prevent PEP.
Topics: Acute Disease; Administration, Rectal; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Diclofenac; Double-Blind Method; Female; Humans; Male; Middle Aged; Pancreatitis; Prospective Studies; Treatment Outcome
PubMed: 31612188
DOI: 10.7417/CT.2019.2156 -
JAMA Network Open Aug 2022Renal colic is described as one of the worst types of pain, and effective analgesia in the shortest possible time is of paramount importance. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Renal colic is described as one of the worst types of pain, and effective analgesia in the shortest possible time is of paramount importance.
OBJECTIVES
To examine whether acupuncture, as an adjunctive therapy to analgesics, could accelerate pain relief in patients with acute renal colic.
DESIGN, SETTING, AND PARTICIPANTS
This single-center, sham-controlled, randomized clinical trial was conducted in an emergency department in China between March 2020 and September 2020. Participants with acute renal colic (visual analog scale [VAS] score ≥4) due to urolithiasis were recruited. Data were analyzed from October 2020 to January 2022.
INTERVENTIONS
After diagnosis and randomization, all patients received 50 mg/2 mL of diclofenac sodium intramuscular injection immediately followed by 30-minute acupuncture or sham acupuncture.
MAIN OUTCOMES AND MEASURES
The primary outcome was the response rate at 10 minutes after needle manipulation, which was defined as the proportion of participants whose VAS score decreased by at least 50% from baseline. Secondary outcomes included response rates at 0, 5, 15, 20, 30, 45, and 60 minutes, rescue analgesia, and adverse events.
RESULTS
A total of 115 participants were screened and 80 participants (66 men [82.5%]; mean [SD] age, 45.8 [13.8] years) were enrolled, consisting of 40 per group. The response rates at 10 minutes were 77.5% (31 of 40) and 10.0% (4 of 40) in the acupuncture and sham acupuncture groups, respectively. The between-group differences were 67.5% (95% CI, 51.5% to 83.4%; P < .001). The response rates of acupuncture were also significantly higher than sham acupuncture at 0, 5, 15, 20 and 30 minutes, whereas no significant difference was detected at 45 and 60 minutes. However, there was no difference between the 2 groups in rescue analgesia rate (difference 2.5%; 95% CI -8.8% to 13.2%; P > .99). No adverse events occurred during the trial.
CONCLUSIONS AND RELEVANCE
These findings suggest that acupuncture plus intramuscular injection of diclofenac is safe and provides fast and substantial pain relief for patients with renal colic compared with sham acupuncture in the emergency setting. However, no difference in rescue analgesia was found, possibly because of the ceiling effect caused by subsequent but robust analgesia of diclofenac. Acupuncture can be considered an optional adjunctive therapy in relieving acute renal colic.
TRIAL REGISTRATION
Chinese Clinical Trial Registry: ChiCTR1900025202.
Topics: Acupuncture Therapy; Diclofenac; Emergency Service, Hospital; Humans; Male; Middle Aged; Pain; Renal Colic; Urolithiasis
PubMed: 35943743
DOI: 10.1001/jamanetworkopen.2022.25735 -
Advanced Science (Weinheim,... Feb 2023CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an...
CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an essential role in immune escape, cell proliferation and tumor angiogenesis, making it an attractive target for cancer therapies. However, there are limited clinical benefits associated with the mainstream enzymatic inhibitors of CD73, suggesting that the mechanism underlying the role of CD73 in tumor progression is more complex than anticipated, and further investigation is necessary. In this study, CD73 is found to overexpress in the cytoplasm of pancreatic ductal adenocarcinoma (PDAC) cells and promotes metastasis in a nucleotidase-independent manner, which cannot be restrained by the CD73 monoclonal antibodies or small-molecule enzymatic inhibitors. Furthermore, CD73 promotes the metastasis of PDAC by binding to the E3 ligase TRIM21, competing with the Snail for its binding site. Additionally, a CD73 transcriptional inhibitor, diclofenac, a non-steroidal anti-inflammatory drug, is more effective than the CD73 blocking antibody for the treatment of PDAC metastasis. Diclofenac also enhances the therapeutic efficacy of gemcitabine in the spontaneous KPC (LSL-Kras , LSL-Trp53 , and Pdx-1-Cre) pancreatic cancer model. Therefore, diclofenac may be an effective anti-CD73 therapy, when used alone or in combination with gemcitabine-based chemotherapy regimen, for metastatic PDAC.
Topics: Humans; Carcinoma, Pancreatic Ductal; Diclofenac; Gemcitabine; Pancreatic Neoplasms; Nucleotidases
PubMed: 36563135
DOI: 10.1002/advs.202206335 -
Molecules (Basel, Switzerland) May 2022Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work,...
Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work, aqueous solutions of sodium diclofenac are investigated, which, like most medicinal compounds, is poorly soluble in water. Classical MD modeling of an aqueous solution of diclofenac sodium showed equilibrium between the hydrated anion and the hydrated dimer of the diclofenac anion. The assignment and interpretation of the bands in the UV, NIR, and IR spectra are based on DFT calculations in the discrete-continuum approximation. It has been shown that the combined use of spectroscopic methods in various frequency ranges with classical MD simulations and DFT calculations provides valuable information on the association processes of medical compounds in aqueous solutions. Additionally, such a combined application of experimental and calculation methods allowed us to put forward a hypothesis about the mechanism of the effect of diclofenac sodium in high dilutions on a solution of diclofenac sodium.
Topics: Anions; Diclofenac; Ions; Solutions; Water
PubMed: 35630826
DOI: 10.3390/molecules27103350 -
International Journal of Molecular... Jan 2018Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium...
Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and increases the cardioprotective effects of lycopene against DFS and tulathromycin. Seven groups (eight per group) of adult Swiss albino mice received saline (control), tulathromycin (a single subcutaneous dose of 28 mg/kg/bw on day 14), DFS (a single oral dose of 100 mg/kg/bw on day 14), tulathromycin plus DFS, or lycopene (oral, 10 mg/kg/bw daily for 15 d) combined with tulathromycin, DFS, or both. Compared to the control group, the administration of tulathromycin or DFS (individually or in combination) caused significantly elevated ( < 0.05) serum levels of Creatine kinase-myocardial B fraction (CK-MB), lactate dehydrogenase, and cardiac-specific troponin-T and tissue levels of nitric oxide and malondialdehyde that were accompanied by significantly decreased tissue reduced glutathione content and glutathione peroxidase, superoxide dismutase, and catalase antioxidant enzyme activity. Upon histopathological and immunohistochemical examination, the mean pathology scores and the percentages of caspase-3-, Bax-, and CK-positive regions were significantly higher in the tulathromycin- and/or DFS-treated groups than in control mice. For all these parameters, the pathological changes were more significant in the tulathromycin-DFS combination group than in mice treated with either drug individually. Interestingly, co-administration of lycopene with tulathromycin and/or DFS significantly ameliorated the changes described above. In conclusion, DFS could potentiate the cardiotoxic effects of tulathromycin, whereas lycopene can serve as a cardioprotective agent against DFS and tulathromycin.
Topics: Animals; Biomarkers; Cardiotoxicity; Carotenoids; Creatine Kinase, MB Form; Diclofenac; Disaccharides; Heart; Heterocyclic Compounds; Immunohistochemistry; L-Lactate Dehydrogenase; Lipid Peroxidation; Lycopene; Male; Mice; Myocardium; Protective Agents
PubMed: 29364179
DOI: 10.3390/ijms19020344 -
Ecotoxicology and Environmental Safety Nov 2022Diclofenac is an emerging surface water contaminant, yet the environmental impact of its degradation products remains elusive. The current study focuses on...
Diclofenac is an emerging surface water contaminant, yet the environmental impact of its degradation products remains elusive. The current study focuses on mineralogy-controlled diclofenac photo-degradation and its potential health impacts. Under irradiated conditions, we studied the effects of kaolinite, hematite, and anatase on diclofenac degradation. Our results showed that kaolinite doubled the diclofenac degradation rate, which can be attributed to the high catalytic effect, mediated via increased surface area and pore size of mineral surface in the low pH. Conversely, anatase, a crystal phase of titanium dioxide (TiO), diminished the diclofenac degradation compared to treatments without TiO. Hematite, on the other hand, showed no effect on diclofenac degradation. Photo-degradation products also varied with the mineral surface. We further assessed in vitro toxicological effects of photo-degraded products on two human cell lines, HEK293T and HepG2. Biological assays confirmed that photo-degraded compound 6 (1-(2,6-dichlorophenyl)indolin-2-one) decreased HEK293T cell survival significantly (p < 0.05) when compared to diclofenac in all concentrations. At lower concentrations, inhibition of HEK293T cells caused by compounds 4 (2-(8-chloro-9H-carbazol-1-yl)acetic acid), and 5 (2-(9H-carbazol-1-yl)acetic acid) was greater than diclofenac. Compound 7 (1-phenylindolin-2-one) was toxic only at 250 µM. Additionally, compound 6 decreased HepG2 cell viability significantly when compared to diclofenac. Overall, our data highlighted that mineralogy plays a vital role in environmental diclofenac transformation and its photo-degraded products. Some photo-degraded compounds can be more cytotoxic than the parent compound, diclofenac.
Topics: Humans; Diclofenac; Kaolin; HEK293 Cells; Titanium; Water Pollutants, Chemical
PubMed: 36201921
DOI: 10.1016/j.ecoenv.2022.114138 -
International Journal of Pharmaceutics Apr 2019Oral Thin Film (OTF) is a newly emerging drug delivery system which has many benefits for patients. Although there has been some formulation of OTF products, these have...
Oral Thin Film (OTF) is a newly emerging drug delivery system which has many benefits for patients. Although there has been some formulation of OTF products, these have mainly been as confectionary or dental health products. The most significant benefit of this dosage format will only be realised once more pharmaceutical products become available. Within this paper, OTF strips containing Diclofenac Sodium were prepared using the solvent casting method and then characterised to ensure the method could conform to acceptable levels of uniformity, the mean (SD) diclofenac sodium content was 25.43 (1.39) mg, range 22.84-27.44 mg. Bioburden was tested against coliforms, yeasts and moulds and all results were confirmed to be <10 CFU/g, also similar dissolution profile when compared to a commercial product to ensure biowaiver. An acceptable level of uniformity of mass was produced. K-F titration was employed to reduce the water content of the strips and it was found to be acceptable, this represented a level of water which would not be viable for microbial growth. The technique employed here in the production of OTF resulted in high quality products and amenability to being up scaled. Furthermore, the characterisation method was also sufficient to assess the quality of the products and may be used for future analysis of OTF pharmaceuticals.
Topics: Administration, Oral; Diclofenac; Drug Contamination; Drug Delivery Systems; Drug Liberation
PubMed: 30772459
DOI: 10.1016/j.ijpharm.2019.01.064 -
Asian Journal of Surgery May 2018Despite many advances in surgery and technology, colonic anastomosis remains a challenge after colonic resection. The purpose of this study is to compare the safety of... (Comparative Study)
Comparative Study
BACKGROUND
Despite many advances in surgery and technology, colonic anastomosis remains a challenge after colonic resection. The purpose of this study is to compare the safety of using diclofenac sodium and paracetamol for analgesia in colonic anastomosis on rats.
METHODS
Wistar-Hannover rats were randomly allocated to four groups: Group 1, sham-operated group; Group 2, control group; Group 3, diclofenac sodium group; Group 4, paracetamol group. After laparotomy, the left colon was transected and a single-layer anastomosis was made with 5/0 vicryl in Groups 2, 3, and 4. Only laparotomy was performed in Group 1. After anastomosis, we administered saline to Group 2, diclofenac sodium to Group 3, and paracetamol to Group 4 for 7 days. Then, all animals were decapitated. The anastomotic region was resected, and bursting pressure was measured. Then, the specimen was sent to the laboratory for histological examination and hydroxyproline analysis.
RESULTS
Bursting pressure and hydroxyproline level were significantly higher in the paracetamol group (p<0.05). When we looked at the fibrosis levels of these groups, it was also higher in paracetamol group.
CONCLUSION
Bursting pressure, hydroxyproline levels, and fibrosis levels indicate that the perioperative use of paracetamol for analgesia when undergoing colonic anastomosis is safer than diclofenac sodium.
Topics: Acetaminophen; Anastomosis, Surgical; Anastomotic Leak; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colon; Diclofenac; Pain, Postoperative; Random Allocation; Rats; Rats, Wistar; Treatment Outcome; Wound Healing
PubMed: 28190750
DOI: 10.1016/j.asjsur.2017.01.002 -
International Journal of Molecular... Oct 2022The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium...
The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Curcumin; Cytokines; Diclofenac; Inflammation; Interleukin-1beta; Interleukin-6; Nanoparticles; Rats; Rats, Wistar; Saline Solution; Tumor Necrosis Factor-alpha
PubMed: 36233038
DOI: 10.3390/ijms231911737