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Biomedicine & Pharmacotherapy =... Jun 2022A narrative review of papers published from January 2011 to December 2021, after a literature search in selected databases using the terms "pharmacokinetics",... (Review)
Review
A narrative review of papers published from January 2011 to December 2021, after a literature search in selected databases using the terms "pharmacokinetics", "ibuprofen", "diclofenac", "acemetacin", "naproxen", "etodolac" and "etoricoxib" was performed. From 828 articles identified, only eight met the inclusion criteria. Selective COX-2 inhibitors are associated with higher cardiovascular risk, while non-selective COX inhibitors are associated with higher gastrointestinal risk. NSAIDs with lower renal excretion with phase 2 metabolism are less likely to induce adverse effects and drug-drug interactions. Patients with frequent NSAID use needs, such as elderly patients and patients with cardiovascular disease or impaired renal function, will benefit from lower renal excretion (e.g. acemethacin, diclofenac, and etodolac) (level of evidence 3). Polymedicated patients, elderly patients, and patients with chronic alcohol abuse will be at a lower risk for adverse effects with NSAIDs that undergo phase 2 liver biotransformation, namely, acemethacin and diclofenac (level of evidence 3). Young patients, patients dealing with acute pain, or with active and/or chronic symptomatic gastritis, selective COX-2 inhibitors (celecoxib or etoricoxib) may be a better option (level of evidence 2). Knowing the individual characteristics of the patients, combined with knowledge on basic pharmacology, offers greater safety and better adherence to therapy. PERSPECTIVE: Although there are several NSAIDs options to treat pain, physicians usually take special care to its prescription regarding cardiovascular and gastrointestinal side effects, despite the age of the patient. In this paper, based on the best evidence, the authors present a review of the safest NSAIDs to use in the elderly.
Topics: Aged; Aging; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Diclofenac; Etoricoxib; Humans; Pain; Prescriptions
PubMed: 35453005
DOI: 10.1016/j.biopha.2022.112958 -
International Journal of Dermatology Jun 2020Actinic keratosis (AK) is a very common skin disease caused by chronic sun damage, which in 75% of cases arises on chronically sun-exposed areas, such as face, scalp,... (Review)
Review
Actinic keratosis (AK) is a very common skin disease caused by chronic sun damage, which in 75% of cases arises on chronically sun-exposed areas, such as face, scalp, neck, hands, and forearms. AKs must be considered an early squamous cell carcinoma (SCC) for their probable progression into invasive SCC. For this reason, all AK should be treated, and clinical follow-up is recommended. The aims of treatment are: (i) to clinically eradicate evident and subclinical lesions, (ii) to prevent their evolution into SCC, and (iii) to reduce the number of relapses. Among available treatments, it is possible to distinguish lesion-directed therapies and field-directed therapies. Lesion-directed treatments include: (i) cryotherapy; (ii) laser therapy; (iii) surgery; and (iv) curettage. Whereas, field-directed treatments are: (i) 5-fluorouracil (5-FU); (ii) diclofenac 3% gel; (iii) chemical peeling; (iv) imiquimod; and (v) photodynamic therapy (PDT). Prevention plays an important role in the treatment of AKs, and it is based on the continuous use of sunscreen and protective clothing. This review shows different types of available treatments and describes the characteristics and benefits of each medication, underlining the best choice.
Topics: Aftercare; Carcinoma, Squamous Cell; Chemexfoliation; Cryotherapy; Curettage; Dermoscopy; Diclofenac; Disease Progression; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Laser Therapy; Photochemotherapy; Practice Guidelines as Topic; Protective Clothing; Skin; Skin Neoplasms; Sunlight; Sunscreening Agents
PubMed: 32012240
DOI: 10.1111/ijd.14767 -
Paediatric Drugs Nov 2022Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial effects of NSAIDs in children and adolescents, there is a lack of comprehensive data in infants. The present review summarizes the current knowledge on the safety and efficacy of various NSAIDs used in infants for which data are available, and includes ibuprofen, dexibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, ketorolac, indomethacin, niflumic acid, meloxicam, celecoxib, parecoxib, rofecoxib, acetylsalicylic acid, and nimesulide. The efficacy of NSAIDs has been documented for a variety of conditions, such as fever and pain. NSAIDs are also the main pillars of anti-inflammatory treatment, such as in pediatric inflammatory rheumatic diseases. Limited data are available on the safety of most NSAIDs in infants. Adverse drug reactions may be renal, gastrointestinal, hematological, or immunologic. Since NSAIDs are among the most frequently used drugs in the pediatric population, safety and efficacy studies can be performed as part of normal clinical routine, even in young infants. Available data sources, such as (electronic) medical records, should be used for safety and efficacy analyses. On a larger scale, existing data sources, e.g. adverse drug reaction programs/networks, spontaneous national reporting systems, and electronic medical records should be assessed with child-specific methods in order to detect safety signals pertinent to certain pediatric age groups or disease entities. To improve the safety of NSAIDs in infants, treatment needs to be initiated with the lowest age-appropriate or weight-based dose. Duration of treatment and amount of drug used should be regularly evaluated and maximum dose limits and other recommendations by the manufacturer or expert committees should be followed. Treatment for non-chronic conditions such as fever and acute (postoperative) pain should be kept as short as possible. Patients with chronic conditions should be regularly monitored for possible adverse effects of NSAIDs.
Topics: Adolescent; Infant; Child; Humans; Meloxicam; Naproxen; Celecoxib; Ibuprofen; Ketoprofen; Diclofenac; Ketorolac; Flurbiprofen; Niflumic Acid; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Anti-Inflammatory Agents; Chronic Disease; Pain
PubMed: 36053397
DOI: 10.1007/s40272-022-00514-1 -
Medicine May 2020Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at conducting a network meta-analysis to assess the efficacy and safety of 5 OTCAs - naproxen, ibuprofen,diclofenac, aspirin, and ketoprofen - in patients with primary dysmenorrhea.
METHODS
The study was registered with PROSPERO (number: CRD42019133556). The search strategy involved a review of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL for relative randomized controlled trials of the 5 analgesics from the date of database establishment to July 2019. The outputs are presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities.
RESULTS
Thirty-five trials with 4383 participants were included in our study. As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18-7.30), ibuprofen (OR 10.08, 95% CI 3.29-30.85), diclofenac (OR 11.82, 95% CI 2.66-52.48), and ketoprofen (OR 5.12, 95% CI 1.57-16.69). The OTCAs were superior to the placebo in terms of pain relief in primary dysmenorrhea. Aspirin was less effective than ibuprofen (OR 0.17, 95% CI 0.04-0.73) and diclofenac (OR 1.17, 95% CI 0.02-0.85). The SUCRA curves showed that diclofenac and ibuprofen were the most and second most effective (85.1% and 83.8%, respectively), followed by ketoprofen, naproxen, and aspirin. Regarding safety, there was no significant difference between the 5 OTCAs included and the placebo. Diclofenac versus ibuprofen (OR 4.31, 95% CI 1.18-15.67), ketoprofen versus diclofenac (OR 0.18, 95% CI 0.04-0.78), and ketoprofen versus aspirin (OR 0.41, 95% CI 0.18-0.97) presented statistically significant differences. Ketoprofen and ibuprofen were ranked the best (SUCRA 90.6% and 79.6%), followed by naproxen, aspirin, and diclofenac.
CONCLUSION
Considering the efficacy and safety, ibuprofen is recommended as the optimal OTCA for primary dysmenorrhea. Further well-designed studies that directly compare these analgesics are needed to support our conclusion.
Topics: Adolescent; Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diclofenac; Dysmenorrhea; Female; Humans; Ibuprofen; Ketoprofen; Middle Aged; Naproxen; Network Meta-Analysis; Nonprescription Drugs; Treatment Outcome; Young Adult
PubMed: 32384431
DOI: 10.1097/MD.0000000000019881 -
Trials May 2022Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS.
METHODS
This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily whilst taking capecitabine for 12 weeks. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) DISCUSSION: The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention.
TRIAL REGISTRATION
Clinical Trials Registry of India CTRI/2021/01/030592 . Prospectively registered on January 19, 2021.
Topics: Antimetabolites, Antineoplastic; Capecitabine; Celecoxib; Cyclooxygenase 2 Inhibitors; Diclofenac; Hand-Foot Syndrome; Humans
PubMed: 35590388
DOI: 10.1186/s13063-022-06353-2 -
Journal of Dental Research Jul 2020Postsurgical dental pain is mainly driven by inflammation, particularly through the generation of prostaglandins via the cyclooxygenase system. Thus, it is no surprise...
Postsurgical dental pain is mainly driven by inflammation, particularly through the generation of prostaglandins via the cyclooxygenase system. Thus, it is no surprise that numerous randomized placebo-controlled trials studying acute pain following the surgical extraction of impacted third molars have demonstrated the remarkable efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen sodium, etodolac, diclofenac, and ketorolac in this prototypic condition of acute inflammatory pain. Combining an optimal dose of an NSAID with an appropriate dose of acetaminophen appears to further enhance analgesic efficacy and potentially reduce the need for opioids. In addition to being on average inferior to NSAIDs as analgesics in postsurgical dental pain, opioids produce a higher incidence of side effects in dental outpatients, including dizziness, drowsiness, psychomotor impairment, nausea/vomiting, and constipation. Unused opioids are also subject to misuse and diversion, and they may cause addiction. Despite these risks, some dental surgical outpatients may benefit from a 1- or 2-d course of opioids added to their NSAID regimen. NSAID use may carry significant risks in certain patient populations, in which a short course of an acetaminophen/opioid combination may provide a more favorable benefit versus risk ratio than an NSAID regimen.
Topics: Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Pain, Postoperative; Pharmaceutical Preparations
PubMed: 32286125
DOI: 10.1177/0022034520914254 -
International Journal of Molecular... Mar 2023Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic... (Review)
Review
Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.
Topics: Humans; Keratosis, Actinic; Aminolevulinic Acid; Diclofenac; Imiquimod; Photochemotherapy; Fluorouracil; Photosensitizing Agents; Treatment Outcome
PubMed: 36902419
DOI: 10.3390/ijms24054989 -
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 -
Theranostics 2022While some non-steroidal anti-inflammatory drugs (NSAIDs) are reported to induce hepatic steatosis, the molecular mechanisms are poorly understood. This study presented...
While some non-steroidal anti-inflammatory drugs (NSAIDs) are reported to induce hepatic steatosis, the molecular mechanisms are poorly understood. This study presented the mechanism by which NSAIDs induce hepatic lipid accumulation. Mouse primary hepatocytes and HepG2 cells were used to examine the underlying mechanism of NSAID-induced hepatic steatosis. Lipid accumulation was measured using Nile-red assay and BODIPY 493/503. The activity of chaperone-mediated autophagy (CMA) was determined by western blotting, qRT-PCR, and confocal imaging. The effect of NSAID on CMA inhibition was evaluated using diclofenac and CMA activator (AR7) administered mice. All tested NSAIDs in this study accumulated neutral lipids in hepatocytes, diclofenac having demonstrated the most potency in that regard. Diclofenac-induced lipid accumulation was confirmed in both mouse primary hepatocytes and the liver of mice. NSAIDs inhibited CMA, as reflected by the decreased expression of lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A) protein, the increased expression of CMA substrate proteins such as PLIN2, and the decreased activity of photoactivatable KFERQ-PAmCherry reporter. Reactivation of CMA by treatment with AR7 or overexpression of LAMP2A inhibited diclofenac-induced lipid accumulation and hepatotoxicity. Upregulation of sorting nexin 10 (SNX10) via the CHOP-dependent endoplasmic reticulum stress response and thus maturation of cathepsin A (CTSA) was shown to be responsible for the lysosomal degradation of LAMP2A by diclofenac. We demonstrated that NSAIDs induced SNX10- and CTSA-dependent degradation of LAMP2A, thereby leading to the suppression of CMA. In turn, impaired CMA failed to degrade PLIN2 and disrupted cellular lipid homeostasis, thus leading to NSAID-induced steatosis and hepatotoxicity.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Autophagy; Chaperone-Mediated Autophagy; Chemical and Drug Induced Liver Injury; Diclofenac; Fatty Liver; Lipids; Lysosomes; Mice; Sorting Nexins
PubMed: 35265214
DOI: 10.7150/thno.70692 -
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