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Molecules (Basel, Switzerland) Aug 2021Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were... (Review)
Review
Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were discovered over 50 years ago, novel practical and asymmetric approaches are still being developed for their synthesis. In addition, this endeavor has enabled access to more potent and selective derivatives from the key frameworks of ibuprofen and naproxen. The development of a synthetic route to ibuprofen and naproxen over the last 10 years is summarized, including developing methodologies, finding novel synthetic routes, and applying continuous-flow chemistry.
Topics: Electrochemistry; Humans; Hydrogenation; Ibuprofen; Naproxen; Oxidation-Reduction; Stereoisomerism
PubMed: 34443379
DOI: 10.3390/molecules26164792 -
Deutsches Arzteblatt International Mar 2021Sore throat is a common reason for consultation of primary care physicians, pediatricians, and ENT specialists. The updated German clinical practice guideline on sore...
BACKGROUND
Sore throat is a common reason for consultation of primary care physicians, pediatricians, and ENT specialists. The updated German clinical practice guideline on sore throat provides evidence-based recommendations for treatment in the German healthcare system.
METHODS
Guideline revision by means of a systematic search of the literature for international guidelines and systematic reviews. All recommendations resulted from interdisciplinary cooperation and were agreed by formal consensus. The updated guideline applies to patients aged 3 years and over.
RESULTS
In the absence of red flags such as immunosuppression, severe comorbidity, or severe systemic infection, acute sore throat is predominantly self-limiting. The mean duration is 7 days. Chronic sore throat usually has noninfectious causes. Laboratory tests are not routinely necessary. Apart from non-pharmacological self-management, ibuprofen and naproxen are recommended for symptomatic treatment. Scores can be used to assess the risk of bacterial pharyngitis: one point each is assigned for tonsil lesions, palpable cervical lymph nodes, patient age, disease course, and elevated temperature. If the risk is low (<3 points), antibiotics are not indicated; if at least moderate (3 points), delayed prescribing is recommended; if high (>3 points), antibiotics can be taken immediately. Penicillin remains the first choice, with clarithromycin as an alternative for those who do not tolerate penicillin. The antibiotic should be taken for 5-7 days.
CONCLUSION
After the exclusion of red flags, antibiotic treatment is unnecessary in many cases of acute sore throat. If administration of antibiotics is still considered in spite of consultation on the usual course of tonsillopharyngitis and the low risk of complications, a risk-adapted approach using clinical scores is recommended.
Topics: Anti-Bacterial Agents; Fever; Humans; Pain; Penicillins; Pharyngitis
PubMed: 33602392
DOI: 10.3238/arztebl.m2021.0121 -
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 -
Frontiers in Physiology 2021Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of...
Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of these widely used drugs is the inhibition of cyclooxygenase 1 and 2 (COX1, 2) enzymes that catalyze the conversion of arachidonic acid into prostaglandins. At higher doses, NSAIDs are used for prevention of certain types of cancer and as experimental treatments for Alzheimer's disease. In the immune system, various NSAIDs have been reported to influence neutrophil function and lymphocyte proliferation, and affect ion channels and cellular calcium homeostasis. Transient receptor potential melastatin 7 (TRPM7) cation channels are highly expressed in T lymphocytes and are inhibited by Mg, acidic pH, and polyamines. Here, we report a novel effect of naproxen, ibuprofen, salicylate, and acetylsalicylate on TRPM7. At concentrations of 3-30mM, they reversibly inhibited TRPM7 channel currents. By measuring intracellular pH with the ratiometric indicator BCECF, we found that at 300μM to 30mM, these NSAIDs reversibly acidified the cytoplasm in a concentration-dependent manner, and propose that TRPM7 channel inhibition is a consequence of cytosolic acidification, rather than direct. NSAID inhibition of TRPM7 channels was slow, voltage-independent, and displayed use-dependence, increasing in potency upon repeated drug applications. The extent of channel inhibition by salicylate strongly depended on cellular PI(4,5)P levels, as revealed when this phospholipid was depleted with voltage-sensitive lipid phosphatase (VSP). Salicylate inhibited heterologously expressed wildtype TRPM7 channels but not the S1107R variant, which is insensitive to cytosolic pH, Mg, and PI(4,5)P depletion. NSAID-induced acidification was also observed in Schneider 2 cells from , an organism that lacks orthologous COX genes, suggesting that this effect is unrelated to COX enzyme activity. A 24-h exposure to 300μM-10mM naproxen resulted in a concentration-dependent reduction in cell viability. In addition to TRPM7, the described NSAID effect would be expected to apply to other ion channels and transporters sensitive to intracellular pH.
PubMed: 34733174
DOI: 10.3389/fphys.2021.727549 -
The Science of the Total Environment Oct 2020Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) represent one of the main therapeutic classes of molecules contaminating aquatic ecosystems worldwide. NSAIDs are commonly... (Review)
Review
Toxicity of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) acetylsalicylic acid, paracetamol, diclofenac, ibuprofen and naproxen towards freshwater invertebrates: A review.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) represent one of the main therapeutic classes of molecules contaminating aquatic ecosystems worldwide. NSAIDs are commonly and extensively used for their analgesic, antipyretic and anti-inflammatory properties to cure pain and inflammation in human and veterinary therapy. After use, NSAIDs are excreted in their native form or as metabolites, entering the aquatic ecosystems. A number of monitoring surveys has detected the presence of different NSAIDs in freshwater ecosystems in the ng/L - μg/L concentration range. Although the concentrations of NSAIDs in surface waters are low, the high biological activity of these molecules may confer them a potential toxicity towards non-target aquatic organisms. The present review aims at summarizing toxicity, in terms of both acute and chronic toxicity, induced by the main NSAIDs detected in surface waters worldwide, namely acetylsalicylic acid (ASA), paracetamol (PCM), diclofenac (DCF), ibuprofen (IBU) and naproxen (NPX), both singularly and in mixture, towards freshwater invertebrates. Invertebrates play a crucial role in ecosystem functioning so that NSAIDs-induced effects may result in hazardous consequences to the whole freshwater trophic chain. Acute toxicity of NSAIDs occurs only at high, unrealistic concentrations, while sub-lethal effects arise also at low, environmentally relevant concentrations of all these drugs. Thus, further studies represent a priority in order to improve the knowledge on NSAID toxicity and mechanism(s) of action in freshwater organisms and to shed light on their real ecological hazard towards freshwater communities.
Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diclofenac; Ecosystem; Fresh Water; Humans; Ibuprofen; Invertebrates; Naproxen
PubMed: 32559537
DOI: 10.1016/j.scitotenv.2020.140043