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Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E -
CMAJ : Canadian Medical Association... Jul 2023
Topics: Humans; Allopurinol; Disease Progression; Drug Hypersensitivity Syndrome
PubMed: 37460122
DOI: 10.1503/cmaj.221575-f -
The Journal of Biological Chemistry Sep 2023Xanthine oxidoreductase is a metalloenzyme that catalyzes the final steps in purine metabolism by converting hypoxanthine to xanthine and then uric acid. Allopurinol, an...
Xanthine oxidoreductase is a metalloenzyme that catalyzes the final steps in purine metabolism by converting hypoxanthine to xanthine and then uric acid. Allopurinol, an analog of hypoxanthine, is widely used as an antigout drug, as xanthine oxidoreductase-mediated metabolism of allopurinol to oxypurinol leads to oxypurinol rotation in the enzyme active site and reduction of the molybdenum Mo(VI) active center to Mo(IV), inhibiting subsequent urate production. However, when oxypurinol is administered directly to a mouse model of hyperuricemia, it yields a weaker urate-lowering effect than allopurinol. To better understand its mechanism of inhibition and inform patient dosing strategies, we performed kinetic and structural analyses of the inhibitory activity of oxypurinol. Our results demonstrated that oxypurinol was less effective than allopurinol both in vivo and in vitro. We show that upon reoxidation to Mo(VI), oxypurinol binding is greatly weakened, and reduction by xanthine, hypoxanthine, or allopurinol is required for reformation of the inhibitor-enzyme complex. In addition, we show oxypurinol only weakly inhibits the conversion of hypoxanthine to xanthine and is therefore unlikely to affect the feedback inhibition of de novo purine synthesis. Furthermore, we observed weak allosteric inhibition of purine nucleoside phosphorylase by oxypurinol which has potentially adverse effects for patients. Considering these results, we propose the single-dose method currently used to treat hyperuricemia can result in unnecessarily high levels of allopurinol. While the short half-life of allopurinol in blood suggests that oxypurinol is responsible for enzyme inhibition, we anticipate multiple, smaller doses of allopurinol would reduce the total allopurinol patient load.
PubMed: 37625592
DOI: 10.1016/j.jbc.2023.105189 -
Journal of Clinical Medicine Sep 2023Febuxostat and allopurinol are the most commonly used uric acid-lowering medications, and their safety is of great concern, especially the cardiovascular adverse...
BACKGROUND
Febuxostat and allopurinol are the most commonly used uric acid-lowering medications, and their safety is of great concern, especially the cardiovascular adverse reactions associated with febuxostat. We propose to study the cardiovascular toxicity of febuxostat and allopurinol using the FDA Adverse Event Reporting System (FAERS) database.
METHODS
A total of 64 quarters of FAERS data were downloaded from 2004 to 2019. Febuxostat- and allopurinol-related cardiovascular adverse events were extracted after data cleaning. Signal detection was conducted by reporting odds ratio (ROR) and proportional reporting ratio (PRR).
RESULTS
There were 2939 and 25,219 reports of febuxostat- and allopurinol-related cardiovascular adverse events (CVAEs), respectively. The most frequent CVAEs with febuxostat and allopurinol were edema peripheral (14.38%) and peripheral swelling (8.76%), respectively. In elderly gout patients, febuxostat is associated with an increased risk of heart failure, ischemic heart disease, hypertension, and cardiomyopathy. Febuxostat in combination with acetic acid derivatives nonsteroidal anti-inflammatory drug (NSAIDS) also increases the risk of cardiovascular adverse events.
CONCLUSIONS
Compared with allopurinol, febuxostat may increase cardiovascular toxicity in patients with gout.
PubMed: 37763029
DOI: 10.3390/jcm12186089 -
Biomedicine & Pharmacotherapy =... Nov 2023Colorectal cancer (CRC) is a globally prevalent malignancy with a high potential for metastasis. Existing cancer treatments have limitations, including drug resistance... (Review)
Review
Colorectal cancer (CRC) is a globally prevalent malignancy with a high potential for metastasis. Existing cancer treatments have limitations, including drug resistance and adverse effects. Researchers are striving to develop effective therapies to address these challenges. Impressively, contemporary research has discovered that many natural products derived from foods, plants, insects, and marine invertebrates can suppress the progression, metastasis, and invasion of CRC. In this review, we conducted a comprehensive search of the CNKI, PubMed, Embase, and Web of Science databases from inception to April 2023 to evaluate the efficacy of natural products targeting mitochondria to fight against CRC. Mitochondria are intracellular energy factories involved in cell differentiation, signal transduction, cell cycle regulation, apoptosis, and tumorigenesis. The identified natural products have been classified and summarized based on their mechanisms of action. These findings indicate that natural products can induce apoptosis in colorectal cancer cells by inhibiting the mitochondrial respiratory chain, ROS elevation, disruption of mitochondrial membrane potential, the release of pro-apoptotic factors, modulation of the Bcl-2 protein family to facilitate cytochrome c release, induction of apoptotic vesicle activity by activating the caspase protein family, and selective targeting of mitochondrial division. Furthermore, diverse apoptotic signaling pathways targeting mitochondria, such as the MAPK, p53, STAT3, JNK and AKT pathway, have been triggered by natural products. Natural products such as diosgenin, allopurinol, and clausenidin have demonstrated low toxicity, high efficacy, and multi-targeted properties. Mitochondria-targeting natural products have great potential for overcoming the challenges of CRC therapy.
PubMed: 37713992
DOI: 10.1016/j.biopha.2023.115473 -
Archives of Medical Science : AMS 2023The aim of the study was to evaluate the preventive effect of 13 drugs on colorectal cancer (CRC) and guide the clinical application of these drugs. (Review)
Review
INTRODUCTION
The aim of the study was to evaluate the preventive effect of 13 drugs on colorectal cancer (CRC) and guide the clinical application of these drugs.
MATERIAL AND METHODS
PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure were searched for randomized controlled trials (RCTs) and cohort studies. The Cochrane bias risk assessment tool and the Newcastle-Ottawa Scale quality evaluation tool were used to evaluate the quality of the included RCTs and cohort studies. The funnel plot was used to analyze publication bias. A network meta-analysis of the extracted data was conducted using Stata16.0 software.
RESULTS
A total of 57 studies (34 RCTs and 23 cohort studies) involving 82719 participants were included. The network meta-analysis revealed that the quality of the included studies was good; the funnel plot showed no obvious publication bias. The network meta-analysis showed that the preventive effect of 13 drugs on CRC was better than that of the placebo. Allopurinol (SUCRA: 97.2%) was found to have the best effect, followed by berberine (SUCRA: 89.9%), non-aspirin NSAIDs (SUCRA: 84.5%), statins (SUCRA: 66.5%), metformin (SUCRA: 66.3%), calcium (SUCRA: 48.9%), mesalazine (SUCRA: 44.5%), ursodeoxycholic acid (SUCRA: 42.6%), vitamin D (SUCRA: 41.4%), mercaptopurine (SUCRA: 39.4%), aspirin (SUCRA: 30.4%), folic acid (SUCRA: 24.9%), and eicosapentaenoic acid (SUCRA: 16.3%).
CONCLUSIONS
The preventive effect of allopurinol on CRC was better than that of the other 13 drugs. These results can help doctors and patients understand the preventative effects of these drugs more intuitively and provide an evidence-based basis for the clinical application of these drugs.
PubMed: 37732038
DOI: 10.5114/aoms/167480 -
Cancer Pathogenesis and Therapy Oct 2023Tumor lysis syndrome (TLS) remains a debilitating cause of hospitalization and death in patients with cancer and is a significant challenge for healthcare providers... (Review)
Review
Tumor lysis syndrome (TLS) remains a debilitating cause of hospitalization and death in patients with cancer and is a significant challenge for healthcare providers despite advancements in its management. This umbrella review analyzed the results of meta-analyses on the use of rasburicase in the treatment of patients with cancer. A literature search was performed of five databases (PubMed, Google Scholar, Cochrane Library, Scopus, Global Index Medicus, and ScienceDirect) for articles with full texts available online. A measurement tool to assess systematic reviews 2 (AMSTAR 2) was used to assess the quality of the included studies, and Review Manager software was used to conduct all statistical analyses. The systematic search identified eight relevant meta-analyses, with primary analyses including outcome data that analyzed mortality, renal failure, and comparisons with allopurinol. The pooled data showed that rasburicase effectively reduced TLS development and serum uric acid levels in children and adults with malignancies. Most outcomes did not differ significantly compared with those of allopurinol. Future trials should focus on the cost-effectiveness of rasburicase compared to that of allopurinol while including high-, intermediate-, and low-risk patients. Rasburicase is safe and effective for managing patients with TLS. However, recent large-scale meta-analyses have reported conflicting results. Most meta-analyses were graded as low to critically low as per AMSTAR 2. The analysis revealed that the benefit of rasburicase did not differ significantly from that of allopurinol, which has higher cost-effectiveness and fewer side effects.
PubMed: 38327601
DOI: 10.1016/j.cpt.2023.07.001 -
Life (Basel, Switzerland) Nov 2023Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with... (Review)
Review
Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat's mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat's primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat's potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat's roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat's multifaceted therapeutic potential.
PubMed: 38004339
DOI: 10.3390/life13112199