痛风和高尿酸血症药物治疗研究现状

痛风是尿酸盐沉积所致的晶体相关性关节病,与高尿酸血症直接相关,目前临床尚未研制出可根治原发性痛风的药物,主要借助控制患者血尿酸水平的方式加以治疗。秋水仙碱、2IL-1R拮抗剂、别嘌醇、非布司他等药物均为当前治疗该病的主要药物。文章就痛风和高尿酸血症的关系、临床表现及治疗与促进尿酸排泄的相关药物现状以及药物研发方向等问题进行了综述,旨在为临床治疗痛风与进行新药研发提供参考。     

EMEA开始审查febuxostat

Ipsen公司已递交febuxostat（Ⅰ）用于治疗症状性高尿酸血症的集中欧盟审批申请。如果获得批准，（Ⅰ）将成为40年来首个治疗高尿酸血症的新药，高尿酸血症与痛风有关。（Ⅰ）是一种口服黄嘌呤氧化酶抑制剂，可降低血中的尿酸水平，并阻止痛风病人关节处尿酸晶体的沉积。（Ⅰ）比现有治疗药物别嘌呤（auopurin01）特异性更强，别瞟呤是通过抑制尿酸通路中的一系列酶发挥作用的。     

痛风药物治疗进展

痛风的生化标志是高尿酸血症,后者不仅可侵犯骨和关节,而且易累及肾脏和心血管系统。控制血液尿酸水平可有效治疗痛风,减少上述并发症的发生。本文结合相关疗效评价研究,综述痛风治疗新药非布索坦、处于研发后期的降尿酸药物及临床治疗方案开发进展。     

痛风药物研究进展

痛风是由高尿酸血症和关节周围的尿酸盐（MSU）晶体沉积引起的病症。综述了用于痛风治疗的相关药物,包括已经在临床上应用的传统药物、正处于临床研究阶段的新药,以及临床前研究阶段的新化合物。为其他研究者在痛风领域的研究提供参考与借鉴。     

Lesinurad:一种选择性尿酸再吸收抑制剂

尿酸盐重吸收转运因子(URAT1)是一种阴离子转运体,它位于肾小管近端小管顶部细胞中,决定尿酸的重吸收,常作为治疗高尿酸血症及痛风药物的靶点。Lesinurad是一种URAT1选择性抑制剂,由阿斯利康制药公司研发,并于2015年底被FDA批准与黄嘌呤氧化酶抑制剂联合用于高尿酸血症及痛风症状的缓解治疗。主要介绍Lesinuard的药物概况、相关研发背景、合成路线、药理作用、药动学、临床试验等方面研究情况,为该药的推广应用以及同类新药研发提供依据。     

痛风的药物治疗新进展

痛风是一种以尿酸钠晶体在关节及其周围组织沉积为特征的关节炎[1].高尿酸血症被认为是发生痛风的前期状态[2],然而并非所有高尿酸血症患者都会发展为痛风.由于疼痛、活动受限以及致残等原因,急性和慢性痛风性关节炎患者的生活质量大大下降.近年来随着人们生活水平的提高,痛风和高尿酸血症的发病率呈上升趋势,因此寻找抗痛风的新药及新的治疗方法越来越引起了人们的重视.目前临床上的药物治疗主要有痛风的急性发作期治疗、高尿酸血症的治疗以及预防期药物治疗等方法.     

抗高尿酸血症药物研究进展

痛风是一种代谢性疾病,危害严重,近年来患病率呈上升趋势。尿酸排泄减少或生成增多所致的高尿酸血症是痛风的主要病因,而高尿酸又与多种疾病密切相关。降低血尿酸水平是治疗痛风,预防痛风复发的重要措施。目前,抗高尿酸血症药物主要有3类,分别是黄嘌呤氧化酶抑制剂、尿酸盐阴离子转运蛋白1(URAT1)抑制剂和尿酸氧化酶类似物。对现有抗高尿酸血症药物的现状以及研究进展进行总结,希望对其研发提供参考。     

警惕别嘌醇片引起的重症药疹

别嘌醇（Allopurinol）为次黄嘌呤的异构体,是黄嘌呤氧化酶（XO）的抑制剂,可阻止次黄嘌呤和黄嘌呤代谢为尿酸,从而减少尿酸的生成,是目前唯一能抑制尿酸合成的药物。剂型为片剂。临床主要用于：（1）原发性和继发性高尿酸血症,尤其是尿酸生成过多而引起的高尿酸血症;（2）反复发作或慢性痛风者;（3）痛风石：（4）尿酸性肾结石和（或）尿酸性肾病：（5）有肾功能不全的高尿酸血症。     

高尿酸血症及其治疗药物与肾脏疾病相关性的研究进展

高尿酸血症是人体内嘌呤代谢紊乱而引起的一种代谢性疾病,也是诱发痛风的生物化学基础。由于肾脏是尿酸排泄的主要器官,其在尿酸平衡中发挥重要作用,高尿酸血症与慢性肾病、糖尿病肾病、IgA肾病等肾脏疾病的发生与发展密切相关。目前,临床常用的降尿酸药物包括：抑制尿酸生成药物（别嘌醇和非布司他）、促进尿酸排泄药物（丙磺舒和苯溴马隆）以及促进尿酸降解药物（拉布立酶和普瑞凯希）,但这些药物在有效性和安全性上仍存在使用缺陷。综述高尿酸血症及其治疗药物与肾脏疾病的关联性,以期为临床中具有肾脏获益的新型降尿酸药物开发提供参考。     

降尿酸药物研究进展

作为常见炎症性关节炎类型之一,痛风是长期高尿酸血症造成的后果之一.所以,痛风管理的主要目标就是降低并长期维持血清尿酸浓度在其饱和度以下.痛风患者高尿酸血症管理长期来几乎完全依赖别嘌呤醇.随着非布司他和培格洛替酶相继获准上市,不能耐受或不适别嘌呤醇治疗以及别嘌呤醇治疗无效的高尿酸血症患者有了替代和后续治疗选择,标志着降尿酸药物研究与开发已获得一次重大进步.本文概要介绍非布司他和培格洛替酶的临床研究数据,并就这两降尿酸新药在痛风患者高尿酸血症管理领域中的作用和地位作一分析.     

Therapeutic voyage of synthetic and natural xanthine oxidase inhibitors

Xanthine oxidase (XO) inhibitors are commonly used to treat gout, nephropathy, and renal stone diseases related to hyperuricemia. However, recent research has shown that these inhibitors may also have potential benefits in preventing vascular diseases, including those affecting the cerebrovasculature. This is due to emerging evidence suggesting that serum uric acid is involved in the growth of cardiovascular disease, and XO inhibition can reduce oxidative stress in the vasculature. There is a great interest in the development of new XO inhibitors for the treatment of hyperuricemia and gout. The present review discusses the many synthetic and natural XO inhibitors that have been developed which are found to have greater potency.     

痛风的现代研究进展

近年来高尿酸血症和痛风的发病率逐年上升,高尿酸血症为痛风的早期阶段,长期高尿酸血症除易诱发痛风外,尚易累及肾脏和心脑血管系统,导致严重的肾脏及心脑血管疾病,因此对高尿酸血症病因、病机及治疗的研究日益增多,本文从中、西医角度对近年来的相关研究作一综述。     

痛风的药物治疗与药学监护

高尿酸血症和痛风是多种心脑血管和代谢疾病的危险因素,是高血压、肾动脉硬化结石、尿酸性肾病、糖尿病的发病和恶化因素。抗痛风药为一组通过抑制尿酸合成和促进尿酸排泄或分解而降低血、尿尿酸水平,或抑制粒细胞浸润而控制关节炎症,对抗痛风发作的药物,其合理应用和药学监护十分重要。通过查阅近年来国内、外相关文献和诊疗指南,对痛风的药物治疗与药学监护进行综述。药师应确立痛风的治疗靶标、按痛风的分期选择用药、针对痛风合并症积极治疗,并从规避诱发尿酸水平升高的药品、急性发作期禁忌的药品、水化和碱化治疗等若干监护点进行干预,体现现代药师在药物治疗中的价值。     

A review on benefits of quercetin in hyperuricemia and gouty arthritis

Hyperuricemia becomes a public health problem worldwide. It is not only a major risk factor for gout but also associated with the development of life-threatening diseases such as chronic kidney disease and cardiovascular diseases. Although there are several available therapeutic drugs, some serious adverse effects and contraindications are concerned. These drive the search for an alternative therapy that is effective and safe. Quercetin is of particular interesting since it has been reported numerous pharmacological activities, especially anti-hyperuricemia, antioxidant, anti-inflammation and amelioration of metabolic syndromes and cardiovascular diseases which are comorbidities of hyperuricemia and gout. In addition, quercetin has been widely used as a health supplement for many diseases however, the use for hyperuricemia and gout has not been indicated. Therefore, this review aims to gather and summarize published data regarding the efficacy in preclinical and clinical studies along with possible mechanism of action, and safety aspect of quercetin in order to support the use of quercetin as a dietary supplement for prevention and management of hyperuricemia and gouty arthritis and/or use as alternative or combination therapy to minimize the side effects of the conventional drugs.     

以黄嘌呤氧化酶为靶点的新型非嘌呤类抗痛风及高尿酸血症药物研究进展

黄嘌呤氧化酶（XO）催化黄嘌呤生成尿酸及次黄嘌呤生成黄嘌呤的过程,是抗高尿酸血症或痛风药物研究的关键靶点。黄嘌呤氧化酶抑制剂由于作用机制明确、疗效显著而倍受关注,研发新型XO抑制剂具有广阔的应用前景。XO的结构生物学及分子模拟技术为新一代非嘌呤类XO抑制剂的合理药物设计奠定了基础。本文综述了以黄嘌呤氧化酶为靶标的新型非嘌呤类小分子杂环化合物及天然产物来源的活性分子在抗高尿酸血症或痛风药物研究领域中的进展。     

Drug discovery for hyperuricemia

Hyperuricemia is associated with an increased risk of developing gout. This increases with the degree and duration of hyperuricemia. Gout can be managed by dietary modification and pharmacologic urate-lowering therapies. The recent identification of the renal apical urate/anion exchanger URAT1 (SLC22A12) and several membrane proteins relevant to the transport of urate play an important role in gaining a better understanding of the mode of action of many drugs used to treat gout. As described in this review, therapeutics designed to modify URAT1 transport activities might be useful in treating pathologies associated with hyperuricemia such as gout and urolithiasis. Continuing studies into the urate transportsome hold promise for the development of new, more effective therapeutics for hyperuricemia.     

Pegloticase for treating refractory chronic gout

Gout is a metabolic disorder of excess uric acid accumulation that manifests clinically as inflammatory arthritis, chronic arthropathy and the formation of deposits of uric acid known as tophi. A primary objective of gout management is to reduce the excess urate burden by regular use of drugs that reduce serum urate levels. Conventional urate-lowering drugs available in the U.S. are allopurinol, febuxostat and probenecid. Some patients are intolerant to or unresponsive to urate-lowering therapies and, therefore, are said to have refractory gout. Recently, a polyethylene glycol-conjugated uricase, pegloticase, was approved for treating refractory gout. In recent clinical trials, pegloticase normalized plasma urate levels, reduced the size of tophi, and improved functional status and quality of life in patients with refractory disease. Immunogenicity to pegloticase is associated with loss of urate-lowering response and the risk of infusion reactions. Pegloticase is effective in treating hyperuricemia and the clinical manifestations of gout in patients who cannot be adequately managed with conventional therapy.     

代谢组学技术在痛风类疾病研究中的应用进展

目的 对近年来代谢组学技术在痛风领域的相关研究进行综述,以期为痛风今后更深入的研究提供思路和方向.方法 通过PubMed检索相关文献,分析和总结代谢组学技术在嘌呤代谢、高尿酸血症和痛风相关疾病研究中的应用.结果 代谢组学技术被广泛应用于痛风类疾病的生物标志物发现、发病机制探索以及药物作用机制研究,同时代谢组学技术与其他...     

原发性痛风的诊治进展

原发性痛风是一种常见的代谢性疾病,随着饮食结构等生活方式的改变,发病率有逐年升高趋势。根据痛风的不同临床表现,可分为不同的疾病时期或阶段,而不同阶段痛风的治疗方法不同。痛风的治疗原则为控制急性痛风性关节炎、预防急性发作、纠正高尿酸血症、治疗慢性并发症。目前痛风的治疗仍存在一定的误区,需规范化。