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。     

高尿酸血症药物治疗进展

高尿酸血症(HUA)是一种以血尿酸水平升高为主要表现的代谢性疾病,长期高尿酸血症会导致尿酸盐沉积于关节、肾脏而出现痛风、肾脏损害等。药物降尿酸是目前主要的治疗方法。本文介绍了依照发病机制降尿酸药物的4个类别,分别为抑制尿酸生成、促进尿酸排泄、同时抑制尿酸生成促进排泄及促进尿酸溶解药物,并对传统及新型降尿酸药物进行了比较及探讨,以期为该类药物的进一步研发提供参考。     

依那普利治疗老年高尿酸血症病人

高尿酸血症和痛风最终会导致关节、肾等重要组织、器官损害而致残、致命。高尿酸血症的治疗主要在于饮食治疗、抑制尿酸合成和加强尿酸排泄等。本研究发现ACEIs-Enalapril,可增加高尿酸血症扣痛风病人对尿酸的廓清,有效地降低血尿酸,与别嘌呤醇合用可控制所有病人的血尿酸水平。     

高尿酸血症研究进展

尿酸是人类嘌呤代谢的终产物 ,主要经过肾脏排泄。近年来高尿酸血症和痛风的发病率逐渐上升 ,长期高尿酸血症易诱发痛风 ,还容易累及肾脏和心血管系统。本文就高尿酸血症与X综合征、嘌呤代谢与尿酸的消除、高尿酸血症的遗传学研究、以及高尿酸血症的发生机制等方面进行了综述     

海军某驻岛部队官兵血尿酸检测结果分析

<正>近年来,随着生活水平的提高和饮食结构的改变,高尿酸血症和痛风的患病率越来越高。高尿酸血症是痛风的重要生化基础,高尿酸血症可能进展为痛风,引起反复发作的急性痛风性关节炎、慢性痛风性关节炎、痛风石、尿酸结石、尿酸性肾病等[1]。目前,在我国尤其沿海地区,高尿酸血症患病情况尤为严重,已严重影响公众健康和部队战斗力。海军驻岛部队地处沿海地区,其高尿酸血症防治工作逐渐受到部队各级领导重视,但高尿酸血症在驻岛部队的发病情况目前尚     

高尿酸血症与痛风的临床治疗分析

目的探讨高尿酸血症与痛风的临床治疗。方法对40例高尿酸血症与痛风患者临床治疗方法资料进行分析。结果 40例高尿酸血症与痛风患者经治疗,治愈18例,好转18例,无效4例,总有效率90.0%。结论防止高尿酸血症尿酸盐沉积的控制;迅速停止急性关节炎的发作,防止尿酸结石的形成和对肾功能损害。     

高尿酸血症和痛风的流行病学及影响因素研究进展

<正>痛风是由于嘌呤代谢紊乱和(或)尿酸排泄障碍所导致的疾病,其临床特点为痛风性急性关节炎反复发作,形成痛风石、痛风石性慢性关节炎及关节畸形,引起间质性肾炎及尿酸肾结石。引起痛风的主要的生化基础是高尿酸血症(hyperuriecemia,HUM),然而痛风的患病率远低于高尿酸     

抗痛风中草药的研究进展

随着社会发展和人类生活水平的提高,痛风疾病的发病率不断增加并且还伴着发病年龄出现低龄化趋势。痛风是一种以高尿酸血症导致尿酸钠晶体在关节及其周围组织沉积为特征的嘌呤代谢性疾病。在西药上常用来抗痛风的药物有秋水仙碱、非甾体类抗炎药、促肾上腺皮质激素、糖皮质激素等。近年来抗痛风药物中草药的研究也取得很大进步,本文就有关抗痛风中草药的研究进行综述。     

痛风的临床治疗

痛风的生化标志是高尿酸血症,是由于嘌呤代谢紊乱导致的一组慢性疾病[1]。其临床特点为高尿酸血症及由此引起的反复发作性、痛风性急性关节炎及痛风石性、慢性关节炎和关节畸形,常累及肾脏引起慢性间质性肾炎和尿酸肾结石形成。     

痛风的药物治疗研究进展

痛风是嘌呤代谢障碍引起的代谢性疾病,高尿酸血症是痛风最重要的生化基础。目前对于痛风的治疗主要以减少尿酸的产生和加强尿酸的排除,以对症治疗为主。临床上治疗痛风的药物以西药为主,包括秋水仙碱、别嘌呤醇、苯溴马隆、非甾体类抗炎药、丙磺舒等,但其均具有一定毒副作用。目前,中药及其他治疗痛风的药物逐渐发展起来,且在实际治疗过程中产生了显著的疗效。现将国内外对痛风治疗的药物进行综述,希望对后续研究提供理论基础。     

痛风治疗药物及其研究进展

近年来,痛风的发病率呈上升的趋势,发病年龄也呈现低龄化的趋势,所以有关痛风的形成机制以及治疗药物的研发已成为人们关注的焦点。尿酸水平升高是痛风形成的生化基础,尿酸可介导血管炎症反应和氧化损伤、促进血管内皮细胞的增殖等,尿酸水平也是用来预测肾损伤的主要指标。本文对近些年来临床应用的治疗痛风的大部分药物,尤其是非嘌呤类黄嘌呤氧化酶抑制剂药物的研究进行综述。     

Febuxostat: A Novel Agent for Management of Hyperuricemia in Gout

Gout is a metabolic disorder characterized by elevated uric acid levels in the body, associated with painful arthritis, tophi and nephropathy. The most frequently used pharmacologic urate lowering strategies involve reducing urate production with a xanthine oxidase inhibitor and enhancing urinary excretion of uric acid with a uricosuric agent. Urate lowering agents are limited in number, availability and effectiveness. The emergence of a new medication, febuxostat, to lower serum urate levels is welcome as no new drug have been approved since the introduction of allopurinol, in 1964, and the drugs that are available have limitations owing to inefficacy or toxicity. Febuxostat is a novel, nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.     

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。     

Febuxostat: a non-purine,selective inhibitor of xanthine oxidase for the management of hyperuricaemia in patients with gout

Febuxostat is a non-purine, selective inhibitor of xanthine oxidase being developed for the management of hyperuricaemia in patients with gout. With febuxostat 10 – 120 mg, the pharmacokinetics are linear. No dose adjustment appears to be necessary in those with renal insufficiency or mild-to-moderate hepatic impairment. Febuxostat 10 – 120 mg/day rapidly and sustainably reduces serum uric acid by 25 – 70% in uric acid underexcretors and overproducers. Prophylaxis with colchicine or a non-steroidal anti-inflammatory drug can mitigate the gout-flare risk from the rapid urate lowering after febuxostat initiation. Febuxostat is well tolerated, the majority of treatment-related adverse events are transient and mild-to-moderate in severity. Febuxostat can broaden the therapeutic options for urate-lowering therapy in those with gout.     

Management of acute and chronic gouty arthritis: present state-of-the-art

There are three stages in the management of gout: (i) treating the acute attack; (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent acute flares. It is important to distinguish between therapy to reduce acute inflammation in acute gout and therapy to manage hyperuricaemia in patients with chronic gouty arthritis.During the acute gouty attack nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs are the preferred treatment in acute gout. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Other treatments include oral and intravenous colchicine, intra-articular and systemic corticosteroids, and intramuscular corticotropin.Optimal treatment of chronic gout requires long-standing reduction in serum uric acid. The urate-lowering drugs used to treat chronic gout are the uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and febuxastat should be used as first-line treatment in patients with renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine) therapy, and urate overproduction. Uricosuric drugs include probenecid, benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering drugs of choice in allopurinol-allergic patients and underexcretors with normal renal function and no history of urolithiasis. The use of recombinant urate oxidase in patients with chronic gout is limited by the need for parenteral administration, the potential antigenicity and production of anti-urate oxidase antibodies, and declining efficacy.The effectiveness of colchicine prophylaxis as an isolated therapy is still to be confirmed by placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no comparative studies with colchicine.     

南极磷虾肽改善高尿酸血症机制研究

目的 探究南极磷虾肽(AKP)对于高尿酸血症模型小鼠的降尿酸功效及其作用机制。方法 采用HPLC法体外筛选出具尿酸合成关键限速酶--黄嘌呤氧化酶(Xanthine oxidase, XOD)抑制活性的AKP,体内动物实验验证AKP的降尿酸活性。雄性SPF级Balb/c小鼠采用高嘌呤饲料(25%酵母浸粉)喂养联合腹腔注射尿酸酶抑制剂(氧嗪酸钾,200 mg.kg^-1.BW^-1)建立高尿酸血症小鼠模型,造模21天后进行AKP干预。小鼠随机分为正常对照组(生理盐水),模型对照组(生理盐水)、阳性药组(非布司他)、AKP低剂量组(450 mg.kg^-1.BW^-1),AKP高剂量组(900 mg.kg^-1.BW^-1),干预30天后检测血清尿酸含量(Uric acid, UA),肝脏尿酸合成关键酶酶活,肾脏及肠道尿酸转运蛋白mRNA的转录水平及形态学改变。结果 AKP体外XOD抑制率可达24.4%。动物实验验证表明AKP可显著降低高尿酸模型小鼠的UA,作用机制为通过抑制肝脏尿酸合成关键酶XOD及腺苷脱氨酶(Adenosine Deaminase, ADA)酶活,从而抑制肝脏尿酸生成;上调肾脏及肠道尿酸分泌转运体三磷酸腺苷结合盒转运蛋白(ATP binding cassette superfamily G member 2, ABCG2)、有机阴离子转运体(organic anion transporter 1, OAT1)转录水平,并抑制尿酸重吸收转运体葡萄糖转运体9(glucose transporter 9, GLUT9)、尿酸转运体1(urate transporter 1, URAT1)转录水平,从而促进肾脏及肠道尿酸排泄。AKP可显著降低血清尿素氮(Blood urea nitrogen, BUN)含量,肾脏及肠道切片观察结果进一步表明,AKP可以显著改善高尿酸血症造成的肾脏及肠道损伤,维护肾脏及肠道尿酸排泄功能。结论 AKP可通过抑制肝脏尿酸生成,促进肾脏及肠道尿酸排泄,维护肾脏及肠道形态及功能,从而改善高尿酸血症。     

Updates on the treatment of gout,including a review of updated treatment guidelines and use of small molecule therapies for difficult-to-treat gout and gout flares

Introduction: Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues.

Areas covered: In this article, we describe the role of currently available drug therapies for managing acute gout flares and used in reducing serum urate levels. Further, we explore the role of novel small molecular therapies and biologic agents in the treatment of refractory or severe gout symptoms. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-June 2017) was conducted utilizing the key words ‘gout’, ‘interleukin-1 inhibitors’, ‘acute gout’, ‘gout treatment’, ‘urate lowering therapies’, ‘hyperuricemia’, ‘colchicine’, ‘pegloticase’, ‘lesinurad’, ‘xanthine oxidase’, ‘xanthine oxidase inhibitors’, ‘allopurinol’, ‘febuxostat’, ‘uricosurics’, ‘probenecid’, and ‘benzbromarone’. All published articles regarding therapeutic management of gout and hyperuricemia were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed.

Expert opinion: Numerous therapies are currently available to managing acute gout flares and for lowering serum urate levels; advances in the understanding of the pathophysiology of this disorder has led to the emergence of targeted therapies and novel biologic preparations currently in development which may improve the clinical management of severe or refractory cases of disease that fail to respond to traditional therapies.     

Virtual and In Vitro Bioassay Screening of Phytochemical Inhibitors from Flavonoids and Isoflavones Against Xanthine Oxidase and Cyclooxygenase‐2 for Gout Treatment

Synthetic drugs such as allopurinol and benzbromarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase and cyclooxygenase‐2 enzymes. In this study, we report the screening of nine compounds of flavonoids from the ZINC and PubChem databases (containing 2092 flavonoids) using the igemdock software tool against the xanthine oxidase and cyclooxygenase‐2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase‐2. Myricetin and luteolin were found to be the potential dual inhibitors of xanthine oxidase and cyclooxygenase‐2 as demonstrated by IC₅₀: 62.7 and 3.29 μg/mL (xanthine oxidase)/70.8 and 16.38 μg/mL (cyclooxygenase‐2), respectively. In addition, structure–activity relationships and other important factors of the flavonoids binding to the active site of xanthine oxidase and cyclooxygenase‐2 were discussed, which is expected for further rational drug design.     

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。