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降尿酸治疗:老年痛风患者的当前选择及未来前景

Urate-lowering therapy: current options and future prospects for elderly patients with gout.

作者信息

Stamp Lisa K, Chapman Peter T

机构信息

Department of Medicine, University of Otago, Christchurch, P. O. Box 4345, Christchurch, 8140, New Zealand,

出版信息

Drugs Aging. 2014 Nov;31(11):777-86. doi: 10.1007/s40266-014-0214-0.

Abstract

Gout is increasingly seen in the elderly population, in large part due to physiological decline in renal function with age, and as a result of therapy for comorbidities, in particular the use of diuretic therapies for hypertension and congestive heart failure. Urate-lowering therapy (ULT) is the cornerstone of successful long-term gout management with the aim of achieving a sustained reduction in urate (<0.36 mmol/L, or lower [<0.30 mmol/L] in those with tophi). After decades during which there has been relatively little interest in developing new agents to treat gout, the last 5-10 years has seen a plethora of new agents with several now used in routine clinical practice. There has also been a renewed focus on the optimal use of established ULT, specifically allopurinol, which remains the first-line therapy for most patients. There is emerging data on its use in patients with renal impairment and better recognition of risk factors of the rare but potentially lethal allopurinol hypersensitivity syndrome (AHS). Febuxostat, a new xanthine oxidase inhibitor, is now established in everyday practice. Uricosuric agents may be indicated in certain patient groups, whilst a new class of recombinant uricases (pegloticase) given by intravenous infusion may achieve dramatic and rapid urate-lowering effects. Cost and other factors have thus far limited its use to the very severe cases. Furthermore, increased understanding of urate metabolism has led to the development of a number of drugs currently under clinical evaluation. Common therapeutic targets are the urate transporters in the kidney and alternative xanthine oxidase inhibition pathways. These advances bode well for the better management of gout and hyperuricaemia in our elderly patients.

摘要

痛风在老年人群中越来越常见,很大程度上是由于肾功能随年龄增长而生理性衰退,以及合并症治疗的结果,特别是用于治疗高血压和充血性心力衰竭的利尿剂疗法。降尿酸治疗(ULT)是成功进行长期痛风管理的基石,目标是使尿酸持续降低(<0.36 mmol/L,有痛风石者更低[<0.30 mmol/L])。在过去几十年里,开发治疗痛风新药物的兴趣相对较少,而在过去5至10年中,出现了大量新药物,其中几种现已用于常规临床实践。人们也重新关注已确立的ULT的最佳使用,特别是别嘌醇,它仍然是大多数患者的一线治疗药物。有关其在肾功能损害患者中使用的数据不断涌现,对罕见但可能致命的别嘌醇超敏综合征(AHS)的危险因素也有了更好的认识。非布司他,一种新型黄嘌呤氧化酶抑制剂,现已在日常实践中确立地位。促尿酸排泄剂可能适用于某些患者群体,而一类新的通过静脉输注给药的重组尿酸酶(聚乙二醇化尿酸酶)可能会产生显著而快速的降尿酸效果。到目前为止,成本和其他因素限制了其仅用于非常严重的病例。此外,对尿酸代谢的进一步了解促使开发了一些目前正在临床评估的药物。常见的治疗靶点是肾脏中的尿酸转运蛋白和黄嘌呤氧化酶抑制的替代途径。这些进展对于更好地管理老年患者的痛风和高尿酸血症是个好兆头。

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