别嘌呤醇致Stevens-Johnson综合征及中毒性表皮坏死松解症的发病机制和治疗

别嘌呤醇是次黄嘌呤的同分异构体,在体内可抑制黄嘌呤氧化酶而抑制体内尿酸合成,是目前临床广泛使用的唯一一个抑制尿酸合成的抗痛风药,其可诱发Stevens-Johnson综合征和中毒性表皮坏死松解症。SJS/TEN虽较为少见,却是危及生命的严重皮肤不良反应。因此对于SJS/TEN发病机制的认识,可以有效预防SJS/TEN的发生,而正确治疗措施的采取将减少并发症的发生,降低病死率。本文就SJS/TEN的发病机制及治疗进行综述。     

别嘌醇致中毒性表皮松解坏死型药疹1例

一例女性患者因尿酸增高口服"别嘌醇(allopurinol)"0.1g,3次/日,用药2天后出现全身瘙痒,服用中药制剂2周后好转。再次服用"别嘌醇"0.2g 1次,20分钟后立刻出现高热、畏寒、皮疹、呕吐等症状,伴瘙痒,全身约90%皮肤暗红色斑、水疱,部分表皮剥脱,尼氏征(+),便潜血(+),肌酐203.1umol/L,诊断:中毒性表皮松解坏死型药疹。给予经过糖皮质激素等药物治疗,严格皮肤黏膜护理,以及对症支持等治疗13天后,皮疹基本消退,便潜血阴性,治愈出院。     

别嘌醇、丙磺舒以及两者联用对马兜铃酸肝肾损害保护作用研究

目的：探讨别嘌醇（A）、丙磺舒（P）以及两者联用对马兜铃酸肝肾毒性的防治作用,并初步探讨其作用机制。方法：将雄性ICR小鼠随机分为5组：正常对照组（C组）、关木通模型组（M组）、别嘌醇组（A组）、丙磺舒组（P组）、剐嘌醇＋丙磺舒组（A-FP组）。C组灌胃等体积饮用水,后4组灌胃给予7g·kg-1·d-1的关木通水煎剂。给药4天后停药3天,持续4周;各给药组从第3周起在给予造模药的同时灌胃给予相应药物即A（70rag·kg·d。）、P（360rag·kg-1·d-1）、A（70mg·kg-1·d-1）＋P（360mg·kg-1·d-1）。实验结束时,测定小鼠血清肌酐（Cr）、尿素氮（BUN）、谷丙转氨酶（ALT）、谷草转氨酶（AST）水平,并记录左肾、左睾系数。结果：与M组相比,各给药组均能显著降低血清Cr、BUN、ALT、AST水平,其中A＋P组各指标改善作用最为显著。结论：A和P对马兜铃酸所致肝肾损伤都具有保护作用。且两药联用的效果优于两药单独应用。     

痛风定胶囊联合西药治疗急性痛风性关节炎随机平行对照研究

[目的]观察痛风定胶囊联合西药治疗急性痛风性关节炎疗效。[方法]使用随机平行对照方法,将82例住院及门诊患者按随机数字表方法分为两组,对照组38例秋水仙碱首剂3mg,1～2h0．5mg,直至症状缓解或出现不良反应。24h内不可超过6mg,并在症状缓解后48h内不需服用,72h后0．5～1mg／片。别嘌呤醇0．1g／次,2～3／d。治疗组44例痛风定胶囊3～4粒／次,3次／d。西药治疗同对照组。连续治疗7d为1疗程。临床症状、关节功能、血尿酸检查、不良反应。治疗1疗程,判定疗效。[结果]治疗组痊愈30例,显效8例,有效4例,无效2例,总有效率95．45％。对照组痊愈20例,显效5例,有效6例,无效7例,总有效率81．58％。治疗组疗效优于对照组（P〈0．05）。[结论]痛风定胶囊联合西药治疗急性痛风性关节炎疗效满意,副作用低,值得推广。     

2020 recommendations from the French Society of Rheumatology for the management of gout: Urate-lowering therapy

ObjectiveTo develop French Society of Rheumatology-endorsed recommendations for the management of urate-lowering therapy (ULT).MethodsEvidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and two Delphi rounds to finalize them.ResultsA set of 3 overarching principles and 5 recommendations was elaborated. The overarching principles emphasize the importance of patient education, especially the need for explaining the objective of lowering serum urate (SU) level to obtain crystal dissolution, clinical symptoms disappearance and avoidance of complications. ULT is indicated as soon as the diagnosis of gout is established. SU level must be decreased below 300 μmol/l (50 mg/l) in all gout patients or at least below 360 μmol/l (60 ml/l) when the 300 μmol/l target cannot be reached, and must be maintained at these targets and monitored life-long. The choice of the ULT primarily relies on renal function: in patients whose estimated glomerular filtration rate (eGFR) is above 60 ml/min/1.73 m², first-line ULT is allopurinol; in those with eGFR between 30 and 60 ml/min/1.73 m², allopurinol use must be cautious and febuxostat can be considered as an alternative; and in those whose eGFR is below 30 ml/min/1.73 m², allopurinol must be avoided and febuxostat should be preferred. Prophylaxis of ULT-induced gout flares involves progressive increase of ULT dosage and low-dose colchicine for at least 6 months. Cardiovascular risk factors and diseases, the metabolic syndrome and chronic kidney disease must be screened and managed.ConclusionThese recommendations aim to provide simple and clear guidance for the management of ULT in France.     

Combination of allopurinol and hyperbaric oxygen therapy： A new treatment in experimental acute necrotizing pancreatitis？

AIM： To investigate the individual and combined effects of allopurinol and hyperbaric oxygen （HBO） therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation （BT） in the experimental rat acute pancreatitis （AP）. METHODS： Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls （sham, Group I ）. AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group H received saline, Group m allopurinol, Group IV allopurinol plus HBO and Group v HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS： Serum amylase levels were lower in Groups Ⅲ, Ⅳ and v compared to Group H （974 ± 110, 384 ± 40, 851 ＋ 56, and 1664 Ⅳ 234 U/L, respectively, P 〈 0.05, for all）. Combining the two treatment optionsrevealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations （13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P 〈 0.01）. Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups m, iV and v compared to Group H （54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P 〈 0.05 for all）. CONCLUSION： The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.     

A simple method for quantification of allopurinol and oxipurinol in human serum by high-performance liquid chromatography with UV-detection

OBJECTIVES: Allopurinol is a uric acid lowering drug used in the treatment of gout and the prevention of tumor lysis syndrome. Allopurinol and its active metabolite oxipurinol inhibit xanthine oxidase, which forms uric acid from xanthine and hypoxanthine. Therapeutic drug monitoring is an important option for evaluation and optimization of allopurinol treatment in case of renal impairment, interaction with uricosuric drugs or to verify patient adherence. In this study we developed and validated a simple quantitative assay using reverse phased high-performance liquid chromatography (HPLC) with UV-detection as a method for quantification of allopurinol and oxipurinol in human serum in the presence of different frequently used drugs. METHODS: The HPLC-UV method uses a mobile phase consisting of sodium acetate (0.02 M; pH 4.5), at a flow rate of 1.0 mL/min. Allopurinol and oxipurinol are detected by UV-absorption at 254 nm with a retention time of 9.9 min for oxipurinol and 12.3 min for allopurinol. Aciclovir is used as internal standard. RESULTS: Validation showed for allopurinol lower and upper limits of quantification of 0.5 and 10mg/L and for oxipurinol 1 and 40 mg/L, respectively. The assay was linear over the concentration range of 0.5-10mg/L (allopurinol) and 1-40 mg/L (oxipurinol). Intra- and inter-day precision showed coefficients of variation <15% over the complete concentration range; accuracy was within 5% for allopurinol and oxipurinol. Endogenous purine-like compounds were separated from allopurinol, oxipurinol and aciclovir with a resolution factor >1.5. Exogenous purine-like compounds and co-medication frequently used by gout patients did not hinder the analysis due to the dichloromethane washing step or to low UV-absorpion at 253 nm. Serum levels of 66 patients prescribed allopurinol 300 mg/day were determined using this HPLC-UV method. Measured serum allopurinol and oxipurinol concentrations in clinical practice showed large variability with a range of <0.5-4.3 mg/L for allopurinol and <1.0-39.2 mg/L for oxipurinol, respectively. CONCLUSION: We developed an easy-to-operate and validated HPLC-UV method for the quantification of allopurinol and oxipurinol in human serum. This method was proven to be valid for samples of gout patients frequently using concomitant medications.     

1例心房纤颤患者痛风急性发作的药学监护

1例79岁女性患者,因心悸、胸闷伴周身乏力入院。既往有慢性喘息性支气管炎、高血压病,入院诊断为肺源性心脏病、心房纤颤、高尿酸血症。给予平喘、稳定心率、降压等治疗的同时,建议改用兼具降尿酸作用的降压药物氯沙坦。入院后第6天,患者出现痛风性关节炎,建议急性期给予秋水仙碱及非甾体类抗炎药,避免使用别嘌醇与苯溴马隆。患者服用秋水仙碱出现腹泻,建议给予蒙脱石散。1周后,患者各项症状好转出院。     

别嘌醇不良反应文献及临床案例分析

目的:了解别嘌醇不良反应发生的总体趋势、特点及相关因素。方法:检索1991～2008年《中国期刊全文数据库》有关别嘌醇不良反应的文献及我院临床案例,并进行汇总、分析、比较。结果:符合卫生部药品不良反应诊断标准的文献共76篇、77例,其中死亡10例(12.99%);临床案例共67例,其中死亡2例(2.99%),死亡率较高。皮肤黏膜损伤最常见,占90%以上,主要表现为药疹与发热,且往往伴有多个器官或系统同时受累。结论:临床上使用别嘌醇时应加强其不良反应监测。     

IgA肾病合并高尿酸血症患者的治疗及预后观察

目的：观察碳酸氢钠和别嘌呤醇结合泼尼松治疗IgA肾病合并高尿酸血症患者的临床效果及预后。方法：选取我科收治的60例IgA肾病合并高尿酸血症患者,分为两组,对照组予以泼尼松治疗,观察组在泼尼松治疗基础上加用碳酸氢钠1.5g/d和别嘌呤醇0.1g,对比两组患者治疗8周前后的血肌酐（Scr）、血尿酸（UA）、24h尿蛋白定量、肾小球滤过率（GFR）、总胆固醇（TC）和低密度脂蛋白（LDL）。结果：组内比较：两组患者治疗8周后血尿酸、总胆固醇和低密度脂蛋白水平均显著低于治疗前,而GFR高于治疗前,差异具有统计学意义（P均〈0.05）;组间比较：观察组治疗8周后Scr、UA、24h尿蛋白定量、TC和LDL低于对照组,GFR高于对照组,差异具有统计学意义（P均〈0.01）。结论：碳酸氢钠和别嘌呤醇结合泼尼松治疗IgA肾病合并高尿酸血症患者,能显著降低患者的血肌酐和血尿酸,改善蛋白尿情况和肾小球滤过率,同时降低患者血脂水平,从而改善患者预后和生活质量。