口服托伐普坦片对男性健康志愿者的药效学作用及其对血电解质的影响*

目的:评价血管升压素受体拮抗剂托伐普坦片对中国健康男性的药效作用和其对血电解质的影响。方法:入选健康男性39名,分四组分别单次口服托伐普坦片15 mg(n=9),30 mg(n=10),60 mg(n=10)和120 mg(n=10),观察48 h内的尿量、血电解质浓度、饮水量变化,以及服药24 h后的体重变化和不良事件。结果:①受试者体重无明显改变,统计学比较无差异。②服药6 h内,6~12 h,12~24 h和24~48 h的4组尿量分别为15 mg组:(1 921±496),(2 977±389),(3 680±724),(3 948±398);30 mg组:(1 361±500),(2 631±661),(3 492±1 094),(4 518±802);60 mg组:(1 268±868),(2 167±1 074),(2 267±1 088),(3 981±1 667);120mg组:(1 302±624),(2 643±1 100),(2 460±660),(4 394±1 132)mL。③血清氯、钠浓度24 h内有升高,48 h恢复服药前水平,氯浓度升高超过正常高限(大于110 mmol.L-1),但未需处理。血钠浓度略高,血钾浓度略低,均在正常范围内变化,无临床意义改变。④血压,心率无明显影响;共有13例次(13/39,33.3%)有口干和口渴的症状,程度轻中度可以耐受。未见严重不良事件。结论:单剂口服托伐普坦片15,30,60或120 mg均有较强的排水利尿作用,且可持续24 h,有剂量依赖性。     

Tolvaptan alleviates excessive fluid retention of nephrotic diabetic renal failure unresponsive to furosemide

Patients with diabetic nephropathy develop nephrotic syndrome and may show limited response to conventional therapy. They often require earlier initiation of renal replacement therapy because they become refractory to diuretics, and experience excessive fluid retention. We aimed to investigate the efficacy of tolvaptan, an oral arginine vasopressin type 2 receptor antagonist, in a case series of 14 severe diabetic renal failure patients who were severely refractory to maximal doses of furosemide and had excessive fluid retention despite preserved cardiac function and residual renal function. All 14 patients experienced immediate and sustained water diuretic effects, resulting in alleviation of congestive heart failure. None required initiation of renal replacement therapy. Tolvaptan promptly increased urine volume and free water clearance, reversed progressive fluid retention, and alleviated congestive heart failure. Thus, tolvaptan could serve as a potential adjunct therapy for severe diabetic renal failure patients with excessive fluid retention and congestive heart failure.     

血管加压素V2受体拮抗剂托伐普坦治疗肝硬化并低钠血症患者临床疗效及安全性评价

目的：探讨血管加压素V2受体拮抗剂托伐普坦治疗肝硬化并低钠血症患者临床疗效及安全性评价。方法：选自我院于2014年1月~2015年12月肝硬化并低钠血症患者72例,按照随机数字表法随机分为观察组36例与对照组36例。对照组采用常规治疗,观察组在对照组基础上结合托伐普坦治疗。两组疗程均为7d。比较两组治疗疗效,治疗前后血钠、尿钠、血尿酸、肾功能指标水平变化及药物不良反应情况。结果：观察组总有效率(88.89%)高于对照组(66.67%)(P<0.05);两组血钠、尿钠、血尿酸水平治疗后增加(P<0.05);观察组血钠、尿钠、血尿酸水平治疗后高于对照组(P<0.05);两组血清BUN和Cr水平治疗前比较无统计学差异(P>0.05);两组血清BUN和Cr水平治疗后前后无变化(P>0.05);两组均未见严重不良反应。结论：血管加压素V2受体拮抗剂托伐普坦治疗肝硬化并低钠血症患者临床疗效显著,且安全性良好,值得研究。     

Advances in chemical pharmacotherapy for managing acute decompensated heart failure

Introduction: Acute decompensated heart failure (ADHF) contributes largely to the burden of heart failure and is associated with a poorer prognosis. Although numerous clinical trials evaluated the benefit of newer medications for ADHF, most of them were not successful.

Areas covered: This review focusses on the updates on recent developments in chemical pharmacotherapy for the management of ADHF. A MEDLINE search for relevant review articles and original investigations on newer drugs for ADHF provided us with necessary literature.

Expert opinion: Currently, popular therapies like diuretics, vasodilators, and inotropes offer symptomatic relief but do not provide survival benefit. Although multiple medications targeting novel pathways in ADHF were studied extensively, they failed to show either symptomatic or mortality benefit in available randomized trials. Improving our understanding of the complex pathophysiology of ADHF along with designing studies which include patients who are more representative of the real-world heart failure population, standardizing methods for endpoint assessment, and evaluating the role on novel biomarkers of organ dysfunction is important to improve ADHF research. Enhancing preventive strategies like improving baseline therapy in chronic heart failure patients and developing strategies for early identification of ADHF are important as our quest for innovative ADHF pharmacotherapy continues.     

Serum Copeptin and Zinc-α2-glycoprotein Levels Are Novel Biomarkers of Tolvaptan Treatment in Decompensated Cirrhotic Patients with Ascites

Objective The efficacy of tolvaptan, an orally active vasopressin V2-receptor antagonist, has recently been reported in patients with massive ascites unresponsive to conventional diuretics. However, the effect of tolvaptan varies among patients. Recently, the prognostic role of the tolvaptan response in cases of decompensated liver cirrhosis (LC) has been attracting increasing attention. Using serum copeptin (vasopressin precursor), zinc-α2-glycoprotein (ZAG), cystatin C (renal biomarker), neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), we explored which factors portend a good response to tolvaptan in LC patients with ascites. Methods We enrolled 113 LC patients and divided them into the tolvaptan treatment group and non-treatment group. Tolvaptan (3.75 or 7.5 mg/day) was administrated to 38 LC patients with ascites, and a follow-up assessment was performed after a 7-day tolvaptan treatment regimen. Results We determined the predictive ability for kidney and/or liver damage of serum copeptin, ZAG, cystatin C, NGAL and L-FABP levels in all patients. After 7-day tolvaptan treatment, 19 patients had lost more than 1.5 kg of body weight (Responders), while 19 showed no marked change in their body weight (Non-responders). Basal blood urea nitrogen (BUN) (p=0.0014), serum copeptin (p=0.0265) and serum ZAG levels (p=0.0142) were significantly higher in the Non-responders than in the Responders. BUN (odds ratio 7.43, p=0.0306), copeptin (odds ratio 9.12, p=0.0136) and ZAG (odds ratio 7.43, p=0.0306) were determined to be predictive factors of drug responsiveness using a multivariate logistic regression analysis. Conclusion Serum BUN, copeptin and ZAG levels predict the patient response to tolvaptan, even when measured prior to treatment.     

Think FIRST to treat Dilutional Hyponatremia in Patients With Heart Failure

Patients with heart failure (HF) are at risk of developing hyponatremia due to retention of fluids which dilutes serum sodium. Studies have demonstrated that health care professionals have inadequate knowledge of managing hyponatremia in patients with HF. We created a mnemonic that provides nurse practitioners with an evidence-based approach to managing hyponatremia in HF. The “FIRST” mnemonic features 5 different treatment options: Fluid restriction, Induced diuresis, Received no specific treatment for hyponatremia, Saline (isotonic and hypertonic), and Tolvaptan.     

托伐普坦治疗老年心力衰竭的回顾性研究

目的：回顾性分析托伐普坦治疗老年心衰的现状，为临床合理应用利尿剂提供指导。方法：收集2015年7月-2018年6月入院并开始服用托伐普坦的老年心力衰竭患者病例资料共63例，分析诊疗情况并行电话随访。结果：63位患者服用托伐普坦已持续（21.2±16.5）个月（最长41个月），最常用剂量为7.5 mg·d^-1（71.4%）；基础心脏疾病主要为缺血性心肌病（39.7%）和老年退行性心脏病（34.9%），心功能分级主要为NYHA Ⅲ级（57.1%）和Ⅳ级（30.2%）；启用托伐普坦的原因分别为难治性心衰（34.9%）、合并低钠血症（25.4%）、合并肾功能不全（23.8%）、合并痛风或高尿酸血症（15.9%）；托伐普坦治疗后日均尿量增加，NT-proBNP值下降，心脏射血分数提高，差异较治疗前均有显著性（P<0.05）；相关药物不良反应主要为口干（11.1%）和血钠升高（4.8%）。结论：托伐普坦可有效利尿和改善心功能，对肾功能无不良影响，老年患者长期服用安全性好。