缬沙坦联合血液透析治疗尿毒症合并顽固性高血压的临床效果

目的探讨缬沙坦联合血液透析治疗尿毒症合并顽固性高血压的临床效果。方法选择2017年5月至2018年5月我院收治的尿毒症合并顽固性高血压患者82例为研究对象,将患者按照不同治疗方式分为参照组(n=41)与联合治疗组(n=41)。参照组采用血液透析治疗,联合治疗组采用缬沙坦联合血液透析治疗。比较两组患者治疗前、治疗1个月后尿蛋白(Upro)、血尿素氮(BUN)、尿微量白蛋白(mALB)水平及临床疗效。结果治疗1个月后,两组患者的Upro、BUN水平均高于治疗前,mALB水平低于治疗前,且联合治疗组优于参照组(P<0.05)。联合治疗组的治疗总有效率高于参照组(P<0.05)。结论缬沙坦联合血液透析治疗尿毒症合并顽固性高血压的临床效果显著,值得临床推广应用。     

前列地尔联合缬沙坦对糖尿病肾病患者氧化应激水平、尿钠排泄及血管内皮活性的影响

目的 探讨前列地尔联合缬沙坦对糖尿病肾病（DN）患者氧化应激水平、尿钠排泄及血管内皮活性的影响。方法 选取武汉市第一医院门诊与病房2021年11月—2022年10月期间收治的DN患者98例。根据治疗方案不同,分为对照组（49例）和试验组（49例）。对照组给予缬沙坦治疗,试验组给予前列地尔联合缬沙坦治疗,比较两组治疗前后氧化应激指标水平[晚期氧化蛋白产物（AOPP）、丙二醛（MDA）、超氧化物歧化酶（SOD）],比较治疗前后两组肾功能情况[肌酐（Scr）、尿素氮（BUN）、24 h尿微量白蛋白定量（MALB）];比较两组治疗前后24 h尿钠及血浆肾素、醛固酮水平情况;比较治疗前后两组血管内皮活性情况[血管内皮生长因子（VEGF）、一氧化氮（NO）、内皮素-1（ET-1）];观察两组临床疗效及不良反应情况。结果 治疗后,两组AOPP、MDA降低,SOD水平上升,且试验组低于对照组（P＜0.05）;治疗后,两组肌酐Scr、BUN、MALB水平降低,试验组更明显（P＜0.05）;治疗后,两组24 h尿钠升高,肾素、醛固酮水平降低,且试验组更明显（P＜0.05）;治疗后,两组VEGF、ET-1水平下降,NO水平升高,且试验组更明显（P＜0.05）,试验组疗效优于对照组（P＜0.05）,两组不良反应无明显差异（P＞0.05）。结论 前列地尔联合缬沙坦治疗DN的疗效满意,可有效降低患者氧化应激水平,提高其尿钠排泄,改善内皮功能,且安全性较高,值得临床推广应用。     

Hydrochlorothiazide added to valsartan is more effective than when added to olmesartan in reducing blood pressure in moderately hypertensive patients inadequately controlled by monotherapy

This study was undertaken to evaluate the effects on blood pressure of hydrochlorothiazide (HCTZ) 12.5 mg added to valsartan 160 mg or to olmesartan 20 mg in hypertensive patients. After a 2-wk placebo period, 130 patients, aged 35 to 75 y, with diastolic blood pressure (DBP) ≥99 and <110 mm Hg were randomly assigned to olmesartan 20 mg once daily or to valsartan 160 mg once daily according to a prospective, parallel-arm study design. After 4 wk of monotherapy, patients whose BP was not controlled (DBP ≥90 mm Hg) were given combination treatment with HCTZ 12.5 mg for an additional 4 wk. At the end of the placebo period and at the end of each treatment period, clinical and ambulatory BP measurements were recorded. At the end of the combination therapy period, venous blood samples were drawn 2, 4, and 24 h after drug intake for evaluation of HCTZ plasma concentrations. Both combinations induced a greater ambulatory BP reduction than monotherapy. However, mean reduction from baseline in the valsartan/HCTZ-treated patients (-21.5/-14.6 mm Hg for 24 h, -21.8/-14.9 mm Hg for daytime, and -20.4/-13.7 mm Hg for nighttime systolic blood pressure [SBP]/DBP) was greater than in the olmesartan/HCTZ-treated patients (-18.8/-12.3 mm Hg for 24 h, -19.3/-12.8 mm Hg for daytime, and -17.4/-10.6 mm Hg for nighttime SBP/DBP). The difference between the effects of the 2 treatments was significant (P<.01). In particular, compared with monotherapy, the add-on effect of HCTZ 12.5 mg was significantly greater in the valsartan group than in those treated with olmesartan; the difference was more evident for nighttime BP values. Plasma concentrations of HCTZ were significantly greater with valsartan than with olmesartan at each determination time (P<.05). These findings suggest that the addition of HCTZ 12.5 mg to valsartan 160 mg monotherapy produces a greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 mg monotherapy.     

血管紧张素Ⅱ对足细胞Notch通路及Nephrin表达的影响

目的探讨血管紧张素Ⅱ(AngⅡ)刺激小鼠足细胞对Notch通路、Nephrin表达的影响。方法 AngⅡ刺激小鼠足细胞并给予缬沙坦干预,采用免疫荧光化学、Western blot、Real-time PCR方法检测Notch1、Notch胞内域1(NICD1)、Hes1、Nephrin的表达情况。结果 AngⅡ呈时间依赖性增加足细胞Notch1、NICD1、Hes1表达,抑制Nephrin表达(P<0.01);缬沙坦可抑制AngⅡ对Notch通路的活化,增加Nephrin的表达(P<0.01)。结论 AngⅡ通过激活Notch通路降低足细胞Nephrin表达。     

缬沙坦联合阿托伐他汀治疗慢性肾炎的临床疗效观察

目的探讨缬沙坦联合阿托伐他汀治疗慢性肾炎的临床疗效。方法将168例慢性肾炎患者随机分入A组与B组,两组患者均接受慢性肾炎常规治疗。A组患者同时接受口服缬沙坦,B组患者接受缬沙坦及阿托伐他汀口服,疗程12月。比较两组治疗前后肾功能、24 h尿蛋白定量、超敏C反应蛋白、肾小球滤过率(GFR)、血脂、血压、肝功能及肌酶等差别。结果治疗12个月后,B组hs-CRP、24h尿蛋白显著优于A组(P<0.05),B组胆固醇及低密度脂蛋白显著降低(P<0.05),两组收缩压、舒张压、肝功能、肌酶水平比较差异无统计学意义(P>0.05)。结论缬沙坦联合阿托伐他汀治疗慢性肾炎可显著降低CRP水平并减少尿蛋白,有利于延缓病情。     

LCZ696: a new paradigm for the treatment of heart failure?

Introduction: Heart failure (HF) represents a significant healthcare issue because of its ever-increasing prevalence, poor prognosis and complex pathophysiology. Currently, blockade of the renin–angiotensin–aldosterone system (RAAS) is the cornerstone of treatment; however, the combination of RAAS blockade with inhibition of neprilysin (NEP), an enzyme that degrades natriuretic peptides, has recently emerged as a potentially superior treatment strategy.

Areas covered: Following the results of the recent Phase III Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure clinical trial in patients with chronic HF with reduced ejection fraction (HF-REF), this review focuses on LCZ696, a first-in-class angiotensin receptor NEP inhibitor. This drug consists of a supramolecular complex containing the angiotensin receptor inhibitor valsartan in combination with the NEP inhibitor prodrug, AHU377. Following oral administration, the LCZ696 complex dissociates and the NEP inhibitor component is metabolized to the active form (LBQ657). Aspects of the trial that might be relevant to clinical practice are also discussed.

Expert opinion: Speculation that LCZ696 will pass the scrutiny of regulatory agencies for HF-REF appears to be justified, and it is likely to become a core therapeutic component in the near future. Replication of the eligibility criteria and titration protocol used in the PARADIGM-HF trial would be valuable in clinical practice and may minimize the risk of adverse events. Although long-term data remain to be generated, the promising results regarding hypertension are likely to expedite acceptance of the drug for HF-REF.     

缬沙坦刻痕片的药学研究

目的 以单面中刻痕的缬沙坦片为例对刻痕片进行药学研究。方法 对缬沙坦刻痕片分割的方法及损失量进行考察,并研究分割后的释放行为和脆碎度。结果 单面中刻痕的缬沙坦片利于分割,且分割后损失量<0.16%,单半片释放行为与整片相似,脆碎度考察后能符合药典要求。结论 单面中刻痕的缬沙坦片可以被均匀的分割,能正常释放,有利于临床的剂量调整。     

卡维地洛联合缬沙坦胶囊治疗伴有冠心病的原发性高血压患者临床疗效观察

目的：观察卡维地洛联合缬沙坦胶囊治疗伴有冠心病的高血压患者临床疗效。方法将68例伴有冠心病的高血压患者分为2组,治疗组（采用卡维地洛联合缬沙坦胶囊治疗）34例,对照组（采用卡维地洛治疗）34例,2组治疗均为12周。对治疗前后的血压、心率及冠心病的临床指标进行监测评价。结果治疗12周后所有患者收缩压和舒张压、24h心绞痛发作的频率、持续时间、心肌缺血总负荷（TIB）,都有所下降（P＜0．05）,治疗组较对照组下降更明显（P＜0．05）,与治疗前比较差异有统计学意义。结论卡维地洛联合缬沙坦胶囊协同降压对于伴有冠心病的高血压患者临床疗效好,不良反应低,安全性好。     

Fixed-dose combination therapy of nebivolol and valsartan for the treatment of hypertension

Recent large clinical trials have refuted earlier suggestions from the Joint National Committee 8 committee that less aggressive targets for blood pressure control were all that could be justified in most hypertensive patients. It now does appear that in fact “lower is better,” with blood pressure targets < 120/80 mm Hg appropriate for many hypertensive patients. Two drug combinations are often indicated as initial therapy if a 20/10 mm Hg or greater blood pressure reduction is necessary to reach target. Combinations consisting of β-blockers and renin-angiotensin-aldosterone system inhibitors have previously been deemed “less effective,” based on partially overlapping mechanisms of action and limited clinical trial evidence. Nebivolol is a vasodilating β₁-selective blocker and β₃- adrenoceptor agonist; β₃-adrenoceptor activation increases nitric oxide concentrations and thus explains the vasodilatory effect. A recent 8-week randomized trial (N=4,161) in individuals with stage 1-2 hypertension demonstrated that single-pill fixed dose combinations (FDC) of nebivolol and valsartan, an angiotensin II subtype 1 receptor blocker, were more effective in reducing blood pressure than the corresponding monotherapies, with comparable tolerability. In addition, an ABPM-biomarkers substudy from that trial (n=805) demonstrated that the FDC prevented a valsartan-induced increase in plasma renin activity, and that the nebivolol/valsartan 20/320 mg/day dose reduced plasma aldosterone concentration significantly more than valsartan 320 mg/day. This article will describe the properties of nebivolol that make it unique and separate it from other β-blockers, and will further support the pharmacological advantages of this particular combination.     

Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization

The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study.