纳洛酮的研究进展

纳洛酮为一特异性阿片受体阻滞剂,广泛用于麻醉剂过量、休克、酒精中毒、脑梗死等方面的治疗.现就纳洛酮的药理学、制剂学及体内分析方法等方面的研究进展作一综述.     

糖尿病患者的护理干预

糖尿病是一种常见的内分泌代谢疾病,有遗传倾向.是由于多种原因引起胰岛素分泌或作用的缺陷,或者两者同时存在而引起的以慢性高血糖为特征的代谢紊乱.除糖类外,尚有蛋白质、脂肪、水及电解质等一系列代谢紊乱.临床表现为多饮、多食、多尿、消瘦、疲乏无力等,即典型的"三多一少症状,久病可引起多系统损害,常伴发心血管、肾、眼即神经等病变.重症或应激时可发生酮症酸中毒、高渗性昏迷等急性代谢性紊乱[1].现将此病的护理总结报告如下.     

腹泻合理应对

病因 1.消化系统疾病:由病毒、细菌等感染所引起的肠道疾病可引起急性腹泻;胃炎、肠结核、胰腺炎、肝硬化、肠道肿瘤等感染及非感染性疾病可引起慢性腹泻. 2.急性中毒:食物中毒及化学药品如砷、磷、铅、汞等可引起急性腹泻. 3.全身性疾病:如败血症、伤寒或副伤寒、钩端螺旋体病等感染性疾病可引起急性腹泻;甲亢、系统性红斑狼疮、尿毒症等可引起慢性腹泻. 4.其他:如服用某些药物如氟尿嘧啶、利血平及新斯的明等,也可引发急性或慢性腹泻. 治疗方案 急性腹泻 大多数由于饮食不洁而导致发热、腹痛、腹泻等症.其元凶多为致病性大肠杆菌或沙门菌属,可服黄连素治疗,每次2～3片(每片100mg),一日3次.或服诺氟沙星(氟哌酸)胶囊,每次2粒(每粒100mg)一日3～4次,小儿、孕妇忌用.     

新型非苯二氮(艹卓)类镇静催眠药扎来普隆

失眠是一种常见的症状,镇静催眠药是主要的治疗手段.新药扎来普隆与苯二氮(艹卓)类镇静催眠药不同.它具有对受体作用选择性强、起效快、不良反应少等特点.本文就扎来普隆的药理作用、临床应用等作一综述.     

给耳朵装个"消音器"

耳鸣是临床常见的一种症状.自觉耳内有嘶嘶声、嗡嗡声、吱吱声、轰鸣声等声响,其声如蝉鸣、气笛、雷鸣、刮风、下雨、潮水等.可发生在一侧耳朵,也可在双侧.常伴有听力下降或耳聋、眩晕症状.     

糖原合成酶激酶-3的研究进展及其生物学意义

糖原合成酶激酶-3(GSK一3)是一种丝/苏氨酸蛋白激酶,广泛存在于各种细胞中,参与调控细胞凋亡,作用于wnt、Hh等多条细胞信号通路.对细胞增殖与分化、肿瘤的发生、侵袭转移等方面起着重要的调节作用.     

冬虫夏草国内文献综述

冬虫夏草是一种极有研究价值的药用植物,主要含有核苷、氨基酸、多糖、甘露醇等成分,具有提高机体免疫功能,抑制肿瘤细胞等广泛的药理作用.本文从冬虫夏草的化学成分、药理作用等方面综述了冬虫夏草的研究进展.     

液质联用快速测定中药样品中的化学药物

蛴螬在祖国传统医学中有着悠久的使用历史.有破血、行瘀、散结、通乳等功效,用于治疗折损瘀痛、破伤风、喉痹、目翳等病症.目前蛴螬的具体化学成分不明确.现代药理研究表明该动物药具有抗肿瘤、保肝、治疗口疮等多种生物活性,是一种极具研究和开发价值的动物药.     

填字游戏

横向:1.形容追求更长远更丰厚的利益2.郑丹瑞、郑裕玲、钟楚红和李美凤主演的一部电影3.前联邦德国的首都4.许多风景区都会有的景点,天空被山、石等遮蔽只剩下狭窄的缝隙5.经常被用来拌豆腐的一种东西6.佛教徒诵经时用来计算次数的一个东西,又名数珠7.一位日本女明星8.法国首都9.华侨对祖国的一种习惯性的称呼10.词的一种,英文简称为adj     

股骨颈骨折的治疗进展

股骨颈骨折约占成人骨折的3.60%[1],是一种常见的骨折.由于股骨颈解剖关系的特殊性,骨折后易发生不愈合、股骨头缺血坏死等不良后果.随着内固定及手术方法的改进,其治疗得到了极大的改善,但仍有许多未解决的问题.本文就股骨颈骨折的解剖、受伤原因、分型、诊断、治疗、展望等做一综述.     

Pharmacokinetic evaluation of ambrisentan

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease characterized by increasing pulmonary vascular resistance leading to right ventricular failure and premature death. Current therapies target three major pathways involving endothelin, prostacyclin and NO. Ambrisentan is an oral, once daily, selective endothelin receptor antagonist. AREAS COVERED: This review focuses on, and critically appraises, the clinical efficacy and safety of ambrisentan as well as its pharmacokinetic and pharmacodynamic properties. The article also gives an expert perspective on the role of ambrisentan in the management of PAH. EXPERT OPINION: Ambrisentan is an effective and safe treatment which is, in the authors' opinion, a valuable addition to the armamentarium against PAH. Ambrisentan offers a relative lack of drug interactions, once daily dosing and reassuring liver safety, offering safety and convenience advantages over bosentan. Presently, there is a lack of comparative studies between PDE5 inhibitors and endothelin receptor antagonists and a lack of data comparing bosentan with ambrisentan. This is hindering data-based conclusions regarding relative efficacy and further studies are needed to define the role of ambrisentan in the management of PAH.     

Ambrisentan

Ambrisentan, an orally active, highly selective antagonist of the endothelin-1 type A receptor, is indicated for the treatment of pulmonary arterial hypertension (PAH). It has a low potential for drug-drug interactions and requires only once-daily administration. Three months’ treatment with ambrisentan 2.5–10mg/day significantly improved exercise capacity, as determined by the distance walked in 6 minutes (6MWD; primary outcome measure), compared with placebo in two double-blind, multicenter studies in patients with PAH (ARIES-1 [n = 202] and -2 [n = 192]). A decrease in dyspnea and a delay in clinical worsening were among the improvements in secondary outcomes generally observed with ambrisentan versus placebo. In ARIES-E, a 2-year extension of ARIES-1 and -2, approved dosages of ambrisentan (5 and 10 mg/day) were associated with a sustained improvement in 6MWD, a generally sustained improvement in dyspnea, and a low risk of clinical worsening and of death. Six months’ treatment with ambrisentan 5 mg/day significantly improved 6MWD (primary outcome measure) and dyspnea relative to baseline in an open-label, non-comparative, multicenter study in a diverse population of patients with PAH or non-PAH forms of pulmonary hypertension (ARIES-3 [n=224]). Ambrisentan was associated with a low risk of clinical worsening and of death. Ambrisentan treatment was generally well tolerated in the various ARIES trials. All available pre-registration and post-marketing data indicate the drug poses only a very low risk of liver injury; the ‘black box’ warning regarding potential liver injury has been removed from the US prescribing information for ambrisentan.     

A Focus on Macitentan in the Treatment of Pulmonary Arterial Hypertension

The approval of macitentan has increased the number of pharmacological treatments of pulmonary arterial hypertension (PAH). Here, we review the effect on PAH of macitentan compared to other endothelin receptor antagonists. Drugs targeting the endothelin (ET) pathway include the selective ET_A receptor antagonist ambrisentan, the ET_A/ET_B receptor antagonists, bosentan and macitentan, which were recently approved for PAH treatment. Macitentan exhibits higher antagonistic potency than bosentan and ambrisentan in pulmonary smooth muscle cells. Compared to ambrisentan and bosentan, macitentan has a longer duration of action, reflected by the longer half‐life, as well as pharmacodynamics attributed to its active metabolite, ACT‐132577. The efficacy of macitentan on PAH was investigated in the phase III SERAPHIN trial (NCT00660179). Macitentan significantly reduced morbidity and mortality. It improved the 6‐min. walk distance (6MWD) among PAH patients. In the AMB‐320/321‐E (NCT00578786) study, ambrisentan improved exercise capacity. In the EARLY study (NCT00091715), bosentan showed improvements in 6MWD which were not statistically significant. Bosentan had an effect on PAH in patients with Eisenmenger syndrome (ES) in the BREATHE‐5 study (NCT00367770), while macitentan did not improve 6MWD in these patients, but there are differences regarding study size and functional class, and that 30% of the patients treated with macitentan were already in treatment with a phosphodiesterase type 5 inhibitor. Macitentan revealed a lower risk of developing peripheral oedema and hepatotoxicity in the SERAPHIN study. In summary, macitentan has an efficiency comparable to bosentan and ambrisentan in the treatment of PAH. Patients treated with macitentan exhibited less adverse effects compared to bosentan and ambrisentan. In patients with PAH associated with ES, the trials with bosentan and macitentan do not seem comparable, and it needs to be clarified whether these drugs are effective when administered as part of a combination treatment in this condition.     

Ambrisentan

Elevated endothelin (ET)-1 levels are strongly correlated with the pathogenesis and prognosis of pulmonary arterial hypertension (PAH). Ambrisentan is an orally active, highly selective ETA receptor antagonist with >4000-fold higher selectivity over the ETB receptor. In two large, well designed, 12-week, placebo-controlled, phase III trials (ARIES-1, n = 202 and ARIES-2, n = 192) in patients with PAH (WHO group I), ambrisentan 2.5-10 mg once daily significantly increased 6-minute walk distance by 31-59 m from baseline (primary outcome measure) versus placebo. The incidence of clinical worsening (secondary outcome measure) was significantly delayed for the combined ambrisentan 5 mg once daily groups versus the combined placebo groups from ARIES-1 and -2. At week 12, WHO functional class distribution was significantly improved with once-daily ambrisentan 5 mg, and Borg dyspnoea scores were significantly improved with ambrisentan 2.5-10 mg versus placebo in combined data from the ARIES-1 and -2 trials. The beneficial effects of ambrisentan on exercise capacity, WHO functional class and Borg dyspnoea scores seen at 12 weeks were maintained at 48 weeks in the ARIES-E phase III extension trial (n = 361). One-year survival rates with ambrisentan were 95-97%. Treatment with ambrisentan for up to 2.8 years was generally well tolerated in clinical trials.     

Ambrisentan,an endothelin receptor type A-selective endothelin receptor antagonist,for the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular proliferation, which leads to right heart failure and death. Prostacyclin, NO and endothelin are felt to be key mediators in the development of PAH. We present the available published and presented data about ambrisentan, an ET_A-selective endothelin receptor antagonist (ERA) and newest ERA agent to be approved by the FDA for the treatment of PAH in patients with WHO functional class II and III symptoms. Randomized, placebo-controlled trials have demonstrated a significant improvement in exercise capacity and decrease in time to clinical worsening, along with evidence to support an improvement in WHO functional class and quality of life for patients receiving ambrisentan. Long-term data have shown a 1-year survival of 95%; of the survivors, 94% remained on ambrisentan monotherapy. Endothelin receptor antagonists as a drug class have previously been associated with peripheral edema, aminotransferases abnormalities and a teratogenic risk to a developing fetus. Peripheral edema was observed in patients receiving ambrisentan; however, a greater percentage was experienced in patients aged > 65 years. In contrast, significant aminotransferase abnormalities were not observed with ambrisentan treatment in the placebo-controlled trials, and in all clinical trials combined the 1-year risk seems to be low (< 3%). Despite these data, the FDA requires monthly liver function tests monitoring. As with other ERAs, monthly pregnancy testing is required in all women of child bearing potential.     

Treatment of pulmonary arterial hypertension in connective tissue disease

Pulmonary arterial hypertension (PAH) is a group of distinct disorders that includes idiopathic PAH (IPAH), familial PAH and PAH associated with other conditions (APAH) such as connective tissue disease (CTD-APAH) or congenital heart disease. PAH is characterized by increased pulmonary arterial pressure and pulmonary vascular resistance. If left untreated, PAH can lead to right heart failure and premature death. CTD-APAH represents an important clinical subgroup of APAH that has a higher risk of death than IPAH. The European treatment guidelines advocate the use of PAH-targeted therapies including bosentan, ambrisentan, sildenafil, inhaled iloprost, intravenous epoprostenol (I-A recommendations), tadalafil or treprostinil (I-B recommendations) for patients in WHO functional class II-III. Not all randomized clinical studies of the approved PAH-targeted therapies have included patients with CTD-APAH. The purpose of this review is to describe the clinical characteristics of CTD-APAH and discuss the approved pharmacological treatments, with a focus on data specific to this subgroup where possible.     

No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers

Ambrisentan is a nonsulfonamide, ET_A-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH. Due to the potential combination use, the pharmacokinetic (PK) interactions between these two drugs were assessed in a crossover study in 26 healthy adults. Single-dose PK of ambrisentan (10 mg) and its metabolite, 4-hydroxymethyl ambrisentan, were determined in the absence and presence of multiple doses of tadalafil (40 mg QD). Similarly, single-dose PK of tadalafil (40 mg) were evaluated in the absence and presence of multiple doses of ambrisentan (10 mg QD). In the presence of tadalafil, ambrisentan maximum plasma concentration (C_max) was similar (105.0% [90% CI: 95.9–115.0%]) and systemic exposure (AUC_0–∞) was slightly decreased (87.5% [84.0–91.2%]), compared with ambrisentan alone. Similar changes were observed with 4-hydroxymethyl ambrisentan. Tadalafil C_max (100.6% [94.4–107.1%]) and AUC_0–∞ (100.2% [92.6–108.4%]) showed no difference in the absence and presence of ambrisentan. The safety profile of the drugs combined was similar to that of either drug alone. No dose adjustments should be necessary when these drugs are coadministered. These results are in contrast to previous reports that the sulfonamide-based ERA bosentan can cause marked decreases in the exposure of tadalafil. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4962–4974, 2009     

Endothelin receptor antagonism: role in the treatment of pulmonary arterial hypertension related to scleroderma

Pulmonary arterial hypertension (PAH) is a devastating disease, which is associated with a 1-year survival of about 50% without specific treatment. Pulmonary vascular remodelling, thrombosis and vasoconstriction are thought to be directly involved in increasing pulmonary vascular resistance (PVR), which, left untreated, ultimately leads to right ventricular failure and death. A total of 10-12% of patients with systemic sclerosis (SSc) develop PAH, which is a leading cause of mortality in these patients. Targeted treatment regimens involving oral therapies, in particular endothelin receptor antagonists (ERAs), such as bosentan, sitaxsentan (sitaxentan) and ambrisentan, are now being used and this approach has improved symptoms as well as survival. 1-Year survival has improved to about 80%, while 3-year survival in advanced SSc-PAH has improved from 44% to 65% since the introduction of ERAs. Subanalysis of BREATHE-1, a pilot study and the STRIDE-2X randomized controlled trials has reported improvements in time to clinical worsening, 6-minute walk distance (6mwd) and right heart haemodynamics in SSc-PAH patients given bosentan and sitaxsentan, respectively, compared with placebo. The ARIES studies have also demonstrated a delay in the time to clinical worsening and improvement in 6mwd in connective tissue associated-PAH patients given ambrisentan compared with placebo. Unfortunately, these drugs are expensive and also have the potential for adverse interactions with other PAH and supportive therapies. Mandatory monthly liver function tests are required for safe administration of bosentan, ambrisentan and sitaxsentan, while dose adjustment of warfarin and careful monitoring are required when sitaxsentan is initiated. Earlier diagnosis and treatment of PAH may further improve outcomes with current ERAs. WHO functional class (FC) has traditionally been used to determine which patients with PAH will start therapy. The EARLY study has reported significant reductions in PVR and time to clinical worsening in mildly symptomatic PAH patients treated with bosentan, and many PAH clinicians now believe WHO FC should be used as a monitoring tool once targeted therapies have been initiated and not as a tool for deciding when to start PAH specific therapies.Many pathways are thought to be involved in the pathophysiology of the PAH. There is growing evidence that combination therapies targeting different pathophysiological steps may be necessary to effectively treat SSc-PAH. The COMPASS-1 study has reported an acute haemodynamic benefit in PAH when a single-dose of sildenafil is used in combination with bosentan and COMPASS-2 will investigate whether this acute response translates into long-term benefit. Well designed morbidity and mortality trials in SSc-PAH should help increase our understanding and treatment of this orphan disease.     

Pulmonary arterial hypertension: on the way to a manageable disease

Pulmonary arterial hypertension (PAH) is an orphan disease for which no specific pharmacological therapy was available until 1996. Pharmacotherapy for PAH is currently dominated by three endothelin receptor antagonists, bosentan, ambrisentan and sitaxentan (which is not yet approved in the US), and the PDE5 inhibitor sildenafil. Drug candidates undergoing phase III clinical trials for PAH include inhalable and oral treprostinil, aviptadil (an inhalable vasoactive intestinal peptide), and the PDE5 inhibitor tadalafil. Riociguat, a soluble guanylate cyclase stimulator, is scheduled to enter phase III clinical trials in 2008. By approximately 2010, the role of infusable or injectable PGs as treatment for PAH will likely diminish significantly, while inhalable nitric oxide will remain as mainstay therapy in neonatal PAH. Benefits in survival and quality-of-life will decide if any of the more experimental approaches that utilize newly discovered molecular pathways in PAH will ultimately result in marketed drugs.     

Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension

The Pregnancy Prevention Program (PPP) is in place to prevent drug-induced developmental malformations. Remarkably, among the ten PPP-enlisted drugs are three endothelin-1 (ET-1) receptor antagonists (ERA's: ambrisentan, bosentan and macitentan), which are approved for the treatment of Pulmonary Arterial Hypertension (PAH). This review describes the effects of ERA's in PAH pathobiology and cardiopulmonary fetal development. While ERA's hamper pathological remodeling of the pulmonary vasculature and as such exert beneficial effects in PAH, they disturb fetal development of cardiopulmonary tissues. By blocking ET-1-mediated positive inotropic effects and myocardial fetal gene induction, ERA's may affect right ventricular adaptation to the increased pulmonary vascular resistance in both the fetus and the adult PAH patient.