洛沙坦的药物基因组学研究进展

洛沙坦是常用的血管紧张素Ⅱ受体拮抗剂,在治疗高血压等心血管疾病中具有重要作用,临床实践发现不同个体对洛沙坦的反应差异大,研究表明遗传因素是导致洛沙坦疗效产生个体差异的重要因素之一。主要对洛沙坦基因遗传多态性的研究进展进行综述。     

洛沙坦及开博通对高血压患者肾功能的影响

目的：评价开博通及洛沙坦对高血压患者血清肌酐、肌酐清除率，尿蛋白排泌，尿酸的影响。方法：选取56例Ⅰ-Ⅱ级，中－高度危险的高血压病患者，停用抗高血压药物1周后分为两组：（1）开博通组：服开博通12.5mg,3次／日。（2）洛沙坦组：服洛沙坦50-100mg，1次／日。两组于治疗前后测定血压，血清肌酐及肌酐清除率，24小时尿蛋白及尿微量白蛋白，血清尿酸水平并观察药物副作用。结果：共51例完成实验，两组患者治疗前后血压比较均有极显著降低（P＜0．01），洛沙坦组血压降低3.33/1.86kPa，开博通组血压平均降低3.38/2.17kPa。两组间降压幅度差异无显著性（P＞0．05）。开搏通组及洛沙坦组治疗前后血清肌酐水平明显差异，但洛沙坦组显著降低（P＜0．05）。结论：开博通及洛沙坦对高血压伴轻，中度肾减退患者有益的，它们均可降低血肌酐及尿蛋白的水平，不影响肌酐清除率，但洛沙坦较开博通更明显降低尿总蛋白的排泌，而且有独特的降尿酸作用，无咳嗽副反应，对高血压患者早期靶器官保护更加有益。     

洛沙坦与苯那普利治疗原发性高血压左室肥厚的对比研究

评价洛沙坦治疗高血压左室肥厚的疗效并与苯那普利作比较。原发性高血压左室肥厚患者５０例,随机分为洛沙坦治疗组（２５～５０ｍｇ／ｄ）、苯那普利治疗组（５～２０ｍｇ／ｄ）,疗程４个月,结果洛沙坦或苯那普利治疗后血压比治疗前显著降低,两组对左室肥厚的逆转率分别为８０％与７２％,逆转作用无差别,不良反应发生率洛沙坦比苯那普利明显减少。本文资料显示,洛沙坦是降低血压、逆转左室肥厚疗效较好的药物。     

AT-Ⅱ受体拮抗剂进展与临床评价(二)

<正> 洛沙坦(Iosartan potassium/Cozaar)洛沙坦是正式用于临床的第一个口服有效的非肽类AT-II型受体拮抗剂,它已经动物和人体广泛研究并被确认对高血压治疗有效。洛沙坦口服吸收迅速(与是否进餐无关),约1小时达到血浆峰值,半衰期1.5～2.5小时。洛沙坦会经细胞色素P_(450)(CYP)同功酶2C9和3A4而发生肝脏首过代谢并生成活性羧酸代谢物EXP-3174,后者在2～4小时内达到血浆峰值并具有6～9小时的半衰期。洛沙坦虽能为CYP同功     

洛沙坦与苯那普利对高血压大鼠左室肥厚的影响

目的 探讨洛沙坦与苯那普利及联合治疗对自发性高血压大鼠（ＳＨＲ）血压、左室肥厚的影响。方法 ２４只１６周龄的雄性ＳＨＲ大鼠，随机分为洛沙坦（Ｌｏｓ）治疗组（ＳＨＲ－Ｌ），苯那普利（Ｂｅｎ）、治疗组（ＳＨＲ－Ｂ；），洛沙坦与苯那普利联合治疗组（ＳＨＲ－ＢＬ）。治疗１６周。年龄、性别配对的ＳＨＲ和ＷＫＹ大鼠作对照组。测定收缩压、左心室重量，计算心体比。结果 Ｌｏｓ降压作用大于Ｂｅｎ、Ｌｏｓ、Ｂｅｎ逆转     

洛沙坦预防兔心肌缺血再灌注损伤的实验研究

目的：研究体外循环中血管紧张素Ⅱ(AngⅡ）与心肌缺血再灌注损伤（MRI）的关系。以及洛沙坦对MRI的保护作用及机制。方法：采用兔的体外循环模型，观察血浆及心肌组织AngⅡ含量的变化，血清一氧化氮（NO）含量和血浆内皮素（ET）含量的变化以及心肌组织的超微结构。结果：在体外循环 缺血再灌注组和洛沙坦组血浆和心肌组织中AngⅡ含量随着时间的延长逐渐升高，洛沙坦组心功能各项指标较缺血再灌注组明显改善，心肌组织，血浆ET水平较缺血再灌注组显著降低，而血清NO水平明显增高，超微结构显示心肌损伤较缺血再灌注组明显减轻，结论：在MRI过程中，AngⅡ起到极其重要的作用，洛沙坦通过拮抗AngⅡ受体AT1较好地保护了心肌。     

洛沙坦治疗高血压的药理学,临床疗效和耐受性

洛沙坦是口服的非肽类血管紧张素Ⅱ受体亚型１拮抗剂，为一类新型抗高血压药物。对轻、中度高血压，洛沙坦５０－１００ｍｇ，１次．ｄ＾－１单药治疗与依那普利、要替洛尔和非洛地平缓释剂的降压幅度相似；与氢氯噻嗪合作，则降压作用较单用强。     

洛沙坦可降低慢性心衰病人的死亡率

默克公司的血管紧张素(AT2)受体拮抗剂洛沙坦(losartan)比ACE抑制剂卡托普利更能降低老年心衰病人的病死率。老年病人洛沙坦评价(ELITE)研究组的研究人员认为,洛沙坦是对任何适应证都能降低死亡率的第一个AT2拮抗剂。另一项大规模(2500个病例)ELITE试验正在进行中,目的在于验证上述发现。洛沙坦是1994年首次上市的,现在仍在美国、欧洲及其他地区用于高血压病人的治疗。1996年该药的销售额达3.39亿美元。默克公司发言人称,临床医师接受洛沙坦的速度比近10年来上市的任何其他抗高血压新药均要快得多。在一项有722名病人参加的临床试验…     

沙坦类抗高血压药的不良反应

沙坦类抗高血压药即血管紧张素Ⅱ(Ang Ⅱ)受体拮抗剂,因名称均以"沙坦"(sartan)结尾而被称为沙坦类抗高血压药.自1994年第1个品种洛沙坦(Losartan)首先在瑞典上市以来,相继有缬沙坦(Valsartan)、伊普沙坦(Eprosartan)、依贝沙坦(Irbesartan)、坎地沙坦(Candisartan)和替米沙坦(Telmisartan)等上市.洛沙坦1998年在我国上市,该类新药临床主要用于治疗高血压,但洛沙坦也一度是用于治疗心衰的一线药.据称与血管紧张素转化酶抑制剂(ACEI)类抗高血压药相比,顺从性好,咳嗽及血管性水肿等不良反应发生率较低是本类药的一大优点.曾有人预测,"沙坦"类药物将成为抗高血压药市场的主角[1],但它的不良反应也不容忽视.     

洛沙坦对大鼠急性水肿性胰腺炎的防治作用

目的 研究洛沙坦对急性水肿性胰腺炎大鼠是否有保护作用及可能的机制.方法 SD大鼠40只,随机分为正常对照组、急性胰腺炎(AP)组、洛沙坦预防组和洛沙坦治疗组.采用雨蛙素腹腔注射诱导AP模型.预防组于造模前90 min给予洛沙坦200 μg/kg,2次,每次间隔1 h;治疗组于造模后30 min给予洛沙坦200 μg/kg,2次,每次间隔1 h.各组于造模后24 h处死大鼠,观察大鼠血浆血管紧张素Ⅱ(AngⅡ)、肾素(PRA)、淀粉酶(AMY)、肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)水平变化,检测胰腺/体重比、胰腺组织病理变化.结果 AP组AngⅡ、PRA、AMY、TNF-α、IL-1β、胰腺/体重比值较对照组明显升高;洛沙坦预防和治疗组血浆AMY、TNF-α、IL-1β较AP组明显下降,AngⅡ、PRA较AP组变化不明显,胰腺组织病理损伤明显减轻.结论 洛沙坦对血浆AngⅡ、PRA水平无明显影响,可以减少TNF-α、IL-1β的产生,对AP具有保护作用.     

Degraded and undegraded carrageenans and experimental gastric and duodenal ulceration

The prevention of histamine-induced gastric and duodenal ulceration in the guinea-pig has been examined using a series of undegraded and degraded carrageenans. Undegraded carrageenans were active at lower doses than degraded carrageenans. The high viscosity of the undegraded carrageenans in solution prevented their use in larger doses. Degradation of carrageenan without serious loss of sulphate, gives a product which allows the dose to be increased to an extent that its effect more than offsets the slight loss in activity caused by the degradation. No single feature of carrageenan structure can be related to anti-ulcer activity although degradation, and hence reduction of molecular size, generally reduces activity. Sulphate contents over 30% have little apparent effect on activity; κ-carrageenans were not consistently different in anti-ulcer activity from Λ-carrageenans. This contrasts with the antipeptic activity of carrageenans where κ-carrageenans are less active than their Λ-counter-parts. As with antipeptic activity, the degree of anti-ulcer activity is probably determined by a combination of structural features which includes molecular size and polyanionic properties.     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Alcohol and Substance Use and Abuse in Women and Children

No abstract available for this article.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.