质子泵抑制剂研究进展

质子泵抑制剂是一类抑制胃酸分泌的新型药物,该文针对其市场情况、研究现状以及发展方向进行了综述.     

奥美拉唑的临床合理应用

奥美拉唑是一种新型胃酸分泌抑制剂,可选择性、非竞争性地抑制壁细胞膜中的质子泵（H^＋-K^＋-ATP酶）,从而阻断胃酸分泌终端步骤,产生强力的、剂量依赖性抑制胃酸分泌作用。临床应用较为广泛,但其不良反应报道较多。对奥美拉唑的作用特点及不良反应进行了分析,旨为临床合理用药提供参考。     

质子泵抑制剂的开发及研究现状

质子泵抑制剂的开发及研究现状王瑞彬，丁惟培（同济医科大学计划生育研究所，武汉４３００３０）胃质子泵Ｈ＋／Ｋ＋－ＡＴＰａｓｅ的发现，给研究抗胃酸分泌药提供了新的目标。目前，世界各国的很多公司，均投入力量进行了新的质子泵抑制剂类药物的研究、开发工作，有关...     

新型抗溃疡药——奥美拉唑

新一代质子泵抑制剂奥美拉唑(omeprazole,OME)是一种新型的抗消化性溃疡药。该药能高度选择性抑制胃部H~ K~ —ATP 酶(质子泵),从阻止胃酸分泌形成至最后的过程,无论对人体的基础胃酸,还是其它形式的应激胃酸分泌均可产生强有效地抑制作用。它还能     

关于质子泵抑制剂的研究

目的:探讨质子泵抑制剂(PPIS)作为抑制胃酸分泌药物的作用机理,药理作用并探讨其不良反应,从而为临床应用提供科学依据,使质子泵抑制剂发挥其最佳的治疗效果。方法:阐述质子泵抑制剂的作用机理、药理作用、不良反应。结果:质子泵抑制剂是目前最先进的治疗消化性溃疡的一类药物,通过迅速抑制胃酸的分泌来达到快速治愈溃疡性疾病,但必须注意合理用药,减少不良反应现象的发生。结论:质子泵抑制剂的特殊抑酸作用使其成为了临床不可或缺的重要药品之一。     

雷贝拉唑在出血性胃病中的应用进展

讨论新型质子泵抑制剂雷贝拉唑的药理机制、药代动力学及应用于出血性胃病中的研究进展.检索近5年来国内外相关研究进行分析.雷贝拉唑作为第2代苯并咪唑类质子泵抑制剂,能有效抑制胃酸分泌,清除幽门螺杆菌,促进血小板凝聚,改善胃出血.     

幽门螺旋杆菌的除菌疗法

由于幽门螺旋杆菌（HP）是在强酸性环境下在胃内繁殖的细菌，因此对其进行除菌治疗的同时，要使用胃酸分泌抑制剂，因为抗菌剂在强酸性条件下大多易失活。现用的除菌药物中应用较多的是MIC值较低的药物。胃酸分泌抑制剂，质子泵抑制剂对HP有直接的抗菌作用。目前，在消化性溃疡的初期治疗时，为了消除HP，经常在应用酸分泌抑制剂的同时合用质子泵抑制剂。对于HP的除菌疗法，至今已试用了各种方法，但单剂疗法的除菌率为10％～30％，而且耐药菌的发生率较高，目前以多剂疗法为基本治疗方案。1经典的三药联用疗法最初在欧美以税制剂为主…     

新型质子泵抑制剂的研究进展

质子泵抑制剂是目前最有效的胃酸分泌抑制剂和抗溃疡药物,在治疗胃渍疡、十二指肠溃疡和反流性食管炎等疾病方面发挥着重要作用。新型质子泵抑制剂的不断涌现为相关疾病治疗带来了新的希望。本文综述近年来出现的几种新型质子泵抑制剂如泰妥拉唑、莱米诺拉唑和盐酸瑞伐拉赞的作用机制及其独特优点,为临床应用提供参考。     

国外质子泵抑制剂研究概况

质子泵抑制剂(proton pump inhibitors)是一类能与胃壁细胞膜中的质子泵发生选择性作用,而发生抑制胃酸分泌的抗消化性溃疡药物。目前,本类药物开发研究较多而又成熟,并用于临床,主要是取代的苯并咪唑类(substituted benzimidazoles)的衍生物。本文将其研究情况作一介绍。     

奥美拉唑药物相互作用分析

奥美拉唑,别名洛赛克,是一种能够有效地抑制胃酸的分泌的质子泵抑制剂。是近年来研究开发的作用机制不同于H2受体拮抗作用的全新抗消化性溃疡药。它特异性地作用于胃黏膜壁细胞,降低壁细胞中的氢钾ATP酶的活性,从而抑制基础胃酸和刺激引起的胃酸分泌。     

胃散对胃溃疡模型大鼠胃黏膜保护作用的研究

目的 研究胃散对胃溃疡大鼠胃黏膜的保护作用。方法 采用乙酸烧灼型胃溃疡模型、幽门结扎型胃溃疡模型、乙醇损伤型胃溃疡模型,检测溃疡指数、胃酸总酸度、胃酸分泌速度和胃蛋白酶活性,综合考察胃散对胃溃疡模型大鼠胃黏膜的保护作用。结果 胃散在1、0.5、0.25 g/kg剂量下,对乙酸烧灼型胃溃疡有非常显著的促愈合作用;对幽门结扎型胃溃疡的形成有显著的抑制作用;对乙醇损伤的胃黏膜也有显著的保护作用;对胃液总酸度、胃酸分泌速度和胃蛋白酶活性有明显抑制作用,显著增加胃液分泌量。结论 胃散具有增加胃液分泌、抑制胃酸分泌、抑制胃蛋白酶活性、保护胃黏膜和防止胃溃疡的作用。     

Personal review: alarmism or legitimate concerns about long‐term suppression of gastric acid secretion?

This article responds to controversial issues about the long-term use of acid suppression raised in a recent article in this journal by Waldum & Brenna. Although rebound acid secretion occurs following proton pump inhibitor therapy, the clinical significance of this is unclear, but the proposal that this is a major driver of acid-related diseases is considered implausible. The polypoid deformity of the gastric corpus that can occur with long-term proton pump inhibitor therapy is not neoplastic, and therefore has no bearing on other issues raised about proton pump inhibitor therapy and gastric malignancy. Current data in humans suggest that the magnitude of serum gastrin elevation from proton pump inhibitor treatment of up to 10 years, and any theoretical risks from this, have been overstated by Waldum & Brenna. Pernicious anaemia is a model of very doubtful validity for the risks of proton pump inhibitor therapy on several grounds. The proposal that diffuse gastric carcinoma arises from acid suppression-induced stimulation of enterochromaffin-like cells is challenged vigorously, because this is based on an implausible and substantially criticized interpretation of histopathology. It is agreed that it is appropriate to be cautious about the safety of long-term acid suppression, because no data are available for lifelong treatment in humans. Such caution should be tempered by a critical assessment of the benefits of this treatment in relation to any possible risks. The substantial data that now exist from long-term treatment of humans with proton pump inhibitors has not thus far revealed any definite risks. The risk of death from anti-reflux surgery, although small, would seem to far exceed any possible risks associated with long-term proton pump inhibitor use. Available data suggest that denial of the benefits of effective acid suppressant therapy to patients with clear-cut troublesome acid related disorders is an overreaction to concerns about the biological effects of inhibiting acid secretion with proton pump inhibitors.     

Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and diffensive gastric mucosal factors in rats

Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been reported to show both ulcer protective and ulcer healing effects in normal as well as in diabetic rats. To study the mechanism of its ulcer protective/healing actions, effects of AIE (500 mg/ kg) was studied on various parameters of offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5 microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity and defensive mucin secretion including life span of gastric mucosal cells in rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated rats. Continuous infusion of PENTA significantly increased the acid secretion after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate while, AIE pretreatment significantly decreased them. AIE inhibited the rat gastric mucosal proton pump activity and the effect was comparable with that of omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though it enhanced life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus, our present data suggest that the ulcer protective activity of AIE may be due to its anti-secretary and proton pump inhibitory activity rather than on defensive mucin secretion. Further, acute as well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose of AIE in mice and no significant alterations in body or tissues weight, food and water intake, haematological profile and various liver and kidney function tests in rats when treated for 28 days with 1 g/kg dose of AIE.     

新型苯胺类苯并咪唑衍生物的合成及其生物活性

目的 设计合成新型苯胺类苯并眯唑衍生物，并评价其对大白鼠胃液分泌和胃酸分泌的作用。方法 以没食子酸、胡椒醛和香草醛为原料，经多步反应合成目标化合物，并通过大白鼠灌胃给药、幽门结扎、测定胃液及和胃酸量，来确定所合成化合物对其胃液和胃酸分泌率的影响。结果 共合成8个新化合物、5个前体及1个对照药物(NC-1300)，经元素分析，IR，^H-NMR和MS确证其结构；其中2个化合物对胃酸分泌抑制作用与NC-l300相当，所有化合物均对胃液分泌无显著影响。在中间体制备中提出了经取代的邻硝基苯甲醛一步催化氢化制备取代的邻氨基苯甲醇的方法及其选择性N，N-二甲基化法。结论 以没食子酸为原料所合成的NC-1300类似物的胃酸分泌抑制作用与NC-1300相当，是强的质子泵抑制剂。     

Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers

BACKGROUND: Triple therapy including two antibiotics and a proton pump inhibitor is a rational approach to the treatment of Helicobacter pylori induced peptic ulcer disease. The interaction of antimicrobial therapy and acid suppression is not yet well elucidated. AIMS: To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady-state conditions in volunteers. METHODS: In two crossover studies omeprazole 20 mg b.d., lansoprazole 30 mg b.d., roxithromycin 300 mg b.d., and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy volunteers over 6 days. Blood plasma levels of the drugs were measured. In addition, roxithromycin concentrations were also determined in gastric juice and gastric tissue obtained during endoscopy. RESULTS: The proton pump inhibitors and roxithromycin did not alter the blood plasma pharmacokinetics of each other. When compared to roxithromycin administered alone, its combination with a proton pump inhibitor significantly increased the roxithromycin concentrations in gastric juice (3.0-5.0 microg/mL vs. 0.3-0.4 microg/mL) and gastric tissue (antrum: 3.8-4.0 vs. 2.8 microg/g, fundus: 5.9-7.4 vs. 4.2-4.4 microg/g). CONCLUSIONS: Proton pump inhibitors and roxithromycin do not alter the systemic bioavailability of each other. However, proton pump inhibitors increase the local concentration of roxithromycin in the stomach which may contribute to the clinically proven synergic beneficial action in eradication therapy of H. pylori.     

Lack of effect of omeprazole, a potent inhibitor of gastric (H+ + K+) ATPase, on hepatic lysosomal integrity and enzyme activity

The substituted benzimidazole, omeprazole, is a potent inhibitor of the ATP-dependent proton pump of the parietal cell. Since there is accumulating evidence that hepatic lysosomes also possess an ATP-dependent proton pump system to maintain internal acidification, and since antibodies to the putative lysosomal proton pump protein are immunologically similar to the parietal cell (H+ + K+) ATPase, we studied the effects in rats of six days of omeprazole treatment on hepatic lysosomal function. Omeprazole, 5 mg kg-1, a dose five times the ED50 for gastric acid secretion inhibition in rats, did not alter the activity of three representative lysosomal enzymes in liver (acid phosphatase, beta-galactosidase and N-acetyl-beta-glucosaminidase) nor did it alter lysosomal enzyme latency, a measure of the integrity of the lysosomal membrane. Furthermore, bile flow and the secretion of lysosomal enzymes into bile were also unaffected by omeprazole. These data indicate that in rats short-term treatment with omeprazole, in doses that markedly inhibit gastric acid secretion, has no major biological effect on liver lysosomal integrity and lysosomal enzyme activity.     

Personal review: is profound acid inhibition safe?

Inhibitors of gastric acid secretion, particular proton pump inhibitors, are effective drugs in the treatment and prophylaxis of acid-related diseases. Proton pump inhibitors are therefore prescribed widely, often for minor complaints. Gastric acidity kills swallowed microorganisms, and acid secretion must be of biological importance because it is maintained in phylogenesis. Acid secretion is controlled by feedback mechanisms, mainly via gastrin. A decrease in acidity always causes an increase in plasma gastrin. The trophic effect of gastrin leads to hyperplasia and neoplasia of the enterochromaffin-like (ECL) cell. ECL cell derived tumours in man were previously regarded as rare, and also as rather benign. It is now clear that the ECL cell gives rise to a significant proportion of gastric carcinomas. Moreover, ECL cell carcinoids secondary to hypergastrinaemia may develop into highly malignant tumours. Treatment with a proton pump inhibitor is followed by rebound acid hypersecretion and decreased efficiency of H2-blockers, thus such treatment may induce a type of physical dependence. It is therefore reasonable to be cautious and not to treat younger (< 50 years) patients for long periods of time with profound inhibitors of gastric acid secretion. Chromogranin A in the blood is a sensitive marker of the ECL cell mass, and it could be used to survey patients on long-term proton pump inhibitors.     

仁和正胃胶囊对胃液分泌功能影响的实验研究

目的研究正胃胶囊对胃液分泌的影响。方法制备正常大鼠胃液分泌及组胺刺激大鼠胃液分泌2个模型,正胃胶囊与对照组中药制剂(胃康灵胶囊、胃泰颗粒)、西药制剂(维U颠茄铝胶囊、铝碳酸镁片)比较,测定正胃胶囊的制酸止痛作用。结果正胃胶囊能显著抑制胃蛋白酶活力,对胃液的pH值有明显升高作用;对组胺刺激的胃液分泌量增加有明显的抑制作用;对正常大鼠胃液分泌量仅有轻度抑制作用。结论正胃胶囊在抑制胃蛋白酶活性、降低胃液pH值、抑制胃液过量分泌等有明显的临床应用优势。     

Relationship between gastric secretion and serum gastrin levels in dogs anesthetized with morphine and urethane.

The serum levels of immunoreactive gastrin (IRG) and secretion of gastric juice were simultaneously determined in dogs anesthetized with morphine and urethane. There was a significant positive linear correlation between secretion and serum IRG level in these dogs. Serum IRG level and gastric secretion were reduced by bilateral vagotomy at the neck. The amount of gastric juice was reduced dose-dependently by an intravenous injection of atropine (0.001--0.016 mg/kg), hexamethonium (0.064--1 mg/kg) and secretin (2--8 U/kg). The reduction of gastric secretion paralleled that of the serum IRG level. However, the reduction of gastric secretion did not parallel that of serum IRG level under the influence of prostaglandin E1 (0.002--0.008 mg/kg i.v.) and duodenal acidification. Prostaglandin E1 and duodenal acidification reduced gastric secretion without the reducing serum IRG level. These findings were discussed in relation to the mechanism of gastric juice stimulation by morphine, and it is suggested that endogenous gastrin release through the vagal and non-vagal pathways participates in morphine-induced gastric secretion. The difference in inhibitory effect between duodenal acidification and secretin suggests the possibility that substances other than secretin may participate in the regulation of gastric secretion in dogs.     

Review article: the pharmacology of rabeprazole

Rabeprazole sodium is a new substituted benzimidazole proton pump inhibitor with several differences compared with existing proton pump inhibitors. In vitro and animal studies have demonstrated that rabeprazole is a more potent inhibitor of H⁺,K⁺-ATPase and acid secretion than omeprazole, and is a more rapid inhibitor of proton pumps than omeprazole, lansoprazole, or pantoprazole. This probably reflects rabeprazole's faster activation in the parietal cell canaliculus. In human studies, once-daily doses of 5–40 mg of rabeprazole inhibit gastric acid secretion in a dose-dependent fashion. A once-daily dose of 20 mg has consistently achieved profound decreases in 24-h intragastric acidity in single and repeat dosing studies, in healthy volunteers and patients with either peptic ulcer disease or gastro-oesophageal reflux disease. Significantly greater decreases in intragastric acidity are achieved on day 1 of dosing with rabeprazole 20 mg than with omeprazole 20 mg. As with other proton pump inhibitors, rabeprazole has in vitro antibacterial activity against Helicobacter pylori , with greater activity against this organism than either lansoprazole or omeprazole. In addition to inhibiting bacterial urease activity, rabeprazole binds to several molecules on H. pylori . Clinical trials are needed to assess the clinical importance of these findings, as well as to assess whether the potential advantages of rabeprazole result in clinical benefit for patients with acid-related diseases.