Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells

BACKGROUND/AIMS: Histamine H2 receptor antagonists are considered to exert their effects on gastric acid secretion more rapidly than proton pump antagonists. However, there are no reports concerning the direct interaction of a histamine H2 receptor antagonist with the human H2 receptor in terms of onset of action. This study aims to characterize how rapidly famotidine and ranitidine, the most widely used histamine H2 receptor antagonists, interact with the human histamine H2 receptor. METHODS: HEK293 cell lines, stably expressing human histamine H2 receptors, were obtained. The dose- and time-dependent effects of famotidine and ranitidine on [3H]-tiotidine binding and histamine-stimulated cAMP production were analyzed. RESULTS: Ranitidine inhibited both [3H]-tiotidine binding and histamine-stimulated cAMP production more promptly than did famotidine. Inhibition of histamine-stimulated cAMP production by Cmax doses of famotidine (20 mg p.o.) and ranitidine (150 mg p.o.) peaked by 15 and 2 min, respectively. [3H]-tiotidine binding was not saturated by 60 min at the famotidine Cmax, while the ranitidine Cmax had produced saturation by 15 min. CONCLUSION: Ranitidine inhibits the human histamine H2 receptor very rapidly.     

Helicobacter pylori infection influences symptomatic response to anti-secretory therapy in patients with GORD—crossover comparative study with famotidine and low-dose lansoprazole

BACKGROUND AND AIM: Helicobacter pylori infection was reported to affect gastric acid secretion. We investigated the heartburn symptoms of patients with gastro-oesophageal reflux disease during sequential treatment with 40 mg of famotidine or 15 mg of lansoprazole to clarify whether H. pylori infection influences symptomatic response to anti-secretory therapy. SUBJECTS AND METHODS: The subjects were 33 gastro-oesophageal reflux disease patients, who had already been treated with a full dose of H2 receptor antagonist. First, famotidine at 20 mg b.i.d. was administered to the patients for 8 weeks. Second, famotidine was replaced with 15 mg of lansoprazole once in the morning for 8 weeks. Finally, 20 mg of famotidine was administered b.i.d. for 8 weeks instead of lansoprazole. Gastro-oesophageal reflux disease symptoms were assessed using an original visual analogue scale. RESULTS: The sequential symptomatic responses to famotidine and lansoprazole administration indicated that gastro-oesophageal reflux disease symptoms of patients during low-dose lansoprazole treatment were significantly less than those during famotidine treatment. Remission of symptoms was obtained significantly more often by famotidine therapy in patients with H. pylori infection than in patients without H. pylori infection. CONCLUSION: Low-dose lansoprazole is more effective than full-dose famotidine for the control of symptoms in patients with gastro-oesophageal reflux disease, and H. pylori infection influences the symptomatic response to H2 receptor antagonists.     

Various durations of a standard regimen (amoxycillin, metronidazole, colloidal bismuth sub-citrate for 2 weeks or with additional ranitidine for 1 or 2 weeks) on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A randomized controlled trial

INTRODUCTION: One of the most economical and effective therapeutic regimens for eradication of Helicobacter pylori is the classic triple therapy with amoxycillin or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor antagonists to these drugs may heighten the rate of eradication and shorten the duration. We therefore performed a randomized controlled trial comparing twice daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult patients with duodenal ulcer and H. pylori infection were randomly assigned to one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid, bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300 mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after starting the treatment. The rapid urease test and histology from antrum and corpus, and/or 14C- urea breath test were used to determine H. pylori eradication six weeks after starting the treatment. RESULTS: In total, 195 patients were followed up for 6 weeks. The most frequent drug side-effects were unpleasant taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution in all treatment groups. Endoscopy and 14C- urea breath test were performed for 178 and 123 patients, respectively. Eradication of H. pylori was documented in 19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3, respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2 versus group 3; difference not significant for group 1 versus group 2). An intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80 (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks post-treatment, the most sensitive test for evaluation of eradication of H. pylori was histology. CONCLUSION: Although combined use of an H2-receptor antagonist and twice daily triple therapy in a two-week regimen is more effective than two-week triple or one-week quadruple therapy in Iranian patients, none of these regimens is ideal in countries with a probable high rate of resistant and strongly toxic strains of H. pylori.     

不同质子泵抑制剂对冠脉支架术后氯吡格雷抗血小板功能的影响

目的:观察埃索美拉唑、雷贝拉唑、雷尼替丁或法莫替丁对急性冠脉综合症（ACS）患者冠脉支架术后应用氯吡格雷抗血小板功能的影响。方法: 150例行经皮冠状动脉介入治疗（PCI）的ACS患者,入院后给予阿司匹林300 mg/d,氯吡格雷300 mg负荷剂量继以75 mg/d维持剂量抗血小板治疗,并随机分为质子泵抑制剂（PPI）A组（A1组:埃索美拉唑40 mg/d,n=30,A2组:雷贝拉唑20 mg/d,n=30）、H2受体拮抗剂(H2RA)B组（B1组:雷尼替丁300 mg/d,n=30,B2组:法莫替丁40 mg/d,n=30）和空白对照C组（C组:n=30）。采用ELISA法检测血浆CD62P、GPⅡb/Ⅲa含量及电阻抗法检测血小板聚集功能。结果: PPI或H2RA治疗前后,A组、B组与C组相比,上述指标的差值组间比较均无明显统计学差异,A1组、A2组、B1组、B2组与C组相比,治疗前后上述指标的差值组间比较均无统计学差异。结论: 埃索美拉唑、雷贝拉唑、雷尼替丁或法莫替丁对氯吡格雷的抗血小板活性无明显的影响。     

Influence of lansoprazole,famotidine, roxatidine and rebamipide administration on the urea breath test for the diagnosis of Helicobacter pylori infection

BACKGROUND AND AIM: The sensitivity of the urea breath test (UBT) has been reported to be influenced by the administration of omeprazole, lansoprazole and ranitidine. However, it is unclear whether other H2 receptor antagonists (H2RA), except ranitidine, and rebamipide, a mucosal protective agent, affect UBT sensitivity. The aim of this study is to clarify the effects of lansoprazole, famotidine, roxatidine and rebamipide administration on UBT sensitivity. METHODS: Subjects comprised 30 volunteers with Helicobacter pylori infection. All subjects were examined by the 13C-UBT on four occasions: (i) without medication (control); (ii) after the administration of 30 mg lansoprazole (u.i.d) for 14 days; (iii) after the administration of 100 mg rebamipide (t.i.d) for 14 days; and (iv) after the administration of 20 mg famotidine or 75 mg roxatidine (b.i.d) for 14 days. In the H2RA study, individuals were randomized into two groups of 15 subjects and were administered either famotidine or roxatidine. RESULTS: Five of the 30 cases administered lansoprazole and one of the 15 cases given roxatidine gave a false-negative UBT result. No negative UBT results were observed in patients administered famotidine or rebamipide. CONCLUSION: Patients showing negative UBT results during the administration of proton pump inhibitors and H2RA should be re-examined after the cessation of these drugs to confirm the true negativity of H. pylori infection.     

3种幽门螺杆菌根除方案和抗生素耐药对其根除率的影响

背景:目前推荐的根除幽门螺杆菌(H.pylori)的治疗方案因H.pylori对大环内酯类和硝基咪唑类抗生素的耐药性快速增加而不能令人满意。目的:评估以质子泵抑制剂(PPI)为基础或以H2受体拮抗剂(H2RA)加铋剂为基础的三联或四联疗法根除H.pylori的疗效和安全性,评估H.pylori的耐药性及其对根除率的影响。方法:120例H.pylori感染的愈合期十二指肠球部溃疡或非溃疡性消化不良患者随机分入3个治疗组,疗程7天。A组:奥美拉唑、克拉霉素和替硝唑;B组:法莫替丁、枸橼酸铋钾、克拉霉素和替硝唑;C组:法莫替丁、枸橼酸铋钾、呋喃唑酮和四环素。根除治疗前取胃窦黏膜活检组织行快速尿素酶试验、H.pylori培养和组织学检查评估H.pylori感染状态。治疗结束后4～6周,采用13C-尿素呼气试验评估H.pylori根除情况。琼脂扩散法药物敏感试验测定抗生素的最小抑菌浓度(MIC)。结果:所有患者均完成治疗和随访。A组、B组和C组的H.pylori根除率分别为80%(32/40)、85％(34/40)和90％(36/40),3组间无显著差异(P>0.05)。耐药菌株与敏感菌株的H.pylori根除率有显著差异。结论:以PPI为基础或以H2RA加铋剂为基础的三联或四联疗法对H.pylori具有较高的根除率。H.py-lori的耐药性是影响根除率的主要因素。     

Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.

Triple therapy has been recommended as the most effective treatment for Helicobacter pylori eradication. Despite achieving a comparatively high eradication result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double antibiotic protocols and is particularly effective when combined with clarithromycin and a nitroimidazole. This study examined the effect of combining triple therapy with omeprazole. A prospective, randomised, unblinded, single centre trial was carried out on consecutive patients with symptoms of dyspepsia and H pylori infection confirmed by rapid urease test, microbiological culture, and histological assessment. Patients were given a five times/day, 12 day course of colloidal bismuth subcitrate chewable tablets (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg) with either 20 mg omeprazole twice daily (triple therapy+omeprazole) or 40 mg famotidine (triple therapy+famotidine) at night. Compliance and side effects were determined using a standard questionnaire form. One hundred and twenty five of 165 triple therapy+omeprazole patients and 124 of 171 triple therapy+famotidine patients returned for rebiopsy four weeks after completion of treatment. Significantly more triple therapy+omeprazole patients achieved eradication 122 of 125 (97.6%) as assessed by negative urease test, culture, and histological assessment, when compared with 110 of 124 (89%) triple therapy+famotidine patients (p = 0.006; chi 2). There were 30 triple therapy+omeprazole (24%) and 26 triple therapy+famotidine (21%) patients with de novo metronidazole resistant H pylori included in the study. Side effects were mild and infrequent and were comparable in both groups, although pain in duodenal ulcer, gastric ulcer, and oesophagitis patients seemed to subside earlier in those taking omeprazole. Compliance (>95% of drugs taken) was achieved by 98% of patients of both groups. A 12 days regimen of triple therapy with omeprazole is more effective in achieving H pylori eradication than is triple therapy plus famotidine. Use of 20 mg omeprazole twice daily rather than 40 mg famotidine with a 12 day, low dose triple therapy enhances eradication to over 97% whether the H pylori is metronidazole sensitive or resistant.     

Acid suppression therapy is not required after one-week anti-Helicobacter pylori triple therapy for duodenal ulcer healing

AIM: To compare healing of Helicobacter pylori-related non complicated duodenal ulcer after one-week eradication triple therapy alone and after triple therapy with further 3-weeks antisecretory treatment with ranitidine. METHODS: Three hundred and forty three patients with symptomatic H. pylori positive duodenal ulcer were included in this randomized double-blind placebo controlled study. H. pylori infection was established by rapid urease test and histopathology of antral biopsies. All patients were treated for one week with ranitidine 300 mg b.i.d., amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d., and then randomly treated for the following 3 weeks either with ranitidine 300 mg once daily (triple therapy + ranitidine, n =180) or placebo (triple therapy alone, n =163). Ulcer healing was assessed by endoscopy 4 weeks after inclusion. H. pylori eradication was established by (13) C-urea breath testing 5 weeks after the end of triple therapy. RESULTS: In intention to treat, duodenal ulcer healed at 4 weeks in 86 % of patients treated with triple therapy + ranitidine and in 83 % of patients treated with triple therapy alone (equivalence: 90 % CI [-3. 8 %; 9.2 %]). The H. pylori eradication rates were 67 % and 69 % respectively. Ulcer healed in 88 % of patients in whom H. pylori eradication was achieved and in 77 % of patients in whom eradication failed. CONCLUSION: These results demonstrate that one-week triple therapy alone is highly effective in healing non complicated H. pylori associated duodenal ulcer without additional antisecretory treatment.     

Duodenal ulcer healing rates in a one-year follow-up study with ranitidine bismuth citrate and antibiotics

BACKGROUND/AIMS: The aim of this study was to determine the one-year outcome of an eradication therapy with ranitidine bismuth citrate and antibiotics in Helicobacter pylori-positive duodenal ulcer patients in respect to ulcer and Helicobacter pylori relapse rates. METHODOLOGY: This multicenter, randomized, double-blind study involved 648 duodenal ulcer patients and had been carried out to compare the following regimens: ranitidine bismuth citrate b.i.d. co-prescribed with either clarithromycin 250 mg q.i.d. or clarithromycin 500 mg b.i.d. or clarithromycin 500 mg b.i.d. plus metronidazole 400 mg b.i.d. for 2 weeks, followed by a further 14 days of treatment with ranitidine bismuth citrate 400 mg b.i.d. to facilitate ulcer healing. H. pylori eradication was assessed by 13C-urea breath test and histology at least 4 weeks, 26 weeks and 52 weeks after the end of treatment. Ulcer relapse and H. pylori status were assessed 4 weeks, 26 weeks and 52 weeks post-treatment or if ulcer symptoms recurred. For the remainder of the follow-up period only serious adverse events were collected. RESULTS: At 12 months data of 438 (69%) patients were evaluable. The observed H. pylori eradication rates were 88-91%. H. pylori relapse rates were 2.1% after 26 weeks and 3.9% after 52 weeks. At the week 26 visit 26 patients (5.6%) and at the week 52 visit 25 patients (5.7%) had documented gastroesophageal reflux disease. CONCLUSIONS: Our data confirm the reduction of duodenal ulcer relapses after the cure of Helicobacter pylori infection.     

Relapse prevention in reflux oesophagitis with regard to Helicobacter pylori status: a double-blind, randomized, multicentre trial to compare the efficacy of pantoprazole versus ranitidine

OBJECTIVE: To compare prospectively the effectiveness of 1 year's treatment with pantoprazole versus ranitidine in order to prevent relapse after initial cure of reflux oesophagitis. For the first time the influence of the initial Helicobacter pylori status on therapeutic results was also taken into account. METHODS: In order to cure reflux oesophagitis, 396 patients with Savary/Miller stage II or III reflux oesophagitis were treated with pantoprazole 40 mg once daily for 8 weeks. Those who were H. pylori positive (n = 140) were also given 1 week of eradication treatment with clarithromycin 2 x 250 mg daily, metronidazole 2 x 400 mg daily, and a further 40 mg pantoprazole daily. The 303 patients who were endoscopically cured after the 8-week period were randomized and treated with either pantoprazole 20 mg (n = 199) or ranitidine 150 mg (n = 104) daily in double-blind fashion. The primary objective was to assess the time to endoscopically proven recurrence of reflux oesophagitis. RESULTS: In the intention-to-treat (ITT) population, 66.3% (118/178) of the pantoprazole group and 34.0% (32/94) of the ranitidine group showed neither endoscopic nor clinical symptoms of relapse after the 1-year treatment period (P < 0.0001) (per-protocol populations: 70.3% [109/155] in the pantoprazole group and 39.4% [28/71] in the ranitidine group). In the pantoprazole group, the relapse rate in initially H. pylori-positive patients who underwent eradication was 30.9% (17/55) and in H. pylori-negative patients 29% (29/100). CONCLUSIONS: Long-term treatment with 20 mg pantoprazole daily to prevent relapse of reflux oesophagitis in H. pylori-negative patients is significantly more effective than 150 mg ranitidine daily. The initial H. pylori eradication treatment does not influence the outcome of the long-term treatment.     

Comparative study of therapeutic effects of PPI and H2RA on ulcers during continuous aspirin therapy

AIM:To compare the therapeutic effects of proton pump inhibitors(PPI) and histamine 2 receptor antagonists(H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin.METHODS:Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI(lansoprazole 30 mg,n = 30) or H2RA(famotidine 40 mg or if famotidine had been administered before assignment,ranitidine 300 mg,n = 30).The therapeutic effects were evalua...     

Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection

BACKGROUND AND AIM: The attenuated antisecretory activity observed during continuous administration of ranitidine has been described as tolerance. However, it remains unclear whether a similar phenomenon occurs with other histamine H2 receptor antagonists (H2RA). We investigated whether tolerance to famotidine, a stronger H2RA than ranitidine, occurs during long-term administration. METHODS: Seven healthy male Japanese subjects without Helicobacter pylori infection participated in a randomized cross-over study in which ranitidine and famotidine were administered for 14 days with a 4-week wash-out period. We performed 24-h intragastric pH monitoring on the first and 14th days of administration of each drug, and measured serum gastrin and plasma drug concentrations on the first, seventh and 14th days. RESULTS: The acid-inhibiting activity of ranitidine and famotidine declined during continuous administration. In particular, the potent nocturnal pH-increasing effect of the H2RA, which was observed on day 1, declined on day 14. Serum gastrin concentrations on day 14 were significantly lower than those on day 7, although plasma drug concentrations remained unchanged. CONCLUSION: Tolerance to famotidine occurs during continuous administration for 14 days, as previously shown in ranitidine studies.     

Famotidine versus omeprazole, in combination with amoxycillin and tinidazole, for eradication of Helicobacter pylori infection

BACKGROUND: Eradication regimens combining two antibiotics with a proton pump inhibitor have been studied intensively. In contrast, only a few studies have focused on the possible role of H2-receptor antagonists in eradication therapy. The mechanism involved in the synergy between antibiotics and proton pump inhibitors is still controversial. OBJECTIVES: To compare the results of two triple-therapy regimens, different only in the antisecretory drugs used, in patients with Helicobacter pylori infection, and to assess the impact of primary resistance to metronidazole on treatment outcome. METHODS: A total of 120 patients with peptic ulcer and non-ulcer dyspepsia were randomly assigned to a 2-week course of either: famotidine 40 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (FAT group; n = 60); or omeprazole 20 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (OAT group; n = 60). Upper endoscopy was performed prior to treatment and at least 4 weeks after completion of treatment and discontinuation of the antisecretory therapy. H. pylori status was assessed by a biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 48 of the 60 patients (80%; 95% confidence interval: 70-90%) in the FAT group, compared to 50 of the 60 patients (83.3%; 95% confidence interval: 74-93%) in the OAT group. In the per protocol analysis, eradication therapy was achieved in 48 out of 53 patients (90.6%; 95% confidence interval: 83-98%) treated with FAT and 50 out of 57 patients (87.7%; 95% confidence interval: 79-96%) treated with OAT (not significant). The primary metronidazole resistance was present in 28.8% of strains. Overall, per protocol eradication rates in strains resistant and susceptible to metronidazole were 83.3% and 91.3% respectively (P > 0.05). CONCLUSIONS: Two-week courses of either high-dose famotidine or omeprazole, both combined with amoxycillin and tinidazole, are equally effective for eradication of H. pylori infection. In a 2-week triple therapy, metronidazole resistance has no significant impact on eradication rates.     

A randomized trial comparing seven-day ranitidine bismuth citrate and clarithromycin dual therapy to seven-day omeprazole, clarithromycin and amoxicillin triple therapy for the eradication of Helicobacter pylori.

OBJECTIVE: To assess Helicobacter pylori eradication after one week dual ranitidine bismuth citrate-clarithromycin (RBC-C) or triple omeprazole, clarithromycin and amoxicillin (OCA) therapy. METHODS: In this multicentre Canadian trial, H pylori-positive patients with functional dyspepsia or inactive peptic ulcer disease were randomized to open-label treatment with RBC-C (ranitidine bismuth citrate 400 mg plus clarithromycin 500 mg) or OCA (omezaprole 20 mg, clarithromycin 500 mg and amoxicillin 1000 mg), given twice a day for seven days. Treatment allocation was randomly assigned. H pylori infection was confirmed by positive 13C-urea breath test (13C-UBT). H pylori status was reassessed by UBT at least four and 12 weeks after treatment (negative: d13CO2 below 3.5 per mil). Intention-to-treat (ITT) eradication rates were determined for all patients with confirmed H pylori infection. Per protocol (PP) rate was determined for all patients treated with at least two evaluable follow-up visits. RESULTS: Three hundred five patients were included in the ITT and 222 in the PP analysis. The ITT eradication rates were 66% for RBC-C and 78% for OCA. The PP success rates were 84% for RBC-C and 96% for OCA. The difference for both ITT 12% (95% CI 2 to 22) and PP 12% (95% CI 4 to 19) were statistically significant, P=0.030 and P=0.007, respectively. Treatment was generally well tolerated. CONCLUSION: The eradication rate for the seven-day dual RBC-C regimen was lower than that for OCA.     

The AMOR study: a randomized, double-blinded trial of omeprazole versus ranitidine together with amoxycillin and metronidazole for eradication of Helicobacter pylori.

BACKGROUND: Besides antibiotics, additionally effective acid inhibition is necessary for the eradication of Helicobacter pylori. OBJECTIVE: To assess the significance of acid suppression and, in particular, treatment with proton pump inhibitors (PPIs) compared with H2 receptor antagonists (H2 RAs). The primary target parameter for the study was H. pylori eradication. In addition, the ulcer healing rate, speed of pain reduction, score for gastritis in the antrum and gastric body, and rate of side effects were recorded. DESIGN: Randomized, double-blinded, multicentre study. PARTICIPANTS: A total of 456 patients between the ages of 18 and 80 years with H. pylori-positive duodenal ulcers were included in the study. METHODS: Using a randomization list, patients were assigned either to a treatment group receiving omeprazole 40 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (OAM), or to a group receiving ranitidine 300 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (RAM). The treatment period was 7 days in both groups. Long-term acid-suppressant treatment was not given. RESULTS: The eradication rate was 87.1% (169/194, intention to treat [ITT]) in the OAM group and 77% (137/ 178, ITT) in the RAM group. The difference of 10.1% (95% CI 2.5-18%) is statistically significant (P= 0.0104). The ulcer healing rate was 93.3% in the OAM group (181/194, ITT) and 92.1% in the RAM group (164/178, ITT, NS). With regard to the speed and intensity of pain reduction, the OAM group was superior to the RAM group. In patients in whom H. pylori eradication was successful, the reduction in the antral and gastric body gastritis score was significantly greater than in patients without eradication. In the OAM group, 39.1% of the patients (n = 90) reported one or more side effects, compared with 44.7% (n = 101) in the RAM group (P= 1.5449, NS). CONCLUSION: Omeprazole (40 mg once daily in the morning) is significantly more effective than ranitidine (300 mg once daily in the morning) with respect to H. pylori eradication when used together with amoxycillin (750 mg three times a day) and metronidazole (500 mg three times a day) for a 7-day treatment period.     

Anaphylactic reaction to drugs commonly used for gastrointestinal system diseases: 3 case reports and review of the literature.

Proton pump inhibitors and H2 receptor antagonists, which are commonly used to treat peptic ulcer and gastroesophageal reflux diseases, are associated with a low incidence of adverse reactions. We report 3 cases of anaphylactic reactions induced by lansoprazole or ranitidine diagnosed in a population of 8304 first-referral patients over a 13-year period. Cutaneous sensitivity to famotidine, ranitidine, omeprazole, pantoprazole, and lansoprazole was evaluated by skin prick tests with a concentration of 10 mg/mL (at 1:1000, 1:100, 1:10 and 1:1 dilutions), and if they were negative, intradermal skin tests were performed with the same dilutions of the extracts. Single-blind, placebo-controlled oral provocation tests were performed with lansoprazole, omeprazole, famotidine, and ranitidine in 2 cases. One case involved anaphylaxis during an oral provocation test with lansoprazole, and 2 cases were anaphylactic reactions to ranitidine. In both cases the skin test was positive for ranitidine and in 1 case an oral provocation test was also positive. The second patient refused that test. Cross reactivity to other H2 receptor antagonists was not demonstrated and a safe alternative drug was found for all 3 patients. Although incidences of anaphylactic reactions induced by proton pump inhibitors or H2 reactions are rare, they can be life threatening.     

Helicobacter pylori eradication versus one-year maintenance therapy: effect on relapse and gastritis outcome.

OBJECTIVE: The aim of this study was to determine ulcer healing and H. pylori eradication rates obtained with triple therapy (omeprazole, amoxicillin and clarithromycin). Ulcer relapsing rate one year after eradication was also assessed. Maintenance therapy with placebo was compared with ranitidine therapy and the effect of eradication on histological variables of the gastric mucosa was studied. METHODS: A prospective, double-blind parallel study was performed in 85 patients endoscopically diagnosed of duodenal ulcer H. pylori positive. Patients were randomized to a 7-days triple therapy (group A) or omeprazole plus antibiotic placebo (group B). All patients were treated only with omeprazole for the next three weeks. Patients with ulcer healing after treatment were entered in a one-year follow up phase with ranitidine placebo (group A) or ranitidine (group B). Endoscopy and biopsies were performed at baseline, after treatment (5 weeks) and after 12 months of follow-up or when relapsing symptoms appeared. RESULTS: Healing rate was 90.2% in group A and 85.7% in group B. Eradication rate was 78% in group A and 0% in group B. Out of 37 healed patients in group A, eradication was achieved in 29 and only one relapse was found (3.4%). Three out of eight patients with healing but without eradication relapsed at 12 months (35%) (p < 0.05). Histopathological results showed statistically significant differences (p < 0.05) between eradicated and non eradicated patients in terms of severity of inflammation and intestinal metaplasia, but not in terms of atrophy. CONCLUSIONS: H. pylori eradication is useful to prevent ulcer relapse and to improve gastric mucosa status.     

Effects of a one-week treatment with acid gastric inhibitors on Helicobacter pylori-infected mice

OBJECTIVE: Antiacid drugs, including omeprazole and ranitidine, were prescribed to Helicobacter pylori-infected subjects in combination with antibiotics during eradication treatment. Several reports suggest that these drugs have additional pharmacological properties, such as antineutrophil, antiapoptotic and antioxidant characteristics. The aim of this work was to study the effects of acid suppressive medication treatment in the H. pylori infection experimental model, focusing on possible additional pharmacological properties. MATERIAL AND METHODS: The ability of gastric acid suppression was assessed in pylorus-ligated animals. Gastric H. pylori colonization levels, myeloperoxidase (MPO) acitivity, macroscopic damage, Bax and Bcl-2 expression and DNA damage levels were assessed in C57BL/6-infected mice after treatment for one week with omeprazole (100 mg kg(-1)) or ranitidine (100 mg kg(-1)). RESULTS: Omeprazole treatment increased bacteria colonization and MPO activity in mice stomachs. Both antiacid drugs efficiently improved macroscopic damage, although only omeprazole restored the expression of the antiapoptotic Bcl-2 protein in gastric mucosa of infected animals. CONCLUSIONS: Some additional omeprazole-related properties, such as antineutrophil properties, were not observed in H. pylori-infected mice after one week of treatment, suggesting that this property is restricted to in vitro approaches. However, the antiapoptotic activity of omeprazole could be attributed to an ability to modify the protein expression of Bcl-2, decreased by H. pylori infection.     

Maintenance treatment is not necessary after Helicobacter pylori eradication and healing of bleeding peptic ulcer: a 5-year prospective, randomized, controlled study

BACKGROUND: It is well accepted that in patients with uncomplicated peptic ulcers, Helicobacter pylori eradication therapy does not need to be followed by further antisecretory treatment. However, it is uncertain whether patients with bleeding peptic ulcers should receive maintenance antiulcer therapy after successful H pylori eradication and ulcer healing. The aim of this 5-year, prospective, randomized, controlled study was to investigate the role of long-term maintenance therapy after successful H pylori eradication and healing of bleeding ulcers. METHODS: A total of 82 consecutive patients with H pylori-associated bleeding peptic ulcers were enrolled in the study. After successful H pylori eradication with the 1-week proton pump inhibitor-based triple therapy and an additional 3-week treatment with 20 mg of omeprazole daily for ulcer healing, the patients were assigned to one of four 16-week maintenance treatment groups as follows: group A received 15 mL of an antacid suspension 4 times daily; group B received 300 mg of colloidal bismuth subcitrate 4 times daily; group C received 20 mg of famotidine twice daily; and group D, the control group, received placebo twice daily. Follow-up included an urea breath test labeled with carbon 13, biopsy-based tests, and repeated endoscopic examination. RESULTS: An analysis of variance revealed no difference in mean age and mean follow-up time among the groups. During a mean follow-up of 56 months, there was no peptic ulcer recurrence among the 3 treatment groups, and all of the patients remained free of H pylori infection during the study period. CONCLUSIONS: In patients with bleeding peptic ulcers, antiulcer maintenance treatment was not necessary to prevent ulcer recurrence after successful H pylori eradication and ulcer healing. In addition, the 1-week proton pump inhibitor-based triple therapy had the efficacy to ensure long-term eradication of H pylori in a region of high prevalence.     

Comparison of the effects of intravenous infusion of omeprazole and H2‐receptor antagonists on intragastric pH in bleeding duodenal ulcer patients

OBJECTIVE : To evaluate the effects of intravenous infusion of omeprazole and H₂‐receptor antagonists on 24‐h intragastric pH levels in patients with bleeding duodenal ulcers. METHODS : Fifty patients with active bleeding duodenal ulcers were randomly assigned to receive one of four treatment regimens: 40 mg omeprazole by intravenous infusion every 12 h, 40 mg famotidine intravenously every 12 h, 50 mg ranitidine intravenously every 6 h, 200 mg cimetidine intravenously every 6 h. Intragastric pH values were monitored in each subject at the baseline level and continuously for 24 h after treatment. RESULTS : Only the omeprazole group produced mean and median intragastric pH values of above 6. The famotidine group had mean and median intragastric pH values above 4. In the other two groups, pH values were both below 4. The mean percentages of time that intragastric pH levels were < 4, < 5 and < 6 over the 24 h period in each of the treatment groups were found to increase in the following order (smallest percentage to largest percentage): omeprazole, famotidine, ranitidine and cimetidine. CONCLUSIONS : The effect of intravenous use of omeprazole in active duodenal ulcer bleeding is superior to that of H₂‐receptor antagonists and the increase in intragastric pH is maintained for a longer period.