1例胃十二指肠溃疡患者的用药分析

胃溃疡与十二指肠溃疡是消化系统最常见的疾病.结合患者的病史和临床表现,正确选择药物是治疗的关键.临床药师在药物疗效、药物相互作用以及药物不良反应的认识方面具有自身的优势.本文通过报道临床药师参与1例胃十二指肠溃疡患者的诊疗过程,反映临床药师在合理用药及为患者提供药学服务方面发挥了重要作用.     

十二指肠溃疡与胃排空的研究进展

近年来质子泵抑制剂和H2受体拮抗剂等药物的使用提高了溃疡病的治愈率，但临床上有相当一部分十二指肠溃疡(DU)患者出现早饱、暖气等胃排空障碍征象，用上述药物不能缓解，常影响溃疡愈合。传统观点认为DU多伴有胃排空增加，但近年来国内外学者提出了不同的观点。现就近年来的进展综述如下。     

Maintenance of gastric pH above 6 with intravenous famotidine in patients with a bleeding duodenal ulcer

Background: The secondary prevention of bleeding from ulcers may be improved if antisecretory drugs are able to maintain a 24-h gastric pH close to neutral. Aim: To evaluate the effect of intravenous famotidine at a conventional dose of 40 mg/day on 24-h intragastric pH in patients with a bleeding duodenal ulcer, and to determine the dose required to maintain gastric pH > 6 by use of a Gastrojet (MIC, Switzerland) device (a pH meter-controlled programmable pump). Methods: Twelve patients (nine men, three women), aged 24–78 years, admitted for a bleeding duodenal ulcer, were studied after active bleeding had stopped for at least 6 h. Gastric pH was recorded for two consecutive 24-h periods, each starting at 16.00 hours. The patients were fasted during these periods and received an infusion of 2.5 L of isotonic glucose. They were given famotidine, as a continuous i.v. infusion of 40 mg during one period, and at a rate determined by the Gastrojet during the other period (in a random sequence), with the aim of maintaining the gastric pH above 6. Results: The 24-h median (interquartile range) pH and the mean (± S.E.M.) percentage of the 24-h period with a gastric pH > 6 were both significantly higher during the Gastrojet period than during the continuous infusion: 6.4 (6.3–6.5) vs. 5.7 (2.7–6.4) (P < 0.01) and 74±5% vs. 44 ± 7% (P < 0.002), respectively. The mean dose of famotidine delivered by the Gastrojet was 172 mg (range: 101–200 mg). The entire available amount of famotidine (200 mg) was delivered in four of the 12 patients. The percentage of time at pH > 6 (mean ± S.E.M.) was significantly higher at night (22.00 to 07.00 hours) than during the rest of the day (88 ± 2 vs. 70 ± 6%; P < 0.005) and the mean quantity of famotidine delivered per hour was significantly lower during the night (6.3 ± 0.8 mg/h vs. 8.4 ± 0.5 mg/h; P < 0.02). Conclusion: We conclude that 40 mg of famotidine delivered as a continuous i.v. infusion is not sufficient to maintain gastric pH > 6 for 24 h in duodenal ulcer patients. Our study with the Gastrojet device shows that it may be possible to achieve this goal by using a much larger dose, preferably delivered during the day.     

Short report: short-term triple therapy for H. pylori-associated duodenal ulcer disease

Thirty consecutive patients with endoscopically proven duodenal ulceration who had Helicobacter pylori infection on culture and histology, were treated with tripotassium dicitrato bismuthate (1 tablet q.d.s., 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. for one week, followed by the bismuth salt for a further 3 weeks. All patients were endoscoped at entry and 4 weeks after cessation of treatment, to check for ulcer healing and H. pylori eradication. Two antral biopsies were taken at each endoscopy for histological and microbiological evidence of H. pylori infection. Complete healing of duodenal ulcers was observed in 27/30 patients (90%). Gastritis improved or completely resolved in 26 patients. Eradication of H. pylori was achieved in 27 patients. Of the three patients who failed to heal, two were H. pylori-positive at follow-up and one was H. pylori-negative.     

The effect of omeprazole on gastric emptying in patients with duodenal ulcer disease.

The effect of a single oral dose of omeprazole (90 mg) on gastric emptying was assessed with a dual isotope scintigraphic technique in eight patients with a history of duodenal ulcer disease. Omeprazole had no significant effect on solid or liquid gastric emptying. The bioavailability (AUC0-2 h) of omeprazole in all patients was greater than that required for total suppression of acid secretion. No adverse clinical or laboratory effects were observed.     

Review article: Helicobacter pylori-negative duodenal ulcer disease

Background  Helicobacter pylori infection rates in duodenal ulcer (DU) patients may be lower than previously estimated.
Aim  To review the real prevalence of H. pylori -negative DUs and its possible causes.
Methods  Bibliographical searches in MEDLINE looking for the terms ' H. pylori ' and 'duodenal ulcer'.
Results  Mean prevalence of H. pylori infection in DU disease, calculated from studies published during the last 10 years including a total of 16 080 patients, was 81%, and this figure was lower (77%) when only the last 5 years were considered. Associations with H. pylori -negative DU were: (1) False negative results of diagnostic methods, (2) NSAID use (21% in studies with <90% infection rate), (3) Complicated DU (bleeding, obstruction, perforation), (4) Smoking, (5) Isolated H. pylori duodenal colonization, (6) Older age, (7) Gastric hypersecretion, (8) Diseases of the duodenal mucosa, (9) Helicobacter ' heilmanii ' infection and (10) Concomitant diseases.
Conclusion  In patients with H. pylori -negative DU disease, one should carefully confirm that the assessment of H. pylori status is reliable. In truly H. pylori -negative patients, the most common single cause of DU is, by far, the use of NSAIDs. Ulcers not associated with H. pylori , NSAIDs or other obvious causes should, for the present, be viewed as 'idiopathic'. True idiopathic DU disease only exceptionally exists.     

幽门螺杆菌感染对胃酸及十二指肠溃疡的影响

为了探讨幽门螺杆菌（HP）感染对胃酸分泌的影响及与十二指肠球部溃疡（DU）的关系,本文对DU患者,HP根治前后的胃液pH,空腹胃酸及氨浓度之间的关系进行了研究。结果表明HP阳性的DU患者其空腹胃酸,氨浓度显著高于正常对照组（P＜0．05）,而根除HP后,空腹胃酸显著下降,接近正常水平（P＞0．05）,氨浓度明显下降,结论：HP感染使DU患者胃酸分泌增多,二者之间的相互作用在DU的发病中占有重要地位。     

Long-term prognosis of duodenal ulcer: follow-up study and survey of doctors' estimates

In 1976 we reviewed a randomly selected cohort of 227 patients with duodenal ulcer first diagnosed in 1963. The cohort comprised cases diagnosed in both hospitals and general practice. Fifty patients had died, 12 had emigrated, and 154 (93%) of the remaining patients were interviewed. Fifty-seven medically treated patients had no symptoms, 44 had mild symptoms, and 19 had more severe symptoms. The remaining 34 patients had been treated surgically. Cases diagnosed in hospital had a more severe prognosis than those diagnosed in general practice. A random sample of 65 general practitioners and 78 medical and surgical gastroenterologists tried to predict the results of this study. The range of the predictions was very wide showing that individual prognostic estimates were highly unreliable. The mean prediction by all doctors differed little from the actual result, suggesting that the collective experience of the medical profession is more reliable. The predictions of general practitioners, physicians, and surgeons showed small systematic differences, presumably reflecting the different types of patients they treat.     

Omeprazole and sucralfate in the treatment of NSAID-induced gastric and duodenal ulcer

Aim:

To establish the healing efficacy of two drugs, omeprazole and sucralfate, when given to patients who had developed gastric or duodenal ulcer while undergoing chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs).

Methods:

Ninety-eight patients with arthritis or arthrosis and NSAID-related gastric or duodenal ulcer were admitted to the endoscopic, single-blind study. They were randomized to receive either omeprazole 20 mg o.m. or sucralfate 2 g b.d. for 4–8 weeks. The patients continued to receive the same NSAID during the trial. Upper gastrointestinal endoscopy was performed at entry and after 4 or 8 weeks.

Results:

Eighty-eight patients completed the 4-week study, but only 81 were available for final analysis at 8 weeks. Omeprazole was significantly superior to sucralfate in inducing gastric ulcer healing after both 4 (87 vs. 52%, P = 0.007) and 8 weeks (100 vs. 82%, P = 0.04). No statistically significant difference in duodenal ulcer healing rates emerged between the two groups either at 4 (79 vs. 55%) or 8 weeks (95 vs. 73%). The healing rates in patients with combined gastric and duodenal ulcer were 67 vs. 33% after 4 weeks and 67 vs. 67% after 8 weeks of treatment. The percentages of asymptomatic patients were similar in the two treatment groups both at 4 (70 vs. 73%) and 8 weeks (70 vs. 75%). H. pylori infection did not influence healing rates, but significantly more H. pylori-positive patients healed with omeprazole.

Conclusions:

The results of this study show that omeprazole is superior to sucralfate in healing NSAID-induced gastroduodenal ulcer in patients who continue to take anti-inflammatory drugs. The good results observed were unrelated to H. pylori status.

     

Furazolidone versus metronidazole in quadruple therapy for eradication of Helicobacter pylori in duodenal ulcer disease

OBJECTIVE: Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking. AIM: A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients. METHODS: Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side-effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test. RESULTS: A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0. 006) in the RABF and RABM groups, respectively. Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0. 04). CONCLUSION: Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.