摘要:

SUMMARYBefore 1977, the treatment of peptic ulcer disease consisted primarily of dietary, antacid, and anticholinergic programmes. There were heated controversies regarding rigidvs.liberal ulcer diets, a variety of antacids and dosing patterns to choose from, and conflicting claims over the benefit of various anticholinergic therapies. It was hoped that the dramatic introduction of the H2‐receptor antagonists would simplify our approach to the treatment of peptic ulcer and reflux oesophagitis. Standard doses of H2‐receptor antagonists are effective for acid/peptic disorders, yet it has become clear that some subsets of patients present special management problems, including recurrent ulcers, non‐steroidal anti‐inflammatory drug (NSAID)‐induced disease, stress ulcers, and refractory oesophagitis. New regimens, such as maintenance therapy and once‐daily nocturnal dosing, have been indicated for peptic ulcer disease. New drugs have been introduced, such as sucralfate, misoprostol, and omeprazole, each with a different mechanism of action. Therefore, while we have learned considerably more about the pathogenesis of peptic disease, treatment decisions have become more complicated.The Transatlantic Conference on Acid/Peptic Disorders was held on 19 21 January 1990, in Wesley Chapel, Florida. A faculty from the United Kingdom, the United States, and Canada reviewed pathophysiology and the role of pharmacologic agents in the treatment of acid/peptic disorders and outlined clinically useful treatment strategies. The conference was organized into five segments: acid suppression and ulcer healing; acid suppression and control of reflux disease; NSAID‐induced ulceration; stress ulceration, rationale for control of rebleeding, and drug interactions; and controversies. The proceedings of the symposium are presented in th

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00743.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThe human stomach has a normal circadian rhythm of intragastric acidity characterized by increasing acidity during the day and peaks in the early hours of the morning. Eating causes a transient decrease of intragastric acidity. Acid appears to be the permissive factor in peptic ulcer disease and to be responsible for symptoms; the patient with duodenal ulcer may secrete too much acid. Pharmacological control of gastric acid secretion will speed ulcer healing. Modern regimens, which typically use a bedtime dose of an H2‐receptor antagonist, produce a pulse of decreased acidity. Intragastric acidity is decreased during the night and early morning, leaving a normal profile of acidity during the day and early evening. Higher or more frequent doses of an antisecretory agent can produce a more profound decrease of 24‐h intragastric acidity. Theoretical problems associated with a sustained or profound decrease of 24‐h intragastric acidity include the threat of enteric infection and infestation, potential bacterial overgrowth with possible N‐nitrosamine formation, and drug‐induced hypergastrinaemia. In light of these potential problems, for the management of simple peptic ulceration, it appears sensible to use the minimum intervention required. Bedtime H2‐receptor blockade is one such regimen. The more potent antisecretory regimens can be used for difficult clinical problems such as the Zollinger–Ellison syndrome, intractable duodenal ulceration, and severe

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00744.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYAlthough in most patients with duodenal ulcer disease the ulcer heals after 8 weeks of treatment with standard doses of H2blockers or other agents, in about 10% the ulcer does not heal. These patients are considered ‘refractory’to treatment. Reasons often cited for non‐healing include poor patient compliance, cigarette smoking, and non‐steroidal anti‐inflammatory drug (NSAID) use. Gastric acid hypersecretion also appears to be an important factor in non‐healing with standard doses of antisecretory agents. We have defined idiopathic gastric acid hypersecretion as a basal acid output of>10 mmol/h in the absence of an elevated fasting serum gastrin level (or a negative secretin test if gastrin level>100 pg/ml) to exclude persons with Zollinger‐Ellison syndrome. Among the acid/peptic‐related disorders in which idiopathic gastric acid hypersecretion should be considered are refractory duodenal ulcer, refractory gastro‐oesophageal reflux disease (especially patients with oesophagitis), postbleeding duodenal ulcer, and certain rare disorders such as hereditary angioedema. Some children with atypical abdominal pain may also be hypersecretors of gastric acid.Once identified, patients with refractory duodenal ulcer or gastrooesophageal reflux disease are treated with incremental doses of ranitidine titrated against the level of gastric acid secretion that remains during therapy. Ranitidine was selected to avoid the dose‐related antiandrogenic effects and potential hepatic cytochrome P450 system‐related drug interactions that may occur with cimetidine. In most cases of refractory duodenal ulcer, doubling the standard dose of ranitidine (to 300 mg b.d.) is sufficient to achieve symptomatic relief and mucosal healing. Higher doses appear to be necessary for refractory oesophagitis. To date, no side effects have been associated with high doses of ranitidine (up to 1800 mg/day) for periods of longer than 6 months. Idiopathic gastric acid hypersecretion is an important factor in explaining why not all patients respond to a ‘standard’ulcer‐healing dose of H2blocker, and it provides a rationale for use of higher‐dose therapy as a safe and effective alternative to omeprazole or to combination drug therapy in r

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00745.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYVirtually all symptoms in patients with Zollinger‐Ellison syndrome are due to acid hypersecretion, thus the control of acid secretion is the first and most important step in the management of patients with this syndrome. Antisecretory medication is prescribed as soon as the diagnosis of Zollinger‐Ellison syndrome is made, as patients may bleed or perforate with little warning. Acid output is reduced to<10 mmol/h to heal mucosal lesions, but in patients with a Billroth I or II gastrectomy and those with severe oesophagitis and stricture formation, acid output is reduced to<5 or<1 mmol/h. Acid output and not symptomatic response is a reliable guide of the adequacy of therapy. In sufficient doses, all H2‐receptor antagonists are useful; however, side effects associated with cimetidine therapy limit its use. The ratio of potencies of cimetidine: ranitidine: famotidine is 1:4:32.Ranitidine given as a 50‐mg intravenous bolus, followed by a continuous infusion of 0.5 mg. kg/h, controls acid hypersecretion acutely in patients with Zollinger‐Ellison syndrome. Acid output is checked after 4 h, and the dose increased until acid output is<10 mmol/h. In 70% of patients with Zollinger‐Ellison syndrome, 1 mg. kg/h reduces acid output to<10 mmol/h; however, doses up to 4 mg. kg/h have been used. When patients are switched to oral ranitidine, a useful dosage conversion is to administer 1.5 times the total daily intravenous dose in four equal doses every 6 h. Four doses of oral drug are given before the infusion is stopped. Six hours after the first/last oral dose, acid output is checked. In our patients, the mean dose of ranitidine was 2100 mg/day (range, 450–9200 mg/day). No serious toxicity was observed.Omeprazole, which has a long duration of action and is a potent inhibitor of gastric acid secretion, has simplified management. Once‐daily dosing is sufficient in most patients, and a reasonable starting dose is 60 mg daily. The dose may be increased to 120 mg once daily; if this dosage fails to control acid secretion, 60 mg is administered every 12 h. In our studies, the median dose was 90 mg/day (range, 20–120 mg/day). Omeprazole was more effective than H2‐receptor antagonists in providing symptom relief and mucosal healing and did not cause significant toxicity. In particular, no gastric carcinoid tumours developed during four years of use. Omeprazole is, therefore, the treatment of choice for control of acid secretion in patients with Zollinger‐Ellison syndrome.Surgery plays a minor role in the control of acid hypersecretion. Parathyroidectomy in patients with Zollinger‐Ellison syndrome as part of multiple endocrine neoplasia type I, or highly selective vagotomy decrease gastric acid output and lower drug requirements but do not cure the patient. Except when resection of gastrinoma is curative, lifelong medical therapy for control of acid secretion in patients with Zollinger‐Ell

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00746.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThe gastric acid inhibitory activities of a peptide‐like gastrin receptor antagonist, Boc‐βAla‐Trp‐Leu‐Asp‐O(CH2)2‐Ph‐4‐F (CH‐486), a non‐peptide gastrin/CCK‐B antagonist (L‐365,260), and a CCK‐A antagonist (L‐364,718), were investigated in the gastric lumen‐perfused anaesthetized rat. A single i.v. injection of CH‐486, 100 μmol/kg, reduced acid secretion stimulated by pentagastrin, 15 μg kg/h, to unstimulated levels, with no recovery within 50 min. Histamine‐, 0.1 μmol kg/min, and carbamylcholine‐, 0.1 mg kg/h, stimulated acid secretion were also reduced to unstimulated levels by CH‐486, 100 μmol/kg, although with these latter two stimulants the inhibition was transient. L‐365,260 and L‐364,718, 10 μmol/kg, significantly inhibited both pentagastrin‐ and histamine‐stimulated acid secretion, the latter again transiently. We conclude that the non‐selective nature of the gastric acid inhibitory activity of gastrin antagonists might allow novel approaches to

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00003.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYPeptic ulcers tend to recur; recurrence may be associated with an increased risk of potentially lethal complications, such as haemorrhage or perforation. Therapy aims to keep ulcers in remission. Currently, the optimal maintenance therapy is long‐term, continuous administration of antisecretory drugs. More than 80% of patients remain in remission during maintenance therapy. Maintenance therapy may be required for the life of the patient, but it is acceptable to patients and is saf

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00747.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThe purpose of this study was to determine whether portal hypertension potentiates intestinal ulceration induced by indomethacin. Portal hypertension was produced in male Sprague‐Dawley rats by two‐staged ligation of the portal vein. Sham‐operated rats were used as controls. The rats were given 20 mg/kg of indomethacin intragastrically, 7 and 14 days, respectively, after complete portal vein ligation. Forty‐eight and 72 h after indomethacin, portal pressures were measured and the whole small intestine removed for quantitative measurement of the percent of the mucosa ulcerated by computerized image analysis. There were no differences in the area of ulceration between the portal hypertensive and sham‐operated rats at either 7 or 14 days, despite the presence of significant portal hypertension. Portal hypertension does not appear to potentiate small intestinal ulceration induced by indomethaci

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00004.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThe safety profile of low‐dose maintenance therapy with H2‐antagonists for duodenal ulcer disease suggests that these agents can be given safely for several years and probably much longer. Because information regarding the use of these compounds for more than 10 years in large numbers of patients is lacking, the safety of these drugs should continue to be monitored. The safety profiles of famotidine and nizatidine will require several additional years of postmarking surveillance data to match the depth of our knowledge regarding cimetidine and ranitidine. Compared to a surgical approach to ulcer disease, continuous H2‐blocker maintenance therapy is cost‐effective and is associated with significantly less morbidity. Patents with a history of bleeding or other ulcer complication should be encouraged to remain on maintenance therapy if they do not undergo surgery. The need for extended maintenance therapy also applies to individuals with frequent symptomatic ulcer relapses, reflux oesophagitis, and a range of less common disorders.Currently, H2‐blockers and sucralfate are the only agents approved by the Food and Drug Administration for maintenance therapy of duodenal ulcer disease. Experience with omeprazole is still limited, and its longterm safety profile must await the completion of controlled trials of maintenance therapy. Given the apparent long‐term safety of the H2‐blockers for maintenance therapy, any new agent must prove to be equally safe in the clinical arena, a task that may be inde

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00748.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYChronic gastro‐oesophageal reflux disease is a common clinical problem. The underlying pathophysiology is considered to be acid injury to the oesophageal mucosa secondary to reflux of gastric contents across an incompetent lower oesophageal sphincter. Evidence suggests that gastrooesophageal reflux disease is primarily a motility disorder, possibly the combined effect of decreased lower oesophageal sphincter pressure, abnormal oesophageal peristalsis, and, perhaps, delayed gastric emptying. The rationale for the use of acid‐suppressing drugs in chronic gastrooesophageal reflux disease is based on control of the known destructive role of acid and pepsin. Recent evidence indicates, however, that standard doses of H2‐receptor blockers are often inadequate to control gastric acid‐induced injury in many patients with chronic reflux. Long‐term maintenance therapy with standard doses of these drugs has proved unsuccessful in approximately 50% of patients. More recent studies show that greater symptom relief and improved healing can be achieved with the use of larger doses of H2‐receptor antagonists. This has been shown particularly with ranitidine at a dosage of 300 mg four

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00749.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

SUMMARYThe effects of 100 mg and 200 mg bedtime doses of cimetidine on nocturnal gastric acid secretion were examined in nine healthy subjects in a double blind, placebo controlled, randomised three way crossover study. Treatment was given at 23.00 hours and the gastric contents continually aspirated from midnight until 07.00 hours the following morning. Hourly aliquots were analysed for pH and acid output. Relative to placebo the 100 mg and 200 mg doses of cimetidine respectively increased mean pH by 2.22 and 2.63 units/h (P<0.001) with mean acid output decreasing by 0.95 and 0.98 mmol/h (P<0.001). Whilst mean pH was higher and mean acid output was lower for 200 mg cimetidine compared to 100 mg cimetidine the difference was not statistically significant. Mean hourly pH was consistently above pH 3 for 100% of the time for both doses of cimetidine whereas mean pH failed to reach this value at anytime on placebo.Low doses of cimetidine taken at bedtime effectively reduced nocturnal gastric acid secretion in healthy individuals.

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1991.tb00006.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY