Evolving perspectives on parenteral H2-receptor antagonist therapy.
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Gastric Mucosa↗
Biomedical subjects
J W Freston
Publications and source records attributed to J W Freston.
H2-receptor antagonists and duodenal ulcer recurrence: analysis of efficacy and commentary on safety, costs, and patient selection.
Maintenance treatment to prevent duodenal ulcer recurrence has been studied in more than 100 trials. These trials, together with reports of long-term safety of maintenance therapy, risk factors of ulcer recurrence, and economic implications of different strategies of long-term ulcer management have been analyzed. Recurrence rates with the FDA-approved drugs for maintenance therapy, cimetidine, ranitidine, and famotidine are comparable when compared as "weighted" or "unweighted" means. H2-blockers reduce the annual recurrence from nearly 70% to about 25%. The duration of maintenance treatment is uncertain, but probably should not be less than 1 yr. Cimetidine maintenance for up to 5 yr has not disclosed new side effects, and the rate of reactions decreases after the first yr. Maintenance is economically superior to intermittent treatment or surgery in the ulcer population, but long-term management should be individualized according to risk factors for recurrence.
Cimetidine↗
The effect of oral potassium chloride on upper gastrointestinal mucosa in healthy subjects: healing of lesions despite continuing treatment.
The effects of two dosage forms of wax-polymer matrix potassium chloride on the upper gastrointestinal mucosa were compared with placebo in 44 healthy volunteers. After 2 weeks of potassium chloride treatment, mucosal toxicity was observed. There was no correlation between the presence of lesions and symptoms. Six of seven volunteers with lesions healed spontaneously despite continuing treatment with potassium chloride.
Administration, Oral↗
Dose-ranging in clinical trials: rationale and proposed use with placebo or positive controls.
Drugs are currently released for general use without substantial knowledge of their minimum and maximum effective dose and their dose-related side effects. There are several plausible explanations for this situation, but in some cases this has resulted in patients receiving larger than necessary or smaller than effective doses and experiencing adverse reactions. A concurrent problem with drug evaluation is the rising concern with the use of placebo controls and the growing pressure to utilize positive-control studies. Such studies have many problems, however, some of which are subtle but nonetheless counterproductive in terms of proving efficacy through rigorous scientific investigation. The use of dose-ranging in clinical trials provides more information regarding a drug's TI and can circumvent some of the problems of placebo- and positive-controlled studies. Thus, such dose-ranging studies should be a feature of the development of most new drugs.
Animals↗
Chronic abdominal pain. Functional or organic?
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Abdomen↗
Membrane damage and the pathogenesis of cardiomyopathies.
Membrane damage plays an important role in the pathogenesis of ischemic damage to the myocardium, and is ultimately responsible for the release of cellular contents-notably intracellular enzymes-after ischemic cell death. This membrane damage may be caused by the incorporation of lipids into myocardial membranes, by the enzymatic actions of lipases that hydrolyze membrane phospholipids, and by free radicals that are produced in the ischemic myocardium. Much less is known of the role of membrane damage in the cardiomyopathies, but direct myocardial membrane damage may occur in some specific forms of this diverse class of diseases. Direct membrane effects of exogenous substances are likely to be of pathogenic significance in alcoholic and some toxic cardiomyopathies, for example those produced by hydrocarbons and adriamycin. Membrane damage may also play a role in the pathogenesis of viral cardiomyopathies, due possibly to incorporation of viral components into the cardiac sarcolemma where these foreign materials can serve as antigens that direct host responses to attack the cells of the heart.
Autoimmune Diseases↗
Upper gastrointestinal polyps in Gardner's syndrome.
Upper gastrointestinal polyps have been considered an uncommon finding in patients with Gardner's syndrome and familial polyposis coli. Investigators from Japan, however, have recently reported finding gastric and duodenal polyps in a high percentage of Japanese patients with these conditions. We endoscopically examined 11 affected members of the originally described Gardner's syndrome kindred to determine if upper gastrointestinal polyps also occurred in patients with Gardner's syndrome living in the United States. Six of the patients were found to have numerous small polyps of the gastric fundus and body. Polyp histology in 5 of the 6 patients was consistent with fundic gland hyperplasia. Biopsy specimens from the remaining patient demonstrated normal mucosa only. Another patient with no fundic polyps had a single antral polyp that was an adenoma. Eight patients exhibited small polyps of the duodenum. Biopsy specimens were obtained in 7 of the 8. All polyps biopsied were adenomas. The terminal ileum was examined by endoscopy in 9 of the 11 study patients. All 9 had ileal polyps, but the polyps were adenomas in 6 patients and lymphoid aggregates in 3 patients. The results indicate that upper gastrointestinal polyps are a common pleiotropic manifestation of the genetic defect responsible for Gardner's syndrome.
Adenoma↗
Cimetidine. I. Developments, pharmacology, and efficacy.
Cimetidine therapy has proved to be effective in healing most duodenal ulcers and in reducing the frequency of reulceration. It is unclear if low-dose maintenance therapy is superior to intermittent full-dose therapy in managing patients whose ulcers recur. Cimetidine is the preferred treatment for patients with the Zollinger-Ellison syndrome, and current evidence indicates efficacy in healing benign gastric ulcers. Some patients with reflux esophagitis improve with cimetidine treatment, but the drug cannot be regarded as first-time therapy. Largely circumstantial evidence suggests a role in preventing bleeding from acute gastric erosions and in preventing the acid aspiration syndrome. Cimetidine therapy has not been found to be useful in controlling acute upper gastrointestinal hemorrhage, acute pancreatitis, or several other conditions for which H2 blockade has been advocated.
Chemical Phenomena↗
Cimetidine: II. Adverse reactions and patterns of use.
Numerous adverse reactions have been attributed to cimetidine, which is understandable in view of the attention and scrutiny the drug has received, its widespread use, and its systemic effects. The reported frequency of side effects has differed considerably but is surprisingly low in all studies. The drug has caused an array of central nervous system disturbances, gynecomastia, and, rarely, hepatotoxicity, interstitial nephritis, bradycardia, hypotension, and even cardiac arrest. The last complication has occurred with rapid-bolus intravenous injection. Blood dyscrasias have also been rare and usually associated with serious underlying disease or multiple drugs, making it difficult to establish cause and effect in most cases. The drug is used widely to treatment conditions for which it is not approved. Some of these conditions are now believed to respond to cimetidine (gastric ulcer); others are known not to respond (acute upper gastrointestinal bleeding and acute pancreatitis).
Cardiovascular Diseases↗
Transport of organic anions into liver cells and bile.
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Aminohippuric Acids↗
Gastrointestinal Polyposis: Syndromes and Genetic Mechanisms.
Adenomas and hamartomas, two genetically transmitted histologic types of gastrointestinal polyposis, are associated in syndromes with extragastrointestinal manifestations. Adenomas that predispose to adenocarcinoma are basic to familial polyposis coli, the Gardner syndrome and the Turcot syndrome. Gastrointestinal polyps and extragastrointestinal lesions serve as a warning, providing time for diagnosis and treatment of adenomas to prevent their malignant transformation in patients and their relatives. Hamartomas with no malignancy potential, but having a tendency toward bleeding and bowel obstruction, are associated with the Peutz-Jeghers syndrome, juvenile polyposis, multiple hamartoma syndrome, basal-cell nevus syndrome and the Cronkhite-Canada syndrome. Most of these lesions and syndromes follow the inheritance pattern of a single autosomal dominant gene.
Adenoma↗
Cimetidine and granulocytopenia.
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Agranulocytosis↗
Antidiarrhoeal agents and laxatives: changing concepts.
Recognition that altered intestinal electrolyte transport (decreased absorption and/or increased secretion) is a primary factor in many types of diarrhoea is shaping the search for new types of antidiarrhoeal agents; it also supports continuing interest in the time-honoured but still largely unproved adsorbents. Recognition that altered intestinal electrolyte transport is also a primary effect of certain of the laxatives is of less immediate practical significance, because of the appropriate emphasis on dietary fibre and other nonpharmacological measures for prevention and correction of functional constipation. However, interest in the laxatives and their mechanisms of action will probably be directed to unanswered problems in bowel motility and the pathogenesis of constipation, which could subsequently modify use of the laxatives.
Adsorption↗
Malignant transformation of esophageal columnar epithelium.
This report describes two patients with esophageal columnar epithelium (Barrett's esophagus) in which microinvasive adenocarcinoma developed. Case 1 had multiple foci of carcinoma in situ contiguous with epithelium resembling gastric and intestinal mucosa. Case 2 had signet-ring type adenocarcinoma. Surveillance for malignant transformation in columnar esophageal epithelium should be routinely performed, and because of its focal nature, multiple biopsies and cytologic examination should be carried out. The presence of carcinoma in situ should lead to consideration of excision of the affected esophagus.
Adenocarcinoma↗
Effect of nighttime anisotropine methyl bromide of duodenal ulcer healing and pain: a double-blind controlled trial.
Anisotropine methyl bromide, an anticholinergic, 80 mg given orally at 8 P.M., suppresses gastric acid secretion through the night without significant side effects. Thirty patients with endoscopy-proved symptomatic duodenal ulcer disease completed a randomized, double-blind, placebo-controlled trial of nighttime anisotropine methyl bromide therapy. Eleven (69 per cent) of 16 anisotropine methyl bromide-treated and six (43 per cent) of 14 placebo-treated subjects healed their ulcers within two weeks of starting treatment. The anisotropine methyl bromide-treated subjects averaged 0.63 +/- 0.27 (mean +/- S.E.) episodes of nocturnal pain during the treatment period versus 2.71 +/- 1.08 episodes in the placebo group (P = 0.06). This is the first reported study of this type designed to evaluate the efficacy of an anticholinergic agent in the healing of duodenal ulcers. Although not conclusive, the results suggest nighttime anisotropine methyl bromide therapy may be useful in the treatment of duodenal ulcer disease. Further studies seem warranted.
Adult↗
Cimetidine, antacid, and hospitalization in the treatment of benign gastric ulcer: a multicenter double blind study.
Two hundred forty patients with benign gastric ulcer were treated in a controlled clinical trial to assess the effect on healing of cimetidine, antacids, and hospitalization. Inpatients and and outpatients were randomly assigned to one of three treatments: cimetidine plus antacid, cimetidine plus dummy antacid, or placebo tablet plus antacid. In 206 patients who met criteria for analysis, ulcer healing as shown by endoscopy occurred by 12 days in 11 to 26 percent and by 42 days in 58 to 76 percent. There were no significant differences in healing between hospitalized and nonhospitalized patients or between treatment subgroups. Symptomatic response was equivalent in all groups. The median antacid consumption was 328 mEq of in vitro buffering capacity per day. Patients taking antacids experienced significant diarrhea compared with those taking no antacid. This investigation suggests that the effect of cimetidine is equivalent to that of large amounts of antacid, but because a true placebo group was not studied it is not possible to conclude from this study alone whether either agent influenced healing. In contrast to widespread belief, initiation of treatment in the hospital did not enhance healing, but because patients were not randomly assigned to inpatient and outpatient status no final conclusion about the effect of hospitalization on healing can be drawn.
Adult↗
Cimetidine in the treatment of gastric ulcer: review and commentary.
Cimetidine therapy in gastric ulcer disease has been evaluated in four complete and one incomplete controlled, double blind trials. A sixth trial, still under way, is partially blind. Treatment duration ranged from 2 to 6 weeks; doses ranged from 0.8 to 1.2 g daily. Two studies also evaluated the influence of hospitalization on ulcer healing and symptoms. Relatively large doses of antacid taken with cimetidine confounded the evaluation of cimetidine efficacy in two of the trials, without answering the question of antacid efficacy. Cimetidine was more effective than were small doses of antacid in healing ulcers in one study but was not significantly superior to treatment with larger quantities of antacid in two other trials. Preliminary results indicate that cimetidine is more effective than carbenoxolone in healing ulcers. Hospitalization for 2 and 3 weeks conferred no advantage, but patients were not randomly assigned to hospitalization. Definitive studies on whether cessation of cimetidine therapy is followed by accelerated ulcer recurrence have not been reported. The efficacy of chronic or intermittent cimetidine therapy has not been studied in gastric ulcer disease.
Antacids↗
A double-blind evaluation of the nocturnal antisecretory effects of anisotropine methylbromide in man. Dose response and duration of action studies.
The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without significantly influencing heart rate, blood pressure, visual acuity, or visual accommodation. The duration of action of large doses was then evaluated in fasted and nonfasted subjects. A single dose reduced acid secretion for up to 8 hours, eliminating the nocturnal elevation of acid secretion characteristic of the normal circadian pattern. Near visual acuity and accommodation decreased, an effect more pronounced in fasted subjects, but the magnitude of visual impairment was small. These findings provide the basis for a controlled trial of high-dose nighttime therapy in peptic ulcer disease.
Adult↗