metiamide and Zollinger-Ellison-Syndrome

Topics: Burimamide; Chemical Phenomena; Chemistry; Cimetidine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Acid; Gastrins; Gastrointestinal Hemorrhage; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Hypersensitivity; Intrinsic Factor; Kinetics; Malabsorption Syndromes; Metiamide; Pancreas; Pepsin A; Ranitidine; Receptors, Histamine H2; Stomach Ulcer; Stress, Psychological; Zollinger-Ellison Syndrome

The uses of the histamine H2 receptor antagonists (H2 antagonists) in the management of peptic ulcer disease and the Zollinger-Ellison syndrome are reviewed. Drugs included in the discussion are burimamide, metiamide and cimetidine. The secretion and the pharmacology of the H2 antagonists are described. A discussion of the clinical use of the H2 receptor antagonists in the treatment of gastric hyperacidity and hypersecretory states, and the side effects encountered is presented. Cimetidine is effective in the treatment of duodenal ulcer, and its use appears promising in Zollinger-Ellison syndrome and gastric ulceration.

Topics: Cimetidine; Gastric Juice; Histamine H2 Antagonists; Humans; Metiamide; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Burimamide; Cimetidine; Creatinine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Juice; Gastritis; Guanidines; Humans; Metiamide; Peptic Ulcer; Receptors, Histamine; Transaminases; Zollinger-Ellison Syndrome

Several new compounds have become available recently which are potent inhibitors of gastric secretion. The therapeutic potential of these inhibitors in the peptic ulcer diathesis is reviewed and it is concluded that the histamine H2-receptor antagonists show most promise at present. The prostaglandins and gastro-intestinal polypeptides are of considerable physiological interest but are unlikely to have clinical importance in the immediate future.

Topics: Animals; Epidermal Growth Factor; Gastric Juice; Gastric Mucosa; Gastrointestinal Hormones; Guanidines; Histamine H2 Antagonists; Humans; Imidazoles; Metiamide; Peptic Ulcer; Prostaglandin Antagonists; Prostaglandins A; Prostaglandins E; Secretin; Somatostatin; Zollinger-Ellison Syndrome

H2-Histamine receptor blocking agents metiamide and cimetidine were assessed in seven patients with Zollinger-Ellison syndrome (serum gastrin greater than 300 microgram/ml, basal acid output greater than 15 meq/h, ratio of basal acid output to maximal acid output greater than 0.5). Intravenous or oral administration of the drugs lowered acid secretion by at least 70% in all cases. Subsequent treatment of six patients for 3 to 15 months (oral therapy) and one patient for 1 month (intravenous therapy) showed that the drugs abolished symptoms in all seven, abolished diarrhea in five, allowed ulcer healing in six, and were well tolerated without adverse effects in seven. No patient failed to respond to the drug, although one died from tumor progression and two required total gastrectomy for complex reasons. The results indicate that patients with Zollinger-Ellison syndrome can be managed medically and, in light of current mortality trends, gain little from the extra risks attending total gastrectomy.

Topics: Adult; Aged; Chlorides; Cimetidine; Clinical Trials as Topic; Female; Gastric Juice; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Metiamide; Middle Aged; Placebos; Potassium; Sodium Chloride; Zollinger-Ellison Syndrome

The histamine H2-receptor antagonist metiamide is an inhibitor of endogenous and stimulated gastric-acid secretion. It appears to have therapeutic possibilities in duodenal-ulcer disease. Three patients exhibiting the Zollinger-Ellison syndrome have been treated with this drug for six months or more. Rapid symptomatic improvement occurred in each case, followed by ulcer healing. There were also reductions in gastric secretion and consistent changes in the fasting serum-gastrin concentration. On patient relapsed temporarily during therapy. There have been no side effects. It is concluded that, in the short term, metiamide is of benefit in the Zollinger-Ellison syndrome.

Topics: Adult; Clinical Trials as Topic; Drug Evaluation; Female; Gastric Juice; Gastrins; Humans; Male; Metiamide; Middle Aged; Remission, Spontaneous; Thiourea; Zollinger-Ellison Syndrome

Topics: Cimetidine; Histamine H2 Antagonists; Humans; Metiamide; Ranitidine; Zollinger-Ellison Syndrome

Review of a 5 year clinical experience with the histamine H2-receptor antagonists metiamide, cimetidine, and ranitidine in 20 patients with Zollinger-Ellison syndrome disclosed a treatment failure rate of 50 percent. The criterion for failure was hemorrhage in four patients, obstruction followed by hemorrhage in one patient, perforation in one, and intractable pain in four. Nine of the 10 patients in whom treatment failed required total gastrectomy for control of complications; the 10th patient refused operation. Retrospective analysis identified hepatic metastases, the multiple endocrine adenomatosis-type I syndrome, refractory diarrhea, and breaks in the medication schedule as being more common in the treatment failure group, but these trends were not statistically significant in our small series of patients. Nonhealing or recurrent ulcers were found in 90 percent of the patients in whom drug therapy failed and in only 10 percent of those patients in whom therapy was successful (p less than 0.01). There were no differences related to age, sex, duration of symptoms, previous gastric operation, ulcer location, presence of diarrhea, or amount of drug prescribed. Basal and peak acid outputs, basal serum gastrin levels, and response to secretin challenge were also nondiscriminatory. The degree of acid inhibition in response to cimetidine was highly variable from one patient to another and on repeat testing in individual patients, and there was no correlation between acid secretory inhibition and clinical course. When severe complications occurred, reinstituting H2-receptor antagonist therapy or increasing the dose did not avert the need for total gastrectomy. Patients refractory to drug treatment who have persistent or recurrent ulcers should be managed with prompt total gastrectomy to prevent life-threatening complications.

Topics: Adult; Aged; Cimetidine; Female; Furans; Gastric Acidity Determination; Histamine H2 Antagonists; Humans; Male; Metiamide; Middle Aged; Ranitidine; Recurrence; Retrospective Studies; Risk; Zollinger-Ellison Syndrome

Topics: Adult; Dose-Response Relationship, Drug; Histamine H2 Antagonists; Humans; Male; Metiamide; Middle Aged; Thiourea; Zollinger-Ellison Syndrome

Continuous treatment of three Zollinger-Ellison patients with histamine H2-receptor antagonists for 14, 26 and 31 months resulted in effective relief of complaints and marked reduction in gastric acid secretion. In one of the patients the dose of cimetidine had to be doubled after 15 months of treatment because of a rise in basal gastric acid secretion accompanied by recurrent diarrhea. Fasting and secretin-stimulated serum gastrin levels were not affected by long-term treatment with histamine H2-receptor antagonists. No side-effects were observed in the three patients on long-term treatment.

Topics: Adult; Cimetidine; Depression, Chemical; Drug Evaluation; Female; Gastric Juice; Gastric Mucosa; Guanidines; Humans; Male; Metiamide; Thiourea; Time Factors; Zollinger-Ellison Syndrome

Histamine H2-receptor antagonists (Burimamide, Metiamide and Cimetidine as the most recent generation) may drastically inhibit gastric acid secretion stimulated by histamine, pentagastrin, insulin, 2-deoxyglucose or an intragastrically instilled meal, respectively. This inhibitory action may explain the beneficial effects of H2-antagonists in the treatment of active peptic ulceration. On Cimetidine administered at a usual dosage over a 4--6 week period, serious side-effects must not be expected. At present studies aim to establish a Cimetidine dosage which, on long-term treatment, may reduce ulcer recurrency.

Topics: Burimamide; Duodenal Ulcer; Gastric Juice; Histamine H2 Antagonists; Humans; Mallory-Weiss Syndrome; Metiamide; Peptic Ulcer; Peptic Ulcer Hemorrhage; Zollinger-Ellison Syndrome

Histamine H2-receptor antagonists metiamide and cimetidine were used in the treatment of severe peptic ulceration in Zollinger-Ellison syndrome. The ulcerations were completely healed in all four patients after treatment lasting from six weeks to four-and-a-half-months. Two patients developed recurrent ulcer after the treatment had stopped, but responded to a second course. One patient developed hepatitis B during cimetidine treatment and it is possible that the course of the hepatitis was unfavourable affected by cimetidine. But no other side effects were noted nor was there a significant change in basal serum-gastrin concentration or an increase in H+ secretion. Total gastrectomy remains the treatment of choice in Zollinger-Ellison syndrome, but cimetidine should be considered if the patient refuses operation or operation is not feasible because of a poor general state.

Topics: Adult; Cimetidine; Female; Gastrins; Hepatitis B; Histamine H2 Antagonists; Humans; Male; Metiamide; Peptic Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Adult; Cimetidine; Female; Gastric Juice; Gastrins; Guanidines; Humans; Male; Metiamide; Thiourea; Zollinger-Ellison Syndrome

Gastric emptying and secretion, as well as intragastric volume and composition, were determined simultaneously in three patients with Zollinger-Ellison syndrome and in seven normal subjects. Gastric hypersecretion was observed in patients with Zollinger-Ellison syndrome and in normal subjects receiving pentagastrin. In contrast, the fraction of gastric contents emptied per minute (fractional rate of emptying) was increased in Zollinger-Ellison patients and unchanged or decreased in normal subjects receiving pentagastrin. The increased fractional rate of gastric emptying in patients with Zollinger-Ellison syndrome persisted despite abolition of gastric hypersecretion by metiamide. Thus, the increased fractional gastric emptying seen in patients with Zollinger-Ellison syndrome is not attributable to hypergastrinemia, or to gastric hypersecretion per se. Instead, it appears to be caused by an undefined nervous or humoral factor.

Topics: Adult; Female; Gastric Juice; Gastric Mucosa; Humans; Male; Mathematics; Methods; Metiamide; Middle Aged; Pentagastrin; Stomach; Water; Zollinger-Ellison Syndrome

Five patients with Zollinger-Ellison syndrome received metiamide per os in doses ranging from 600 to 1,200 mg/day for a minimum period of 2 weeks. Drug produced an inhibition of basal gastric acid secretion ranging from 5 to 100% with relief of symptoms. Survey of patients during and after metiamide course showed sometimes a prolonged antisecretory effect up to 26 days after the end of treatment or, on the contrary, a reduced drug activity in spite of increasing doses.

Topics: Adult; Dose-Response Relationship, Drug; Female; Gastric Juice; Gastrins; Humans; Male; Metiamide; Middle Aged; Secretory Rate; Thiourea; Time Factors; Zollinger-Ellison Syndrome

Inhibition of acid secretion by an H2-receptor antagonist (metiamide) was assessed in three patients with the Zollinger-Ellison syndrome. Metiamide (200 or 300 mg) inhibited acid secretion transiently (2 1/2 hours) by 85 to 100 per cent in all patients. Although anticholinergic drugs alone inhibited acid secretion by only 0 to 35 per cent in these patients, the combination of metiamide and anticholinergic markedly prolonged the inhibitory effect of metiamide. Total gastrectomy was refused by one patient, and was impossible in another; both were treated with metiamide and anticholinergic for five and 10 months. A third patient was treated with metiamide and anticholinergic for three weeks in preparation for total gastrectomy. Ulcer pain and diarrhea disappeared, and each gained weight. H2-receptor antagonists may be useful in the treatment of some patients with the Zollinger-Ellison syndrome.

Topics: Adult; Drug Evaluation; Drug Therapy, Combination; Female; Glycopyrrolate; Histamine H1 Antagonists; Humans; Male; Metiamide; Propantheline; Receptors, Drug; Thiourea; Time Factors; Zollinger-Ellison Syndrome

Topics: Antibody Formation; Guanidines; Histamine H1 Antagonists; Humans; Imidazoles; Metiamide; T-Lymphocytes; Thiourea; Zollinger-Ellison Syndrome

Histamine H2-receptor antagonists, including burimamide, metiamide and cimetidine, are effective antagonists of histamine-stimulated acid secretion from mammalian, avian or reptilian gastric mucosa. Acid secretion stimulated by gastrin or pentagastrin is also inhibited by these drugs, but there is disagreement about the effects of these drugs on acid secretion resulting from activation of acetylcholine receptors. Based on the pharmacological evidence possibilities of treatment by these drugs were discussed in cases with excessive stimulation of acid secretion due to high blood levels of histamine or gastrin. The positive results in several trials on Zollinger-Ellison syndrome and peptic ulcer were very impressive. Some practical problems have still to be solved, for example the appropriate phase for applying the drugs. The demonstrated clinical effectiveness, however, against peptic ulceration offers a clear alternative to surgery for many patients.

Topics: Burimamide; Gastric Juice; Gastrins; Guanidines; Histamine H2 Antagonists; Humans; Imidazoles; Metiamide; Parasympatholytics; Peptic Ulcer; Zollinger-Ellison Syndrome

A new group of drugs, the histamine2 (H2)-receptor antagonists, act on receptors in the stomach to reduce acid secretion when this is stimulated by histamine, pentagastrin, the vagus nerve or food. The reduction in acid secretion is profound and may approach the degree of reduction brought about by gastric surgery. The H2-receptor antagonist metiamide, administered orally, has been used successfully in the treatment of duodenal ulcer and the Zollinger-Ellison syndrome, but it has been shown to cause agranulocytosis. Trials are in process with an analogue, cimetidine (Tagamet, SKF), which has a different chemical structure from metiamide and has not caused haematological changes in animals or man. These drugs offer the prospect of successful medical management of duodenal ulcer, while a study of their effects on H2-receptors elsewhere in the body may reveal other therapeutic benefits.

Topics: Depression, Chemical; Duodenal Ulcer; Gastric Juice; Histamine H1 Antagonists; Humans; Intestinal Absorption; Metiamide; Neutropenia; Receptors, Histamine; Zollinger-Ellison Syndrome

The relationship between the serum gastrin and calcium concentrations has been examined in patients with multiple endocrine neoplasia type I. Variations in gastrin concentrations were induced by metiamide and secretin; calcium concentrations were altered by parathyroidectomy and by calcium infusion. Changes in the serum gastrin concentrations were not accompanied by changes in the serum calcium concentration. However, alteration of the serum calcium was accompanied by significant parallel changes in the serum gastrin. It is concluded that acute changes in the serum calcium may induce changes in the serum gastrin. Parathyroidectomy in these patients produced a fall in the serum gastrin, but the ability to produce large quantities of gastrin remains. It is postulated that the thyro-parathyroid hormones may modulate the relationship between calcium and gastrin.

Topics: Adult; Aged; Calcium; Female; Gastrins; Humans; Male; Metiamide; Middle Aged; Multiple Endocrine Neoplasia; Neoplasms, Multiple Primary; Parathyroid Neoplasms; Secretin; Zollinger-Ellison Syndrome

Two cases of Zollinger-Ellison syndrome are reported in which metiamide produced marked reduction in gastric acid secretion and control of symptoms, so that elective gastrectomy was performed without mortality or morbidity.

Topics: Depression, Chemical; Female; Gastric Juice; Humans; Metiamide; Middle Aged; Preoperative Care; Thiourea; Zollinger-Ellison Syndrome

Topics: Adult; Female; Guanidines; Humans; Imidazoles; Male; Metiamide; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Histamine; Humans; Male; Metiamide; Receptors, Drug; Thiourea; Zollinger-Ellison Syndrome

Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations.

Topics: Adult; Delayed-Action Preparations; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H1 Antagonists; Humans; Male; Metiamide; Middle Aged; Receptors, Drug; Secretin; Secretory Rate; Thiourea; Zollinger-Ellison Syndrome

Topics: Administration, Oral; Adult; Depression, Chemical; Gastric Acidity Determination; Gastric Juice; Humans; Male; Metiamide; Propantheline; Thiourea; Zollinger-Ellison Syndrome