Comparison of the results of the treatment with pirenzepine combined with cimetidine and sucralfate of stomach ulcer resistant to cimetidine

Increased inhibition of gastric acid release through simultaneous blockade of H2-receptors and muscarine-receptors or administration of gastroprotective agent is theoretically justified in patients with peptic ulcer unresponsive to cimetidine. The study involved 70 patients with peptic ulcer previously treated with cimetidine in daily dose 1000 mg for 6 weeks without an effect. Patients were divided into two groups: group 1 treated with cimetidine plus pirenzepine, and group 2 given sucralfate in daily dose 4.0 g. Pirenzepine to patients of group 1 was given in a single dose of 50 mg before bedtime. Both groups were comparable in age, sex, disease onset, smoking, gastric acid secretion, and ulcer size. Healing was evaluated with endoscopic technique following 2 and weeks of therapy. Ulceration healed up within 2 weeks in 40% of patients treated with cimetidine combined with pirenzepine and in 31.4% patients treated with sucralfate. After 4 weeks, healing of ulceration was 71.4% and 68.6%, respectively. Large ulcers (over 1 cm in diameter) and previous partial gastrectomy did not affect healing rate. The obtained results suggest that administered therapies enable recovery in over 2/3 of patients with peptic ulcer unresponsive to a 6-week therapy with cimetidine alone.     

Therapeutic effect of cimetidine in patients undergoing haemodialysis.

Blood concentrations of cimetidine were measured and the therapeutic effect of the drug assessed patients undergoing maintenance haemodialysis. Thirteen patients were given a single oral 200-mg dose of cimetidine a mean of 2.7 hours before the start of dialysis. Dialysing for 6--12-6 m2 hours led to a mean fall of 71% in blood cimetidine concentration during haemodialysis. Nine patients with various upper gastrointestinal lesions diagnosed endoscopically were treated for up to six weeks with a reduced cimetidine dose of 200 mg 12-hourly; two patients received two courses of treatment. Repeat endoscopy after treatment disclosed satisfactory healing, and the drug did not accumulate. This lower dose regimen is recommended for patients receiving dialysis who develop upper gastrointestinal lesions for which a histamine H2-receptor antagonist is indicated.     

Prophylactic effect of cimetidine in duodenal ulcer disease.

Fifty-seven symptom-free patients with duodenal ulcer entered a double-blind trial to assess the prophylactic effect of cimetidine. Patients were randomly allocated to receive cimetidine 400 mg twice daily (29 patients) or placebo (28 patients). The trial was designed to imitate daily clinical practice, so duodenal ulcer disease was diagnosed by means of x-ray examination. Three patients from each group withdrew from the trial. All remaining patients continued to receive treatment for 12 months or until symptoms recurred. Three out of 26 patients suffered relapses during cimetidine treatment, compared with 20 out of 25 receiving placebo. No side effects were attributable to cimetidine. Long-term cimetidine treatment had no curative effect as relapses occurred soon after treatment was stopped. The estimated chance (cumulative remission rate +/- 2 SE) of remaining symptom-free 13 weeks after one year''s cimetidine treatment had been completed was 47 +/- 21%. Maintenance treatment with cimetidine is a suitable alternative to elective in surgery in patients with duodenal ulcer subjects frequent relapses. Further study is needed to establish the optimal duration and safety of prolonged cimetidine treatment.     

Cost effectiveness of screening for and eradication of Helicobacter pylori in management of dyspeptic patients under 45 years of age.

OBJECTIVE--To assess the cost effectiveness of screening for and eradicating Helicobacter pylori in patients under 45 years of age presenting with dyspepsia. DESIGN--A decision analytic model composed of a decision tree to represent the epidemiology of dyspepsia and a Markov process to model the outcomes of treatment. PATIENTS--Patients under the age of 45 years presenting to their general practitioner with (peptic type) dyspepsia. INTERVENTIONS--Conventional empirical treatment with healing and maintenance doses of cimetidine v eradication treatment solely in patients with confirmed peptic ulcer; and conventional empirical treatment for all dyspeptic patients compared with the use of a serology test to identify patients with H pylori, who then receive endoscopy to investigate the presence of peptic ulcer disease and, when disease is found, are given eradication treatment with a breath test to confirm successful eradication. MAIN OUTCOME MEASURES--Expected cumulative costs over a period of 10 years. The proportion of time patients spend without a recurrent ulcer. RESULTS--After receiving eradication treatment, patients with confirmed ulcer spend an average of 99% of their time free from recurrent ulcer disease compared with 95% after treatment with cimetidine. Eradication treatment costs less than that with cimetidine. When the initial cost of identifying appropriate patients to receive eradication treatment is added to the analysis, however, these cost savings take almost eight years to accrue. CONCLUSIONS--Enthusiasm for introducing testing for and eradication of H pylori for dyspeptic patients in general practice should be tempered by an awareness that cost savings may take many years to realise.     

Controlled comparison of cimetidine and carbenoxolone sodium in gastric ulcer.

Fifty-four outpatients with endoscopically diagnosed benign gastric ulcer were allocated at random to treatment with either cimetidine 800 mg daily for six weeks or carbenoxolone sodium 300 mg daily for one week then 150 mg daily for five weeks. Ulcers were reassessed by endoscopy at the end of the trial. The endoscopist was unaware of the treatment and did not take part in the clinical care of the patients. Twenty-one of the 27 patients (78%) given cimetidine and 14 of the 27 (52%) given carbenoxolone had healed ulcers. Symptomatic response occurred earlier with cimetidine but was not significantly better. Unwanted effects were more common in the carbenoxolone group: 12 patients developed hypokalaemia, four of whom needed oral potassium supplements. The results suggest that histamine H2-receptor blockade is at least as effective as carbenoxolone sodium for benign gastric ulcer and produces fewer side effects.     

Early results of the studies of the effect of cimetidine on selected parameters of humoral and cellular immunity in patients with peptic ulcer

The study aimed at evaluating an early effect of cimetidine on the blood IgG, IgA, IgM, number and functioning of T-cells in peripheral blood of patients with ulcerative disease. The study involved 27 patients (9 women and 8 men), aged between 27 and 70 years (mean 52.6 +/- 10.9 years). Nine of these patients suffered from the peptic ulcer and 8--from duodenal ulcer. Cell-mediated and humoral immunity were evaluated simultaneously in all patients prior to and after a 4-week treatment with cimetidine administered orally in the dose of 200 mg four times daily. Rosette test with theophylline and leukocyte migration test were used to assess cell-mediated immunity. It was found that cimetidine significantly increases blood serum IgG (p less than .01), the number of theophylline-resistant lymphocytes in TRFC-TR (P less than 0.01), and T-cell response to higher mitogen concentrations (PHA and Con-A) (p less than .005 and p less than .001, respectively).     

Cimetidine and ranitidine in duodenal ulcer.

Two histamine H2 antagonists, cimetidine and ranitidine, given in doses of 1 g daily and 200 mg daily to 18 and 20 patients respectively proved equivalent in promoting healing of duodenal ulcer. No adverse effects occurred during the trial, though serum urea and creatinine concentrations tended to rise slightly during treatment with cimetidine but not ranitidine. Choice between the two drugs is likely to be influenced by overall patterns of adverse effects rather than considerations of individual potency.     

Changes of arterial arachidonic acid metabolites in hypertensive patients during haemodialysis

It is well known that in haemodialysis patients suffering from oligoanuria, extracellular hypervolaemia develops and this hypervolaemia is the main reason for hypertension occurring in some of the patients. The absence of vasorelaxation during hypervolaemia may be secondary to an increased activity of vasoconstrictor systems and/or a decreased formation of vasodilator agents like prostaglandin E2(PGE2) and prostaglandin I2(PGI2). In the present study, arterial PGE2 and leukotriene C4(LTC4)-like activities and the effect of fluid removal on these arachidonic acid metabolites during haemodialysis were measured in normotensive and hypertensive patients. Plasma PGE2 and LTC4-like activities were significantly different between hypertensive and normotensive patients. PGE2/LTC4 ratio did not change in normotensive patients while it was increased in hypertensive patients after haemodialysis. These results indicate that haemodialysis alters the synthesis of arachidonic acid metabolites especially in hypertensive patients.     

Proximal gastric vagotomy versus long-term maintenance treatment with cimetidine for chronic duodenal ulcer: a prospective randomised trial.

Forty-four patients with chronic duodenal ulceration were allocated randomly to either long-term maintenance treatment with cimetidine or proximal gastric vagotomy. All were followed up both clinically and endoscopically for periods of one to four years. The rate of recurrence of ulcer during and after medical treatment was 54% while after surgery it was 10%. One patient developed severe allergic hepatitis while receiving maintenance treatment with cimetidine, and two others had to stop treatment because of possible drug reactions. Patients whose ulceration recurs while they are receiving treatment with cimetidine should be offered the possibility of operation.     

Intermittent treatment of duodenal ulcer with cimetidine.

Intermittent treatment with short courses of cimetidine given only when symptoms recurred was assessed in patients with duodenal ulcer as an alternative to maintenance treatment. Their progress was followed up for up to 22 months. Gastroscopy was carried out in most attacks to confirm recurrence of the ulcer and subsequent healing. Out of 125 patients treated, 83 relapsed, of whom 21 defaulted. After retreatment 36 patients relapsed again. The pattern of relapse and remission for the group as a whole was similar after both courses of treatment, indicating an unchanged natural history. Nevertheless, wide variation occurred in individual patients, so that the pattern of relapse could not be predicted by the duration of the initial remission. Most patients had one or two or rarely three symptomatic relapses a year, which were rapidly treated successfully with cimetidine. Therefore, unless the necessity for long-term maintenance treatment is established, intermittent treatment provides an adequate alternative in most patients with duodenal ulcer.     

Cimetidine for recurrent ulcer after vagotomy or gastrectomy: a randomised controlled trial.

In a randomised controlled trial cimetidine 1 g daily for six weeks was compared with placebo in the treatment of recurrent ulcers after gastrectomy or vagotomy for duodenal ulcer. Healing, assessed endoscopically, was seen in seven out of 12 patients given cimetidine and in five out of 12 controls. Four of the controls whose ulcers did not heal were subsequently treated with cimetidine, and in two the ulcers healed after six weeks. Pain recorded by the patient and consumption of alkalis were each slightly but not significantly less in the cimetidine-treated patients. When cimetidine is to be used for recurrent ulceration probably the dosage and duration of treatment should be increased.     

Peptic ulceration,gastric secretion,and renal transplantation.

Fifty-four patients on haemodialysis for chronic renal failure underwent renal transplantation. Basal and maximum acid output and the incidence of peptic ulcer before transplantation were not significantly different from those of controls. But after renal transplantation the incidence of symptoms of peptic ulcer was high (22%) and four out of six patients who developed gastrointestinal bleeding died from this complication. In men peak acid output was significantly increased after renal transplantation and was associated with a 30% incidence of symptoms of peptic ulcer compared with 10% in women, who showed no significant change in mean basal or peak acid output. Peptic ulceration after transplantation was not associated with steroid dosage, hyperparathyroidism, or the height of blood urea concentrations. Given criteria of a history of dyspepsia, abnormal barium meal findings, or gastric hypersecretion, it was not possible to identify patients at risk from peptic ulceration or life-threatening complications after renal transplantation. Thus the routine screening of these patients for peptic ulcer has no practical value, and the incidence of fatal complications is not high enough to justify routine prophylactic anti-ulcer surgery aimed at reducing acid secretion before renal transplantation.     

Comparison of cimetidine 800 mg once daily and 400 mg twice daily in acute duodenal ulceration.

A double blind trial was conducted in seven centres to evaluate the safety and efficacy of cimetidine 800 mg given at night compared with 400 mg given at breakfast and at bedtime. Altogether 197 patients with active duodenal ulcer confirmed by endoscopy entered the study, of whom 187 were eligible for analysis. After four weeks'' treatment the ulcer was healed in 76 of 91 patients (84%) receiving the once daily regimen and in 65 of the 96 patients (68%) receiving the twice daily regimen (p less than 0.05). Both dosage regimens were equally effective in reducing ulcer pain and consumption of antacids. Pain relief was considerable within the first two weeks, and most of the patients were free of symptoms by the end of treatment. No patients were withdrawn because of adverse events as these were few and mild, consistent with the proved safety profile of cimetidine. Cimetidine 800 mg given at night is as effective as 400 mg twice daily; the single dose regimen may improve patient compliance, thus facilitating treatment.     

Effect of vitamin C and zinc on osmotic fragility and lipid peroxidation in zinc-deficient haemodialysis patients

Peroxidation of the membrane lipid structure of red blood cell leads to haemolysis and anaemia in haemodialysis patients. Dietary constituents of antioxidant vitamins and trace elements may play an important role in protecting against oxidant damage. In this study, the effects of supplementation of vitamin C and zinc on osmotic fragility and lipid peroxidation of erythrocytes were investigated in 34 zinc-deficient haemodialysis patients. Sixteen sex- and age-matched normal volunteers acted as controls. Patients were randomized to receive vitamin C (250 mg day(-1)), zinc (20 mg day(-1)) or a placebo treatment for 3 months. The levels of vitamin C, zinc, malondialdehyde (MDA) and osmotic fragility were measured initially and 3 months after supplementation. Mean serum concentration of vitamin C and zinc increased significantly in the groups at the end of the respective study periods. Supplementation with vitamin C and zinc improved osmotic fragility, and decreased the level of MDA in the groups, but some side-effects (i.e. nausea, vomiting, fever, muscle pain, weakness) were observed during the zinc treatment. The results showed that the supplementation of both treatments decreased osmotic fragilty and MDA in zinc-deficient haemodialysis patients. However, vitamin C treatment was found to be safer than zinc supplementation.     

Effect of histamine H2-receptor antagonist therapy on the mutagenic activity of gastric juice

There is concern at present that treatment with histamine H2-receptor antagonists might promote the development of gastric cancer by producing conditions which favour intragastric formation of N-nitroso compounds. If H2-receptor antagonist therapy causes increased intragastric levels of N-nitroso compounds, an issue not yet resolved by analytical studies, corresponding changes in the mutagenic activity of gastric juice might be anticipated. In this study mutagenic activity and pH were measured in fasting gastric aspirate from 18 peptic ulcer patients before and during the final week of therapy with ranitidine (n = 10) or cimetidine (n = 8). Mutagenic activity was assessed using Salmonella typhimurium TA98 and TA100 in a modified pre-incubation "fluctuation" test. No significant change in mutagenic activity was detected after therapy. Of 15 patients found to have significant mutagenic activity in their fasting gastric juice before treatment, 14 remained mutagenic following treatment. Mutation frequencies (sum of positive wells in duplicate 96-well microtitre plates, mean +/- SD) for TA98 and TA100 were respectively, 20 +/- 34 and 100 +/- 64 before compared with 10 +/- 6 and 102 +/- 65 after therapy (p greater than 0.05). Changes in mutagenic activity were similar in both treatment groups and unrelated to duration of therapy, changes in gastric pH or ulcer healing. In vitro, neither cimetidine in aqueous solution, nor gastric juice preincubated with cimetidine showed significant mutagenic activity. These results provide no evidence that increased intragastric levels of genotoxic chemicals, such as N-nitroso compounds, occur during H2-receptor antagonist therapy.     

Is cimetidine being prescribed indiscriminately? An analytic survey of patients who present with symptoms of peptic ulcer disease.

An analytic survey was done to determine the influence of previously documented peptic ulcer disease (PUD) on the frequency of prescribing cimetidine to patients who present at a family medicine centre with symptoms of PUD. It was found that of 293 patients who presented with such symptoms over 1 year cimetidine was prescribed to 57 (19%). From the 236 patients who did not receive cimetidine 57 patients were selected at random for comparison. Information on these two groups of patients was obtained by chart review. The patients who received cimetidine were found to be significantly more likely (p less than 0.001) to have previously documented PUD than those who did not receive cimetidine. In patients in whom subsequent confirmation of PUD was not obtained, either because the results of investigations were negative or because the investigations were not ordered, cimetidine was prescribed to 63% of those who had previously documented PUD, compared with only 6% of those who did not. Of the patients who were investigated 73% of those with previously documented PUD had positive results, compared with 8% of those without previously documented PUD. The positive results were obtained by endoscopic examination in 88% of the patients with previously documented PUD, whereas upper gastrointestinal tract roentgenography was the definitive test in 73% of the patients without previously documented PUD. These findings suggest that previously documented PUD influences both the frequency of prescribing cimetidine and the investigations that are carried out.     

THE ROLE OF ENDOGENOUS ACID IN THE DEVELOPMENT OF ACUTE GASTRIC ULCER INDUCED BY ISCHEMIA-REPERFUSION IN THE RAT

We investigated the role of endogenous gastric acid in the development of gastric ulcer from erosion induced by ischemia-reperfusion of the celiac artery in the rat. A half-hour clamping of the celiac artery (ischemia) caused acute gastric erosions 1 hour after reperfusion and such acute injuries progressed to ulcers 48–72 hours after reperfusion without any necrotizing agents. Gastric acid secretion decreased immediately after ischemia and didn't recover until 12 hours after reperfusion. Intraperitoneal administrations of cimetidine (100 mg/kg, every 12 hours) or omeprazole (30 mg/kg, every 24 hours) were started at 1, 6, or 12 hours after reperfusion. When administrations were started 1 hour after reperfusion, both drugs significantly decreased the total damaged area and prevented the progression of gastric erosions to ulcers. However, administrations started 6 or 12 hours after reperfusion failed to inhibit the total damaged area and to prevent ulcer formation. These results suggest that endogenous gastric acid may play an important role in the progression of gastric erosions to ulcers although ischemia itself reduces acid secretion. Furthermore, treatment with anti-acid-secretory drugs in the early stage of mucosal damage may be important for the prevention of ulcer. © 1997 Elsevier Science Inc.     

Does treatment with cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate?

Cimetidine 1 g daily is often continued for a fixed period beyond the time of healing of duodenal ulcer on the assumption that it might reduce the subsequent relapse rate. To test this, 194 patients whose ulcers had healed after one month of cimetidine 1 g daily were allocated at random to three groups for further treatment with cimetidine 1 g daily for two months (n = 63) or five months (n = 66) or placebo (n = 65). Thereafter all patients received placebo. Endoscopy was done routinely every three months, or earlier if symptoms recurred. During follow-up in the placebo phase, which lasted for up to 25 months, the estimated total proportions of patients in the three groups with symptomatic recurrences of ulcer were 80%, 90%, and 77%, respectively; the corresponding proportions with silent plus symptomatic relapses were 92%, 90%, and 100%. The relapse rates were also similar in all three groups. Statistical analysis showed a significant variation in relapse rate but the differences were regarded as clinically unimportant. These findings show that full-dose cimetidine continued for several months beyond the time of healing of duodenal ulcer dose not decrease the risk of subsequent relapse.     

Cimetidine in patients with gastric ulcer: a multicentre controlled trial.

Forty-five adult outpatients with endoscopically confirmed gastric ulceration completed a double-blind trial of either cimetidine (1 g/day) or placebo. After six weeks 18 of the 23 patients receiving cimetidine showed complete ulcer healing compared with only six of the 22 patients receiving placebo. The cimetidine group also had fewer days with pain than the placebo group but the difference was not statistically significant. Cimetidine therefore seems to promote healing of gastric ulcers without severe side effects, although its effect on pain is less pronounced than in patients with duodenal ulcers.     

Effect of histamine and cimetidine on amino acid meal-stimulated gastrin release at a controlled intragastric pH in healthy human beings

Results of several experiments have suggested that histamine-2 receptors play an inhibitory role in regulating gastrin release. We evaluated this prospectively in healthy human beings by infusing intravenously either histamine (0.33 μg/kg/min) or cimetidine (3.33 mg/min) during a continuous 3-h intragastric infusion of a 3% mixed amino acid meal, a potent stimulus of gastrin release. In order to be certain that effects of histamine or cimetidine on gastrin release were independent of their known effects on gastric acid secretion, intragastric pH was maintained at 5.0 by in vivo intragastric titration with sodium bicarbonate or hydrochloric acid. Although histamine and cimetidine had significant effects on gastric acid secretion, neither significantly affected the rises in serum gastrin concentrations during intragastric amino acid infusion. For example, mean gastrin rises above basal concentrations were 39 ± 9 pg/ml on the control day, 39 ± 9 pg/ml on the histamine day and 44 ± 11 pg/ml on the cimetidine day (P > 0.05). Thus, blockade or stimulation of H₂-receptors at the doses tested had no effect on gastrin release in response to an amino acid meal in humans when intragastric pH was maintained at 5.0.