Anti-ulcer Therapy Research Articles

The use of proprietary medicines by patients presenting with peptic ulcer haemorrhage.

1. Medication, social and symptom histories were compared in patients with severe haemorrhage from a peptic ulcer (n = 71) and matched control subjects. Self-medication with proprietary agents was catalogued in addition to therapy prescribed by general medical practitioners. 2. Prior to the bleed, only 4% of ulcer patients had been free of symptoms normally associated with peptic ulceration, whereas 76% of the control group had been asymptomatic. 3. Gastro-irritant proprietary medicines were used regularly by 23% of ulcer patients compared with only 4% of controls. However, proprietary antacids were used chronically by 46% of ulcer patients compared with only 7% of controls. Bicarbonate was the antacid of choice used by 13% of ulcer patients. The odds ratio for the association between development of bleeding peptic ulcer and the use of indigestion remedies was 11.5% (95% CI 1.1, 121). 4. Fifty-one percent of ulcer patients were prescribed agents known to cause gastro-intestinal damage, whereas only 25% of the control group were prescribed similar agents. Only 7% of the control group were prescribed anti-ulcer therapy compared with 37% of those with bleeding ulcer. 5. A large proportion of patients with haemorrhage from a peptic ulcer had had symptoms sufficient to warrant recourse to self-medication with antacids without medical knowledge. Exacerbation of peptic ulcer by self-medication with proprietary products is likely to be of lesser significance.

The Health Assessment Questionnaire as a predictor of non-steroidal peptic ulceration.

To assess the possibility of a relationship between the degree of physical disability in arthritic patients and non-steroidal peptic ulceration, patients were endoscoped immediately after performing their arthritic functional assessments. The Health Assessment Questionnaire was used and patients were classified into three main groups: I, scoring 0-1; II, 1.1-2; and III, 2.1-3. Ulcers, found in 36 out of 89 patients studied (36/89, 40%), were distributed as follows: 15/22 (68%) in group III compared with 9/28 (32%) in group I (chi 2 = 5.2, P < 0.02), and 12/39 (31%) in group II (chi 2 = 7.24, P < 0.01). Patients with debilitating arthritis appear to have a higher prevalence of non-steroidal peptic ulceration. This finding might be relevant to the process of selecting patients for prophylactic anti-ulcer therapy.

Procyanidin gels based on cellulose and carraghenan derivatives

The formulation of procyanidin gels based on cellulose and carraghenan derivatives was studied. These gels need to have pH values compatible with anti-ulcer therapy, and a satisfactory viscosity. Their consistency was evaluated by measuring their spreading diameter, and by a rheological study. The speading diameter and viscosity of the formulations based on cellulose derivatives were linearly related.

Endoscopy-negative upper gastrointestinal bleeding in a patient with chronic pancreatitis

Dr. C. Me1 Wilcox: A 54-year-old man with a history of alcohol-induced chronic pancreatitis presented to the hospita1 with worsening abdominal pain, hematemesis, melena, and postural symptoms. He was in his usual state of health until 3 months before admission, when he underwent esophagogastroduodenoscopy for an exacerbation of chronic epigastric pain after an unsuccessful empirie trial of antiulcer therapy. Endoscopic findings included mild esophagitis and proximal gastritis. At that time, the hemoglobin was 130 g/L (13 g/dL) and the serum amylase concentration was 2.47 pkat/L (148 U/L) [upper limit of normal, 1.83 pkat/L (110 U/L)]. To further evaluate the abdominal pain, abdominal ultrasonography was performed demonstrating a sonolucent structure in the head of the pancreas measuring 5.1 X 3.8 cm, compatible with a pseudocyst. The common bile duet was noted to be 1.2 cm in diameter. Abdominal computed tomography (CT) at that time with IV contrast confirmed the presence of a pancreatic pseudocyst. In addition, abundant pancreatic calcifications were noted. He was begun on H,blocker therapy with some amelioration of pain. Six weeks before admission, a subsequent abdominal ultrasonography showed no change in the size or appearance of the pseudocyst. The pseudocyst was to be observed for another 6 weeks before deciding on therapy. Five days before admission, he noted the onset of worsening epigastric pain characterized as crampy and burning. The following day he noted the presence of black stool. Over the next 3 days, intermittent nausea and vomiting of bright red blood as wel1 as postural symptoms occurred, and he went to the hospital. In the emergency department, a nasogastric tube aspirate showed 50 mL of bright red blood and toffee-grounds material, which cleared after 500 mL of tap water lavage. He was thus admitted. His medical history was notable for alcohol-induced chronic pancreatitis and mild intermittent chronic abdominal pain of 3 years’ duration. Two years before admission, he was found to have an esophageal ulcer by esophagogastroduodenoscopy, presumed to be acid-peptic in origin by endoscopic and histopathological criteria. He underwent a laparotomy for colonic perforation after colonoscopic polypectomy 2 years previously. There was no pancreatie disease in his family history. He smoked one pack of cigarettes per day for more than 20 years. Although previously drinking six or more beers per day, he was currently consuming one to three beers per week. Admission physical examination showed a thin man in no apparent distress with blood pressure 155,/105 mmHg, pulse 104 beats/min, respirations 20 breaths/min, and temperature 37°C. With upright posture, his blood pressure decreased to 140/90 mmHg with a pulse increase to 120 heats/ min. Head and neck examination showed no abnormalities. The lungs were remarkable for an increased expiratory phase. Cardiac examination showed a tachycardia and a soft flow murmur at the base. Soft bruits were present over the femoral arteries. The abdomen was scaphoid with a well-healed midline star. Bowel sounds were present and no abdominal bruits were audible. Mild epigastric tenderness was present with palpation in the absente of any mass lesions; hepatosplenomegaly and rebound

Patterns of Dyspepsia During the Course of Duodenal Ulcer

Dyspepsia patterns during the course of duodenal ulcer (DU) were examined in terms of the number of consecutive months that patients experienced dyspepsia either intermittently or continuously, or were dyspepsia-free. The patients (n = 224) were community-based. After ulcer healing, they were evaluated every 3 months for less than or equal to 7 years. Antiulcer agents were prescribed at the physicians' discretion. We analyzed the data on a patient-month basis using a 2-state Markov chain model. The fitted mean number of consecutive months with dyspepsia and the number of months dyspepsia-free were, respectively, 1.7 and 14 in patients on antiulcer agents, and 1.5 and 9 in patients not taking them. On average, patients experienced dyspepsia during 15% of months studied if they were on antiulcer agents, and during 20% of months if not. Regardless of antiulcer therapy, dyspepsia periods were lengthened by age, especially greater than 60 years; male sex; widowhood/divorce/separation; increasing acetaminophen use; and increasing length of time since initial onset of ulcerlike dyspepsia. Dyspepsia-free periods were lengthened by age greater than 70 years, and shortened by widowhood/divorce/separation and increasing cigarette consumption. These results suggest that dyspepsia occurs for less than or equal to 20% of the time in DU patients on about a yearly basis. The least dyspepsia may be expected in patients neither widowed, divorced, nor separated, in whom length of time since the initial onset of ulcerlike dyspepsia does not exceed 7 years, and who neither smoke nor use analgesics regularly.

Non‐steroidal anti‐inflammatory drug‐induced gastroduodenal injury: therapeutic recommendations

Non-steroidal anti-inflammatory drug (NSAID) use is associated with gastro-duodenal erosions and ulcers. Bleeding and perforation are reported complications in NSAID users. Therapeutic recommendations for NSAID-induced gastroduodenal injury are necessary because of our rapidly growing geriatric population, a steady increase in prescriptions for NSAIDs, and the widespread use of over-the-counter NSAIDs. Studies seem to indicate that there is no relationship between acute NSAID-induced mucosal injury and potential damage from chronic NSAID ingestion. Ranitidine (150 mg) b.d. effectively reduces the incidence of duodenal ulcer in NSAID users, but the same dose does not reduce the incidence of gastric ulcer. Misoprostol is effective in reducing the incidence of gastric ulcer in NSAID users, although confirmatory data on its effectiveness in preventing NSAID-induced duodenal ulcer are lacking. In addition to anti-ulcer therapy, treatment of NSAID-induced ulcers includes discontinuing the drug, reducing the dose, or switching to a less potent NSAID. Longer courses of anti-ulcer treatment may be required to achieve expected healing rates when NSAIDs are not discontinued. Results of treatment of NSAID-related ulcers with currently available anti-ulcer medications vary. Several studies have shown that 150 mg ranitidine b.d heals both gastric and duodenal NSAID-induced ulcers. Sucralfate has also been shown to heal NSAID-induced duodenal ulcers. Misoprostol treatment of NSAID-induced ulcers is not well documented, although there are placebo-controlled data that substantiate its benefit in gastric ulcer patients not taking NSAIDs.

A Dosage form for Procyanidins Gels Based on Cellulose Derivatives

The formulation of procyanidin gels based on cellulose derivatives is described. Type and optimal concentration of gelling agents were determined to obtain stable, limpid gels of satisfactory viscosity and pH compatible with anti-ulcer therapy.

Reversal of hepatorenal syndrome in four patients by peroral misoprostol (prostaglandin E1 analogue) and albumin administration

Four consecutive patients with alcoholic cirrhosis and hepatorenal syndrome were treated with misoprostol, a synthetic methylester prostaglandin E1 analogue at twice the dosage advocated for anti-ulcer therapy (i.e., 0.4 mg four times per day orally) and albumin infusions. The mean urinary output obtained over the 3 days preceding misoprostol administration was 250, 315, 550 and 195 ml per 24 h, respectively, in the four patients, despite adequate volume expansion by plasma albumin to reach normal or high central venous pressure. Diuresis increased to 1450, 2440, 925 and 1300 ml, respectively, on days 2-4 after onset of therapy. Serum creatinine levels were 71, 51, 33 and 35 mg/l before and dropped to 26, 21, 13 and 17 mg/l during treatment. All patients had hyponatraemia (117-128 mequiv/l) which normalized, although they were continued on a low sodium intake of less than 10 mequiv per 24 h. Urinary sodium excretion increased from 0.4-3 mmol per 24 h, to 15-40 in the first two cases and only slightly to 3-5 in the last two patients. Three patients died after 10, 30 and 40 days due to oesophageal bleeding, encephalopathy or pulmonary infection, whereas one patient underwent an orthotopic liver transplantation when her serum creatinine attained a level of 13 mg/l. In the first patient, hepatorenal syndrome recurred 10 days after stopping the misoprostol treatment. High doses of misoprostol in the presence of adequate volume expansion thus seem to produce marked diuresis and creatininuria as well as mild natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Long‐term maintenance treatment of gastric ulcers with ranitidine

One hundred and twenty patients with gastric ulcer disease, who had been receiving maintenance treatment with ranitidine (150 or 300 mg/day) for periods up to 7 years, were studied retrospectively. The proportion of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment was 97% after 1 year; 90% after 3 years; and 79% after 5 years. No patient developed haemorrhage or perforation during maintenance treatment. None of the demographic features was shown to be associated with a significantly increased risk of ulcer recurrence during maintenance treatment. Comparison of the recurrence rates during maintenance treatment with those during periods without active anti-ulcer therapy, using life table and incidence density analysis, showed a significant difference in favour of maintenance treatment. We conclude that maintenance treatment with ranitidine for 5 years significantly reduces the risk of symptomatic ulcer recurrence in patients with gastric ulcer.

Risk Factors for Clostridium difficile Toxin-Associated Diarrhea

AbstractThe hospital-wide attack rate for Clostridium difficile-associated diarrhea at our tertiary-care university hospital was 0.02 per 100 patient discharges (0.02%) in 1982, but 0.41% and 1.47% in 1986 and 1987, respectively, with a peak incidence of 2.25% in the fourth quarter of 1987. Hospital antibiotic usage patterns showed concurrent increased use of third-generation cephalosporins, and intravenous vancomycin and metronidazole. Thirty-seven cases selected for study were older than 37 control patients, more likely to have an underlying malignancy and less likely hospitalized on the obstetrics/gynecology service. Their mean duration of hospitalization prior to diagnosis was 21 days, versus a mean total length of stay of eight days for controls. All cases received antibiotics, compared to 24 of the controls. Cases were given more antibiotics for longer periods, and more often received clindamycin, third-generation cephalosporins, aminoglycosides and vancomycin. Gender, race, duration of hospitalization, prior surgery and antiulcer therapy were not significant by logistic regression analysis. Epidemiologic variables with significantly different adjusted odds ratios (95% confidence intervals) were age greater than 65 years (14.1, 1.4-141), intensive care unit residence (39.2, 2.2-713), gastrointestinal procedure (23.2, 2.1-255) and more than ten antibiotic days (summation of days of each antibiotic administered) (16.1, 2.2-117). Control measures included encouraging earlier isolation and treatment of suspected cases and formulary restriction of clindamycin, with use of metronidazole for therapy of anaerobic infections. By the second half of 1988, the attack rate had dropped progressively to 0.74%.

Risk Factors for Clostridium difficile Toxin-Associated Diarrhea

The hospital-wide attack rate for Clostridium difficile-associated diarrhea at our tertiary-care university hospital was 0.02 per 100 patient discharges (0.02%) in 1982, but 0.41% and 1.47% in 1986 and 1987, respectively, with a peak incidence of 2.25% in the fourth quarter of 1987. Hospital antibiotic usage patterns showed concurrent increased use of third-generation cephalosporins, and intravenous vancomycin and metronidazole. Thirty-seven cases selected for study were older than 37 control patients, more likely to have an underlying malignancy and less likely hospitalized on the obstetrics/gynecology service. Their mean duration of hospitalization prior to diagnosis was 21 days, versus a mean total length of stay of eight days for controls. All cases received antibiotics, compared to 24 of the controls. Cases were given more antibiotics for longer periods, and more often received clindamycin, third-generation cephalosporins, aminoglycosides and vancomycin. Gender, race, duration of hospitalization, prior surgery and antiulcer therapy were not significant by logistic regression analysis. Epidemiologic variables with significantly different adjusted odds ratios (95% confidence intervals) were age greater than 65 years (14.1, 1.4-141), intensive care unit residence (39.2, 2.2-713), gastrointestinal procedure (23.2, 2.1-255) and more than ten antibiotic days (summation of days of each antibiotic administered) (16.1, 2.2-117). Control measures included encouraging earlier isolation and treatment of suspected cases and formulary restriction of clindamycin, with use of metronidazole for therapy of anaerobic infections. By the second half of 1988, the attack rate had dropped progressively to 0.74%.

Adverse effects of antiulcer therapy

Adverse effects of antiulcer therapy

The Clinical Importance of Drug Interactions with Antiulcer Therapy

The overall safety of a given drug is determined by its toxicity, side effects, and drug-drug interactions. Thus, a clarification of the mechanisms, importance, and clinical implications of any drug-drug interaction with antiulcer therapy is critical to the use of antiulcer medications. Drug-drug interactions may occur as a result of changes in absorption, metabolism, distribution, or excretion. Fortunately, drug distribution or protein binding is unchanged by antiulcer therapy. Antiulcer drugs may affect absorption by several mechanisms. Ionized medications may bind to the divalent cations of antacids and sucralfate to result in poorly absorbed complexes. Reduced gastric acid may decrease the absorption of medications that are weak bases while enhancing the absorption of weak acids. Drug absorption may be impaired by delayed gastric emptying. Several H2-receptor antagonists, including cimetidine and to a lesser extent ranitidine, and the proton pump inhibitor, omeprazole, may reduce the hepatic degradation of drugs metabolized by the cytochrome P450 system. The degree to which such agents alter drug metabolism is determined by the patient's age, genetics, duration of therapy, degree of cytochrome P450 binding, and the regimen. Because the clinical importance of this interaction cannot always be predicted, caution is recommended whenever drugs metabolized by this system are used concurrently. Development of an understanding of the ways in which drug metabolism interactions occur may lead to more effective and safe use of these medications.

6. The Effect of Maintenance Treatment with Ranitidine on the Complications of Duodenal Ulcer Disease

A population of 392 patients with duodenal ulcers were studied to determine the rate of development of the complications of ulcer disease during long-term maintenance treatment with ranitidine. By the product limit method of survival analysis, the proportions of patients who remained free from haemorrhage associated with ulcer recurrence during maintenance treatment were 98-99% at 1 year, 97-98% at 3 years, and 97-98% at 6 years. During periods of time when 124 of 392 patients were not receiving active anti-ulcer therapy, the proportion of patients who developed haemorrhage (15.2% at 3 years) was significantly greater than that observed in the remaining 268 patients (1.3% at 3 years), who continued to take ranitidine throughout the follow-up period (P< 0.0001, logrank test). No cases of perforation were observed, and only one patient developed pyloric stenosis. Maintenance treatment with ranitidine for up to 6 years successfully reduced the risk of haemorrhage in patients with duodenal ulcer disease.

Why Do Ulcers Heal with Sucralfate?

It is unknown why ulcers in general heal. Some clues are worth considering. What is known is (i) that ulcer healing occurs spontaneously, (ii) that ulcers heal more quickly in the duodenum than in the stomach, (iii) that mucosal blood flow at ulcer edge improves with healing, and (iv) that healing can be speeded up by (a) not smoking, (b) removing acid from the stomach, and (c) using non-antisecretory mucosal protective agents such as sucralfate and colloidal bismuth. The difference in healing rates between duodenal and gastric ulcers may be related to ulcer size, duodenal alkalinity due to the secretion of the Brunner's glands, and other uninvestigated factors such as epidermal growth factor and mucosal blood flow. The difference between smokers and non-smokers may be related to inhibition of prostaglandin synthesis and impairment of mucosal blood flow due to smoking and to higher acid secretion in smokers. The success with antisecretory agents indicates that acid inhibits the healing process. The success of sucralfate and bismuth indicates that cytoprotective mechanisms play a role in ulcer healing. The literature also shows that ulcer healing is less affected by smoking in patients treated with sucralfate than in those treated with antisecretory agents, suggesting that cytoprotective mechanisms play a more important part than acid inhibition in counteracting the adverse effects of smoking on healing. Furthermore, ulcer relapse occurs sooner in patients treated with antisecretory agents than in those treated with sucralfate or bismuth, suggesting that withdrawal of antisecretory agents speeds up relapse and/or that cytoprotective mechanisms are associated with longer-lasting remission. It is concluded that sucralfate healing involves cytoprotective mechanisms and that these cannot be ignored in the planning of any anti-ulcer therapy. Despite the understanding of the various site-protective and cytoprotective mechanisms, as discussed in the previous article, it is not clear why ulcers heal with sucralfate. In fact, there is no clear answer to the fundamental question as to why ulcers in general heal with the known therapeutic agents, including H2-receptor antagonists, antacids, proton pump inhibitors, anticholinergics, site-protective agents, and cytoprotective agents. This review examines this question, using sucralfate as a model.

5. Maintenance Treatment versus No Treatment in Patients with Duodenal Ulcer Disease

population of 388 patients with duodenal ulcers, 265 patients received continuous maintenance treatment with ranitidine (RNT MT group) and 123 patients had periods of time without active anti-ulcer therapy (RNT NOMT group). The proportions of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment (RNT MT) were 93% at 1 year, 87% at 3 years, and 85% at 5 years, compared with 51% at 1 year, 25% at 3 years, and 14% at 5 years in patients who were not receiving treatment (RNT NOMT). This result was highly significant (P = 0.0001, logrank test). Incidence density analysis of all patients showed that the average number of symptomatic recurrences per month was 0.0057 during maintenance treatment and 0.0629 during periods without active treatment (P = 0.0001). This study showed that maintenance treatment with ranitidine for 5 years significantly reduced the rate of symptomatic recurrence of ulcer in patient with duodenal ulcer disease.

NSAID-Induced Gastrointestinal Damage

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause acute diffuse injury to the gastroduodenal mucosa, and also cause chronic focal ulcers that may bleed or perforate without warning symptoms. Acute and chronic lesions are distinct, are pathogenetically different, respond differently to drugs, and require different management strategies. The principal rationale for antiulcer therapy in NSAID users is to prevent or reduce potentially fatal outcomes; to date no evaluated drug meets this criterion for efficacy. Antacids and H2-receptor antagonists, based on open uncontrolled studies, appear to heal both gastric and duodenal ulcers, and maintain them healed during continued NSAID use; larger gastric ulcers show delayed healing with conventional doses of H2-receptor antagonists during NSAID therapy. No such delay occurs with omeprazole therapy. The suggests that if NSAID-associated gastric ulcers are treated with H2-receptor antagonists, larger doses should be given for longer periods. In patients with no pre-existing ulcer disease, H2-receptor antagonists given prophylactically prevent duodenal but not gastric ulcers; sucralfate does the same. In individuals without peptic ulcer disease taking NSAIDs, misoprostol, given as prophylaxis, reduces the development of gastric ulcers; its beneficial effects on ulcer healing or symptoms during continued NSAID therapy, or its ability to prevent duodenal ulcers or ulcer complications, are not established. Because of diarrhea, the 400 micrograms/day dosage is recommended, especially in the elderly.

Campylobacter pylori-related gastrointestinal disease in children. Incidence and clinical findings.

Over a one-year period, 95 children and adolescents presenting with epigastric pain and/or vomiting, and without associated risk factors for development of peptide disease, underwent endoscopic antral biopsies for pathologic diagnosis and to detect presence of Campylobacter ss. pylori (C. pylori). Additional biopsies of the esophagus, stomach, and duodenum were obtained for histologic evaluation. C. pylori was identified in 16 patients (16.8%), all of whom had evidence of acute and/or chronic gastritis. Significant discriminating factors between C. pylori-positive and -negative subjects included age at presentation (positive vs negative = 14.6 vs 9.9 years, P less than 0.01), biopsy-confirmed gastritis (100% vs 30.4%, P less than 0.001), and diagnosis of duodenitis alone (0% vs 46.8%, P less than 0.001). Risk for bacterial colonization was significantly higher in the presence of endoscopic gastritis (P less than 0.001). Among C. pylori-positive patients, none responded to standard antiulcer therapy (H2-receptor antagonists, antacids). Symptomatic and histologic remission was achieved utilizing combined therapy with bismuth subsalicylate and antibiotics. Seven of 79 C. pylori-negative patients with biopsy-proven gastritis who responded poorly to antisecretory therapy had the organism identified in follow-up antral biopsies; these patients improved clinically following treatment for C. pylori. These data suggest that C. pylori is a significant factor in the etiology of upper gastrointestinal tract inflammatory disease in pediatrics, and presence of the organism should be evaluated, particularly in children with evidence of acute and/or chronic gastritis.

Gastroduodenal ulcer incidence in patients with venous thromboembolism

The presence of peptic ulcer disease implies a high risk of bleeding in patients on heparin therapy. We reviewed our experience with 166 consecutive patients admitted because of venous thromboembolism. Of these 166 patients, 29 were referred for upper gastrointestinal endoscopy in order to detect the presence of any lesion that might contraindicate heparin therapy. A gastric ulcer was found in 10 patients, a duodenal ulcer in 11, and gastric erosions with signs of bleeding in 3 patients. Given the unexpectedly high frequency of ulcer in these patients, an upper gastrointestinal endoscopy was routinely performed early in the course of admission in 50 consecutive patients with venous thromboembolism. A gastric ulcer was found in 5 patients (10%), a duodenal ulcer in 7 (14%), and erosions in 2. Five of these patients had an unsuspected ulcer. A case can be made for prophylactic antiulcer therapy for all patients placed on anticoagulants for venous thromboembolism. Upper gastrointestinal endoscopy is indicated in patients with ulcer symptoms, in those with a previous history of peptic ulcer disease, and perhaps, in patients developing occult blood in the stools while on treatment with anticoagulants.

Zinc acexamate: the beginning of a new direction for antiulcer therapy?

Zinc acexamate: the beginning of a new direction for antiulcer therapy?