Therapy For Peptic Ulcer Disease Research Articles

Maintenance therapy in duodenal and gastric ulcer disease: survey of practice amongst British gastroenterologists.

We have used a postal questionnaire to obtain data on the practice of maintenance therapy for peptic ulcer disease by members of the British Society of Gastroenterology. Completed questionnaires were returned by 434 members. Ninety-six per cent used maintenance therapy for patients with duodenal ulcer and 81% for gastric ulcer. Maintenance therapy was considered to be safe (duodenal ulcer 91%; gastric ulcer 78%), acceptable to patients (duodenal ulcer gastric ulcer 89%; gastric ulcer 80%) and to reduce the incidence of ulcer complications (duodenal ulcer 81%; gastric ulcer 68%). There was consensus that increasing age of patient, current use of non-steroidal anti-inflammatory drugs, previous ulcer complications, and ulcer relapse after surgery were relatively strong indications for maintenance therapy. However, the proportion of patients who received maintenance therapy varied widely amongst respondents (from < 10% to > 50%). There was no agreement on the optimal duration of therapy, nor on management of patients who relapsed during maintenance therapy. It appears that the criteria for use of maintenance therapy need to be better defined, and that established knowledge about the practice of maintenance therapy should be better disseminated and acted upon.

CONTROL OF GASTRIC ACID SECRETION: Histamine H2-Receptor Antagonists and H+K+-ATPase Inhibitors

Gastric acid secretion is regulated by an intricate interplay of neural (acetylcholine), hormonal (gastrin), and paracrine (histamine, somatostatin) mechanisms. Receptors for each of these agents and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of acetylcholine and gastrin is mediated by an increase in cytosolic calcium, whereas that of histamine is mediated by activation of adenylate cyclase and generation of cAMP. Strong potentiation between histamine and either gastrin or acetylcholine reflects postreceptor interaction between the distinct pathways as well as the ability of acetylcholine and gastrin to release histamine from mucosal ECL cells. The inhibitory effects of somatostatin on acid secretion are mediated by receptors coupled by guanine nucleotide-binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, the proton pump of the parietal cell. Precise information on the mechanisms involved in gastric acid secretion has led to the development of potent drugs capable of inhibiting acid secretion. These include competitive antagonists that interact with stimulatory receptors (e.g., histamine H2-receptor antagonists) as well as noncompetitive inhibitors of H+K(+)-ATPase (e.g., omeprazole). The histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, and nizatidine) continue as first-line therapy for peptic ulcer disease and are effective in preventing relapse. Although they are generally well tolerated, histamine H2-receptor antagonists may cause untoward CNS, cardiac, and endocrine effects as well as interference with the absorption, metabolism, and elimination of various drugs. Omeprazole is a weak base that reaches the parietal cell through the bloodstream, diffuses through the cytoplasm, and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. It covalently binds to H+K(+)-ATPase, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main drawback to its use is its extreme potency, which leads to virtual anacidity, gastrin and ECL cell hyperplasia, hypergastrinemia, and, in rats, to the development of carcinoid tumors.

Medical Therapy of Peptic Ulcer Disease

The gastric duodenal mucosa normally is protected from the damaging effects of gastric acid and pepsin by ill-defined mechanisms. Ulcers may arise when there is an imbalance between the aggressive and defensive factors that renders the mucosa susceptible to damage. A variety of factors have been identified that may favor the development of peptic ulcers, but no single pathophysiologic defect applies in all ulcer patients. In duodenal ulcers, gastric acid hypersecretion is observed in as many as one third of patients; however, most patients with duodenal ulcers secrete normal amounts of gastric acid. Decreased mucosal bicarbonate secretion may be important in at least some duodenal ulcer patients. Use of NSAIDs may cause either gastric or duodenal ulcers, probably through the inhibition of mucosal prostaglandin synthesis and disruption of mucosal defenses. Finally, a recently identified bacterium, H. pylori, causes a chronic gastritis that is found in the overwhelming majority of patients with duodenal ulcers and non-NSAID-associated gastric ulcers. This bacterium may play a pivotal role in ulcer pathogenesis and, especially, in ulcer recurrences. A number of drugs of proved efficacy are available for the treatment of acute duodenal and gastric ulcers. The H2 receptor antagonists administered once daily remain the mainstay of ulcer therapy because of their efficacy, ease of use, and excellent safety profile. More thorough and long-lasting acid inhibition is afforded by the H+/K(+)-ATPase inhibitor omeprazole. This agent also promotes more rapid ulcer healing, but in most patients, this minor advantage may not justify the higher cost. It is not known whether more rapid healing will translate into lower ulcer complication rates. Until further data are available, this drug may be preferable in patients with large or complicated ulcers. In patients with refractory ulcers, omeprazole is clearly superior to other available agents. Agents that promote mucosal defense mechanisms are becoming increasingly popular in the treatment of duodenal ulcers but have undergone less testing than in gastric ulcers. Sucralfate 1 g four times daily is equivalent to H2 antagonists in the treatment of duodenal ulcers and, probably, gastric ulcers. Its requirement for multiple daily doses makes it somewhat less attractive at present to most patients. Low- to medium-dose Al-containing antacids are inexpensive and efficacious in duodenal ulcer therapy. They should remain as therapeutic options for the compliant patient in whom cost considerations are important. Colloidal bismuth subcitrate 120 mg four times a day is comparable to other agents in the acute treatment of duodenal ulcers and likely gastric ulcers.(ABSTRACT TRUNCATED AT 400 WORDS)

Practical pharmacology and cost-effective management of peptic ulcer disease

The clinical approach to the therapy of peptic ulcer disease has changed over the years as our understanding of its pathogenesis has grown. No longer is excess acid production seen as the single cause of ulcer disease; rather, its pathogenesis is viewed as the disturbance of a complex balance of ulcerogenic and protective factors. Today, the clinician's aim is to restore the balance between protective and aggressive factors. Simultaneously, the development of new classes of medications has provided the clinician with the tools to decrease intragastric acidity, neutralize or suppress acid production, and enhance the protective and restorative properties of the mucosa.

Injection Therapy for Hemostasis of Bleeding Peptic Ulcers: Techniques and Results of Randomized Prospective Trials

One of the most serious sequelae of peptic ulcer disease is active gastrointestinal hemorrhage. Numerous endoscopic modalities have been developed to control bleeding. A simple, inexpensive, readily available means of treating hemorrhage is injection of the lesion with a sclerosant or other hemostatic agent. The authors review the current status, technique, and types of injectable agents and provide analysis of prospective trials on injections therapy for peptic ulcer disease.

Omeprazole

Omeprazole is the first of a new class of drugs, the acid pump inhibitors, which control gastric acid secretion at the final stage of the acid secretory pathway and thus reduce basal and stimulated acid secretion irrespective of the stimulus. In patients with duodenal or gastric ulcers, omeprazole as a single 20 mg daily dose provides more rapid and complete healing compared with ranitidine 150 mg twice daily or 300 mg at nighttime, or cimetidine 800 or 1000 mg/day. Patients poorly responsive to treatment with histamine H2-receptor antagonists respond well to omeprazole--most ulcers healed within 4 to 8 weeks of omeprazole 40 mg/day therapy. Omeprazole 20 or 40 mg/day has been administered as maintenance therapy for peptic ulcer disease for up to 5.5 years with very few ulcer recurrences. In patients with erosive or ulcerative oesophagitis, omeprazole 20 or 40 mg/day produces healing in about 80% of patients after 4 weeks, and is superior to ranitidine with respect to both healing and symptom relief. Healing rates of greater than 80% are achieved after 8 weeks in patients with severe reflux oesophagitis unresponsive to H2-receptor antagonists. Maintenance therapy with a daily 20 mg dose prevents relapse in about 80% of patients over a 12-month period. Omeprazole is considered to be the best pharmacological option for controlling gastric acid secretion in patients with Zollinger-Ellison syndrome. Daily dosages of 20 to 360 (median 60 to 70 mg successfully reduce basal acid output to target levels (less than 10 mmol/h or less than 5 mmol/h in patients with severe oesophagitis or partial gastrectomy) during treatment for up to 4 years. Omeprazole is well tolerated in short term studies (up to 12 weeks); the reported incidence of serious side effects (about 1%) being similar to that seen in patients treated with an histamine H2-receptor antagonist. The longer term tolerability of omeprazole has been investigated in patients treated for up to 5.5 years. Slight hyperplasia, but no evidence of enterochromaffin-like (ECL) cell dysplasia or neoplasia or ECL cell carcinoids has been reported. ECL cell carcinoids have been observed in rats after life-long treatment with high doses of omeprazole or ranitidine, or in rats with partial corpectomy; the weight of experimental evidence indicates that this is a result of prolonged hypergastrinaemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Maintenance therapy for peptic ulcer disease

Peptic 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 safe.

Overview of Medical Therapy of Peptic Ulcer Disease

Medical management of peptic ulcer disease continues to evolve with the recent introduction of new H2-receptor antagonists, prostaglandin analogs, and a proton pump inhibitor, and clarification of the relationship between suppression of gastric acidity and ulcer healing. Nizatidine and roxatidine acetate, the new H2 blockers, are safe and effective but do not appear to have new properties of clinical importance. The modes of action of omeprazole and the prostaglandins have been clarified. Omeprazole is a prodrug that is protonated and secured in the secretary canaliculus of the parietal cell where the active derivative covalently binds sulfhydryl groups of H+/K(+)-ATPase, thereby irreversibly and profoundly blocking acid secretion. Prostaglandins bind a receptor on the basolateral membrane of the parietal cell, releasing a protein that inhibits cyclic AMP, the second messenger of histamine-stimulated acid secretion. The ulcer-healing properties of prostaglandins can be attributed largely if not entirely to their inhibition of acid secretion. Antacids, on the other hand, may heal ulcers by effects other than acid neutralization, as the low-dose regimens that heal ulcers only weakly neutralize acid. The way in which sucralfate and colloidal bismuth heal ulcers remains unclear; they may do so through multiple effects including, in the case of bismuth, eradication of C. pylori. H2-receptor antagonists continue as first-line treatment for acute DU and GU and the prevention of recurrence. The antacid and sucralfate regimens are less convenient but safe and effective. Misoprostol has a disadvantageous safety profile relative to available agents but is effective in preventing NSAID-induced gastric ulcers. The efficacy of omeprazole in acid-peptic disease is established but the way in which it should be used is still unclear because of long-term safety concerns.

Peptic ulcer disease, cytoprotection, and prostaglandins

To the Editor .—The editorial in the October 1988 issue of theArchives 1 outlines the prospects of oral prostaglandin E therapy for peptic ulcer disease. In theory, the bimodal fashion of action, suppressing gastric acid secretion in addition to enhancing defensive factors (cytoprotection), makes prostaglandin E analogues ideal antiulcer drugs. In practice, however, the promise remains unfulfilled, and in light of recent controlled trials on arbaprostil, enprostil, misoprostol, rioprostil, and trimoprostil in peptic ulcer disease (reviewed elsewhere 2-4 ) the viewpoints1 appear overoptimistic. First, in doses lower than those required to decrease acid secretion, prostaglandin E analogues retain cytoprotective properties, but are no better than placebo in healing duodenal (arbaprostil and misoprostol) and gastric ulcers (misoprostol). Second, in fully antisecretory doses some prostaglandin E analogues (arbaprostil, enprostil, and misoprostol) accelerate ulcer healing compared with placebo, and some analogues (enprostil and misoprostol, but not trimoprostil) provide healing rates about as high

Peptic Ulcer Disease, Cytoprotection, and Prostaglandins

<i>To the Editor</i>.—The editorial in the October 1988 issue of theArchives¹outlines the prospects of oral prostaglandin E therapy for peptic ulcer disease. In theory, the bimodal fashion of action, suppressing gastric acid secretion in addition to enhancing defensive factors (cytoprotection), makes prostaglandin E analogues ideal antiulcer drugs. In practice, however, the promise remains unfulfilled, and in light of recent controlled trials on arbaprostil, enprostil, misoprostol, rioprostil, and trimoprostil in peptic ulcer disease (reviewed elsewhere^2-4) the viewpoints1 appear overoptimistic. First, in doses lower than those required to decrease acid secretion, prostaglandin E analogues retain cytoprotective properties, but are no better than placebo in healing duodenal (arbaprostil and misoprostol) and gastric ulcers (misoprostol). Second, in fully antisecretory doses some prostaglandin E analogues (arbaprostil, enprostil, and misoprostol) accelerate ulcer healing compared with placebo, and some analogues (enprostil and misoprostol, but not trimoprostil) provide healing rates about as high

Pathogenesis and Therapy of Peptic Ulcer Disease

The epithelial cells of the stomach and duodenum are normally protected from the damaging effects of acid and pepsin by a balancing mechanism of mucosal resistance. If an imbalance occurs, peptic ulcer may result. Traditional teaching has emphasized the importance of acid (and pepsin) as the cause of this imbalance; however, it is clear that acid and pepsin are not the only important factors in the pathogenesis of peptic ulcer. More recent investigative efforts have been directed at what constitutes mucosal resistance and how it can be disrupted to produce, in the presence of gastric acid, a peptic ulcer. Depletion of endogenous prostaglandins and Helicobacter pylori gastritis have emerged as prominent theories. As evidence exists both to support and refute these theories in humans, any definitive conclusions cannot be made at this time. The acute management of peptic ulcer disease is directed at relieving pain, accelerating ulcer healing, and preventing complications. Peptic ulcers can be healed with antisecretory agents (i.e., H2-receptor antagonists, omeprazole), antacids, prostaglandins, and sucralfate. Because they are effective, safe, and convenient, the H2-receptor antagonists are the most widely used agents for the management of peptic ulcer disease. Because the H2-receptor antagonist agents are equally effective in their indicated uses and are equally safe based on scientifically valid data, selection should be based primarily on cost. Omeprazole is the newest antisecretory agent: a single morning dose of 20 mg suppresses acid secretion for 24 h. The agent offers little advantage over H2-receptor antagonists for the majority of patients with peptic ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid and Barriers: Current Research and Future Developments for Peptic Ulcer Therapy

Medical therapy for peptic ulcer disease has been targeted at inhibiting acid secretion based on the belief that ulcers occur due to an imbalance between aggressive and protective factors. New antisecretory agents are unlikely to show any dramatic improvement over the success and safety of histamine H2 receptor antagonists or the recently introduced H+K+ATPase proton pump antagonist omeprazole. The development of specific muscarinic M3 and gastrin receptor antagonists will provide useful agents to suppress acid and pepsinogen secretion by alternative means and may prevent the associated hypergastrinaemia seen with anti-secretory therapy. Enhancement of mucosal defence by site protective agents will be based on a better understanding of the vascular and immune factors involved in maintaining mucosal integrity and the growth factors that regulate wound healing. Molecular techniques are likely to produce the 'model anti-ulcer' agent which will effectively inhibit acid secretion and also enhance wound healing thus providing a cure for this chronic disease.

Peptic Ulcer Disease in the Pediatric Population

Peptic ulcer disease occurs in infants, children, and adolescents. Primary and stress ulcers pose a challenge to the pediatrician, who needs to arrange for appropriate diagnostic and therapeutic services. Highlights of our understanding of the pathophysiology, genetics, natural history, diagnosis, and therapy of peptic ulcer disease are presented.

Assessment of two new therapies for peptic ulcer disease: omeprazole and the prostaglandin analogues.

Assessment of two new therapies for peptic ulcer disease: omeprazole and the prostaglandin analogues.

Induction of theophylline toxicity and inhibition of clearance rates by ranitidine

<h3>Purpose</h3> Theophylline is metabolized by the hepatic microsomal oxidase system, as is ranitidine, although the latter has a much lower affinity for the system. The incidence of theophylline toxicity is rare when the two drugs are administered simultaneously. We observed the development of clinical and chemical toxicity in three elderly patients receiving oral theophylline therapy for chronic obstructive pulmonary disease after the administration of ranitidine therapy for peptic ulcer disease. <h3>Patients and methods</h3> Three patients with chronic obstructive pulmonary disease who had been receiving theophylline for prolonged periods of time were studied. Two patients presented with complaints of epigastric pain, which was attributed to acid-peptic disease; the other patient presented with hematemesis, which was shown to be due to gastric and duodenal ulcers. Ranitidine was administered for treatment of acid-peptic disease. Theophylline clearance rates were determined before, during, and after ranitidine treatment. When symptoms of theophylline toxicity developed, the dose of theophylline was either stopped or reduced. Subsequently, patients were readministered their usual dose of theophylline. <h3>Results</h3> The effect of simultaneous administration of both drugs resulted in similar reductions in theophylline clearance rates. Serum theophylline levels returned to pretreatment values after cessation of ranitidine treatment. In one patient, rechallenge with ranitidine during steady-state theophylline treatment resulted in recurrence of clinical and chemical theophylline toxicity. <h3>Conclusion</h3> These observations suggest that treatment with ranitidine may cause clinically apparent interactions with theophylline since both drugs are metabolized by the same cytochrome P-450 isozymes.

Advances in drug therapy for peptic ulcer disease.

Recently, three new drug types have emerged to treat peptic ulceration. We compared the mechanism of action of omeprazole and somatostatin-14, both inhibitors of gastric acid, with that of tetraprenylacetone, a drug thought to be cytoprotective in the upper gut. Omeprazole and somatostatin-14 caused potent inhibition of meal-stimulated acid secretion in the dog (92% +/- 6% and 97% +/- 1%, respectively). On the other hand, tetraprenylacetone had no significant inhibitory effect on acid secretion (4% +/- 17%). In separate studies, tetraprenylacetone was shown to be a stimulant of gastric bicarbonate secretion in the rabbit, increasing bicarbonate secretion from a basal level of 0 to 86 +/- 28 pmol/2 h. Tetraprenylactone was also found to be a strong stimulant of canine pancreatic bicarbonate secretion. The ability of tetraprenylacetone to stimulate endogenous bicarbonate secretion may explain its ability to heal ulcers both experimentally and clinically.

Misoprostol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease.

Misoprostol is an analogue of prostaglandin E1 and is the first synthetic prostaglandin analogue to be made available for the treatment of peptic ulcer disease. It inhibits gastric acid secretion in man, and there is also some evidence that it limits the extent of gastrointestinal damage induced by ulcerogenic agents in animals and healthy volunteers at doses lower than those required to inhibit acid secretion. This 'cytoprotective' activity has been explained by several mechanisms, but its contribution to the clinical efficacy of misoprostol in healing established ulcers is doubtful since the drug does not appear to be effective in healing peptic ulcers at non-antisecretory dosages. In clinical trials, ulcer healing has been reported in 60 to 85% of patients with duodenal ulcers and 32 to 54% with gastric ulcers receiving misoprostol 200 micrograms 4 times daily for 4 weeks--the recommended dosage. In comparative studies, the percentage of patients with healed ulcers after misoprostol (800 micrograms daily) was not significantly different from that with cimetidine (1200 mg daily), although there was greater pain relief with cimetidine. No study has yet been published concerning the use of misoprostol as maintenance therapy for the prevention of ulcer recurrence, and no long term tolerability data are available. However, in acute ulcer healing studies (2 to 12 weeks in duration) misoprostol has been well tolerated. Diarrhoea was the most commonly reported symptom, and this was only rarely of sufficient severity to interfere with treatment. No evidence of histopathological changes in the gastric mucosa induced by misoprostol have been reported in man. Evidence of uterine stimulant effects in women receiving misoprostol during the first trimester of pregnancy has resulted in the drug being contraindicated during pregnancy. Thus, misoprostol is a new type of antiulcer drug, providing an alternative approach to the therapy of peptic ulcer disease. It has been shown to be effective and well tolerated in the healing of both gastric and duodenal ulcers. Future studies need to identify the specific types of patients likely to obtain most benefit from treatment, in order to define more clearly the place of misoprostol in the treatment of these indications, as well as addressing the possibility of ulcer prevention with lower doses of misoprostol.

Actions of cimetidine and ranitidine at some cholinergic sites: Implications in toxicology and anesthesia

Cimetidine and ranitidine are specific and potent H 2-receptor antagonists widely used in the effective therapy of peptic ulcer disease. The drugs also possess other pharmacological properties unrelated to H 2-receptor antagonism. More recently large experimental doses of cimetidine or ranitidine were found to have anti-cholinesterase, ganglion blocking and neuromuscular blocking activities. Actions of the drugs at such cholinergic sites may account for some of their clinically documented adverse effects. The toxicological implications of these findings including the potential for drug interactions to occur, especially during some anesthetic procedures, are discussed.

Diagnosis and Treatment of Peptic Ulcer Disease in Children

With advances in diagnostic technology, specifically upper gastrointestinal tract endoscopy, peptic ulcer disease in infants and children should no longer be considered rare. Whereas secondary ulcers are usually gastric and are often multiple, primary ulcers occur with almost equal frequency in the duodenum or stomach and tend to be solitary. In spite of intensive scientific investigation, the etiology of peptic ulcer disease remains unclear. Genetic factors appear to play a role and a polygenic mode of inheritance has been proposed. Emotional factors also seem to be important. Children with peptic ulcer disease tend to be of above-average intelligence, are often overachievers who have trouble dealing with frustation, and tend to internalize their feelings. Hydrochloric acid has traditionally been implicated in the pathogenesis of peptic ulcer and most therapies are directed at either "neutralizing" acid or blocking its secretion. Recently, local factors such as gastric mucus, alkaline secretion by the gastric mucosal cells, gastric blood flow, and prostaglandins have been shown to be important in local tissue resistance to acid and to digestive enzymes. The diagnosis of peptic ulcer disease depends on a high index of suspicion. Although pain is the most common symptom, there is no typical or characteristic pattern. Nausea and vomiting may also occur in conjunction with the pain. The finding of occult blood in the stool definitely warrants a diagnostic evaluation. An upper gastrointestinal tract radiographic series with small bowel follow-through should be done first. If this is nondiagnostic in a child with persistent pain or in a child with blood in the stool, upper gastrointestinal tract endoscopy is indicated. When performed by a skilled pediatric gastroenterologist, this procedure can usually be done under local sedation with minimal discomfort, either psychologic or physical, to the patient. Antacids have been the cornerstone of therapy for peptic ulcer disease and are recommended for the patient younger than 3 years of age. Cimetidine, an H2-receptor blocker, although not officially approved for use in children, is recommended for patients 3 to 12 years of age. Ranitidine, another H2 blocker, is useful in patients older than 12 years of age because of its less frequent (twice daily) dosage schedule. Sulcrafate, a coating agent, is an effective alternative to the above for the treatment of duodenal ulcer. Therapy should continue for 6 to 8 weeks. Repeat gastrointestinal series or endoscopy is only necessary if symptoms persist during therapy or return following cessation of therapy. With earlier diagnosis and newer therapeutic modalities, the long range outlook for complete recovery is good.

Diagnosis and Treatment of Peptic Ulcer Disease in Children

With advances in diagnostic technology, specifically upper gastrointestinal tract endoscopy, peptic ulcer disease in infants and children should no longer be considered rare. Whereas secondary ulcers are usually gastric and are often multiple, primary ulcers occur with almost equal frequency in the duodenum or stomach and tend to be solitary. In spite of intensive scientific investigation, the etiology of peptic ulcer disease remains unclear. Genetic factors appear to play a role and a polygenic mode of inheritance has been proposed. Emotional factors also seem to be important. Children with peptic ulcer disease tend to be of above-average intelligence, are often overachievers who have trouble dealing with frustation, and tend to internalize their feelings. Hydrochloric acid has traditionally been implicated in the pathogenesis of peptic ulcer and most therapies are directed at either neutralizing acid or blocking its secretion. Recently, local factors such as gastric mucus, alkaline secretion by the gastric mucosal cells, gastric blood flow, and prostaglandins have been shown to be important in local tissue resistance to acid and to digestive enzymes. The diagnosis of peptic ulcer disease depends on a high index of suspicion. Although pain is the most common symptom, there is no typical or characteristic pattern. Nausea and vomiting may also occur in conjunction with the pain. The finding of occult blood in the stool definitely warrants a diagnostic evaluation. An upper gastrointestinal tract radiographic series with small bowel follow-through should be done first. If this is nondiagnostic in a child with persistent pain or in a child with blood in the stool, upper gastrointestinal tract endoscopy is indicated. When performed by a skilled pediatric gastroenterologist, this procedure can usually be done under local sedation with minimal discomfort, either psychologic or physical, to the patient. Antacids have been the cornerstone of therapy for peptic ulcer disease and are recommended for the patient younger than 3 years of age. Cimetidine, an H2-receptor blocker, although not officially approved for use in children, is recommended for patients 3 to 12 years of age. Ranitidine, another H2 blocker, is useful in patients older than 12 years of age because of its less frequent (twice daily) dosage schedule. Sulcrafate, a coating agent, is an effective alternative to the above for the treatment of duodenal ulcer. Therapy should continue for 6 to 8 weeks. Repeat gastrointestinal series or endoscopy is only necessary if symptoms persist during therapy or return following cessation of therapy. With earlier diagnosis and newer therapeutic modalities, the long range outlook for complete recovery is good.