enprostil and Peptic-Ulcer

Deficiency of prostaglandins (PGs) by non-steroidal anti-inflammatory drugs (NSAIDs) causes a loss of gastroduodenal mucosal integrity, leading to development of ulceration. PG derivatives such as misoprostol and enprostil have been proven effective in prevention and treatment of NSAIDs-induced gastroduodenal ulcers. Although side effects such as diarrhea limit the use of PG derivatives, the efficacy of these drugs in NSAIDs-induced injuries is approximately equal to that of proton pump inhibitors. Mucoprotective drugs such as rebamipide also have been reported to be effective for prevention of NSAIDs-induced ulcers. Since misoprostol and some mucoprotective drugs can prevent NSAIDs-induced small intestinal injuries, these drugs, especially misoprostol, should be used as first-line therapy for NSAIDs-induced gastrointestinal injuries with attention paid to the side effects.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Enprostil; Humans; Misoprostol; Peptic Ulcer; Prostaglandins

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bicarbonates; Carnosine; Chalcone; Chalcones; Diterpenes; Enprostil; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Mucus; Organometallic Compounds; Peptic Ulcer; Piperidines; Prostaglandins; Sucralfate

Topics: Alprostadil; Anti-Ulcer Agents; Cytokines; Dinoprostone; Drug Therapy, Combination; Enprostil; Helicobacter Infections; Helicobacter pylori; Humans; Misoprostol; Peptic Ulcer; Secondary Prevention

Topics: Anti-Ulcer Agents; Dose-Response Relationship, Drug; Drug Evaluation; Enprostil; Gastric Acid; Gastric Mucosa; Humans; Peptic Ulcer; Prostaglandins E, Synthetic

The expectation that prostaglandin analogues would improve the ulcer healing abilities of other agents by combining mucosal protection with decreased acid secretion has been proved unwarranted. The ulcer healing capabilities of these drugs reflect their antisecretory potency. A role for these drugs in ulcer healing is questionable but their use has been advocated most strongly to prevent ulceration developing during treatment with non-steroidal anti-inflammatory drugs. While some evidence supports this role, an important clinical benefit of reducing complication rates has yet to be demonstrated.

Topics: Alprostadil; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Enprostil; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Smoking

Prostaglandin analogues have been expected to outperform other antisecretory drugs as ulcer healing agents. This expectation arises from their ability to combine 'cytoprotection' with gastric secretory inhibition. Evidence of the existence of these two separate functions abounds in animals and in humans, but a clinical advantage has not evolved. Whereas most clinical trials show no difference between prostaglandin analogues and H2-receptor antagonists, some studies have shown the prostaglandins to be significantly less effective or no better than placebo. The role of cytoprotection in ulcer healing (as opposed to prevention) may be questioned and the present clinical role for these agents is unclear.

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Enprostil; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Prostaglandins; Prostaglandins E, Synthetic; Smoking

Over the past ten years there have been major advances in the physician's ability to treat patients with peptic ulcer disease. Cimetidine continues to be the standard against which newer therapies are generally compared, although ranitidine is equally effective for short-term therapy, more effective for maintenance therapy, and has a superior safety profile. Famotidine is an even more potent H2 receptor antagonist, and initial clinical studies are promising. The initial concern for the development of gastric carcinoid lesions in rodents, maintained for long periods on high doses of omeprazole, defused the initial enthusiasm for this hydrogen-potassium ATPase "proton pump" inhibitor, but recent studies continue to show a marked efficacy of this agent for the short-term care of patients with gastric or duodenal ulcers and for the management of patients with the Zollinger-Ellison syndrome. Sulcrate continues to enjoy wide popularity for acute and chronic care of acid peptic disorders because of its local action and minimal adverse effects. Pirenzepine is effective in achieving and maintaining healing, but prevalence of anticholinergic side-effects has hampered enthusiasm for its widespread use. The 2 forerunners in the prostaglandin analogues arena, misoprostol and enprostil, are antisecretory agents when given in sufficiently high doses. These orally administered prostaglandins have a favourable safety profile, and their only adverse effect is that of the development of transient mild diarrhea. Finally, while antacids continue to be used in large amounts because of their over-the-counter availability, their clinical usefulness is limited by their unpalatable taste and the relatively large amounts usually required to achieve ulcer healing.

Topics: Alprostadil; Antacids; Anti-Ulcer Agents; Cimetidine; Drug Resistance; Enprostil; Famotidine; Histamine H2 Antagonists; Humans; Misoprostol; Omeprazole; Peptic Ulcer; Pirenzepine; Prostaglandins; Prostaglandins E, Synthetic; Ranitidine; Sucralfate; Thiazoles

Enprostil, a synthetic analogue of prostaglandin E2, is effective in the treatment of patients with duodenal or gastric ulcers. As demonstrated in pharmacological studies in healthy volunteers and in patients with inactive ulcer disease, gastric acid secretion is suppressed by up to 80% for almost 12 hours after single doses of enprostil. The drug also reduces the secretion of pepsin, another 'aggressive' factor in peptic ulcer disease. Interestingly, in contrast to the H2-receptor antagonists, which either increase or have no effect on serum gastrin concentrations, enprostil inhibits basal and postprandial gastrin release. Although the possible effects of enprostil on 'defensive' factors in peptic ulcer disease-which are thought to protect the mucosa-require much further clarification, some evidence obtained in man indicates that bicarbonate secretion is enhanced by enprostil. Further, data from animal studies suggest that microvascular integrity may be preserved by a direct action of enprostil on the gastric mucosa. In healthy volunteers, the administration of enprostil in antisecretory doses protects the gastric mucosa against of enprostil in antisecretory doses protects the gastric mucosa against aspirin-induced injury. Cumulative rates of ulcer healing observed in patients with duodenal ulcers after 4 weeks' treatment with enprostil 35 micrograms twice daily were about 50 to 80%, which were similar to those seen in comparative trials with usual therapeutic doses of cimetidine or pirenzepine, but less than occurred with ranitidine. Moreover, enprostil has been shown to relieve daytime pain in a similar percentage of patients as do these H2-receptor antagonists, but night-time pain appears to respond less well to therapy with the prostaglandin. As evidenced by a few controlled trials in patients with gastric ulcers, treatment with enprostil 35 micrograms twice daily for 6 weeks provides ulcer healing in parallel with pain relief as effectively as cimetidine and ranitidine in a high percentage of patients (about 80% after 6 weeks). Prophylactic treatment with enprostil after initial ulcer healing has reduced the rate of duodenal ulcer relapse in patients 'at risk', but to a lesser extent than has ranitidine. Gastrointestinal symptoms-abdominal cramping and pain, flatulence, nausea and notably, diarrhoea-are the most frequently reported side effects during therapy with enprostil. Diarrhoea occurs in about 10% of patients, but is rarely of a severity nece

Topics: Animals; Enprostil; Humans; Peptic Ulcer; Prostaglandins E, Synthetic

The expectation that prostaglandin analogues would improve the ulcer healing abilities of other agents by combining mucosal protection with decreased acid secretion has been proved unwarranted. The ulcer healing capabilities of these drugs reflect their antisecretory potency. A role for these drugs in ulcer healing is questionable but their use has been advocated most strongly to prevent ulceration developing during treatment with non-steroidal anti-inflammatory drugs. While some evidence supports this role, an important clinical benefit of reducing complication rates has yet to be demonstrated.

Topics: Alprostadil; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Enprostil; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Smoking

Milligram-range doses of E2 prostaglandins have long been used to induce labor or abortion in the second and third trimesters of pregnancy. Enprostil, a synthetic dehydroprostaglandin E2 structural analogue, is administered in microgram doses for the treatment of acute duodenal ulcer and acute gastric ulcer. This study examined the effect of the ulcer-healing dose and twice the ulcer-healing dose upon women in the first trimester of pregnancy. Two hundred and seven women who had requested legal abortion in the first trimester participated in two randomized, double-blind, placebo-controlled, parallel studies. They received two doses of enprostil 35 micrograms (the recommended dose for the treatment of duodenal and gastric ulcer) (n = 51), 70 micrograms (twice the recommended dose) (n = 53), or placebo (n = 103) 12 h apart. No drug-induced abortions occurred in any of the first-trimester pregnancies. Vaginal bleeding occurred in 4% of volunteers receiving the lower dose and 4% receiving the higher dose of enprostil. Vaginal bleeding occurred in up to 2% of volunteers on placebo. Although not recommended for pregnant women, if enprostil is given inadvertently to pregnant women with ulcers, it is unlikely to endanger the pregnancy during the first trimester.

Topics: Abortifacient Agents; Abortion, Induced; Adult; Double-Blind Method; Enprostil; Female; Humans; Peptic Ulcer; Pregnancy; Pregnancy Trimester, First; Prostaglandins E, Synthetic; Randomized Controlled Trials as Topic

Prostaglandin analogues have been expected to outperform other antisecretory drugs as ulcer healing agents. This expectation arises from their ability to combine 'cytoprotection' with gastric secretory inhibition. Evidence of the existence of these two separate functions abounds in animals and in humans, but a clinical advantage has not evolved. Whereas most clinical trials show no difference between prostaglandin analogues and H2-receptor antagonists, some studies have shown the prostaglandins to be significantly less effective or no better than placebo. The role of cytoprotection in ulcer healing (as opposed to prevention) may be questioned and the present clinical role for these agents is unclear.

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Enprostil; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Prostaglandins; Prostaglandins E, Synthetic; Smoking

Prostaglandin-E analogues inhibit gastric acid secretion after oral administration. Therefore, these drugs are tested in clinical trials and one of them--Misoprostol--has recently been registered. With regard to healing rate of peptic ulcers and improvement of clinical signs and symptoms the prostaglandin analogues are superior to placebo but only equally effective or even slightly inferior to H2-receptor blockers. Side effects such as diarrhea or uterotropic actions will probably limit their broad application. The exact therapeutic effectiveness of prostaglandin analogues in treatment of peptic ulcer remains to be evaluated in greater detail. The substituted benzimidazole omeprazole is the first drug which exerts a long lasting and almost complete suppressive effect on gastric acid secretion in humans. This unique inhibition leads to a significant and more rapid healing rate of duodenal ulcers compared to treatment with H2-blockers. Additionally, peptic ulcers resistant to H2-blocker therapy can be treated effectively with omeprazole. In spite of these promising results the exact therapeutic effectiveness of this drug requires further evaluation.

Topics: Alprostadil; Anti-Ulcer Agents; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Enprostil; Humans; Misoprostol; Omeprazole; Peptic Ulcer; Prostaglandins E, Synthetic; Ranitidine

This study was performed to examine the effects of additional enprostil administration on hypergastrinemia and gastric acid suppression induced by omeprazole. Serum gastrin concentrations were measured in 10 peptic ulcer patients (six Helicobacter pylori-positive and four Helicobacter pylori-negative patients) before treatment, after two weeks of omeprazole (20 mg/day), and after two weeks of omeprazole and enprostil (50 micrograms/day). The additional acid inhibitory effect of enprostil was evaluated by 24-hr intragastric pH measurements in five healthy Helicobacter pylori-negative volunteers. After omeprazole treatment, the serum gastrin level of Helicobacter pylori-positive patients (3.5-fold of control) was markedly higher than that of Helicobacter pylori-negative patients (1.7-fold of control). Additional treatment with enprostil suppressed serum gastrin levels to 0.4-fold and 0.7-fold of omeprazole treatment levels in Helicobacter pylori-positive and Helicobacter pylori-negative patients, respectively. In healthy volunteers, median pH recorded during the nonmeal daytime interval increased significantly with additional enprostil. Thus, enprostil reduces undesirable omeprazole-induced hypergastrinemia, especially in Helicobacter pylori-positive patients, and effectively suppresses acid secretion.

Topics: Adult; Aged; Anti-Ulcer Agents; Drug Therapy, Combination; Enprostil; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Peptic Ulcer

Topics: Alprostadil; Anti-Ulcer Agents; Arbaprostil; Dinoprostone; Enprostil; Humans; Misoprostol; Peptic Ulcer; Prostaglandins E, Synthetic

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Enprostil; Gastric Acid; Gastric Mucosa; Humans; Misoprostol; Peptic Ulcer; Prostaglandins E, Synthetic

Circulating prostaglandin E2 antibodies were produced in 12 rabbits immunized with prostaglandin E2-thyroglobulin conjugate and ulcers occurred in 10, usually in the stomach and less often in the small intestine. Immunization of rabbits with both prostaglandin E2 and 6-keto prostaglandin F1 alpha significantly increased the number of gastric ulcers compared with rabbits immunized with prostaglandin E2 alone. Gastrointestinal ulceration in prostaglandin E2-immunized rabbits was not prevented by oral enprostil. Gastrointestinal ulcers occurred as early as 6 wk after beginning immunization and often perforated with resulting fatality. Neither prostaglandin E2 antibodies nor ulcers developed in rabbits immunized with thyroglobulin vehicle (controls). Passive immunization of unimmunized rabbits with prostaglandin E2-hyperimmune plasma led to acute gastric ulcers within 9 days, whereas passive transfer of nonimmune plasma did not produce ulcers. This latter finding suggests that prostaglandin E2 antibodies per se were responsible for ulcer formation.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antibody Formation; Cross Reactions; Dinoprostone; Enprostil; Immunization; Immunization, Passive; Male; Peptic Ulcer; Prostaglandins E; Prostaglandins E, Synthetic; Rabbits

Prostaglandin-E-analogues inhibit gastric acid secretion after oral administration. Therefore, these drugs are tested in clinical trials and two of them- misoprostol and rosaprostol-has recently been registered. With regard to healing rate of peptic ulcer and improvement of clinical signs and symptoms the prostaglandin analogues are superior to placebo but only equally effective or even slightly inferior to H2-receptor blockers. The relapse rates following successful therapy with prostaglandin analogues are similar to that with H2-blockers. Side effects such as diarrhea or uterotropic actions will probably limit their broad application. The exact therapeutic effectiveness of prostaglandin analogues in treatment of peptic ulcer remains to be evaluated in greater detail. As in the treatment of peptic ulcer disease prostaglandin-analogues are only effective in preventing NOSAC-induced peptic lesions when given in antisecretory doses.

Topics: Alprostadil; Anti-Ulcer Agents; Cimetidine; Enprostil; Humans; Misoprostol; Peptic Ulcer; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Recurrence; Rioprostil; Wound Healing

Topics: Animals; Enprostil; Gastric Mucosa; Humans; Peptic Ulcer; Prostaglandins E, Synthetic

The potent antiulcer prostaglandin enprostil binds with high affinity to porcine gastric mucosal tissues. This binding is saturable, dissociable and displaceable by compounds with similar structures. Various characteristics of binding such as pH optimum and displacement potencies suggest that enprostil binds to mucosal PGE2 sites. Structure-activity and gastric mucosal binding relationships were also examined.

Topics: Animals; Binding Sites; Binding, Competitive; Cell Membrane; Dinoprostone; Enprostil; Gastric Acid; Gastric Mucosa; In Vitro Techniques; Kinetics; Peptic Ulcer; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Swine