misoprostol and Ulcer

Our knowledge of the mechanism by which aspirin and traditional NSAIDs work and damage the gastrointestinal mucosa, recently markedly improved, has suggested a number of measures for the prevention of the NSAID-induced GI lesions. Among these, perhaps the most innovative approach seems to be the nitric oxide-releasing NSAIDs or compounds, like amtolmetin guacyl, that work by increasing the endogenous biosynthesis of NO selectively at gastric mucosa level. Further data, stemming from large RCTs and confirming the results of experimental studies and the initial clinical experiences, are needed to better define the true clinical impact of this approach.

Topics: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cytoprotection; Duodenal Ulcer; Female; Gastrointestinal Diseases; Glycine; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Intestinal Diseases; Male; Middle Aged; Misoprostol; Pyrroles; Risk Factors; Stomach Ulcer; Sucralfate; Ulcer

The guiding principle of ulcer therapy for many years has been "No acid, no ulcer" and many still adhere to it. Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to cause ulcers primarily through prostaglandin depletion rather than through an acid-based mechanism. These ulcers affect a large number of patients and give few warning signs, often none, until it is too late. The profound relief offered to arthritis patients by NSAIDs, in the absence of equally effective remedies, means that rheumatologists must continue to deal with specific and quantifiable risks of NSAID-related gastrointestinal (GI) ulceration and its associated complications. The prostaglandin analog, misoprostol, may address many of these concerns because it reverses the patient's prostaglandin depleted condition. It is effective in preventing NSAID-induced ulcers, and does not interfere with the desired analgesic or anti-inflammatory effects of NSAIDs. The tools to assess the risk of NSAID-related hospitalization or death due to GI complications are available and patients at greatest risk can be identified. Physicians whose patients are at risk may wish to consider therapy with misoprostol 400 to 800 micrograms/day in divided doses. It is recommended that misoprostol be coadministered with the NSAID after meals. The most common side effects that the patient may experience are some mild and transient diarrhea and cramps upon initiation of misoprostol therapy and these can be minimized by taking misoprostol with meals and avoiding magnesium-containing antacids. For misoprostol's protective role to be demonstrated, it should be coprescribed with the NSAID for the duration of the NSAID therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Drug Combinations; Drug Interactions; Humans; Misoprostol; Ulcer

Topics: Alprostadil; Anti-Ulcer Agents; Clinical Trials as Topic; Humans; Misoprostol; Ulcer

With capsule endoscopy, the ulcerogenic effect of low-dose enteric-coated aspirin on the small bowel and the therapeutic effect of misoprostol on intestinal injury were evaluated.. Eleven patients who developed gastric ulcers while undergoing low-dose enteric-coated aspirin therapy were enrolled. They continued aspirin therapy while taking proton pump inhibitors (PPIs) for 8 weeks to heal the gastric ulcers. Then misoprostol 200 microg 4 times a day was administered instead of PPIs for 8 weeks. When the patients could not tolerate misoprostol as a result of side effects, they received another 8 weeks of PPI therapy.. Capsule endoscopy performed after 8 weeks of PPI treatment identified red spots and mucosal breaks in 100% (11/11) and 90.9% (10/11) of patients, respectively. In 7 patients who completed the study protocol, misoprostol significantly decreased the median number of red spots and mucosal breaks, with complete disappearance of mucosal breaks in 4 patients. Intestinal lesions tended not to heal in 3 patients who discontinued misoprostol.. Low-dose enteric-coated aspirin frequently damages the small intestine, and misoprostol is effective in the treatment of aspirin-induced enteropathy.

Topics: Aged; Anti-Ulcer Agents; Aspirin; Capsule Endoscopy; Female; Humans; Intestine, Small; Male; Middle Aged; Misoprostol; Pilot Projects; Prospective Studies; Tablets, Enteric-Coated; Treatment Outcome; Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Double-Blind Method; Endoscopy; Humans; Misoprostol; Omeprazole; Ranitidine; Secondary Prevention; Ulcer; Wound Healing

The differential diagnosis for ulcerating small bowel strictures is extensive and includes exposure to non-steroidal anti-inflammatory drugs (NSAIDs), Crohn's disease, infections, gastrointestinal lymphoma and vasculopathy. It also encompasses the exceptionally rare and poorly understood diagnosis of cryptogenic multifocal ulcerative stenosing enterocolitis (CMUSE), often a diagnosis of exclusion and considerable difficulty. We present a case of persistent proximal jejunal ulcerating stenoses in a 75-year-old Caucasian man, which continued despite cessation of NSAIDs. After extensive clinical, radiographic, laboratory and ultimately surgical pathological appraisal-as well as failure to improve with both misoprostol and budesonide-he was diagnosed with CMUSE and managed with limited small bowel resection. In the presentation of this case, we aim to underscore the diagnostic challenges that clinicians face in differentiating CMUSE from other more common diagnoses, particularly NSAIDs-induced enteropathy.

Topics: Abdominal Pain; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Constriction, Pathologic; Diagnosis, Differential; Enteritis; Humans; Intestinal Obstruction; Intestine, Small; Male; Misoprostol; Tomography, X-Ray Computed; Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Double-Blind Method; Humans; Misoprostol; Ulcer

Clinical studies indicate that prostaglandins of E class (PGEs) may promote healing of tissue injury e.g., gastroduodenal and dermal ulcers. However, the precise roles of PGEs, their E-prostanoid (EP) receptors, signaling pathways including cAMP and cAMP response element-binding protein (CREB), and their relation to VEGF and angiogenesis in the tissue injury healing process remain unknown, forming the rationale for this study. Using an esophageal ulcer model in rats, we demonstrated that esophageal mucosa expresses predominantly EP2 receptors and that esophageal ulceration triggers an increase in expression of the EP2 receptor, activation of CREB (the downstream target of the cAMP signaling), and enhanced VEGF gene expression. Treatment of rats with misoprostol, a PGE1 analog capable of activating EP receptors, enhanced phosphorylation of CREB, stimulated VEGF expression and angiogenesis, and accelerated esophageal ulcer healing. In cultured human esophageal epithelial (HET-1A) cells, misoprostol increased intracellular cAMP levels (by 163-fold), induced phosphorylation of CREB, and stimulated VEGF expression. A cAMP analog (Sp-cAMP) mimicked, whereas an inhibitor of cAMP-dependent protein kinase A (Rp-cAMP) blocked, these effects of misoprostol. These results indicate that the EP2/cAMP/protein kinase A pathway mediates the stimulatory effect of PGEs on angiogenesis essential for tissue injury healing via the induction of CREB activity and VEGF expression.

Topics: Animals; Cell Line; CREB-Binding Protein; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Esophageal Diseases; Esophagus; Humans; Male; Misoprostol; Mucous Membrane; Neovascularization, Physiologic; Phosphorylation; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin E, EP2 Subtype; RNA, Messenger; Second Messenger Systems; Time Factors; Ulcer; Up-Regulation; Vascular Endothelial Growth Factor A; Wound Healing

Topics: Animals; Anti-Ulcer Agents; Female; Horse Diseases; Horses; Misoprostol; Pregnancy; Ulcer

A case of a 40-year-old man with chronic anaemia because of nonspecific ulcerating and stenosing enteropathy is presented. The diagnosis was made on the basis of capsule endoscopy, histology of resected ileum and no use of NSAIDs. He showed a clinical response to treatment with misoprostol, and therefore, he was investigated for a possible impairment in eicosanoid biosynthesis compared with healthy controls. No deficient synthesis of prostacyclin, prostaglandin E2 and thromboxane was found on examination of metabolites in blood and urine. This suggests a normal release of arachidonic acid from phospholipids. Ex-vivo cyclooxygenase (COX) assays showed normal COX-1 and COX-2 activities. The clinical response to treatment with the prostaglandin E1 analogue misoprostol suggests a defective prostaglandin E synthesis in the intestinal mucosa.

Topics: Adult; Anemia, Iron-Deficiency; Humans; Intestinal Diseases; Male; Misoprostol; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Ulcer

A 15-year-old Quarter Horse gelding and a 26-year-old Thoroughbred gelding were evaluated because of hematuria of 4 to 6 days' duration following prolonged oral administration of phenylbutazone.. The horses had received either treatment with phenylbutazone for 3 months or intermittent long-term phenylbutazone treatment prior to development of hematuria. Each horse was systemically stable but had orthopedic or neurologic problems. Clinicopathologic findings included normochromic normocytic anemia in both horses and hypoalbuminemia and high BUN concentration in 1 horse. In both horses, urinalysis revealed proteinuria and RBCs, but no evidence of WBCs or bacteria. Ulceration and hemorrhage of the urinary bladder with no evidence of uroliths were observed via cystoscopy. Gastric ulceration along the margo plicatus was observed via gastroscopy.. For each horse, phenylbutazone treatment was discontinued and a synthetic prostaglandin (misoprostol) was administered. The hematuria resolved, and results of a follow-up CBC, serum biochemical analysis, urinalysis, and cystoscopy 25 or 30 days after cessation of phenylbutazone treatment were unremarkable in both cases.. Given the known adverse effects of NSAID treatment in several species, phenylbutazone and its metabolites were suspected to have caused ulceration of the urinary bladder, resulting in hematuria, in the 2 horses. A definitive cause of urinary bladder ulceration was not confirmed in these cases; however, resolution of ulceration after discontinuation of phenylbutazone treatment and administration of synthetic prostaglandins and exclusion of other causes suggested an association between phenylbutazone administration and ulcerative cystitis in these horses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cystitis; Hematuria; Horse Diseases; Horses; Male; Misoprostol; Omeprazole; Phenylbutazone; Ulcer

Esophageal ulceration is a common and important cause of morbidity in patients with acquired immunodeficiency syndrome (AIDS). After known causes are excluded, a subgroup remains with unexplained esophageal ulceration, known as idiopathic esophageal ulceration (IEU). The current therapy of IEU includes corticosteroids or, less frequently, thalidomide, although no placebo-controlled trials have been reported. The aim of this retrospective study was to determine the outcome of treating IEU with misoprostol and viscous lidocaine.. A retrospective review of esophageal ulceration in AIDS identified seven subjects with IEU at our institution. IEU in these subjects was treated successfully with misoprostol, 200 microg, crushed and suspended in 2% viscous lidocaine, 15 ml, given orally a.c. and h.s. for 4 wk.. All patients reported symptomatic improvement within 2-3 days and complete resolution of their symptoms within 15 days. Healing of esophageal ulcerations was confirmed in five of seven subjects at a repeat endoscopy 8-12 wk later.. Misoprostol, an antiulcer drug, has GI cytoprotective properties, and viscous lidocaine, a topical anesthetic, coats mucosal surfaces. We speculate that misoprostol when delivered topically is 3-6 times more effective than when delivered systemically. Considering the rapid resolution of symptoms, healing of ulcers, and lack of side effects, we believe that misoprostol crushed and suspended in viscous lidocaine should be considered for further evaluation in prospective, placebo-controlled trials of IEU.

Topics: Acquired Immunodeficiency Syndrome; Administration, Topical; Adult; Anesthetics, Local; Anti-Ulcer Agents; Drug Combinations; Esophageal Diseases; Female; Humans; Lidocaine; Male; Middle Aged; Misoprostol; Retrospective Studies; Suspensions; Ulcer; Viscosity

Using misoprostol prophylaxis as an example, many of the methods employed in economic analyses that incorporate mathematical models were described. These included: decision analysis, cost effectiveness analysis (including incremental cost effectiveness analysis), one-way, multi-way, and probabilistic sensitivity analysis, and the estimation of quality adjusted life years for use in cost utility analysis. In the case of misoprostol prophylaxis, the cost effectiveness analysis demonstrated that, compared to the no prophylaxis alternative, prophylaxis cost an extra $650, on average, for every additional ulcer prevented, and was potentially cost saving for some high risk groups. The cost utility analysis demonstrated that prophylaxis resulted (on average) in modest additional costs and no additional quality of life benefits. Sensitivity analysis demonstrated that, at worst, prophylaxis reduced quality of life; at best, the incremental cost effectiveness ratio was $9333 for each quality adjusted life-year gained by prophylaxis compared to no prophylaxis. The results of the cost utility analysis also showed that prophylaxis may be cost saving in high risk groups, confirming the results of the cost effectiveness analysis. Finally, and perhaps most importantly, this analysis illustrated the importance of incorporating measures of health related quality of life into economic evaluation.

Topics: Cost-Benefit Analysis; Humans; Misoprostol; Models, Econometric; Outcome Assessment, Health Care; Quality-Adjusted Life Years; Ulcer

Small bowel ulceration is an increasingly recognised complication of therapy with non-steroidal anti-inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers.. We have retrospectively examined the effect of therapy with the prostaglandin E1 analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy.. All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol-treated group rose significantly from median (range) 9.1 (6.2-10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5-16.8) g/dL (95% confidence intervals 10.06, 11.82); P = 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5-10.6) g/dL to 8.1 (5.6-14.7) g/dL (P = N.S.).. Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Intestinal Diseases; Male; Middle Aged; Misoprostol; Retrospective Studies; Rheumatic Diseases; Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cost-Benefit Analysis; Drug Therapy, Combination; Gastritis; Humans; Misoprostol; Ulcer

Based on an American multicenter study, an economic evaluation of prophylactic misoprostol was undertaken in Sweden. The study included 420 patients with osteoarthritis and nonsteroidal anti-inflammatory drug (NSAID)-associated abdominal pain, but no gastric ulcer at inclusion. The frequency of ulcer development with and without prophylactic misoprostol was assessed at 21.7% and 5.6%, respectively, for a 3-month period. All costs for drugs, ambulatory care, hospital care, loss of production, as well as other factors such as dosage and compliance, were transferred to Swedish conditions. It was concluded that in patients with osteoarthritis and NSAID-induced abdominal pain, prophylaxis with misoprostol is cost-effective in Sweden, which is similar to what is found for other countries. A prerequisite for this result is a frequency of ulcer development of 15%. A patient compliance to prophylactic treatment of more than 60% is also presupposed (79% was observed in the above study). Due to the high age of the osteoarthritis patient population, the cost-effectiveness is influenced to only a minor extent by whether indirect costs are included in the calculation.

Topics: Adult; Aged; Ambulatory Care; Anti-Inflammatory Agents, Non-Steroidal; Cost-Benefit Analysis; Drug Costs; Hospitalization; Humans; Middle Aged; Misoprostol; Models, Econometric; Osteoarthritis; Sweden; Ulcer