misoprostol and Gastrointestinal-Hemorrhage

Recent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Capsule Endoscopy; Gastrointestinal Hemorrhage; Humans; Intestinal Diseases; Intestine, Small; Misoprostol; Peptic Ulcer

In addition to their cardiac, renal, hepatic, cutaneous and neuropsychological adverse effects, nonsteroidal anti-inflammatory drugs (NSAIDs) can have severe effects on the entire gastrointestinal tract, including bleeding, perforation and occlusion. Which anti-ulcer drugs reduce the risk of the severe gastrointestinal adverse effects of NSAIDs, and which patients should receive them? To answer these questions, we conducted a review of the literature, using the standard Prescrire methodology. The main risk factors for severe gastrointestinal adverse effects during NSAID therapy are: a high dose regimen; age over 65 years; a history of gastric or duodenal ulcer or gastrointestinal bleeding; heavy use of both alcohol and tobacco; and concomitant treatment with a corticosteroid, antiplatelet drug, anticoagulant, or selective serotonin reuptake inhibitor (SSRI) antidepressant. Gastrointestinal symptoms and ulceration (on endoscopy) are poor predictors of severe gastrointestinal reactions. A meta-analysis examined randomised placebo-controlled trials of misoprostol in more than 11 000 patients. The results were mainly based on a large trial including about 9000 rheumatoid arthritis patients with an average age of 68 years. Misoprostol (400 microg to 800 microg/day, in 4 doses) prevented about 4 severe gastroduodenal events when 1000 patients over 60 years of age were treated for 6 months. Diarrhoea and other mild gastrointestinal disorders were frequent. There are no randomised trials comparing proton pump inhibitors (PPIs) and histamine H2 receptor antagonists versus misoprostol or versus placebo therapy for the prevention of severe adverse effects associated with NSAIDs. PPIs and H2 antagonists both reduce the incidence of gastric or duodenal ulceration detected by routine endoscopy. A randomised trial compared an H2 antagonist (famotidine) versus a PPI (pantoprazole) in 128 patients with an average age of 69 years who had a very high risk of serious gastrointestinal adverse effects while taking low-dose aspirin. After 48 weeks of treatment, pantoprazole was more effective than famotidine for the prevention of overt gastrointestinal bleeding. The symptomatic effects of PPIs and H2 antagonists may create a false sense of security, leading some patients to increase their NSAID use and resulting in a paradoxical increase in severe gastrointestinal effects. In practice, anti-ulcer drugs are not sufficiently effective to warrant their use by NSAID-treated adults

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Proton Pump Inhibitors

Aspirin is widely used for the prevention of thrombotic cardiovascular disease. The effect of platelet antiaggregation is achieved with low doses of 75-325 mg/day. Due to COX-1 inhibition, associated gastrointestinal adverse effects can occur. Other drugs whose platelet antiaggregant effect is achieved through different mechanisms of action have been developed, such as clopidogrel and ticlopidine, which do not inhibit COX-1. The proportion of patients taking low-dose aspirin alone or in combination with other antiaggregants is high and consequently the use of these drugs should be optimized by reducing their gastrointestinal adverse effects to a minimum. Knowledge of the risk factors that increase the risk of gastrointestinal adverse effects with platelet antiaggregants, such as age, concomitant use of other drugs such as anticoagulants or non-steroidal anti-inflammatory drugs, a history of peptic ulcer -whether complicated or uncomplicated-, and Helicobacter pylori infection, would help to allow management to be individually tailored to each patient. The use of proton pump inhibitors and/or H. pylori eradication should allow a positive balance, even in patients with gastrointestinal risk factors.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Clopidogrel; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dinoprostone; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Middle Aged; Misoprostol; Peptic Ulcer Hemorrhage; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Risk Factors; Thromboxanes; Ticlopidine

Gastrointestinal toxicity is a common adverse effect of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and patients at risk should receive prevention therapies. Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) are safer to the gastrointestinal tract than traditional NSAIDs. Current prevention strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as coxibs and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive cotherapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone. However, patients with a previous bleeding ulcer should receive the combination of a coxib plus a PPI, and Helicobacter pylori should be tested for and treated if present. Coxib and NSAID therapy should be prescribed with caution in patients with increased cardiovascular risk and should be prescribed at the lowest possible dose and for the shortest period of time. These patients will probably be treated with low-dose aspirin or other antiplatelet agents, which puts them at increased risk of upper gastrointestinal complications. The risk of gastrointestinal toxicity with combined therapy of aspirin and coxib may be lower than that with traditional NSAIDs plus aspirin, but all these patients may benefit from PPI cotherapy. When the lower gastrointestinal tract is of concern, coxib instead of NSAID therapy should be considered. Coxib therapy has better gastrointestinal tolerance than traditional NSAIDs and PPI therapy is effective both in the treatment and prevention of NSAID-induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclooxygenase 2 Inhibitors; Drug Combinations; Dyspepsia; Evidence-Based Medicine; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Misoprostol; Proton Pump Inhibitors

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Proton Pump Inhibitors; Risk Assessment

Gastrointestinal harm, known to occur with NSAIDs, is thought to be lower with NSAID and gastroprotective agent, and with inhibitors selective to cyclooxygenase-2 (coxibs) at usual plasma concentrations. We examine competing strategies for available evidence of reduced gastrointestinal bleeding in clinical trials and combine this evidence with evidence from clinical practice on whether the strategies work in the real world, whether guidance on appropriate prescribing is followed, and whether patients adhere to the strategies.. We used a series of systematic literature searches to find full publications of relevant studies for evidence about the efficacy of these different gastroprotection strategies in clinical trials, and for evidence that they worked and were adhered to in clinical practice--whether they were effective. We chose to use good quality systematic reviews and meta-analyses when they were available.. Evidence of efficacy of coxibs compared to NSAIDs for upper gastrointestinal bleeding was strong, with consistent reductions in events of about 50% in large randomised trials (34,460 patients), meta-analyses of randomised trials (52,474 patients), and large observational studies in clinical practice (3,093 bleeding events). Evidence on the efficacy of NSAID plus gastroprotection with acid suppressants (proton pump inhibitors, PPIs, and histamine antagonists, H2As) was based mainly on the surrogate measure of endoscopic ulcers. The limited information on damage to the bowel suggested that NSAID plus PPI was more damaging than coxibs. Eleven observational studies studied 1.6 million patients, of whom 911,000 were NSAID users, and showed that 76% (range 65% to 90%) of patients with at least one gastrointestinal risk factor received no prescription for gastroprotective agent with an NSAID. The exception was a cohort of US veterans with previous gastrointestinal bleeding, where 75% had gastroprotection with an NSAID. When gastroprotection was prescribed, it was often described as inadequate. A single study suggested that patient adherence to prescribed gastroprotection was low.. Evidence for efficacy of gastroprotection strategies with NSAIDs is limited. In clinical practice few patients who need gastroprotection get it, and those who get it may not take it. For coxibs, gastroprotection is inherent, although probably not complete.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Cyclooxygenase 2 Inhibitors; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Gastrointestinal Tract; Histamine Antagonists; Humans; Inflammation; Meta-Analysis as Topic; Misoprostol; Patient Compliance; Practice Patterns, Physicians'; Proton Pumps; Treatment Outcome

Upper gastrointestinal bleeding continues to plague physicians despite the discovery of Helicobacter pylori and advances in medical therapy for peptic ulcer disease. Medical therapy with new nonsteroidal anti-inflammatory medications and somatostatin/octreotide and intravenous proton pump inhibitors provides hope for reducing the incidence of and treating bleeding peptic ulcer disease. Endoscopic therapy remains the mainstay for diagnosis and treatment of upper gastrointestinal bleeding. Many methods of endoscopic hemostasis have proven useful in upper gastrointestinal hemorrhage. Currently, combination therapy with epinephrine injection and bicap or heater probe therapy is most commonly employed in the United States. Angiography and embolization play a role primarily when endoscopic therapy is unsuccessful.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Hemostatic Techniques; Humans; Laser Coagulation; Misoprostol; Octreotide; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Sclerotherapy; Somatostatin; United States

Current evidence suggests that PPIs might be effective in maintaining patients in remission during continued NSAID use and that the combination of omeprazole plus diclofenac is as effective as treatment with celecoxib in preventing recurrent bleeding. Larger outcome studies comparing the combination of a PPI with other nonselective NSAIDs and a selective COX-2 inhibitor (and the combination of a selective COX-2 inhibitor with a PPI or misoprostol) are required to determine whether or not any regimen will further decrease or eliminate the risk of ulcer complications in high-risk individuals.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Celecoxib; Cyclooxygenase Inhibitors; Diclofenac; Enzyme Inhibitors; Gastrointestinal Hemorrhage; Humans; Lactones; Misoprostol; Omeprazole; Osteoarthritis; Proton Pump Inhibitors; Pyrazoles; Randomized Controlled Trials as Topic; Sulfonamides; Sulfones

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cost-Benefit Analysis; Decision Trees; Drug Costs; Gastrointestinal Hemorrhage; Humans; Misoprostol; Peptic Ulcer

Nonsteroidal antiinflammatory drugs (NSAIDs) are used in large amounts for analgesic, antiinflammatory, and antithrombotic indications. This use is not without side effects on the gut and other organs, and some of these side effects may be serious and even lethal. No NSAID has been shown to be without side-effect potential. Use increases with age, and age poses additional risks to patients with side effects. The most serious side effects are perforation of peptic and gut ulcers and gastrointestinal (GI) bleeding, which NSAIDs, and especially acetylsalicylic acid (ASA; aspirin), may promote from both ulcer and nonulcer lesions of both the upper and lower GI tract (i.e., both acid- and nonacid-dependent). Upper GI mucosal lesions range from trivial--petechiae and superficial erosions--to significant and potentially serious deep (chronic) peptic ulcers, esophagitis, and, less commonly, small and large gut ulcers. Symptoms may occur independently of observable lesions, and serious lesions may occur without any prior symptoms. The risk of ulceration due to therapeutic doses of NSAIDs is estimated at 5- to 10-fold. NSAIDs also delay healing of conventional peptic ulcers. Moreover, ASA abuse, often surreptitious and discoverable by serum salicylate level measurement, may cause totally intractable gastric or duodenal ulceration. Surgery is contraindicated because relapse is inevitable and progressively more serious. The rational use of NSAIDs is discussed, and prophylactic and treatment strategies are proposed. None seems entirely satisfactory, and the best prophylaxis would be to avoid the use of NSAIDs except for proven indications. Until the mechanisms whereby NSAIDs both cause injury and provide therapeutic benefits can be separated, the problem of side effects and their prevention or treatment remains unresolvable.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Digestive System; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Intestinal Perforation; Intestine, Large; Intestine, Small; Misoprostol; Omeprazole; Osteoarthritis; Peptic Ulcer; Sucralfate

Severe upper gastrointestinal (GI) bleeding is a serious adverse effect of nonsteroidal antiinflammatory drugs (NSAIDs) and the elderly are at increased risk of developing this complication. Bleeding episodes can be prevented. Replacing NSAIDs with acetaminophen may be appropriate when a simple analgesic is needed that eliminates the risk of GI bleeding. Using the lowest effective NSAID dose may decrease the incidence and severity of NSAID gastropathy. Histamine H2-receptor antagonists, sucralfate, and misoprostol have been studied for the prevention of NSAID gastropathy, but only misoprostol prevents mucosal injury in both the stomach and duodenum. Patients who have a history of peptic ulcer disease or gastric bleeding from NSAIDs are candidates for prophylactic measures. Although other patients are at risk, no one knows who should receive prophylactic therapy for NSAID gastropathy. Future studies should attempt to define patient populations that warrant prophylactic therapy.

Topics: Acetaminophen; Aged; Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Contraindications; Gastrointestinal Hemorrhage; Humans; Misoprostol; Risk Factors

Aspirin and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal bleeding is recognized as an important health problem. We performed a single-center randomized clinical trial to compare the effect of high-dose intravenous proton pump inhibitor (omeprazole) alone (group 1) with omeprazole in combination with a low-dose prostaglandin analog (misoprostol; group 2) on clinical outcomes in patients with aspirin/NSAID-induced upper gastrointestinal bleeding. Additionally, we evaluated the contribution of Helicobacter pylori eradication therapy on the late consequences. Patients were recruited to the study if they had upper gastrointestinal bleeding with history of taking aspirin or other NSAIDs within the week before the onset of bleeding. All were evaluated in terms of probable risk factors. After the standard treatment protocol, patients with histologically proven H pylori infection were prescribed a triple eradication therapy for 14 days. The primary end points were recurrent bleeding, surgery requirement, and death rates before discharge and at the end of follow-up period. This study lasted for 2 years. A total of 249 patients with upper gastrointestinal bleeding were admitted, and 49.7% of these patients were users of aspirin/NSAIDs. There were 67 patients in group 1 and 56 in group 2. The distributions for gender, age, comorbidity, H pylori infection, and high-risk ulcer rate were similar in both groups. Among aspirin/NSAID users, endoscopy revealed duodenal ulcer in 47 (38.2%), gastric ulcer in 10 (8.1%), and erosive gastropathy in 33 (26.8%). The overall rebleeding occurred in 12.2%, death in 2.4% of the patients. The in-hospital death (P=.414), rebleeding (P=.925), and surgery (P=.547) rates were similar in both treatment groups. After the follow-up period of 3 months, overall rebleeding occurred in 4.1%, and death in 4.8% of the patients. The overall mortality rate was highest in those >65 years old, who were chronic low-dose aspirin users with comorbidity. One died of transfusion-related graft-versus-host disease. In this pilot study, we indicated that adding misoprostol (600 microg/day) to standardized proton pump inhibitor treatment did not improve or change the rebleeding or mortality rates of patients with upper gastrointestinal bleeding related to aspirin/NSAID use. Other prospective studies on higher doses of misoprostol are needed to establish the coeffect. One should bear in mind that all blood products must be irradiated befo

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Comorbidity; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Misoprostol; Omeprazole; Pantoprazole; Pilot Projects; Prospective Studies; Recurrence

Prophylactic misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury.. To compare nabumetone vs. co-therapy of naproxen with low-dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users.. NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long-term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 microg b.d.), or nabumetone (1000-1500 mg/day) and placebo misoprostol for 24 weeks. The primary end-point was recurrent upper gastrointestinal bleeding. The secondary end-point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia.. A total of 90 patients were included in the intention-to-treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98-11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group.. Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low-dose misoprostol nor nabumetone is adequate for high-risk NSAID users.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Misoprostol; Nabumetone; Naproxen; Prospective Studies; Recurrence

To determine the incidence of gastrointestinal (GI) tract bleeding in dogs undergoing spinal surgery with adjunct corticosteroid treatment, and to determine the protective efficacy of cimetidine, sucralfate, and misoprostol against such bleeding in these dogs.. 40 dogs that underwent spinal surgery.. Myelography and surgery were performed on the first or second day of hospitalization. Methylprednisolone sodium succinate was given at a dosage of 30 mg/kg of body weight prior to myelography, followed by a second full or half dose 2 to 4 hours later at clinician discretion. Spinal surgery was performed in conventional manner, postoperative administration of analgesics was done, and dogs were fed a diet lacking red meat. Dogs were assigned at random to 1 of the 3 treatment groups or to the control group. Dogs of the treatment groups received cimetidine, sucralfate, or misoprostol. Physical examination and determination of PCV and serum total protein values were performed daily. A fecal sample was examined daily for gross and occult blood.. 36 of 40 dogs had GI tract bleeding during a hospitalization period of 3 to 6 days. There was no significant difference in development of bleeding between the control group and any of the treatment groups.. Gastrointestinal tract bleeding occurred in 90% of dogs undergoing spinal surgery combined with administration of methylprednisilone sodium succinate, a higher rate than that found in previous studies. This bleeding was not life-threatening. Prophylactic benefit from any of the GI protectants tested was not found.

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Blood Loss, Surgical; Body Weight; Cimetidine; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Gastrointestinal Hemorrhage; Incidence; Methylprednisolone Hemisuccinate; Misoprostol; Myelography; Occult Blood; Spine; Sucralfate

A multicenter, double-blind, placebo-controlled study was carried out to determine whether the synthetic prostaglandin E1 analog misoprostol is effective in preventing gastric and duodenal lesions induced by nonsteroidal anti-inflammatory drugs. Two hundred fifty-six patients under nonsteroidal anti-inflammatory drug treatment (diclofenac, naproxen, piroxicam, ibuprofen, indomethacin, ketoprofen, or tiaprofenic acid) for osteoarthritis, rheumatoid arthritis, or other rheumatic diseases were included in the study. None of the patients had patent gastroduodenal damage at entry (0 to 3 mucosal erosions or subepithelial hemorrhages on endoscopy). Patients were randomly assigned to treatment with misoprostol 400 micrograms/d (M 400), misoprostol 800 micrograms/d (M 800) or a placebo. Results of the follow-up endoscopy on day 28 in the 186 evaluable patients showed that gastric erosions were significantly less common (p < or = 0.02) in the two misoprostol groups (5% and 2% in the M 400 and M 800 groups respectively) than in the placebo group (19%). Similar small numbers of patients in the three groups had gastric subepithelial hemorrhages or duodenal lesions. Three patients developed gastric ulcers in the placebo group, versus none in the misoprostol groups. Misoprostol therapy did not modify the efficacy of the nonsteroidal antiinflammatory agent on pain or other rheumatologic manifestations. Diarrhea occurred in 1%, 10%, and 5% of patients in the M 400, M 800, and placebo groups, respectively. In conclusion, misoprostol given in combination with a nonsteroidal anti-inflammatory agent for 28 days significantly reduced the incidence of gastric erosions in a random sample of patients with a variety of rheumatic diseases. The daily dosage associated with the best risk/benefit ratio may be 400 micrograms/day.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Duodenal Ulcer; Duodenoscopy; Duodenum; Female; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Middle Aged; Misoprostol; Stomach; Stomach Ulcer

Indomethacin, a nonsteroidal anti-inflammatory drug, may cause gastric mucosal damage as shown by fecal blood loss. A randomized, double-blind, placebo-controlled, parallel group study was conducted to determine the effects of 400 mcg b.i.d. misoprostol, a synthetic prostaglandin E1 analog, on intestinal blood loss caused by 50 mg t.i.d. indomethacin. Forty-two arthritic patients, mean age 59 years, received indomethacin for 14 days. Those with baseline blood loss of at least 1.5 ml/day during the first 7 days were randomized to 400 mcg of misoprostol or placebo (days 8 to 14). Fecal blood loss was measured using 51Cr labelled red blood cell technique. Success was defined as a reduction in mean daily blood loss of at least 50% during the treatment period compared to mean daily blood loss during the baseline (pre-treatment) phase. The mean daily blood loss on treatment days 9-15 was not significantly reduced from baseline in either group. These data neither confirm nor deny the effectiveness of misoprostol in reducing fecal blood loss caused by indomethacin. The results may have been confounded by the administration of misoprostol twice daily while indomethacin was administered three times daily. In addition, fecal blood loss as an indicator of gastrointestinal mucosal damage is not a sensitive measure; it is characterized by poor reproducibility and wide fluctuations within individual responses. Inappropriate laboratory techniques may have further reduced the sensitivity and reliability of this procedure.

Topics: Arthritis, Rheumatoid; Double-Blind Method; Female; Gastrointestinal Hemorrhage; Humans; Indomethacin; Male; Middle Aged; Misoprostol; Occult Blood; Osteoarthritis; Treatment Outcome

A randomized, double-blind, controlled study was performed with 18 arthritic dogs administered aspirin (25 mg/kg of body weight, PO, q 8 h) and excipient (control group) or aspirin and misoprostol (100 micrograms, PO, q 8 h). Dogs in the misoprostol (n = 10) and control (n = 8) groups were primarily compared by use of sequential gastroduodenoscopy, changes in PCV, and prevalence of clinical signs of gastrointestinal disturbance over a 14-day treatment period. The misoprostol/aspirin-treated group had significantly (P < 0.05) less gastroduodenal hemorrhage and ulceration and a significantly (P < 0.05) lower prevalence of vomiting than did the control group.

Topics: Animals; Aspirin; Diarrhea; Dog Diseases; Dogs; Double-Blind Method; Duodenoscopy; Female; Gastrointestinal Hemorrhage; Gastroscopy; Male; Misoprostol; Osteoarthritis; Peptic Ulcer; Vomiting

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Misoprostol

Nonsteroidal anti-inflammatory drugs are used to control pain and inflammation in arthritic disorders. When used at recommended anti-inflammatory dose levels, however, they often produce injury to the gastric and duodenal mucosa and concomitant blood loss. A double-blind, parallel, placebo-controlled study was conducted to assess the effectiveness of misoprostol, a synthetic analogue of prostaglandin E1, in preventing gastrointestinal blood loss induced by acetylsalicylic acid in patients with degenerative joint disease. Forty-five arthritic patients (22 women and 23 men) were admitted to the study. All patients had received treatment with 3,900 mg of acetylsalicylic acid per day in four divided doses for at least two weeks and continued to receive that regimen for the duration of the study. Red blood cells were tagged with chromium-51, and fecal blood loss was determined from Days 4 to 7. Patients with a mean blood loss of at least 1.5 ml per day were randomly allocated to receive either placebo or 200 micrograms of misoprostol four times daily for seven days. Fecal blood loss was measured daily, and the results were compared with baseline determinations. Of 41 patients who completed the study, 19 were treated with misoprostol. Of these, 11 patients (57.9 percent) had at least a 50 percent reduction in blood loss. Of 22 patients receiving placebo, only one had a 50 percent reduction in blood loss (p = 0.003; Fisher's exact test). Mean blood loss in patients using misoprostol was reduced from 3.65 +/- 2.51 to 1.57 +/- 0.86 ml per day, whereas among those taking placebo, mean blood loss did not significantly change (2.98 +/- 1.24 to 2.79 +/- 1.63 ml per day). The difference in blood loss between the misoprostol and placebo groups was significant (p = 0.0023; Wilcoxon test). In those patients who completed the study, no significant changes were detected on laboratory tests. In conclusion, misoprostol effectively reduced fecal blood loss in arthritic patients treated with acetylsalicylic acid.

Topics: Alprostadil; Anti-Ulcer Agents; Aspirin; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis

This randomized, double-blind, placebo-controlled study compared the cytoprotective effects of misoprostol, a synthetic analog of prostaglandin E1, and cimetidine on ethanol-induced gastric mucosal damage. Forty-five healthy male subjects were accepted, following endoscopy to exclude those with upper gastrointestinal disease. Injury to the gastric mucosa was induced by spraying it with 80% ethanol solution. Misoprostol (200 micrograms) intragastrically or cimetidine (300 mg) orally or placebo was administrated before the ethanol challenge. The gastric mucosa was graded using a seven-point endoscopic scale by two endoscopists 15 and 30 min after ethanol instillation. Thirty minutes following the instillation of ethanol, the gastric mucosa of placebo-treated subjects showed marked damage, with an endoscopic score (mean +/- standard deviation) of 5.5 +/- 0.9. Cimetidine partially prevented gastric mucosal damage, with an endoscopic score of 4.5 +/- 1.7 as compared to placebo (p = 0.04). Misoprostol significantly prevented gastric mucosal injury with a mean endoscopic score of 1 +/- 1.7 when compared to placebo (p = 0.0001) and to cimetidine (p = 0.0002). This cytoprotective action of misoprostol may prove to be clinically very important and warrants further investigation.

Topics: Adult; Alprostadil; Anti-Ulcer Agents; Cimetidine; Clinical Trials as Topic; Double-Blind Method; Ethanol; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Misoprostol; Random Allocation

Misoprostol (SC-29333), a synthetic prostaglandin E1 methyl ester analog, was given simultaneously with acetylsalicylic acid in a double-blind, placebo-controlled randomized prospective study of 32 healthy human male subjects. Fecal blood loss was measured for eight days using the 51Cr-labeled red blood cell technique. Aspirin (650 mg qid) and misoprostol (25 micrograms qid) or placebo were given during days 3, 4, and 5. There was a significant (P less than 0.05) increase in median blood loss (modified Friedman test) from 0.81 to 6.05 ml/day in the aspirin with placebo group (N = 16). Median blood loss was increased (from 0.75 to 3.75 ml/day) in the aspirin with misoprostol group (N = 16), but this was significantly less (Mann-Whitney U test, P less than 0.01) than the placebo group. Mean serum salicylate concentrations in the placebo and misoprostol groups were similar (7.8 and 6.8 micrograms/ml, respectively). There were no significant changes in laboratory values in any of the subjects studied, nor were any major side-effects encountered. This study demonstrates that oral misoprostol reduces aspirin-induced gastrointestinal bleeding even when administered simultaneously and at a dose level below its threshold for significant acid inhibition. This indicates a potential role for misoprostol in the prevention of gastric mucosal damage in selected patients.

Topics: Adult; Aspirin; Chromium Radioisotopes; Double-Blind Method; Drug Evaluation; Feces; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Prostaglandins E, Synthetic; Random Allocation

The cytoprotective effects of misoprostol, a synthetic analog of prostaglandin E1, were investigated in healthy human subjects using randomized and placebo-controlled studies. Misoprostol significantly inhibited established aspirin (975 mg q.i.d.)-induced gastric microbleeding at 50 micrograms q.i.d., and to some extent, but not significantly, at 25 micrograms q.i.d. Misoprostol also reduced acid and chloride secretion significantly at 50 micrograms q.i.d., but not at 25 micrograms q.i.d. When administered concurrently with aspirin 650 mg q.i.d., misoprostol 25 micrograms q.i.d. significantly inhibited aspirin-induced fecal blood loss without affecting plasma salicylate concentration. The fact that misoprostol was tested at a sub-therapeutic gastric antisecretory dose (25 micrograms) indicates that the inhibition of fecal blood loss was not due to its gastric antisecretory property. Misoprostol tended to reduce antral erosion and DNA content of gastric fluid, but increased mucus concentrations in subjects with ethanol-induced damage. However, the dose of ethanol used produced gastric damage in only six of the 10 subjects and did not provide a satisfactory baseline. Misoprostol attenuated the drop in transmucosal potential difference induced by sodium taurocholate. It is concluded that misoprostol has cytoprotective activity in man. These effects may be of great importance in the treatment of acid peptic disease of the gastrointestinal tract.

Topics: Adult; Alprostadil; Anti-Ulcer Agents; Aspirin; Bile Acids and Salts; DNA; Drug Evaluation; Duodenum; Ethanol; Feces; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Male; Membrane Potentials; Misoprostol

Acid suppressants such as histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are effective in preventing gastrointestinal (GI) bleeding in nonsteroidal anti-inflammatory drugs (NSAIDs) users. Despite widespread acid suppressant use, there remain concerns about several potential risks of long-term use. Therefore, we investigated whether gastroprotective agents (GPAs) other than acid suppression therapy are effective in preventing NSAID-related GI injury. To this end, we studied 9,133 patients with osteoarthritis or rheumatoid arthritis who used NSAIDs for ≥1 month. A decrease of 2 g/dL or more in the hemoglobin level was considered a GI injury indicator. The GPAs included acid suppressants and other mucoprotective agents. Acid suppressants included PPIs and H2RAs. Other mucoprotective agents included misoprostol, rebamipide, and eupatilin. During a median follow-up period of 27 (range, 4.3-51.3) weeks, occult GI bleeding occurred in 1,191 (13%) patients. A comparison of patients who used GPAs concomitantly with that of nonusers in a multivariable analysis revealed the hazard ratios (HRs; 95% confidence intervals [CIs]) for occult GI bleeding were 0.30 (0.20-0.44), 0.35 (0.29-0.43), 0.47 (0.23-0.95), 0.43 (0.35-0.51), and 0.98 (0.86-1.12) for PPIs, H2RAs, misoprostol, rebamipide, and eupatilin, respectively. Compared to PPI co-treatment, H2RA, misoprostol, rebamipide, and eupatilin co-treatments were associated with occult GI bleeding HRs (95% CIs) of 1.19 (0.79-1.79), 1.58 (0.72-3.46), 1.44 (0.96-2.16), and 3.25 (2.21-4.77), respectively. Our findings suggest that mucoprotective agents, such as rebamipide and misoprostol, as well as acid suppressants, are effective in reducing the risk for GI injury in NSAID users.

Topics: Adult; Aged; Alanine; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cohort Studies; Female; Flavonoids; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Hemoglobins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis; Proton Pump Inhibitors; Quinolones; Treatment Outcome

Poor adherence to gastroprotective agents (GPAs) is common among users of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (ASA). There are little data on the utilization of GPAs among NSAID and ASA users complicated by ulcer bleeding.. To study the utilization of GPA among NSAID and ASA ulcers before the onset of ulcer bleeding.. We conducted a cross-sectional study to determine the exposure to NSAIDs, ASA, and GPAs within 4 weeks before endoscopically confirmed ulcer bleeding. Sensitivity analysis was performed to study how improving adherence to GPA use would reduce the risk of ulcer bleeding in high-risk users.. Between 2000 and 2009, 1093 and 2277 patients had NSAID- and ASA-associated ulcer bleeding respectively. The incidence of NSAID-associated ulcer bleeding declined by 40%, whereas that of ASA-associated ulcer bleeding increased by 46%. Thirty-nine per cent of NSAID users and 75% of ASA users belonged to high ulcer risk category. Although GPA prescription rate has increased over time, only 41.6% and 30.6% of high-risk NSAID and ASA users received GPAs before ulcer bleeding respectively. Sensitivity analysis showed that if GPAs could reduce bleeding risk by 50%, improving adherence would prevent up to 35% of ulcer bleeding in high-risk users.. A substantial proportion of high-risk NSAID and ASA users had not received prophylaxis with gastroprotective agents before ulcer bleeding. These bleeding episodes may be preventable with better adherence to gastroprotective agent use.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Cross-Sectional Studies; Drug Utilization; Female; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Medication Adherence; Middle Aged; Misoprostol; Patient Compliance; Proton Pump Inhibitors; Receptors, Histamine H2; Stomach Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Female; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Proton Pump Inhibitors; Receptors, Histamine H2

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Female; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Proton Pump Inhibitors; Receptors, Histamine H2

Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used drugs worldwide; however, they are not innocuous. The spectrum of upper gastrointestinal (GI) tract damage caused by NSAIDs has been well established, and strategies to prevent this have been widely studied and implemented. Removing modifiable risk factors, the selection of less toxic NSAIDs and treatment with gastroprotective drugs, if necessary, are the main strategies employed. However, injury of the NSAIDs-related lower GI tract remains poorly characterized. In the last decade, there has been an increasing interest in this field and the search for effective preventive treatments is under way. Use of cyclooxygenase-2 inhibitor, prostaglandin, antibiotic or drugs that are not yet commercially available such as nitric oxide-releasing and hydrogen sulfide (H(2) S)-releasing NSAIDs compounds seem to reduce lower GI injury, but more evidence are needed before any of them are recommended in high-risk patients.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Misoprostol; Prostaglandins; Proton Pump Inhibitors

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Gastrointestinal Hemorrhage; Humans; Misoprostol

Peptic ulcer (PU) bleeding is the main cause of non-variceal gastrointestinal bleeding. Negative outcomes include re-bleeding and death, and many of the deaths are associated with decompensation of coexisting medical conditions precipitated by acute bleeding event. Accurate analysis of risk for clinical features can help physician to decide treatment modality. Endoscopy can detect bleeding stigmata and perform therapeutic hemostasis. Proton pump inhibitor (PPI) compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in upper gastrointestinal (UGI) bleeding significantly reduces the proportion of patients with stigmata of recent hemorrhage (SRH) at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with endoscopic hemostasis for those with major SRH, is likely to be the most cost-effective. The treatment of H. pylori infection was found to be more effective than anti-secretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone and eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies to prevent ulcer bleeding among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective treatment. This review focuses specifically on the current treatment of patients with acute bleeding from a peptic ulcer.

Topics: Anti-Ulcer Agents; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Hemostasis, Endoscopic; Humans; Misoprostol; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors

Misoprostol is an important drug in obstetrics and gynecology because of its uterotonic and cervical-ripening activities. The side effects are dose-related, usually transitory, and well tolerated. The toxic dosage in humans is unknown, and there is no specific antidote.. An adolescent developed upper gastrointestinal bleeding after self-medication with misoprostol orally (12 mg) to cause abortion. She presented with multiorgan failure, acute abdominal signs, and hemodynamic instability. Emergency laparotomy showed gastric and esophageal necrosis. After several episodes of cardiac arrest, and despite resuscitation efforts, the patient died.. Temporal relationship (48 hours after the beginning of medication) strongly suggests that misoprostol was the agent directly involved in the maternal death. The mechanism implicating misoprostol in gastrointestinal ischemia and necrosis is unknown.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adolescent; Diagnosis, Differential; Esophagus; Fatal Outcome; Female; Gastrointestinal Hemorrhage; Humans; Misoprostol; Multiple Organ Failure; Necrosis; Pregnancy; Stomach

Multiple treatment guidelines for nonsteroidal anti-inflammatory drugs (NSAIDs) suggest that patients with one or more risk factors for NSAID-related ulcer complications should be prescribed preventive strategies such as acid-suppressive drugs, misoprostol or COX-2-specific inhibitors to reduce their risk of serious ulcer complications. However data are lacking as to how many patients have been on preventive measures in accordance to the National Institute for Clinical Excellence (NICE) criteria in our population. We therefore evaluated the extent to which patients with acute gastrointestinal bleeding have been under ulcer-preventive strategies at the time of hospital entry. In a one-year-bleeding-study at the Waid city hospital, Zürich, ulcer preventive treatment was practiced in only 25% of 214 patients with acute gastrointestinal bleeding. We conclude that ulcer prevention in everyday medical practice is still being seldom applied.

Topics: Acute Disease; Aged; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Chemoprevention; Cyclooxygenase 2 Inhibitors; Female; Gastrointestinal Hemorrhage; Guideline Adherence; Humans; Male; Misoprostol; Peptic Ulcer; Practice Guidelines as Topic; Prospective Studies; Risk Factors; Switzerland; Treatment Outcome

To identify the unbiased differences in the risk of hospitalization with peptic ulcer disease (PUD) or gastrointestinal (GI) hemorrhage among populations using 4 nonsteroidal antiinflammatory drugs (NSAID): nabumetone, Arthrotec, diclofenac plus a cytoprotective agent dispensed separately (diclo+coRx), and naproxen.. A population based historical cohort study using linked data from provincial healthcare databases. The population of the province of Saskatchewan, Canada, entitled to drug plan benefits in 1995 was eligible (roughly 91% of 1 million people). Participants were identified if they filled a prescription for one of the 4 study NSAID (18,424 individuals). They were then followed for 6 months to determine outcomes. Logistic regression was used to produce estimates of the risk of admission to hospital with a primary diagnosis of PUD or GI hemorrhage associated with the study drugs unbiased by known confounders.. Compared to Arthrotec the adjusted odds of hospitalization for PUD for participants taking nabumetone was 2.6 (95% CI 1.0-6.6), diclo+coRx 6.8 (95% CI 3.5-13.4), and naproxen 7.9 (95% CI 3.9-15.9). Compared to nabumetone the adjusted odds of hospitalization for PUD for participants taking diclo+coRx was 2.7 (95% CI 1.2-6.0) and naproxen 3.1 (95% CI 1.3-7.1). No significant differences were noted in terms of admissions for GI hemorrhage.. Participants taking nabumetone and Arthrotec had significantly lower risk of hospitalization for PUD than those taking the other study drugs. Arthrotec was superior to nabumetone in a head to head comparison and especially when compared with the diclo+coRx and naproxen groups. No short term differences were seen in the rates of admission for GI hemorrhage. It appears that inherent gastroprotective strategies with Arthrotec and to a lesser extent with nabumetone do translate into decreased serious GI side effects at the population level in the short term.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Cohort Studies; Databases, Factual; Diclofenac; Drug Combinations; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Misoprostol; Nabumetone; Naproxen; Peptic Ulcer; Risk Factors; Saskatchewan

Topics: Age Factors; Aged; Aged, 80 and over; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Cardiovascular Diseases; Gastric Mucosa; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Meta-Analysis as Topic; Middle Aged; Misoprostol; Peptic Ulcer; Peptic Ulcer Hemorrhage; Platelet Aggregation Inhibitors; Risk Factors

Although the administration of gastroprotective drugs may reduce the risk of gastrointestinal (GI) bleeding due to intake of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin during chronic treatment, no consensus exists as to whether such co-therapy is effective in short-term prevention, particularly in old age. The aim of our study was to evaluate the risk of bleeding associated with acute and chronic NSAID or aspirin therapy in elderly subjects, and the influence of gastroprotective treatment on such a risk.. The study included 467 elderly NSAID or aspirin users and 1784 non-users, who consecutively underwent upper GI endoscopy. The use of NSAIDs and/or aspirin as well as gastroprotective drugs (misoprostol, H2-blockers, proton pump inhibitors) was evaluated during a structured interview. Upper GI tract bleeding was diagnosed on the basis of symptoms and endoscopic signs of recent hemorrhage.. 54.2% of patients were acute and 45.8% chronic users of NSAIDs or aspirin. The risk of bleeding was higher in acute [odds ratio (OR) 4.14, 95% CI 2.97-5.78] than chronic users (OR 1.71, 95% CI 1.1-2.67). The risk of bleeding, adjusted for age, gender, Helicobacter (H) pylori infection, and gastroprotective drug use were 7.87 (CI 4.90-12.60) in acute users and 3.97 (95% CI 2.27-6.96) in chronic users of NSAIDs and/or aspirin. The risk of bleeding was significantly associated with acute but not chronic use of regular-dose aspirin (OR 5.53, 95% CI 2.29-13.3), diclofenac (OR 4.44, 95% CI 2.21-8.93), ketorolac (OR 4.81, 95% CI 2.13-10.9), naproxen (OR 14.9, 95% CI 4.23-52.4) or nimesulide (OR 4.06, 95% CI 1.2-13.8). Piroxicam increased the risk of bleeding in both acute (OR 5.36, 95% CI 1.94-14.8) and chronic therapy (OR 5.53, 95% CI 1.23-24.9). In acute users, concomitant therapy with proton pump inhibitors reduced the risk of bleeding compared with non-users (OR 1.05, 95% CI 0.19-5.65), whereas co-treatment with H2-blockers was associated with a significantly higher risk of bleeding than in non-users (OR 3.40, 95% CI 1.28-9.02). Chronic users of NSAIDs or aspirin co-treated with proton pump inhibitors had a lower risk of bleeding (OR 1.12, 95% CI 0.21-6.07) than those treated with misoprostol (OR 1.91, 95% CI 0.33-10.9) or H2 blockers (OR 2.26, 95% CI 0.81-6.36).. The risk of upper GI bleeding is significantly higher in elderly acute vs chronic users of NSAIDs or regular-dose aspirin. In acute NSAID or aspirin users, co-treatment with proton pump inhibitors, but not with H2-blockers, may reduce the risk of bleeding compared with non-users.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Drug Administration Schedule; Female; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Male; Misoprostol; Proton Pump Inhibitors; Risk Assessment

To compare rates of upper gastrointestinal haemorrhage among elderly patients given selective cyclo-oxygenase-2 (COX 2) inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs).. Observational cohort study.. Administrative data from Ontario, Canada, used from 17 April 2000 to 31 March 2001 to identify population based, NSAID-naive cohorts of patients.. Subjects aged > or =66 years who started taking non-selective NSAIDs (n=5391), diclofenac plus misoprostol (n=5087), rofecoxib (n=14 583), or celecoxib (n=18 908) and a randomly selected control cohort not exposed to NSAIDs (n=100 000).. Rate ratios of hospital admission for upper gastrointestinal haemorrhage in each drug cohort with adjustment for potential confounders.. Relative to controls, the multivariate model revealed an increased short term risk of upper gastrointestinal haemorrhage for users of non-selective NSAIDs (adjusted rate ratio 4.0 (95% confidence intervals 2.3 to 6.9)), diclofenac plus misoprostol (3.0 (1.7 to 5.6)), and rofecoxib (1.9 (1.3 to 2.8)) but not celecoxib (1.0 (0.7 to 1.6)). Relative to celecoxib, significantly higher risks of upper gastrointestinal haemorrhage were observed for non-selective NSAIDs (4.4 (2.3 to 8.5)), diclofenac plus misoprostol (3.2 (1.6 to 6.5)), and rofecoxib (1.9 (1.2 to 2.8)). Relative to rofecoxib, non-selective NSAID users were at significantly higher risk of upper gastrointestinal haemorrhage (1.9 (1.0 to 3.5)).. This population based observational study found a lower short term risk of upper gastrointestinal haemorrhage for selective COX-2 inhibitors compared with non-selective NSAIDs.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cohort Studies; Cyclooxygenase 2; Diclofenac; Drug Combinations; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hospitalization; Humans; Isoenzymes; Lactones; Male; Membrane Proteins; Misoprostol; Multivariate Analysis; Proportional Hazards Models; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Risk Factors; Sulfonamides; Sulfones

Use of low-dose aspirin is associated with gastroduodenal mucosal damage and increased risk of upper gastrointestinal (GI) bleeding. Many patients on low-dose aspirin should receive prophylactic treatment, because they often present several risk factors that may lead to upper GI complications in nonsteroidal anti-inflammatory drug (NSAID) users. It is reasonable to assume that effective therapy (e.g., omeprazole, misoprostol, and high-dose famotidine) in the prevention of NSAID-induced gastroduodenal ulcers will also be effective in this setting. However, the best therapeutic approach to reducing GI toxicity in low-dose aspirin users is not defined, because only a few studies have focused on this problem. Omeprazole seems very effective in reducing both acute gastroduodenal mucosal damage and upper GI bleeding in the high-risk patient taking low-dose aspirin, but data with other antiulcer agents are lacking (misoprostol) or inconsistent (ranitidine) at present. No data are available on the effect of these drugs on dyspepsia or chronic gastroduodenal ulcers in the long-term use of low-dose aspirin. The role of Helicobacter pylori is controversial, but it may increase mucosal damage and the risk of upper GI bleeding in these patients. More data are needed to define the best therapeutic regimen in patients taking low-dose aspirin.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Misoprostol; Omeprazole; Peptic Ulcer; Ranitidine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Ethics, Medical; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Lactones; Middle Aged; Misoprostol; Naproxen; Proton Pump Inhibitors; Risk Factors; Sulfones

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Case-Control Studies; Confounding Factors, Epidemiologic; Gastrointestinal Hemorrhage; Humans; Misoprostol; Omeprazole; Peptic Ulcer; Recurrence; Research Design

To determine whether administration of misoprostol prevents gastric hemorrhage in healthy dogs treated with high doses of methylprednisolone sodium succinate (MPSS).. 18 healthy hound-type dogs of both sexes.. All dogs were given high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, q 6 h for a total of 48 hours) IV. Dogs were assigned randomly to receive concurrent treatment with misoprostol (4 to 6 microg/kg, PO, q 8 h; n = 9) or an empty gelatin capsule (9). Gastroduodenoscopy was performed before and after treatment. Hemorrhage was graded from none (0) to severe (3) for each cardia, fundus, antrum, and duodenum. A total stomach score was calculated as the sum of the regional stomach scores. Food retention was recorded, and pH of gastric fluid was determined. Gastric and fecal occult blood was measured.. Gastric hemorrhage was evident in all dogs after MPSS administration, and its severity was similar in both groups. Median total stomach score was 6 for misoprostol-treated dogs and 5.5 for dogs given the gelatin capsule. Difference in gastric acidity, frequency of food retention, and incidence of occult blood in gastric fluid and feces was not apparent between the 2 groups.. Administration of misoprostol (4 to 6 microg/kg, PO, q 8 h) does not prevent gastric hemorrhage caused by high doses of MPSS. Alternative prophylactic treatment should be considered.

Topics: Animals; Anti-Ulcer Agents; Biopsy; Dog Diseases; Dogs; Endoscopy, Gastrointestinal; Female; Gastric Juice; Gastrointestinal Hemorrhage; Male; Methylprednisolone Hemisuccinate; Misoprostol; Neuroprotective Agents; Occult Blood; Pylorus; Random Allocation

We report a case where an acquired deficit in platelet aggregation was associated with the use of misoprostol and contributed to increased gastrointestinal blood loss. A 70-year-old man presented with chronic gastrointestinal blood loss secondary to widespread telangiectases. Investigations showed prolonged bleeding time and severely impaired platelet aggregation in vitro. Withdrawal of misoprostol resulted in resolution of the prolonged bleeding time and improvement in the platelet dysfunction. We conclude that misoprostol can lead to impaired platelet function and may exacerbate blood loss.

Topics: Aged; Anti-Ulcer Agents; Bleeding Time; Chronic Disease; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Telangiectasis

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Buffers; Gastrointestinal Hemorrhage; Humans; Misoprostol; Tablets, Enteric-Coated

Topics: Clinical Trials as Topic; Double-Blind Method; Gastrointestinal Hemorrhage; Humans; Misoprostol

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Gastrointestinal Hemorrhage; Humans; Misoprostol

Patients who take nonsteroidal anti-inflammatory drugs (NSAIDs) are at increased risk of upper gastrointestinal tract bleeding, which may be prevented with prophylactic prescription of misoprostol. Using data from the literature, we estimated rates of gastrointestinal tract bleeding in NSAID users, direct medical costs, years of life lost, and cost-effectiveness of a 1-year course of misoprostol in three clinical populations of NSAID users: all users, users aged 60 years or older, and users with rheumatoid arthritis. The incremental cost-effectiveness ratios for misoprostol as primary prevention were $667,400 per year of life saved for all NSAID users; $186,700 per year of life saved for users aged 60 years or older; and $95,600 per year of life saved for users with rheumatoid arthritis. Misoprostol as secondary prevention for those who continued to take NSAIDs despite having had an episode of gastrointestinal tract bleeding in the previous year was associated with incremental cost-effectiveness ratios less than $40,000 per year of life saved in all patient groups. We conclude that misoprostol is costly as primary prevention for NSAID-induced gastrointestinal tract bleeding in the groups examined but may be cost-effective as secondary prevention in patients with a proved history of gastrointestinal tract bleeding.

Topics: Aged; Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Costs and Cost Analysis; Decision Trees; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Life Expectancy; Middle Aged; Misoprostol; Patient Compliance; Probability; Sensitivity and Specificity; Stomach Ulcer

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cost-Benefit Analysis; Decision Trees; Drug Evaluation; Gastrointestinal Hemorrhage; Misoprostol

Topics: Alprostadil; Drug Therapy, Combination; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Misoprostol; Postoperative Complications; Ranitidine; Stress, Psychological

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Female; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Osteoarthritis; Peptic Ulcer

Aspirin induces ulceration, cellular exfoliation, and blood loss associated with decreases in gastric mucosal potential difference (PD). Certain prostaglandins prevent the development of experimental gastric and duodenal ulcers and modify indices related to ulceration. Misoprostol, a synthetic PGE1 derivative with gastric antisecretory and mucosal protective activities, was examined at gastric antisecretory doses in dogs with Heidenhain pouches, to determine its effect on aspirin-associated changes in PD, K+ efflux, blood loss, and cell shedding, as measured by DNA release. These parameters were examined before, during, and up to 4 hours after exposure of the pouches to aspirin. Disruption of the gastric mucosal barrier (GMB) by aspirin was associated with a fall in PD and losses of K+, DNA, and blood into the pouches. Misoprostol inhibited the fall in PD and prevented blood loss over the entire period examined. Cell loss was inhibited only during the recovery period immediately following aspirin. The effect of misoprostol on GMB is consistent with studies in which prostaglandins preserve the GMB and prevent necrotic ulcerations while allowing superficial cell damage.

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Aspirin; DNA; Dogs; Dose-Response Relationship, Drug; Epithelium; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Membrane Potentials; Misoprostol; Potassium; Stomach Ulcer

Fasted rats were given a single oral dose of one of the following: a synthetic prostaglandin E1 analog, misoprostol (low dose = 100 micrograms/kg, or high dose = 1 mg/kg), cimetidine (low dose = 100 micrograms/kg, or high dose = 50 mg/kg), phosphate buffer, or absolute ethanol. A second group of rats received a single oral dose of misoprostol, cimetidine, or phosphate buffer intragastrically, followed 30 min later by a second oral dose of absolute ethanol. Stomachs were either surgically removed and examined grossly or were fixed in situ and prepared for histological observation 15 or 30 min after the initial dose, or 15 or 30 min after the second dose. Absolute ethanol alone produced grossly visible hemorrhagic lesions and extensive hyperemia and microscopic damage to the glands, which was largely confined to the crests of the rugae. Microscopic examination of nonhemorrhagic areas showed extensive damage of the superficial and gastric pit epithelial cells as well as some endothelial cells and adjacent structures in the lamina propria. Pretreatment with phosphate buffer, or either dose of cimetidine, did not obviate the gross hemorrhagic lesions or the histologic damage produced by absolute ethanol. Both the low and high doses of misoprostol protected the stomach against ethanol-induced gross hemorrhagic lesions but did not completely protect against microscopic damage to the superficial mucosa.. the protective action of misoprostol involves mechanisms that prevent hemorrhagic lesions but do not completely shield the superficial mucosa from damage. These mechanisms appear to be independent of misoprostol's antisecretory effects.

Topics: Alprostadil; Animals; Anti-Ulcer Agents; Buffers; Cimetidine; Ethanol; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Misoprostol; Necrosis; Phosphates; Rats; Rats, Inbred Strains

Topics: Adult; Alprostadil; Anti-Ulcer Agents; Cimetidine; Ethanol; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol