misoprostol and Rheumatic-Diseases

Rheumatic diseases often have gastrointestinal(GI) manifestations, and may present as GI bleeding and perforation due to peptic ulcer associated with high mortality. Major causes of peptic ulcer related to rheumatic diseases are drugs such as nonsteroidal anti-inflammatory drug(NSAID) and corticosteroid, and vasculitis. The analgesic effects of NSAID often mask abdominal pain until they cause GI bleeding and perforation. Therefore, it is important to make early diagnosis of peptic ulcer with upper gastrointestinal endoscope. Fundamental treatment of NSAID induced peptic ulcer is to quit it, however it is difficult because of activity of rheumatic diseases. Also, most NSAID induced peptic ulcers heal by administration of proton pump inhibitor or misoprostol. Corticosteroid pulse therapy or administration of immunosuppressant agents is effective for vasculitis induced peptic ulcer, however it is difficult to make diagnosis of it. Development of NSAID with less side effects such as cyclooxygenase-2 selective inhibitors and establishment of diagnosis and treatment of peptic ulcer related to rheumatic diseases are expected.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Histamine H2 Antagonists; Humans; Lupus Erythematosus, Systemic; Misoprostol; Omeprazole; Peptic Ulcer; Polyarteritis Nodosa; Proton Pump Inhibitors; Rheumatic Diseases

The new class of antiinflammatory and analgesic drugs, the selective cyclooxygenase (COX-2) inhibitors, which promise to be devoid of the types of toxicity associated with nonsteroidal antiinflammatory drugs (NSAID), especially adverse gastrointestinal effects, are under clinical trial but are not yet available for use. All NSAID, including those most recently introduced, exhibit nonselectivity of action, producing therapeutic blood levels that inhibit constitutive COX-1 and deplete tissue protective prostaglandins. Among NSAID, the diclofenac/misoprostol combination (Arthrotec) is unique in possessing an active component, misoprostol, to help prevent NSAID induced gastrointestinal damage. Ulcer damage and associated serious complications probably represent only the tip of the iceberg in relation to clinically significant side effects associated with the use of NSAID. In this context, metaanalysis of 8 large multicenter studies reported here has shown that patients taking NSAID show a mean decrease in hemoglobin over 4 - 12 weeks' assessment, with some 10-20% of patients exhibiting clinically significant decreases (> or = 1 g/dl) early in treatment. Patients taking diclofenac/misoprostol showed significantly less of a decline in hemoglobin and up to 50% fewer clinically significant decreases than patients receiving diclofenac alone. The misoprostol component of diclofenac/misoprostol may also help to restore homeostasis in tissues other than the gut. Inhibition of the activity or release of various tissue damaging agents and inflammatory cytokines, e.g., thromboxane and interleukin 1, are described, as are in vivo animal studies that have revealed synergistic or potentiating analgesic and antiinflammatory activities between misoprostol and NSAID, particularly diclofenac. Clinical studies in postsurgical dental pain in more than 500 patients have now shown enhanced analgesia, with greater relief over a longer period, for the diclofenac/misoprostol combination compared with diclofenac alone. The relevance of these findings to pain and inflammation control in arthritis is discussed. Enhanced control of morning stiffness provided by diclofenac/misoprostol, possibly also the result of misoprostol/diclofenac synergy, is also reported, and the development of an objective system that measures 24 hour ambulatory activity is described. Using this Numact recorder, improved mobility in patients receiving diclofenac 75 mg/misoprostol 200 microg was observed compared w

Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Combinations; Drug Synergism; Hemoglobins; Humans; Misoprostol; Rheumatic Diseases

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment for rheumatic diseases. However, a significant number of patients receiving these drugs experience upper gastrointestinal side effects, including physical injury to the gastroduodenal mucosa. This may range from clinically insignificant bleeding and minor erosive changes to deeper ulceration, with attendant risk of haemorrhage or perforation. The majority of the published literature concerning healing of NSAID-associated peptic ulcer with antisecretory drugs involves studies of the use of the H2-receptor antagonists, ranitidine and cimetidine. Peptic ulcers associated with NSAID use can be healed with these H2-receptor antagonists using the same doses as those used for healing of idiopathic gastric or duodenal ulceration. Most ulcers heal within 4-8 weeks in those patients who are able to discontinue their anti-inflammatory therapy. If the NSAID is continued, healing may be slightly delayed. At present, limited data only are available with respect to the use of the proton pump inhibitor, omeprazole, and no firm conclusions can be drawn regarding the use of the prostaglandin analogue, misoprostol, for the healing of NSAID-associated peptic ulceration.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cimetidine; Gastric Acid; Gastric Mucosa; Histamine H2 Antagonists; Humans; Misoprostol; Peptic Ulcer; Prostaglandins, Synthetic; Ranitidine; Rheumatic Diseases

The secondary gastrointestinal effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are well documented in the medical literature. The "iatrogenic" cost arising from the treatment of these secondary effects, however, is less well known. Existing epidemiologic and clinical studies report that the cost of NSAIDs is multiplied by a coefficient that ranges from 1.36 to 3 when the cost of treating the induced gastroduodenal damage is taken into account. A simple methodology has been developed to calculate the "shadow price" of an NSAID by incorporating the costs of treating the gastroduodenal damage, thus yielding a figure that reflects the real economic burden of NSAID therapy. Using study data from seven countries, the cost effectiveness of prophylactic treatment with misoprostol--a prostaglandin analogue whose efficacy has been proven in the prevention of gastroduodenal ulcers in arthritic patients treated with NSAIDs--is reviewed. In the majority of cases, the financial benefits of preventing the ulcers equal or surpass the cost of prevention.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Belgium; Cost-Benefit Analysis; France; Gastrointestinal Diseases; Humans; Misoprostol; Netherlands; Rheumatic Diseases; Sweden; United States

The iatrogenic cost factor of treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is defined as the increase in cost resulting from NSAID-induced gastroduodenal ulcers. The iatrogenic cost factor of NSAIDs for the National Health Service (NHS) in the United Kingdom was calculated using the model of de Pouvourville (1992). The cost factor is defined as the ratio of the shadow price of the NSAID to the NHS price. The shadow price is calculated from the incidence of NSAID-induced gastroduodenal ulcers and the costs of treating them and the price of the drugs. The NHS iatrogenic cost factors of 10 NSAIDs were similar to those calculated by de Pouvourville for the French national health insurance system, Assurance-Maladie, and ranged from 1.08 for diclofenac/misoprostol to 2.38 for ibuprofen.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cost of Illness; Diclofenac; Drug Combinations; Gastrointestinal Diseases; Humans; Misoprostol; National Health Programs; Rheumatic Diseases; United Kingdom

Aspirin and other nonsteroidal antiinflammatory drugs (NSAID) have been associated with various degrees of gastroduodenal damage. The agents currently available for the treatment of gastric mucosal damage caused by NSAID are histamine2-receptor antagonists, antacids, sucralfate and prostaglandins. Although all of these agents are effective in healing gastric and duodenal injury if NSAID are discontinued, currently available data suggest that there may be significant differences among these drugs in healing gastric mucosal injury if NSAID are continued in the presence of such injury. In particular, the synthetic prostaglandin misoprostol appears to be therapeutically superior to agents in the other drug classes in such a context. Reviewed herein are data from the literature on both treatment and prevention of gastrointestinal damage due to NSAIDs.

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Gastric Mucosa; Histamine H2 Antagonists; Humans; Misoprostol; Prostaglandins, Synthetic; Rheumatic Diseases; Stomach Ulcer; Sucralfate

To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 microg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions.. This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 microg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months.. Pantoprazole was superior to misoprostol (p < 0.001) with regard to 'therapeutic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or 'likely' or 'definitely' related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to 'endoscopic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events 'likely' or 'definitely' related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups.. Pantoprazole 20 mg o.d. is superior to misoprostol 200 microg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Benzimidazoles; Double-Blind Method; Drug Administration Schedule; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Misoprostol; Omeprazole; Pantoprazole; Rheumatic Diseases; Risk Factors; Sulfoxides

A clinical trial of arthrotek (Searle) in 60 RA patients aged 16-77 years demonstrated its high anti-inflammatory activity in 47 of them. These patients have received a complete treatment course, 10 patients were not included in the overall estimations because of side affects (gastric pains and nausea) causing them to withdraw early in the treatment course, 3 patients were nonresponders. The responders experienced attenuation of joint pain, morning stiffness. Inflammation in some joints declined, the articular index decreased.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Combinations; Female; Humans; Male; Middle Aged; Misoprostol; Remission Induction; Rheumatic Diseases; Russia; Tablets

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antirheumatic Agents; Humans; Immunosuppressive Agents; Misoprostol; Peptic Ulcer; Rheumatic Diseases; Rheumatology

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; Arthritis, Rheumatoid; Diclofenac; Drug Combinations; Gastrointestinal Diseases; Humans; Misoprostol; Osteoarthritis; Rheumatic Diseases

Topics: Advertising; Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Humans; Misoprostol; Rheumatic Diseases; Risk Factors; Stomach Diseases

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Gastritis; Humans; Misoprostol; Rheumatic Diseases