In addition to concurrent low-dose aspirin use, age 65, prior upper GI events, concomitant use of anticoagulation or corticosteroid therapy and use of multiple NSAIDs or high-dose NSAIDs have all been consistently shown to increase the risk of GI complications [6,8,16]. Review of current guidelines Current guidelines for the management of patients who need pharmacotherapy for treatment of pain both acknowledge the risk of GI clinical events associated with NSAIDs as well as address the factors known to increase the risk. events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing Bemegride upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone. Introduction It is estimated that at least 50 million people in the United States suffer from chronic pain conditions while an additional 25 million people suffer from acute pain . Pain affects patient quality of life and is a major reason for healthcare utilization , Bemegride accounting for 20% of out-patient visits and 12% of all prescriptions . Non-steroidal anti-inflammatory drugs (NSAIDs) remain a main stay of therapy due to their efficacy as anti-inflammatory/analgesic agents. In 2004, persons in the United States spent more than $2.5 billion on over-the-counter NSAIDs and filled more than 100 million NSAID prescriptions . Worldwide, over 73,000,000 prescriptions for NSAIDs are written each year . NSAIDs and gastrointestinal toxicity While NSAIDs are effective for the treatment of pain and are overall well tolerated, their use is associated with potentially important adverse effects. Gastrointestinal (GI) toxicity from NSAIDs includes dyspepsia, ulcers and bleeding [6,7]. Of individuals taking NSAIDs, the drugs produce symptoms of dyspepsia and ulcer disease in up to 50% and up Bemegride to 20%, respectively . Approximately 15 to 30% of regular NSAID users are found to have gastric or duodenal ulcers on upper endoscopy and many of these ulcers are asymptomatic . While most patients who develop NSAID-induced ulcers do not develop clinical events, the annual rate of upper GI clinical events is approximately 2.5 to 4.5% . Epidemiologic studies suggest that NSAID use increases the risk of GI complications two to Grem1 six times . Bemegride GI toxicity from NSAIDs is associated with substantial morbidity and mortality. Reports in the literature estimate 3,200 to 16,500 deaths each year in the United States from complications of NSAID-associated ulcer perforations and bleeding [10-13]. Additionally, an estimated 100,000 hospitalizations occur each year in the United States due to NSAID-associated ulcer perforations and bleeding . Furthermore, the cost associated with complications of NSAID use is substantial. Studies suggest that for every $1 spent on NSAIDs, $0.66 to $1.25 is spent on managing NSAID-associated adverse GI effects [14,15]. Risk factors for the development of NSAID-associated gastrointestinal complications Any person taking NSAIDs is at risk of developing GI complications. Several well-established factors have been identified that significantly increase this risk. In addition to concurrent low-dose aspirin use, age 65, prior upper GI events, concomitant use of anticoagulation or corticosteroid therapy and use of multiple NSAIDs or high-dose NSAIDs have all been consistently shown to increase the risk of GI complications [6,8,16]. Review of current guidelines Current guidelines for the management of patients who need pharmacotherapy for treatment of pain both acknowledge the risk of GI clinical events associated with NSAIDs as well as address the factors known to increase the risk. Recommended strategies to decrease GI toxicity in NSAID users include Bemegride co-therapy with misoprostol, histamine type-2 receptor antagonists (H2RAs) or proton-pump inhibitors (PPIs) and/or the use of cyclooxygenase-2 selective inhibitors [11,17]. The American College of Gastroenterology recommends that patients requiring NSAID therapy who are at high risk should receive alternative therapy – or, if anti-inflammatory treatment is absolutely necessary, a selective cyclooxygenase type-2 inhibitor (coxib) and/or co-therapy with misoprostol or high-dose PPI is recommended . The First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents concludes that patients with high GI risk, but average cardiovascular (CV) risk, should receive either a nonselective NSAID plus a PPI or misoprostol, or should receive a coxib plus a PPI or misoprostol . The Health Technology Assessment’s economic modeling in 2006 suggested that, with regard to the prevention of endoscopic ulcers, H2RA plus NSAID was a dominant, cost-effective option . Although subsequent to this report, less expensive generic and over-the-counter PPIs have become available that would reduce the cost of PPI gastroprotection considerably. There has not been a follow-up cost-effectiveness study incorporating lower priced PPIs nor are there head-to-head comparative studies evaluating efficacy of the competing strategies. Pharmacokinetics H2RAs inhibit acid secretion by competitively blocking histamine type-2 receptors on the parietal cell, thus reducing basal and stimulated gastric acid secretion. Pepsin secretion is also reduced, which results in decreased peptic activity . PPIs instead block acid secretion by irreversibly binding to and inhibiting the hydrogen-potassium ATPase pump on the luminal surface of the parietal cell membrane. Absorption of H2RAs is reduced by concurrent antacid administration. Likewise, PPIs which rely on an activated parietal cell work less well in persons also taking other antisecretory agents such as misoprostol or an H2RA. H2 receptor antagonists for NSAID gastro-protection The use of H2RAs can suppress gastric acid production.
Posted in RNAPol.