NSAID-induced

Identify desired therapeutic outcomes for patients with HP-associated ulcers and NSAID-induced ulcers. 

Devise an algorithm for evaluation and treatment of a patient with signs and symptoms suggestive of an HP-associated or NSAID-induced ulcer. 

In patients at risk for NSAID-induced ulcers, proton pump inhibitors (PPIs) at standard doses reduce the risk of both gastric and duodenal ulcers as effectively as misoprostol and are generally better tolerated. 

Risk factors for NSAID-induced peptic ulcers and complications are presented in Table 15-2. Several important principles should be considered when estimating the risk for developing PUD in a patient taking an NSAID (1) risk factors are generally additive (2) some risk factors (e.g., corticosteroid therapy) are not by themselves a risk factor for ulceration but increase PUD risk substantially when combined with NSAID therapy and (3) many of the risk factors postulated to increase PUD... 

Direct irritation of the mucosal lining by NSAIDs occurs because NSAIDs are weak acids. Topical irritation is therefore most pronounced with more acidic NSAIDs such as aspirin. While the direct irritant effects of NSAIDs play a contributory role in the development of NSAID-induced gastritis, this mechanism generally plays a minor role in the evolution of NSAID-induced PUD. 

The treatment selected for PUD depends on the following factors (1) the etiology of the ulcer (2) whether the ulcer is new or recurrent and (3) the presence of any ulcer-related complications. Figure 15-2 contains an algorithm for the evaluation and treatment of a patient with signs and symptoms suggestive of an H. pylori-associated or NSAID-induced ulcer. 

General Recommendations HP-Associated and NSAID-induced Ulcers... 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Significant mortality is associated with NSAID gastropathy. G. Singh and G. Triadafilopoulos, Epidemiology of NSAID induced gastrointestinal complications, Journal of Rheumatology, 1999, 26, 56,18-24, by permission of Oxford University Press. 

Davies NM, Jamali F Pharmacological protection of NSAID-induced intestinal permeability in the rat Effect of tempo and metronidazole as potential free radical scavengers. Hum Exp Toxicol 1997 16 345-349. 

Peptic ulcer disease (PUD) refers to a group of ulcerative disorders of the upper GI tract that require acid and pepsin for their formation. Ulcers differ from gastritis and erosions in that they extend deeper into the muscularis mucosa. The three common forms of peptic ulcers include Helicobacter pylori (HP)-associated ulcers, nonsteroidal antiinflammatory drug (NSAID)-induced ulcers, and stress-related mucosal damage (also called stress ulcers). 

Pain does not always correlate with the presence of an ulcer. Asymptomatic patients may have an ulcer at endoscopy, and patients may have persistent symptoms even with endoscopically proven healed ulcers. Many patients (especially older adults) with NSAID-induced, ulcer-related complications have no prior abdominal symptoms. 

For treatment of NSAID-induced ulcers, nonselective NSAIDs should be discontinued (when possible) if an active ulcer is confirmed. Most uncomplicated NSAID-induced ulcers heal with standard regimens of an H2RA, PPI, or sucralfate (see Table 29-2) if the NSAID is discontinued. If the NSAID must be continued, consideration should be given to reducing the... 

Ranitidine is a histamine receptor antagonist. It acts essentially on the H2 receptor and blocks acid production. Ranitidine is used in the treatment and prevention of ulcers, NSAID-induced ulcers, Zollinger-Ellison syndrome and gastro-oesophageal reflux disease. 

Arthritis patients at high risk of w/cers Treatment of the signs and symptoms of osteoarthritis or rheumatoid arthritis in patients at high risk of developing NSAID-induced gastric and duodenal ulcers and their complications. 

Misoprostol should not be used for reducing the risk of NSAID-induced ulcers in women of childbearing potential unless the patient is at high risk of developing complications from gastric ulcers associated with NSAIDs or of developing gastric ulceration. In such patients, misoprostol may be prescribed if the patient ... 

Rostom A, Dube C, Wells G, Tugwell P, Welch V, Joli-coeur E et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002. 

Co-morbid factors that increase the risk of NSAID-induced GI bleeding include history of ulcer disease, advanced age, poor health status, treatment with certain drugs (discussed later), long duration of NS AID therapy, smoking, and heavy alcohol use. Because of their renal effects, NSAIDs must be used with caution in... 

Geriatric Considerations-Summary Adjust dose based on creatinine clearance. Not effective in preventing NSAID-induced gastric ulceration and bleeding proton pump inhibitors should be used for this indication instead. 

Unlabeled Uses H. pytori-associated duodenal ulcer (wifh amoxicillin and clarilhro-mycin), prevenfion and treatment of NSAID-induced ulcers, frealmenf of acfive benign gastric ulcers... 

A major iimitation to the use of NSAIDs is gastrointestinal ulceration and bleeding, particularly in the stomach, due to suppression of protective gastric prostaglandins (PGs). NSAID-induced ulceration. The concomitant administration of the PGEl analogue, misoprostol, is more effective but is expensive and associated with an appreciable incidence of side effects, notably diarrhoea Renal adverse effects... 

For patients with ulcers caused by aspirin or other NSAIDs, either H2 antagonists or proton pump inhibitors provide rapid ulcer healing so long as the NSAID is discontinued however continued use of the NSAID impairs ulcer healing. In patients with NSAID-induced ulcers who require continued NSAID therapy, treatment with a once- or twice-daily proton pump inhibitor more reliably promotes ulcer healing. 

---