Peptic ulcer disease NSAIDs

Peptic ulcer disease NSAIDs, anticoagulants Gastrointestinal hemorrhage... 

Contraindications fc>r nonsalicylate NSAID therapy are the same as those for aspirin (see Box 7-I).The formation of a gastric ulcer or erosion that may bleed profusely is a serious potential problem with NSAIDs. Consequently, the nonsalicylate NSAIDs should be avoided or used with great caution in patients with active peptic ulcer disease. NSAIDs may increase the risk of GI complications even when used in conjunction with low-dose aspirin for cardioprotection. In addition, because of potential crosssensitivity to other NSAIDs, the nonsalicylate NSAIDs should not be given to patients in whom aspirin or other NSAIDs have caused symptoms of asthma, rhinitis, urticaria, angioedema, hypotension, bronchospasm, or of symptoms of hypersensitivity reactions. Opioids, tramadol, or acetaminophen may be suitable alternatives for patients with known or suspected susceptibility. 

O Patients with peptic ulcer disease should avoid exposure to factors known to worsen the disease, exacerbate symptoms, or lead to ulcer recurrence [e.g., non-steroidal anti-inflammatory drug (NSAID) use or cigarette smoking]. 

Previous peptic ulcer disease or upper gastrointestinal bleeding Cardiovascular disease and other comorbid conditions Multiple NSAID use (e.g., low-dose aspirin in conjunction with another NSAID)... 

H2RA, histamine2-receptor antagonist NSAID, nonsteroidal anti-inflammatory drug PPI, proton pump inhibitor. (Adapted from Berardi RR, Welage LS. Peptic ulcer disease. In DiPiro JT, Talbert RL,... 

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. 

The analgesic effects of NSAIDs are attributed to inhibition of the COX-2 enzyme, whereas the negative GI effects are due to inhibition of COX-1.28 Patients taking oral anticoagulants, those with a history of peptic ulcer disease, or others at high risk for GI complications may be considered candidates for a COX-2 inhibitor or a combination of a nonselective NSAID with a gastroprotective agent such as a proton pump inhibitor (PPI). Because most PPIs are available by prescription only, such patients should be referred to a physician. 

Although the risk of GI complications is relatively small with short-term therapy, coadministration with a proton pump inhibitor should be considered in elderly patients and others at increased GI risk. NSAIDs should be used with caution in individuals with a history of peptic ulcer disease, heart failure, uncontrolled hypertension, renal insufficiency, coronary artery disease, or if they are receiving anticoagulants concurrently. 

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). 

For prevention of peptic ulcer disease avoiding ulcerogenic medication such as NSAIDs, including aspirin, is probably the most important strategy. Reducing gastric acidity is also the main approach for the treatment of reflux esophagitis. 

Answer Peptic ulcer disease is most frequently secondary to either Helicobacter pylori infection or use of NSAIDs. The patient does admit to NSAID use (naproxen), but should also be checked for concomitant H. pylori infection at time of endoscopy or by a serology test. If the patient was found to have H. pylori, an appropriate eradication regimen should be prescribed. The patient should also be counseled to avoid NSAIDs. The patient should be prescribed a proton pump inhibitor for 8 weeks to heal the ulcer. A repeat endoscopy should be done at that time to document ulcer healing and rule out gastric cancer. In addition, the patient should be counseled to stop smoking, which is a risk factor for more severe peptic ulcer disease. 

COX-2 specific inhibition good choice for patients with inflammatory conditions who are at high risk of gastrointestinal adverse effects (e.g., older than 60 years history of peptic ulcer disease prolonged, high-dose NSAID therapy concurrent use of corticosteroids or anticoagulants)... 

Contraindications Active peptic ulcer disease, chronic inflammation of GI tract, GI bleeding or ulceration, history of hypersensitivity to aspirin or NSAIDs... 

The author commented that 50-75% of gastrocolic fistulas are related to benign gastric ulcers secondary to the use of NSAIDs. The use of aspirin plus prednisone, as in this patient, increases the risk of complication of peptic ulcer disease two- to fourfold. 

All NSAIDs have the potential to cause gastric and duodenal ulcers and bleeding through direct (topical) or indirect (systemic) mechanisms. Risk factors for NSAID-associated ulcers and ulcer complications (perforation, gastric outlet obstruction, GI bleeding) include increased age, comorbid medical conditions (e.g., cardiovascular disease), concomitant corticosteroid or anticoagulant therapy, and history of peptic ulcer disease or upper Gl bleeding. 

Gastrointestinal. Patients taking continuous steroid, especially in combination with a nonsteroidal antiinflammatory drug (NSAID), have an excess incidence of peptic ulcer and haemorrhage of about 1-2%. It is plainly unreasonable to seek to protect all such patients by routine prophylactic antiulcer therapy, i.e. to treat 98 patients unnecessarily in order to help two. But such therapy (proton pump inhibitor, histamine H -receptor blocker, sucralfate) is appropriate when ulcer is particularly likely, e.g. a patient with rheumatoid arthritis taking an NSAID, or for patients with a history of peptic ulcer disease. There is increased incidence of pancreatitis. 

Observational cohort or case control designs have been used to determine ADR relationships with specific therapeutic classes. " Medical claims data are often used in these studies and caution should be warranted due to lack of definite confirmation of drug exposure and the potential for confounding variables. However, these studies have been beneficial in determining risk of ADRs with specific classes (e.g., NSAIDs and the risk of peptic ulcer disease). 

A meta-analysis has helped to clarify this issue (96). The aim was to assess the presence and magnitude of any possible interaction in peptic ulcer disease between these two susceptibility factors, with particular attention to bleeding peptic ulcer disease, the sites of ulceration, and the effect of H. pylori eradication. In all, 61 relevant studies were identified, 36 of which were excluded for various reasons. Thus, 25 studies were left for analysis, of which 16 observational studies (eight cross-sectional studies, seven case-control studies, and one cohort study) provided data on the prevalence of peptic ulcer disease in 1633 NSAID users, with data on H. pylori status for 1625 patients. The pooled frequency of peptic ulcer disease in NSAID users was 42% in those who were H. py/on-positive and 25% in those who were H. py/on-negative (OR = 2.12 95% Cl = 1.68, 2.67). 

The frequencies of uncomplicated peptic ulcer disease in NSAID users and non-users were compared in eight case-control studies however, the NSAID users and controls were not matched by age in three studies and so, because H. pylori infection is age-dependent, the prevalence of infection was analysed in only five studies. 

Overall, H. pylori infection was diagnosed in 47% of the NSAID users and 46% of the controls, but peptic ulcer disease was significantly more common in the NSAID users (36% versus 8.3% OR = 5.14 Cl = 1.35, 20). Compared with patients who were H. py/ori-negative and were not taking NSAIDs, the risk of ulcer in H. py/ori-infected NSAID users was very high (OR = 61 Cl = 10, 373). H. pylori infection increased the risk of peptic ulcer disease in NSAID users 3.53 times in addition to the risk associated with NSAID use (OR = 19). Similarly, in the presence of a risk of peptic ulcer disease associated with H. pylori infection (OR = 18) the use of NSAIDs increased the risk of peptic ulcer disease 3.55 times. H. pylori infection and NSAID use, respectively, increased the risk of ulcer bleeding 1.79 times and 4.85 times the risk of ulcer bleeding increased to 6.13 when both factors were present. 

The meta-analysis also showed that one-third of patients taking long-term NSAIDs have gastric or duodenal ulcers, irrespective of H. pylori status and study design. However, peptic ulcer disease was significantly more common in H. py/on-infected NSAID users than in non-infected users, suggesting a possible interaction between NSAID use and H. pylori infection for the development of peptic ulcers. 

Martin DF, Montgomery E, Dobek AS, Patrissi GA, Peura DA. Campylobacter pylori, NSAIDS, and smoking risk factors for peptic ulcer disease. Am J Gastroenterol 1989 84(10) 1268-72. 

Piscitelli SC. Zollinger-Ellison disease/NSAID-induced gastropathy/peptic ulcer disease. In Carter BL, Angaran DM, Lake KD, Raebel MA, eds. Pharmacotherapy self-assessment program, 2nd edition. Kansas City American College of Clinical Pharmacy, In press. 

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