Patients who develop peptic ulcers while on NSAIDs should be tested and treated for H pylori and the NSAID should be discontinued if possible. Acid-suppressive medication, usually with a proton pump inhibitor, should also be administered. Proton pump inhibitors block acid secretion by irreversibly binding and inhibiting the hydrogen-potassium ATPase that resides on the luminal surface of the parietal cell. The proton pump inhibitors include omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole. The use of a proton pump inhibitor or a prostaglandin analog,misoprostol, reduces the recurrences of ulcers especially if the patient needs to continue to take NSAIDs. Unfortunately, misoprostol at 200 mcg four times daily is often associated with cramps, diarrhea, and poor patient compliance.
Drugs that selectively inhibit COX-2 were developed to have similar analgesic and anti-inflammatory effects as traditional NSAIDs but with a reduced risk of GI complications. Several studies have suggested that COX-2 inhibitors help treat musculoskeletal as well as arthritic conditions with fewer ulcer complications because they do not inhibit the gastric mucosal prostaglandins. However, they are also associated with an increased risk of cardiovascular and thrombotic events.The exact mechanisms for this are not clear but may be related to the fact that thromboxane A2 is COX-1– mediated product that causes irreversible platelet aggregation, vasoconstriction, and smooth muscle proliferation. In contrast, prostacyclin is synthesized from COX-2 and is an inhibitor of platelet aggregation while causing vasodilation and inhibition of smooth muscle proliferation. Selective inhibition of COX-2 may lead to an imbalance in these products that promotes thrombosis. The addition of low-dose aspirin to a COX-2 inhibitor increases the ulcer rate to that seen with nonselective NSAIDs.
The use of enteric-coated or buffered aspirin does not substantially reduce the risk of ulcer complications compared with uncoated aspirin due to the systemic effects of these drugs. A recent study of patients with ulcer bleeding from aspirin has shown that administration of a proton pump inhibitor with aspirin significantly reduces recurrent ulcer bleeding as compared with substituting the aspirin for another antiplatelet agent, clopidogrel.Also, as expected, the use of both aspirin and clopidogrel significantly increase the bleeding risk compared with use of aspirin alone. Although recent studies suggest that the use of nitric oxide–releasing NSAIDs may help reduce ulcer complications, they are not yet available for clinical use. In small trials, for example, adding a nitric oxide–donating moiety to aspirin was associated with less GI mucosal damage and yet provided similar inhibition of platelet aggregation and thromboxane B2 production as traditional aspirin. Long-term studies are needed to determine whether nitric oxide–releasing aspirin is truly safer and provides the same benefits as traditional aspirin.
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