期刊
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
卷 58, 期 6, 页码 587-600出版社
WILEY
DOI: 10.1111/j.1365-2125.2004.02198.x
关键词
aspirin; COX/5-LOX; H. pylori; haeme-oxygenase; NO-NSAID; PPI
Gastrointestinal (Gl) toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is still an important medical and socio-economic problem-despite recent pharmaceutical advances. To prevent NSAID-induced gastropathy, three strategies are followed in clinical routine: (i) coprescription of a gastroprotective drug, (ii) use of selective COX-2 inhibitors, and (iii) eradication of Helicobacter pylori. Proton pump inhibitors are the comedication of choice as they effectively reduce gastrointestinal adverse events of NSAIDs and are safe even in long-term use. Co-medication with vitamin C has only been little studied in the prevention of N SAID-induced gastropathy. Apart from scavenging free radicals it is able to induce haeme-oxgenase 1 in gastric cells, a protective enzyme with antioxidant and vasodilative properties. Final results of the celecoxib outcome study (CLASS study) attenuated the initial enthusiasm about the Gl safety of selective COX-2 inhibitors, especially in patients concomitantly taking aspirin for cardiovascular prophylaxis. Helicobacter pylori increases the risk for ulcers particularly in NSAID-naive patients and therefore eradication is recommended prior to long-term NSAID therapy at least in patients at high risk. New classes of COX-inhibitors are currently evaluated in clinical studies with very promising results: NSAIDs combined with a nitric oxide releasing moiety (NO-NSAID) and dual inhibitors of COX and 5-LOX. These drugs offer extended anti-inflammatory potency while sparing gastric mucosa.
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