Current approaches to prevent NSAID-induced gastropathy--COX selectivity and beyond.
Gastrointestinal (GI) 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 NSAID-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 GI 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.
Becker
Jan C
JC
Department of Medicine B, University of Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany. beckeja@uni-muenster.de
Domschke
Wolfram
W
Pohle
Thorsten
T
D000863:Antacids / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002626:Chemistry, Pharmaceutical; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D016481:Helicobacter Infections / Q000517:prevention & control; D016480:Helicobacter pylori; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D054328:Proton Pump Inhibitors
D000863:Antacids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors