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Titolo:
Preferential COX-2 inhibition: Its clinical relevance for gastrointestinalNSAID toxicity
Autore:
Dammann, HG;
Indirizzi:
Klin Forsch Hamburg, Wissenschaftliches Inst, D-20249 Hamburg, Germany Klin Forsch Hamburg Hamburg Germany D-20249 st, D-20249 Hamburg, Germany
Titolo Testata:
ZEITSCHRIFT FUR GASTROENTEROLOGIE
fascicolo: 1, volume: 37, anno: 1999,
pagine: 45 - 58
SICI:
0044-2771(199901)37:1<45:PCIICR>2.0.ZU;2-S
Fonte:
ISI
Lingua:
GER
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ANTI-INFLAMMATORY DRUGS; PROSTAGLANDIN G/H SYNTHASE-1; ARACHIDONIC-ACID METABOLISM; BLEEDING PEPTIC-ULCER; ASPIRIN-LIKE DRUGS; SELECTIVE-INHIBITION; RHEUMATOID-ARTHRITIS; DIFFERENTIAL INHIBITION; CYCLOOXYGENASE ACTIVITY;
Keywords:
cyclooxygenase; COX-2-inhibitors; gastrointestinal NSAID tolerability;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
125
Recensione:
Indirizzi per estratti:
Indirizzo: Dammann, HG Klinamburg, Hamburg, Wissenschaftliches Inst, Robert Koch Str 26, D-20249 H Klin Forsch Hamburg Robert Koch Str 26 Hamburg Germany D-20249
Citazione:
H.G. Dammann, "Preferential COX-2 inhibition: Its clinical relevance for gastrointestinalNSAID toxicity", Z GASTROENT, 37(1), 1999, pp. 45-58

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain. These drugs tend to cause significant side effects, however, including gastric and intestinal toxicity. The mechanism of action of NSAIDs is through their inhibition of the key enzyme of prostaglandin biosynthesis the cyclooxygenase. Recently, two forms of cy-clooxygenasehave been found to exist: COX-1 and COX-2, the constitutive and inducible forms, respect tivly . COX-1 exist; in the stomach, intestine, kidneys and platelets, while COX-2, the inducible form, is expressed during inflammation. The therapeutic effects of NSAIDs are largely the result of inhibition of the enzyme cyclooxygenase-2 (COX-2), whereas as the toxic effects (e. g.,gastrointestinal, renal and platelet effects) are primarily due to the inhibition of COX-I. Individual NSAIDs show different potencies against COX-1 compared with COX-2 and this explains the variations in the side effects ofNSAIDs at their anti-inflammatory gr doses. Drugs with high potency against COX-2 and a better COX-2-/COX-1 activity ratio will have anti-inflammatory activity) with fewer gastrointestinal side effects. In contrast piroxicamand indomethacin, which drugs have a much higher potency against COX-1 than against COX-2, are amongst those with the highest gastrointestinal toxicity. Based on the e findings, COX-2 seems to be an ideal target for the development of new anti-inflammatory drugs. Several compounds with preferentialor specific COX-2 inhibiting properties have been synthesized and evaluated in pre-clinical and clinical studies i. e. Meloxicam, Celecoxib, MK-966, Flusolid and L - 745, 337. The COX-2 selectivity of these novel NSAIDs relate well to their favorable gastrointestinal tolerability profile. Clinical trials have shown meloxicam and celecoxib to be as effective as currently available NSAIDs: but with an improved gastrointestinal tolerability profile. Further clinical trials and large-scale postmarketing surveillance programs are needed, however to confirm the potential therapeutic: benefits; of those novel preferential or specific COX-2 inhibitors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 15:56:42