Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks.

摘要: Non steroidal anti-inflammatory drugs (NSAIDs) are still the most commonly used remedies for rheumatic diseases. But NSAIDs produce serious adverse effects, important being gastric injury up to ulceration and renal damage. Several strategies have been adopted in order avoid these shortcomings, especially gastrointestinal toxicity. So, non associated with gastroprotective agents that counteract damaging effects of prostaglandin synthesis suppression: however, a combination therapy introduces problems pharmacokinetics, toxicity, patient s compliance. Also incorporation nitric oxide (NO)-generating moiety into molecule several was shown greatly attenuate their ulcerogenic activity: findings suggest possible involvement NO pathogenesis arthritis subsequent tissue destruction. A promising approach seemed be preparation novel NSAIDs, specific inducible isoform cyclooxygenase (COX-2): they appear devoid spare mucosal synthesis. However, number recent studies raised questions about two central tenets support this approach, namely prostaglandins mediate inflammation pain produced solely via COX-2 function COX-1. increasing evidence shows (not only COX-1) also plays physiological role body functions that, conversely, COX-1 COX-2) may induced at sites inflammation. Moreover, selective lost cardiovascular protective non-selective which mediated through inhibition (in addition, has sustaining vascular prostacyclin production). The products generated by 5-lipoxygenase pathway (leukotrienes) particularly inflammation: indeed, leukotrienes increase microvascular permeability potent chemotactic agents; moreover, indirectly reduces expression TNF-alpha (a cytokine key inflammation). This explains efforts obtain able inhibit both cyclooxygenases: so-called dual acting drugs. Such compounds retain activity classical while avoiding main drawbacks, curtailed production is concurrent gastro-damaging bronchoconstrictive leukotrienes. thanks mechanism action, could not merely alleviate symptoms diseases, but might satisfy, least part, criteria curative Indeed, pro-inflammatory, permeability, attract eosinophils, neutrophils monocytes synovium. Finally, data strongly inhibitors neurodegeneration.