NEW NONSTEROIDAL ANTIINFLAMMATORY DRUGS - SELECTIVE INHIBITORS OF THEINDUCIBLE CYCLOOXYGENASE

Citation
Do. Stichtenoth et al., NEW NONSTEROIDAL ANTIINFLAMMATORY DRUGS - SELECTIVE INHIBITORS OF THEINDUCIBLE CYCLOOXYGENASE, Medizinische Klinik, 93(7), 1998, pp. 407-415
Citations number
117
Categorie Soggetti
Medicine, General & Internal
Journal title
ISSN journal
07235003
Volume
93
Issue
7
Year of publication
1998
Pages
407 - 415
Database
ISI
SICI code
0723-5003(1998)93:7<407:NNAD-S>2.0.ZU;2-F
Abstract
Mode of Action of Non-Steroidal Anti-inflammatory Drugs: Non-steroidal anti-inflammatory drugs (NSAID) exert their major therapeutic and adv erse effects by inhibition of prostanoid synthesis. Also the interacti ons with antihypertensive drugs and lithium are caused by this mechani sm of action, Cyclooxygenation is a key enzymatic step in the synthesi s of prostanoids. 1990 2 isoforms of the enzyme cyclooxygenase have be en identified: Prostanoids synthesized by the constitutive cyclooxygen ase (COX-1) are involved in physiological homeostasis. In contrast, th e inducible cyclooxygenase (COX-2) produces large amounts of prostanoi ds, mainly contributing to the pathophysiological process of inflammat ion. COX-2 Selective NSAID: The discovery of the cyclooxygenase-isoenz ymes ushered in a new generation of NSAID: A drug with selectivity for COX-2 would inhibit proinflammatory prostanoid synthesis while sparin g physiologic prostanoid synthesis. Thus, a selective COX-2 inhibitor should be anti-inflammatory with less or no gastrointestinal or other NSAID-typical adverse effects. The experiences with currently used NSA ID, which show an increasing incidence of side effects as COX-1 inhibi tion increases, and studies with the COX-2 selective NSAID salsalate a nd meloxicam, which have less adverse effects than nonselective COX in hibitors in equivalent antiphlogistic dosage, prove the concept of sel ective COX-2 inhibition to avoid the NSAID typical side effects. devel oped drugs with a very high selectivity for COX-2 are now tested in cl inical trials. Conclusion: So far the results suggest, that selective and highly selective COX-2 inhibitors have significantly fewer gastroi ntestinal and renal adverse effects and do not inhibit platelet aggreg ation.