Do. Stichtenoth et al., NEW NONSTEROIDAL ANTIINFLAMMATORY DRUGS - SELECTIVE INHIBITORS OF THEINDUCIBLE CYCLOOXYGENASE, Medizinische Klinik, 93(7), 1998, pp. 407-415
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.