Clinical perspectives of anti-inflammatory therapy in the elderly: the lipoxigenase (LOX)/cycloxigenase (COX) inhibition concept.
Non steroidal anti-inflammatory drugs (NSAIDs) are one of the categories of drugs most frequently used by elderly people, and maybe the most self-prescribed drugs. Both coronary events, and stroke, can be prevented by daily aspirin assumption. Other NSAIDs, except selective COX-2 inhibitors (coxibs), seem to reduce the incidence of cardiovascular events, but a definitive judgement is yet impossible. Moreover, these drugs cause more than 100,000 serious gastric adverse events each year in the US, and the risk increases exponentially in the elderly. Coxibs cause less gastric damage, but their cost is very high. Moreover, NSAIDs inhibit renal function and reduce the efficacy of diuretics and angiotensin converting enzyme (ACE) inhibitors, often used by elderly patients. Recent studies show that even COX-2 is important in the renal physiology, so that even coxibs appear not to be avoided of renal toxicity. Both gastric and renal toxicity induced by traditional NSAIDs and coxibs seem to be related to the fact that these drugs inhibit the synthesis of prostaglandins (PGs), but not those of leukotrienes (LTs), important mediators of inflammation and of many other physiopatological events. Newly developed anti-inflammatory drugs block both COX and the 5-LOX metabolic pathways, inhibiting the formation of PGs, thromboxanes (TXs) and LTs. The inhibition of the LT synthesis increases the anti-inflammatory efficacy (especially in pneumological and rheumatological diseases), reducing the risk of gastric damage. Even if preliminary data seem to be very interesting, further clinical safety data on these drugs obtained from elderly oriented trials need to be available before to give a final evaluation.
Gaddi
Antonio
A
Medicine and Applied Biotechnology Department D. Campanacci, Atherosclerosis and Dysmetabolic Diseases Study Center G. Descovich, Bologna, Italy. gaddiats@med.unibo.it
Cicero
Arrigo F G
AF
Pedro
Egidio J
EJ
D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases