Utjecaj terapije za astmu na cerebrovaskularnu bolest i neurodegeneraciju

After a short time of clinical experience, COX-2 inhibitors such as Viox and Rofecoxib were removed from the market because they increased the incidence of stroke and acute myocardial infarction. Recent studies have shown that COX-1/COX-2 inhibitors also have very similar side effects. The next step in asthma therapy was the introduction of 5-lipoxygenase inhibitors (Zileuton) and Cysleukotriene antagonists (Zafirlukast, Montelukast, Prankulast). There was a very good drug response within the first 4-13 weeks in mild or moderate asthma patients but side effects such as hypersensitivity reactions, dyspepsia, elevations of liver function tests and increased bleeding tendency were also present (large trials). At this point, we should ask ourselves what should be the alternative and strategies in asthma therapy, which would not affect other systems. Some recent studies have shown that there are some 6% of people in the population who have variant 5-LOX genotype (lacking the common allele) and increase in inflammatory products and intima-media thickness as well. Also, there are a number of studies investigating dietary intake of n-6 (arachidonic acid) and n-3 polyunsaturated (eicosapentaenoic acid) fatty acids, and its effect on leukotriene synthesis. Eicosapentaenoic acid is a poor substrate for COX-2 and the products of eicosapentaenoic acid inflammatory eicosanoids of series 3 and 5 are less inflammatory potent than the products of arachidonic acid inflammatory eicosanoids of series 4. We suggest that asthma patients should substitute n-6 polyunsaturated fatty acids with n-3 polyunsaturated acids in their daily diet in order to decrease eicosanoid series 2 and 4 production and to prevent cardiovascular and cerebrovascular disorders and neurodegeneration.Nakon kratkotrajne primjene u kliničkoj praksi COX-2 inhibitori Viox i Rofecobix su povučeni s tržišta, jer su primijećene nuspojave u smislu povećanja incidencije moždanog i srčanog udara. Kliničke studije su pokazale da COX-1/COX-2 inhibitori imaju vrlo slične nuspojave. Slijedeći korak u terapiji astme bilo je uvođenje 5-LOX inhibitora (Zileuton) i CysLT antagonista (Zafirlukast, Montelukast, Prankulast). Primjena ovih lijekova izazvala je vrlo dobar terapijski odgovor u prvih 4-13 tjedana u bolesnika s blažom i srednje jakom astmom, no zabilježene su i nuspojave kao što su alergijske reakcije, dispepsija, povišene vrijednosti jetrenih proba, povećana sklonost krvarenju. Razmatrajući sve ove činjenice postavlja se pitanje učinkovite terapije astme koja neće utjecati na druge organske sustave. U općoj populaciji oko 6% ljudi ima 5-LOX genotip (nedostaje im uobičajeni alel) kod kojeg je povećana aktivnost 5-LOX, njezinih krajnjih proupalnih proizvoda, a prema nekim istraživanjima i pojačana disfunkcija endotela krvnih žila (povećan IMT). Brojne studije koje su istraživale utjecaj unosa n-6 (arahidonska kiselina) i n-3 (eikosapentanska kiselina) polinezasićenih masnih kiselina na proizvodnju leukotriena pokazale su da je eikosapentanska kiselina loš supstrat za COX-2, te da su proupalni proizvodi serija 3 i 5 manje aktivni od proupalnih proizvoda arahidonske kiseline serija 2 i 4. Upravo zbog tih rezultata povećan unos eikosapentanske kiseline u svakodnevnoj prehrani bolesnika smanjio bi opasnost od kardiovaskularnih i cerebrovaskularnih bolesti te neurodegeneracije