Kim Annink

153 Allopurinol: old drug, new indication in neonates? Figure 2: Before birth, during perinatal hypoxia, several pathways are activated, including the production of hypoxanthine and xanthine-oxidase. Because of hypoxia, ATP is con- verted to adenosine monophosphate (AMP) and adenosine diphosphate (ADP), AMP leads to the production of adenosine and consequently to inosine, which increases the concen- tration of hypoxanthine in the blood. Also, xanthine-oxidase concentrations rise because of hypoxia by the production of xanthine dehydrogenase. After birth, the supply of extra oxygen during reperfusion leads to the production of superoxide. Xanthine-oxidase causes a reaction in which hypoxanthine and oxygen are converted to uric acid and superoxide. Allopurinol inhibits xanthine-oxidase and thereby reduces the formation of superoxide. Further, allopurinol is thought to have a direct hydroxyl radical scavenger effect and is a non-protein-bound iron chelator. 7