The future potential of eicosanoids and their inhibitors in paediatric practice.
Eicosanoids may have many potential uses in paediatric practice. Since E-type prostaglandins were first applied to treat ductus-dependent congenital heart diseases in paediatric practice, many eicosanoid-related drugs have been examined for the treatment of pathophysiological conditions in children. Prostaglandins (PG), thromboxane (TX) and leukotrienes (LT), produced from arachidonic acid in the phospholipids of cell membranes, are considered to be biologically active eicosanoids. Corticosteroids reduce eicosanoid production by impairing phospholipase A2 activation, while cyclo-oxygenase inhibiting drugs such as the nonsteroidal anti-inflammatory drugs (NSAID) suppress PG and TX production. PGE1 (alprostadil) and PGE2 (dinoprostone) therapy has been shown to improve oxygenation in neonates whose pulmonary and systemic blood flow are dependent on a patent ductus arteriosus, while epoprostenol (prostacyclin, PGI2) and beraprost (beraprost sodium), another PGI2 analogue, are often effective as acute vasodilators in paediatric pulmonary hypertension. Synthetic PGE analogues such as misoprostol have gastric antisecretory and cytoprotective effects, and are effective in both prophylaxis and treatment of NSAID-induced gastroduodenal mucosal lesions. Both alprostadil and epoprostenol have been shown to be effective in treating peripheral vascular and skin diseases. Since TX, a platelet aggregator and vasoconstrictor, has been implicated as a potential mediator of asthma, its inhibition by agents such as seratrodast (AA-2414) and ozagrel (OKY-046) has proven effective in the treatment of adult patients with asthma; studies of these agents in paediatric patients is awaited with interest. Developing the clinical use of eicosanoid-related drugs and assessing the potential use of these drugs requires a 3-phase approach: reducing the complications in the treatment of neonates with ductus-dependent congenital heart diseases and primary pulmonary hypertension requiring PGE1, PGE2 and PGI2 therapy; conducting clinical trials of the synthesis inhibitors and receptor antagonists of TXA2 and LT that have already been used in the treatment of adult patients with bronchial asthma; and evaluating the efficacy of new modulators of eicosanoid biosynthesis, such as eicosapentaenoic acid and antiallergy drugs, in the treatment of eicosanoid-related diseases in children.
Shimizu
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Department of Paediatrics, Juntendo University, School of Medicine, Tokyo, Japan.
D002648:Child; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy; D015777:Eicosanoids / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D012871:Skin Diseases / Q000188:drug therapy; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D020024:Leukotriene Antagonists; D013928:Thromboxane A2; D015118:Eicosapentaenoic Acid