Shimizu T
Department of Paediatrics, Juntendo University, School of Medicine, Tokyo, Japan.
Drugs. 1998 Aug;56(2):169-76. doi: 10.2165/00003495-199856020-00001.
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.
类二十烷酸在儿科实践中可能有许多潜在用途。自从E型前列腺素首次应用于儿科实践中治疗依赖动脉导管的先天性心脏病以来，许多与类二十烷酸相关的药物已被研究用于治疗儿童的病理生理状况。由细胞膜磷脂中的花生四烯酸产生的前列腺素（PG）、血栓素（TX）和白三烯（LT）被认为是具有生物活性的类二十烷酸。皮质类固醇通过损害磷脂酶A2的激活来减少类二十烷酸的产生，而诸如非甾体抗炎药（NSAID）等环氧化酶抑制药物则抑制PG和TX的产生。已证明前列腺素E1（前列地尔）和前列腺素E2（地诺前列酮）疗法可改善肺循环和体循环血流依赖动脉导管未闭的新生儿的氧合，而依前列醇（前列环素，PGI2）和另一种PGI2类似物贝拉前列腺素（贝拉前列腺素钠）通常作为小儿肺动脉高压的急性血管扩张剂有效。合成的前列腺素E类似物如米索前列醇具有胃抗分泌和细胞保护作用，并且在预防和治疗NSAID引起的胃十二指肠黏膜损伤方面均有效。前列地尔和依前列醇均已证明在治疗周围血管和皮肤疾病方面有效。由于TX作为血小板聚集剂和血管收缩剂，被认为是哮喘的潜在介质，因此其被诸如塞曲司特（AA - 2414）和奥扎格雷（OKY - 046）等药物抑制已被证明对成年哮喘患者的治疗有效；人们饶有兴趣地期待着对这些药物在儿科患者中的研究。开发与类二十烷酸相关药物的临床用途并评估这些药物的潜在用途需要采取三个阶段的方法：减少依赖动脉导管的先天性心脏病和需要前列腺素E1、前列腺素E2和前列环素治疗的原发性肺动脉高压新生儿治疗中的并发症；对已经用于治疗成年支气管哮喘患者的血栓素A2和白三烯的合成抑制剂和受体拮抗剂进行临床试验；以及评估类二十烷酸生物合成的新调节剂，如二十碳五烯酸和抗过敏药物，在治疗儿童类二十烷酸相关疾病中的疗效。
