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The future potential of eicosanoids and their inhibitors in paediatric practice
1Department of Paediatrics, Juntendo University, School of Medicine, Tokyo, Japan.
Insights
Eicosanoid drugs, including prostaglandins and thromboxane inhibitors, show promise in treating various pediatric conditions like congenital heart disease and pulmonary hypertension. Further research is needed for asthma and other eicosanoid-related diseases in children.
Area of Science:
- Pediatric Pharmacology
- Eicosanoid Therapeutics
- Cardiovascular and Respiratory Medicine
Background:
- Eicosanoids, derived from arachidonic acid, play crucial roles in various physiological processes.
- Eicosanoid-related drugs have demonstrated utility in pediatric practice, particularly prostaglandins (PG).
- Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids modulate eicosanoid production.
Purpose of the Study:
- To review the current and potential applications of eicosanoid-related drugs in pediatric practice.
- To highlight the therapeutic benefits of prostaglandins (PGE1, PGE2, PGI2) in neonates.
- To explore the potential of thromboxane (TX) and leukotriene (LT) inhibitors in pediatric conditions.
Main Methods:
- Review of existing literature on eicosanoid drug applications in pediatric patients.
- Discussion of the mechanisms of action for prostaglandins, thromboxanes, and leukotrienes.
- Outline of a phased approach for developing new eicosanoid-related therapies for children.
Main Results:
- PGE1 (alprostadil) and PGE2 (dinoprostone) improve oxygenation in neonates with ductus-dependent congenital heart disease.
- Epoprostenol (PGI2) and beraprost are effective vasodilators for pediatric pulmonary hypertension.
- Synthetic PGE analogues like misoprostol treat NSAID-induced gastroduodenal lesions.
- TX inhibitors show promise for asthma, with pediatric studies anticipated.
Conclusions:
- Eicosanoid-based therapies offer significant benefits for neonates with critical cardiovascular conditions.
- Further clinical trials are warranted for TX and LT inhibitors in pediatric asthma.
- Evaluating novel eicosanoid biosynthesis modulators is essential for advancing pediatric treatment.
Abstract:
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.