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      Pulmonary hypertension occurring with diazoxide use in a preterm infant with hypoglycemia

      case-report

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          Abstract

          Pharmacologic modulation to open the K ATP channels with diazoxide is useful in treating hyperinsulinemia. Diazoxide is being used more often in neonates with hyperinsulinemic hypoglycemia. This report highlights a case of severe pulmonary hypertension (PH) with re-opening of ductus arteriosus in an extremely premature infant after the use of diazoxide. The rapid onset of PH with respiratory failure was completely reversible. This case emphasizes the need for extreme caution with use of diazoxide in the premature infant population, especially those with chronic lung disease of prematurity. In addition, the use of diazoxide should be limited to the persistent form of congenital hyperinsulinism, after adequate work up has been completed to evaluate for other causes of hypoglycemia. It is postulated that development of PH could be related to K ATP agonsim.

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          Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

          Abstract Congenital hyperinsulinism is a rare disease, but is the most frequent cause of persistent and severe hypoglycaemia in early childhood. Hypoglycaemia caused by excessive and dysregulated insulin secretion (hyperinsulinism) from disordered pancreatic β cells can often lead to irreversible brain damage with lifelong neurodisability. Although congenital hyperinsulinism has a genetic cause in a significant proportion (40%) of children, often being the result of mutations in the genes encoding the KATP channel ( ABCC8 and KCNJ11), not all children have severe and persistent forms of the disease. In approximately half of those without a genetic mutation, hyperinsulinism may resolve, although timescales are unpredictable. From a histopathology perspective, congenital hyperinsulinism is broadly grouped into diffuse and focal forms, with surgical lesionectomy being the preferred choice of treatment in the latter. In contrast, in diffuse congenital hyperinsulinism, medical treatment is the best option if conservative management is safe and effective. In such cases, children receiving treatment with drugs, such as diazoxide and octreotide, should be monitored for side effects and for signs of reduction in disease severity. If hypoglycaemia is not safely managed by medical therapy, subtotal pancreatectomy may be required; however, persistent hypoglycaemia may continue after surgery and diabetes is an inevitable consequence in later life. It is important to recognize the negative cognitive impact of early‐life hypoglycaemia which affects half of all children with congenital hyperinsulinism. Treatment options should be individualized to the child/young person with congenital hyperinsulinism, with full discussion regarding efficacy, side effects, outcomes and later life impact.
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            Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide.

            Diazoxide, the only U.S. Food and Drug Administration-approved drug to treat hyperinsulinemic hypoglycemia, has been associated with several adverse events, which has raised concerns about the safety of this drug. Existing reports are limited to small studies and case reports.
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              K(ATP) channel therapeutics at the bedside.

              The family of potassium channel openers regroups drugs that share the property of activating adenosine triphosphate-sensitive potassium (K(ATP)) channels, metabolic sensors responsible for adjusting membrane potential-dependent functions to match cellular energetic demands. K(ATP) channels, widely represented in metabolically-active tissue, are heteromultimers composed of an inwardly rectifying potassium channel pore and a regulatory sulfonylurea receptor subunit, the site of action of potassium channel opening drugs that promote channel activity by antagonizing ATP-induced pore inhibition. The activity of K(ATP) channels is critical in the cardiovascular adaptive response to stress, maintenance of neuronal electrical stability, and hormonal homeostasis. Thereby, K(ATP) channel openers have a unique therapeutic spectrum, ranging from applications in myopreservation and vasodilatation in patients with heart or vascular disease to potential clinical use as bronchodilators, bladder relaxants, islet cell protector, antiepileptics and promoters of hair growth. While the current experience in practice with potassium channel openers remains limited, multitude of ongoing investigations aims at defining the benefit of this emerging family of therapeutics in diverse disease conditions associated with metabolic distress.
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                Author and article information

                Journal
                Drug Healthc Patient Saf
                Drug Healthc Patient Saf
                Drug, Healthcare and Patient Safety
                Drug, Healthcare and Patient Safety
                Dove Medical Press
                1179-1365
                2019
                04 March 2019
                : 11
                : 7-10
                Affiliations
                Division of Neonatal-Perinatal Medicine and Developmental Biology, Department of Pediatrics, The University of Arizona, College of Medicine, Tucson, AZ, USA, rkylat@ 123456gmail.com
                Author notes
                Correspondence: Ranjit I Kylat, Division of Neonatal-Perinatal Medicine and Developmental Biology, Department of Pediatrics, University of Arizona, College of Medicine, PO BOX 245073, 1501 N, Campbell Avenue, Tucson, AZ 85724, USA, Tel +1 520 626 6627, Fax +1 520 626 5009, Email rkylat@ 123456gmail.com
                Article
                dhps-11-007
                10.2147/DHPS.S198255
                6407670
                30881142
                ef1d2d57-2ca2-4496-b59a-ab87c58e1846
                © 2019 Kylat. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Case Report

                Public health
                hypoglycemia,hyperinsulinemia,pulmonary hypertension,diazoxide,katp channels,ductus arteriosus

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