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PERINATAL PHARMACOLOGY: INDIVIDUALIZED NEONATAL THERAPY Edited by J. V. Aranda V. Fanos J. N. van den Anker

18 FIGURES 17 TABLES 2012


PERINATAL PHARMACOLOGY: INDIVIDUALIZED NEONATAL THERAPY © 2012 Hygeia Press di Corridori Marinella Via Montecatini, 53 – Quartu Sant’Elena (Cagliari) – Italy www.hygeiapress.com First edition: October 2012 ISBN 9788890651434 Cover pictures: a case of drug-induced liver disease (DILI). On the front cover: macrovesicular steatosis; on the back cover: microvesicular steatosis (Prof. Gavino Faa, with permission).

Editing: Marinella Corridori Editorial coordination: Eleonora Fanos English revision: David C. Nilson Printing and binding: Grafiche Ghiani srl S.S. 131 km 17,450 – Z. I. – Monastir (CA) – Italy

Disclaimer. Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of this publication. Drug dosage. The authors, editors and publisher have exerted every effort to be certain that drug selection and dosage set forth in this book are in accordance with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. All rights reserved. All materials are protected by Italian law and by international conventions. No part of this work may be translated into other languages, reproduced or utilized in any form or by any means without the prior written permission of the publisher.


Contents

1.

Contributors

15

Preface

21

Abbreviations

23

Developmental pharmacology John N. van den Anker, Natella Y. Rakhmanina, Karel Allegaert Drug absorption • Drug distribution • Drug metabolism • Phase I enzymes • Drug excretion • Other factors influencing the absorption, distribution, metabolism and excretion of drugs in neonates and young infants • Pharmacogenomics: impact for pediatric populations • Developmental pharmacodynamics • Conclusions • References

2.

27

Drug-induced liver injury in neonates: a developmental approach Gavino Faa, Daniela Fanni, Clara Gerosa, Sonia Nemolato, Yukio Gibo, Massimo Castagnola, Vassilios Fanos Pharmacokinetics in neonates • Drug-induced liver injury in neonates • Liver disease due to widely utilized drugs in newborns • Conclusions and future challenges • References

3.

49

Influence of prenatal drug treatments on kidney function during fetal and neonatal life Laura Cuzzolin, Vassilios Fanos Pathophysiological mechanisms and renal syndromes • Prenatal exposure to drugs • Conclusions • References

4.

83

Excipients in neonatal drug formulations: friend and foe? Roosmarijn De Cock, Catherijne Knibbe, Karel Allegaert About the compounds we routinely administer, but never prescribe • The STEP database • The ESNEE research initiative • The Leuven propylene glycol research project to illustrate feasibility and limitations • Perspectives • References

99


5.

Pharmacotoxic effects of aminoglycosides and loud environmental noise: an overlooked risk for hearing loss in preterm infants Amir Lahav, Emily Zimmerman The prevalence of hearing loss in preterm neonates • From the protected environment of the womb to the ototoxic environment in the neonatal intensive care unit • Aminoglycosides-induced ototoxicity • Synergistic ototoxicity induced by aminoglycoside and noise exposure • Implications for clinical care • References

6.

109

Clinical pharmacology of analgosedatives in neonates: between the hammer and the anvil? Karel Allegaert, John N. van den Anker On the relevance of (in)adequate analgesia in neonates • Clinical pharmacology of analgesics: from pharmacokinetics towards pharmacodynamics • New compounds: new tools or new toys? • Clinical practice: between the hammer and the anvil? • References

7.

119

New treatments of persistent pulmonary hypertension of the newborn Nicoletta Iacovidou, Aggeliki Syggelou, Spyros Kloudas, Theodoros Xanthos Definitions • Pulmonary vasculature physiology – Pathophysiology of PPHN • Etiology of PPHN – Classification – Predisposing factors • Diagnosis of PPHN • Management of PPHN • References

8.

129

Inotropic and vasopressor drugs in the newborn Hercília Guimarães, Gustavo Rocha, Paulo Soares, Henrique Soares, Maria Beatriz Guedes Inotropic agents • Epinephrine • Norepinephrine • Dopamine • Dobutamine • Isoproterenol • Milrinone • Levosimendan • References

9.

149

Role of vasopressin and terlipressin in newborns and infants with hypotension and shock Paolo Biban, Davide Silvagni Biology of endogenous vasopressin • Role of endogenous vasopressin in shock • Pharmacology of vasopressin and terlipressin • Exogenous vasopressin and terlipressin in neonatal and pediatric shock • Safety and adverse effects of vasopressin and terlipressin • Conclusions • References

10

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Contents


10. Pharmacological treatment of patent ductus arteriosus: the last days of indomethacin? Bart Van Overmeire Indomethacin • Ibuprofen, the preferred drug? • Gastrointestinal effects of NSAIDs • Renal adverse effects of NSAIDs • Pulmonary hypertension • Bilirubin and ibuprofen • Appropriate NSAIDs dosing • Adapted ibuprofen dosing • Oral administration • Paracetamol? • Conclusion • References

169

11. The role of caffeine in neonatology Pier Paolo Bassareo, Vassilios Fanos, Giuseppe Mercuro Caffeine: short-term effects • Caffeine: long-term effects • Conclusions • References

181

12. Pulmonary surfactant in newborn infants Virgilio P. Carnielli, Stefano Nobile, Paola E. Cogo Background and history • Composition and pharmacodynamics • Methods for pharmacokinetic studies • Surfactant therapy • References

191

13. Meconium aspiration syndrome: do we know the treatment? Murat Yurdakök Pathophysiology of meconium aspiration syndrome • Prophylaxis of meconium aspiration • Management of infants with meconium aspiration • Conclusions • References

203

14. Treatment of chronic lung disease Fabio Mosca, Valentina Polimeni, Francesca Ciuffini, Massimo Agosti, Monica Fumagalli, Mariarosa Colnaghi Caffeine • Diuretics • Postnatal corticosteroids • Surfactant • Bronchodilators • Inhaled nitric oxide • Pulmonary vasodilators • Anti-oxidants • Stem cells • Conclusion • References

215

15. Postnatal steroids for the prevention and treatment of bronchopulmonary dysplasia Eren Özek Postnatal corticosteroids for bronchopulmonary dysplasia • Background • Current evidence of postnatal steroid use • Choice of glucocorticoids • Timing, dosage and duration of corticosteroids • Other systemic or inhaled glucocorticoids • Summary of current evidence based recommendations • References

Contents

225

11


16. Molecular and clinical pharmacology of retinopathy of prematurity Kay D. Beharry, Jacob V. Aranda, Daniel Canal-Tristancho, Gloria B. Valencia, Douglas R. Lazarro Epidemiology and clinical considerations • Pharmacologic interventions in ROP • Caffeine • NSAIDs and COX blockade in ROP • Antioxidant use in ROP • Long chain polyunsaturated fatty acids (LCPUFA) • Growth factors, IGF-1, VEGF and VEGF-antibodies • Beta-blockers • Other pharmacologic interventions • Summary • References

243

17. How to treat hypoxic-ischemic encephalopathy with drugs Serafina Perrone, Gemma Stazzoni, Maria Luisa Tataranno, Giuseppe Buonocore Pathophysiology of HIE • Promising pharmacological interventions • Combined therapies • Conclusions • References

261

18. Does the best antioxidant come from the brain? Melatonin for the newborn: present and future Ignazio Barberi, Salvatore Aversa, Lucia Marseglia, Eloisa Gitto 273

Utility of melatonin in newborns • Future prospectives • References

19. Invasive fungal infections in the nursery: the state of the art Paolo Manzoni, Elio Castagnola, Eveline Jacqz-Aigrain, Mauro Stronati, Daniele Farina Risk factors • Prevention • Treatment of neonatal invasive fungal disease: antifungal drugs • References

281

20. News on management of Cytomegalovirus infections Marcello Lanari, Maria Grazia Capretti, Paola Sogno Valin, Tiziana Lazzarotto Prenatal strategies to prevent CMV congenital infection • Neonatal diagnosis of CMV congenital infection • Postnatal CMV infection transmitted via mother’s milk • Neuroimaging of CMV congenital infected newborns • CMV and antiviral therapy • Conclusions • References

291

21. Global (pharmacological and non pharmacological) prevention of RSV infection Giovanni Corsello, Bruna Gabriele, Mario Giuffrè Respiratory syncytial virus infections • Non pharmacological prophylaxis • Pharmacological prophylaxis • Conclusions • References

12

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22. Clinical review of pharmacologic agents for infants with severe viral bronchiolitis Corrado Moretti, Paola Papoff, Carla Cerasaro, Caterina Silvia Barbàra, Serena Salvadei, Fabio Midulla Antibiotics • Beta agonists, epinephrine and hypertonic saline • Corticosteroids • DNase • Caffeine • Surfactant • Anesthetics • Conclusions • References

315

23. Perinatal antiretroviral therapy Natella Y. Rakhmanina, Sahera Dirajlal-Fargo, John N. van den Anker Antiretroviral therapy during pregnancy and delivery • Neonatal antiretroviral prophylaxis • Safety of perinatal antiretroviral therapy • Conclusions • References

323

Index

347

Contents

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Perinatal Pharmacology: individualized neonatal therapy - Hygeia Press - Contents