OPIATES AND NEONATAL ABSTINENCE SYNDROME: TOWARDS A BETTER UNDERSTANDING OF THE PHARMACOLOGY

neonatal abstinence syndrome;opiate;Clinical Investigation

Lewis, Tamorah RaeAlexander, G. Caleb ;

Johns Hopkins University

关键词: neonatal abstinence syndrome;    opiate;    Clinical Investigation;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39381/LEWIS-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Neonatal Abstinence Syndrome (NAS), either as a result of in utero opiate exposure or medical exposure in the intensive care unit, carries morbidity for neonates. There is no definitive research regarding optimal care for these infants. Thus, optimal medications, most effective dosing and strategies for mitigation of long-term developmental issues are unknown. In utero opiate exposure leads to chronic neuronal changes in opiate receptor signaling and the derangement of these pathways underlies the physical manifestations of NAS. Medical opiate exposure, as opposed to in utero exposure, involves high doses for shorter periods of time, but the resultant NAS is similar in manifestation and treatment. The introduction reviews the most current research on opiate tolerance and dependence mechanisms.Understanding prescribing patterns of pain and sedation medications in the ICU sheds light on NAS risk. Chapter I describes a cohort study quantifying the cumulative medical opiate exposure in high risk neonates. Opiate exposure has significantly increased over a decade, and this new knowledge may lead to more scrutiny of pain protocols, more diligent use of pain scores and opiate weaning protocols to standardize pain and sedation treatment in the NICU.In utero acquired NAS is treated with replacement opiate when symptoms are uncontrolled with non-pharmacologic interventions.In part due to a lack of pharmacologic research in these infants, there currently are multiple empiric morphine dosing regimens for NAS leading to widely different lengths of treatment and cost of care between institutions. There is no clear understanding of how dose correlates with exposure and how exposure correlates with clinical outcomes. Chapter II describes a pharmacokinetic (PK) study in infants with NAS, quantifying bioavailability of enteral morphine and internally validating models for use in future studies.Medicine is undergoing a paradigm shift away from blanket clinical approaches to individualized medicine. Maternal opiate maintenance therapy and resultant NAS must not be left behind. Chapter III reviews the potential for pharmacogenetics to vastly increase our understanding of opiate transfer across the placenta. The goals of my research program are to individualize maternal opiate medication choice and dosing, predict severity of NAS, and individualize NAS treatment.