Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments

Tang, Fei; Ng, Chee M.; Bada, Henrietta S.; Leggas, Markos

doi:10.1111/cts.12994

Cited by 5 publications

(3 citation statements)

References 127 publications

(456 reference statements)

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“…However, there is a considerable uncertainty regarding the relationship of opioids with episodes of bradycardia, hypotension, or severe apneas [90]. Therefore, the use of standardized protocols for pain management have been suggested to minimize the exposure to opioids [87,91].…”

Section: Opioidsmentioning

confidence: 99%

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

Kontou,

Agakidou,

Chatziioannidis

et al. 2024

Preprint

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Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

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Section: Opioidsmentioning

confidence: 99%

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

Kontou,

Agakidou,

Chatziioannidis

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Recent data also show that POE neonates who display NOWS symptoms at birth have better outcomes than POE neonates that did not display NOWS, likely a function of the treatments used to alleviate NOWS potentially having lasting protective effects ( Leyenaar et al, 2021 ). Despite the proven potential for treatments to improve the lives of neonates with POE, there has been a lack of new treatments as current first-line treatments for both pregnant women with OUD and neonates displaying NOWS remain opioid maintenance therapies, such as methadone and buprenorphine ( Committee Opinion, 2017 ; Ghazanfarpour et al, 2019 ; Tang et al, 2021 ; Zankl et al, 2021 ). As a consequence, it is difficult to separate the pharmacology of POE and NOWS treatments as well as other environmental factors, both independently and in combination with each other across the human lifespan.…”

Section: Introductionmentioning

confidence: 99%

Prenatal methadone exposure selectively alters protein expression in primary motor cortex: Implications for synaptic function

et al. 2023

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As problematic opioid use has reached epidemic levels over the past 2 decades, the annual prevalence of opioid use disorder (OUD) in pregnant women has also increased 333%. Yet, how opioids affect the developing brain of offspring from mothers experiencing OUD remains understudied and not fully understood. Animal models of prenatal opioid exposure have discovered many deficits in the offspring of prenatal opioid exposed mothers, such as delays in the development of sensorimotor function and long-term locomotive hyperactivity. In attempt to further understand these deficits and link them with protein changes driven by prenatal opioid exposure, we used a mouse model of prenatal methadone exposure (PME) and preformed an unbiased multi-omic analysis across many sensoriomotor brain regions known to interact with opioid exposure. The effects of PME exposure on the primary motor cortex (M1), primary somatosensory cortex (S1), the dorsomedial striatum (DMS), and dorsolateral striatum (DLS) were assessed using quantitative proteomics and phosphoproteomics. PME drove many changes in protein and phosphopeptide abundance across all brain regions sampled. Gene and gene ontology enrichments were used to assess how protein and phosphopeptide changes in each brain region were altered. Our findings showed that M1 was uniquely affected by PME in comparison to other brain regions. PME uniquely drove changes in M1 glutamatergic synapses and synaptic function. Immunohistochemical analysis also identified anatomical differences in M1 for upregulating the density of glutamatergic and downregulating the density of GABAergic synapses due to PME. Lastly, comparisons between M1 and non-M1 multi-omics revealed conserved brain wide changes in phosphopeptides associated with synaptic activity and assembly, but only specific protein changes in synapse activity and assembly were represented in M1. Together, our studies show that lasting changes in synaptic function driven by PME are largely represented by protein and anatomical changes in M1, which may serve as a starting point for future experimental and translational interventions that aim to reverse the adverse effects of PME on offspring.

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“…Recent data also show that POE neonates who display NOWS symptoms at birth have better outcomes than POE neonates that did not display NOWS, likely a function of the treatments used to alleviate NOWS potentially having lasting protective effects (Leyenaar, Schaefer et al 2021). Despite the proven potential for treatments to improve the lives of neonates with POE, there has been a lack of new treatments as current first-line treatments for both pregnant women with OUD and neonates displaying NOWS remain opioid maintenance therapies, such as methadone and buprenorphine (2017, Ghazanfarpour, Najafi et al 2019, Tang, Ng et al 2021, Zankl, Martin et al 2021). As a consequence, it is difficult to separate the pharmacology of POE and NOWS treatments as well as other environmental factors, both independently and in combination with each other across the human lifespan.…”

Section: Introductionmentioning

confidence: 99%

Prenatal methadone exposure selectively alters protein expression in primary motor cortex: implications for synaptic function

Haggerty

Grecco

Huang

et al. 2022

Preprint

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As problematic opioid use has reached epidemic levels over the past two decades, the annual prevalence of opioid use disorder (OUD) in pregnant women has also increased 333%. Yet, how opioids affect the developing brain of offspring from mothers experiencing OUD remains understudied and not fully understood. Animal models of prenatal opioid exposure have discovered many deficits in the offspring of prenatal opioid exposed mothers, such as delays in the development of sensorimotor function and long-term locomotive hyperactivity. In attempt to further understand these deficits and link them with protein changes driven by prenatal opioid exposure, we used a mouse model of prenatal methadone exposure (PME) and preformed an unbiased multi-omic analysis across many sensoriomotor brain regions known to interact with opioid exposure. The effects of PME exposure on the primary motor cortex (M1), primary somatosensory cortex (S1), the dorsomedial striatum (DMS), and dorsolateral striatum (DLS) were assessed using quantitative proteomics and phosphoproteomics. PME drove many changes in protein and phosphopeptide abundance across all brain regions sampled. Gene and gene ontology enrichments were used to assess how protein and phosphopeptide changes in each brain region were altered. Our findings showed that M1 was uniquely affected by PME in comparison to other brain regions. PME uniquely drove changes in M1 glutamatergic synapses and synaptic function. Immunohistochemical analysis also identified anatomical differences in M1 for upregulating the density of glutamatergic and downregulating the density of GABAergic synapses due to PME. Lastly, comparisons between M1 and non-M1 multi-omics revealed conserved brain wide changes in phosphopeptides associated with synaptic activity and assembly, but only specific protein changes in synapse activity and assembly were represented in M1. Together, our studies show that lasting changes in synaptic function driven by PME are largely represented by protein and anatomical changes in M1, which may serve as a starting point for future experimental and translational interventions that aim to reverse the adverse effects of PME on offspring.

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Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 5 publications

References 127 publications

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

Antibiotic Analgesic-Sedative and Antiseizure Medications Frequently Used in Critically Ill Neonates: A Narrative Review

Prenatal methadone exposure selectively alters protein expression in primary motor cortex: Implications for synaptic function

Prenatal methadone exposure selectively alters protein expression in primary motor cortex: implications for synaptic function

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