Perinatal Pharmacology
[chapter]
Obstetric Anesthesia Handbook
Effective and safe drug administration should be based on knowledge that integrates the evolving physiological characteristics of the individual patient who will receive the drug with the pharmacokinetics (PK) and pharmacodynamics (PD) of the prescribed drug. Consequently, clinical pharmacology in neonates and pregnant women is as dynamic and diverse as the specific populations considered [1, 2] . Despite this diversity, there is currently little integration of available knowledge to guide and
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... ptimize pharmacotherapy in these populations [3] [4] [5] [6] . Mothers are commonly exposed to drugs during pregnancy, at delivery, or in the postpartum period, and this includes women with preexisting comorbidities. Despite this, dosing regimens are still commonly extrapolated from regimens initially validated in adults and do not consider the pregnancy related changes in physiology nor issues related to fetal effects before or breastfeeding related exposure after delivery [1, 6] . The same holds true for neonates. The most obvious covariates in neonates relate to growth and development, reflected and quantified by birth weight, current weight, or age-either postnatal, gestational, or postmenstrual age. There is already at least one log order of variability in weight (<0.5 up to 5 kg) while both the height velocity rate (10-20 cm/year) and the increase in body weight (50% increase in the first 6 weeks) reflect the dynamics of a rapidly evolving biological system during perinatal life. The maturation related variability is further aggravated by interfering disease characteristics (e.g., renal failure, sepsis, and growth restriction) or treatment modalities (e.g., comedication, extracorporeal membrane oxygenation, and whole body cooling). Since infants and pregnant women warrant a focused approach due to the physiological changes related to maturation (fetus, newborn) or pregnancy, understanding these changes to predict exposure/effects is necessary. Modelling emerged as a promising tool to improve prediction of exposure/effects [3, 4, 6] . However, these methods need further validation before this approach can be implemented. In addition, both effects and side effects may be population specific. This necessitates the validation of biomarkers (e.g., liver enzymes, renal biomarkers, and blood pressure) commonly applied in other populations or exploration to develop, evaluate, and validate new approaches to assess drug effect or side effects (PD) in infants or pregnant women that are valid and appropriate for clinical use. Finally, practices and clinical care also evolve. Mothers undergo surgical interventions during pregnancy to improve fetal outcome, while hypothermia to improve neurodevelopment outcome
doi:10.1007/0-387-31529-2_3
fatcat:expubgtqzzdlvhynpwaylqrdli