Metabolism

Drug metabolism is slower at birth in full-term infants compared to adolescents and adults, with further delay in premature neonates. Phase I reactions and enzymes, such as oxidation and alcohol dehydrogenase, are impaired in premature neonates and infants and do not fully develop until later childhood or adolescence. Accordingly, the use of products containing ethanol or propylene glycol can result in increased toxicities, including respiratory depression, hyperosmolarity, metabolic acidosis, and seizures, and should be avoided in neonates and infants. Cytochrome P450 isoenzymes (e.g., CYP2C9, CYP1A2) develop at various ages, ranging from a few months to 3 years of age, with delayed development in premature infants.15

Among phase II reactions, sulfate conjugation by sulfotransferases is well developed at birth in term infants. Glucuronidation by the uridine diphosphate glucurono-syl transferases, on the other hand, is immature in neonates and infants, requiring at least several months to develop to adult values at approximately 4 years of age. In neonates this deficiency results in adverse effects including cyanosis, ash gray color of the skin, limp body tone, and hypotension, also known as "gray baby syndrome" with use of chloramphenicol.19 Products containing benzyl alcohol or benzoic acid should be avoided in neonates due to immature glycine conjugation, resulting in accumulation of benzoic acid. This accumulation can lead to "gasping syndrome," which includes respiratory depression, metabolic acidosis, hypotension, seizures or convul-

sions, and gasping respirations. Acetylation via #-acetyltransferase reaches adult maturation at around 1 year of life, but its impact is not well understood regard-

ing neonatal drug therapy. Thus, reduced dosing of medications undergoing hepatic metabolism may be required for full-term and premature neonates. Conversely, hepatic enzyme activity increases to nearly twice as much as adults at 6 months of age and may continue to be high through puberty, around 9 to 12 years of age.14

These children may require higher doses per kilogram of body weight for hepatically metabolized medications. Common examples include antiepileptic medications such as phenytoin, carbamazepine, and valproic acid. This increase in metabolism slows to adult levels as the child goes through puberty into adulthood.14

Anxiety and Depression 101

Anxiety and Depression 101

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