Q2. Diazepam experiences a significant first-pass effect. What is the first-pass effect, and how can first-pass metabolism be circumvented? A 75-year-old woman develops symptoms of a cold and buys an over-the-counter cold medication at the grocery store. The medication contains diphenhydramine, acetaminophen, and phenylephrine. She takes the recommended adult dose, but soon after taking the medication, she becomes very confused and disoriented. • Q3. What is likely causing the signs of confusion?
Question Four
Warfarin is an anticoagulant that is metabolized in the liver, primarily by the P450 enzyme system, with CYP2C9 being the significant isoform involved. Warfarin is highly protein-bound to albumin. Warfarin crosses the placental barrier, resulting in fetal plasma levels that are the same as maternal values. As a result, it causes bleeding in the fetus and may cause spontaneous abortion, preterm birth, stillbirth, and neonatal death (Patel et al., 2023).
Question Five
Hepatic drug metabolism in children aged one year and older usually starts to resemble that of adults; however, it has notable differences. The hepatic enzyme’s expression and activity, particularly those of the P450 system, increases with age, and by adolescence, it reaches adult levels. Also, the drug-metabolizing enzyme maturation varies with individuals, which influences the drug pharmacokinetics. Overall, infants have a lesser hepatic enzyme activity than older children and adults, influencing drug clearance and metabolism (Zimmerman et al., 2019).
Question Six
In neonates, protein binding is usually lower than in adults. Neonates have lower albumin levels, the main proteins that help in drug binding, resulting in elevated levels of unbound drugs in the bloodstream. Given that only unbounded drugs are pharmacologically active, this can lead to increased drug concentrations and increased neonate pharmacological effects (Zimmerman et al., 2019), ultimately causing toxicity.
References
Dhaliwal, J. S., Rosani, A., & Saadabadi, A. (2023, August 28). Diazepam. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK537022/#:~:text=Diazepam%20is%20an%20anxiolytic%20benzodiazepine
Herman, T. F., & Santos, C. (2023, November 3). First-pass effect. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK551679/
Patel, S., Singh, R., Preuss, C. V., & Patel, N. (2023, March 24). Warfarin. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK470313/
Sicari, V., & Zabbo, C. P. (2023, July 10). Diphenhydramine. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK526010/
Zimmerman, K. O., Benjamin, D. K., & Becker, M. L. (2019). Neonatal therapeutics: Considerations for dosing. American Journal of Perinatology, 36(S 02), S18–S21. https://doi.org/10.1055/s-0039-1691772