Review and respond to the below Discussion post
Valium is a benzodiazepine and is commonly used as a muscle relaxer or anti-anxiety medication. Benzodiazepines act to depress the central nervous system by increase the inhibitory effects of gamma-aminobutyric acid (GABA), the chief neuronal depressant found in the human body. Dizziness is a common side effect of CNS depression, where balance and awareness are compromised by sensory inhibition, these effects are known to worsen with age. The first pass effect is the extent to which the drug is destroyed or diluted prior to reaching its intended target in the body.(Nahler, 2022) Valium is metabolized by the liver, which significantly reduces the overall concentration that reaches target receptors, using different delivery routes, such as intravenous injection is one was to avoid this unwanted dilution. (Roche, 2008)
Diphenhydramine is a common ingredient in many over-the-counter cold remedies, and it is known to cause confusion, especially in older people, due to its anticholinergic effects. Acetylcholine is a prominent neurotransmitter in the brain, and anticholinergic medications, such as Benadryl, can cause inhibition resulting in confusion and short-term memory loss.(López-Álvarez et al., 2019)
Warfarin is metabolized in the kidneys and works to reduce the amount of vitamin K active in the body, thereby preventing the formation of clotting factors. Warfarin has a low molecular weight and is easily able to cross the placental barrier.(Patel et al., 2022)
Hepatic metabolism undergoes rapid changes in the first few weeks of life, with the body adjusting to a lack of maternal blood supply, as a result, “drug-metabolizing capacity by the liver enzymes is reduced in newborns particularly in premature babies but increases rapidly during the first few weeks and months of life.”(Drug Times, 2022, section 2) Many of the isoenzymes systems used in adult liver metabolism are immature at birth, with some, such as glucuronosyltransferase, no reaching adult levels until 3-6 months of age.(Lu & Rosenbaum, 2014a, Table 2)
Protein binding is reduced in neonates, which may allow for more active molecules to be absorbed at active sites, rather than to remain bound with proteins in the plasma. Due to a decreased overall number of available plasma proteins, as well a reduction in binding affinity, there are a likely high number of unbound drug molecules that are able to diffuse across membranes to active receptor sites. (Lu & Rosenbaum, 2014a)
References
Drug Times. (2022, December 19). Drug metabolism and clearance in neonates children and elderly – drug monitoring methods. https://www.drugtimes.org/monitoring-methods/drug-metabolism-and-clearance-in-neonates-children-and-elderly.html
López-Álvarez, J., Sevilla-Llewellyn-Jones, J., & Agüera-Ortiz, L. (2019). Anticholinergic drugs in geriatric psychopharmacology. Frontiers in Neuroscience, 13. https://doi.org/10.3389/fnins.2019.01309
Lu, H., & Rosenbaum, S. (2014a). Developmental pharmacokinetics in pediatric populations. The Journal of Pediatric Pharmacology and Therapeutics, 19(4), 262–276.
Lu, H., & Rosenbaum, S. (2014b). Developmental pharmacokinetics in pediatric populations. The Journal of Pediatric Pharmacology and Therapeutics, 19(4), 262–276. Retrieved January 4, 2022, from https://doi.org/10.5863/1551-6776-19.4.262
Nahler, G. (2022). First pass effect. Dictionary of Pharmaceutical Medicine, 75–75. https://doi.org/10.1007/978-3-211-89836-9_566
Patel, S., Singh, R., Patel, N., & Pruess, C. (2022). Warfarin. Statpearls. Retrieved January 4, 2022, from
Roche. (2008). 013263s083lbl [PDF]. U.S. Food and Drug Administration. Retrieved January 4, 2022, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/013263s083lbl.pdf
