Description
Q1. Explain the cause of this patient’s difficulty in maintaining her balance.
Q2. Diazepam experiences a significant first-pass effect. What is the first-pass effect, and how can first-pass metabolism be circumvented?
Diazepam is a benzodiazepine group of drugs and the main side effects are ataxia, dystonia, and asthenia. As she has a history of 15 years of using diazepam this may also cause difficulty maintaining the balance.
The first-pass effect is a pharmacological phenomenon that specifies the medication metabolism at a specific location in the body. The first-pass effect reduces the drug concentration while reaching systemic circulation and the liver is a major site of drug metabolism (Herman, T & Santos, C. 2023).
Q3. What is likely causing the signs of confusion?
The over-the-counter cold medications such as diphenhydramine, acetaminophen, and phenylephrine overdose cause loss of appetite, vomiting, weakness, confusion, ringing in your ears, upper stomach pain, dark urine, no urination, very dry eyes and mouth, jaundiced skin, dilated pupils, fast heartbeats, tremor, agitation, hallucinations or seizure. If an individual used an MAO inhibitor in the past 14 days there is a dangerous drug interaction may occur. (Multum, C. 2023).
Q4. How is warfarin metabolized? Does warfarin cross the placental barrier?
Warfarin metabolism is both stereo and regioselective. The major pathway of metabolism is oxidation to various hydroxywarfarins, which contain 80- 85 % of total metabolites. CYP2C9 is the major enzyme catalyzing the 6- and 7-hydroxylation of S-warfarin while 4′-hydroxylation occurs through CYP2C18 with minor contributions from CYP2C19. Warfarin is absorbed completely and reaches a maximum plasma concentration between 2 and 6 hours. It is eliminated by hepatic metabolism with a very small clearance and the elimination half-life is 35 hours. Yes, Warfarin crosses the placental barrier during pregnancy which causes fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. (Drug Bank Online, 2023).
Q5. Explain the hepatic drug metabolism of children 1 year and older. How do they compare with the hepatic drug metabolism of infants and adults?
In young children, hepatic metabolic clearance is influenced by maturational changes in the expression and activity of drug-metabolizing enzymes, changes in hepatic blood flow and perfusion, plasma protein binding, and active transport processes. (Constance, J.E & et al, 2016) There are significant changes in neonatal liver blood flow and hepatic oxygenation due to the cessation of umbilical blood supply, increase in portal vein blood flow, and the closure of ductus Venus’s shunt. In adults, there is a reduction of hepatic blood flow of about 40%, and 30% in liver mass impairs the hepatic drug clearance and alters the hepatic metabolism (Ching, M.S & et al. 2001).
Q6. Explain protein binding in the neonate.
Neonate infants have low levels of plasma albumin which contributes to a decrease in protein binding. It increases with age. Protein binding helps to enhance or reduce the drug performance. Less protein-bound agents penetrate tissue better than the highly bound and it excrete faster (Scheife, R.1989)
Reference
Constance, J.E & et al, 2016. Hepatic Drug Metabolism in Pediatric Patients. Retrieved from: https://www.sciencedirect.com/science/article/abs/pii/B9780128029497000080
Ching, M.S & et al. 2001. Neonatal hepatic drug elimination. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/11169155/
Drug bank online.2023. Retrieved from: https://go.drugbank.com/drugs/DB00682
Herman, T & Santos, C. 2023. First-Pass Effect. National Library of medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK551679/
Multum, C. 2023. Acetaminophen, diphenhydramine, and phenylephrine. Drugs.com. Retrieved from: https://www.drugs.com/mtm/acetaminophen-diphenhydramine-and-phenylephrine.html#:~:text=Acetaminophen%2C%20diphenhydramine%2C%20and%20phenylephrine%20is,%2C%20diphenhydramine%2C%20and%20phenylephrine%20available
Scheife, R.1989. Protein binding: what does it mean? National Library of Medicine. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/2669380/#:~:text=Protein%20binding%20can%20enhance%20or,they%20are%20excreted%20much%20faster.
