Understanding Balance Issues Associated with Long-Term Diazepam Use- A Case Study Analysis

Understanding Balance Issues Associated with Long-Term Diazepam Use- A Case Study Analysis

Question One

The patient’s difficulty in maintaining balance can be explained by the cumulative effects of diazepam. Diazepam’s mechanism of action involves promoting the inhibitory effects of gamma-aminobutyric acid (GABA) in the CNS. Some of the side effects of diazepam include drowsiness, sedation, and impaired coordination. Long-term diazepam use, 15 years for this patient, leads to accumulation of the drug and increases adverse effects, including impaired coordination and balance (Dhaliwal et al., 2023).

Question Two

The first-pass effect is a pharmacological process where a medication endures metabolism at a particular location in the body. During the first-pass effect, the concentration of the active drug is decreased before reaching the target site of action or systemic circulation. First-pass metabolism can be circumvented by using alternative routes in drug administration, like intravenous administration. Administering the drug directly into the systemic circulation helps bypass the first-pass effect of organ-avoiding metabolism (Herman & Santos, 2023).

Question Three

The signs of confusion in the patient are most likely caused by the anticholinergic effects of diphenhydramine. Being a first-generation antihistamine, diphenhydramine crosses the blood-brain barrier into the central nervous system, where it causes effects such as confusion, particularly in older adults who are at risk of anticholinergic side effects (Sicari & Zabbo, 2023).

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

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Post your answers to the 6 questions corresponding to this week’s content on primary care medication management. Provide your responses and rationales. Support your rationales with high-level evidence. (See Post Expectations)
A 70-year-old woman is in your office complaining of recently having trouble maintaining her balance after taking diazepam (valium). She occasionally takes diazepam when she feels anxious and has trouble sleeping. She has a 15-year history of taking diazepam.

• 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?
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?