Q1. Explain the cause of this patient’s difficulty in maintaining her balance?> One of the challenges of taking anti-psychotropic medications especially to older population is gait or coordination problems. Due to this reason majority of geriatric patients are at risk for falls and other injuries. Diazepam is categorized as one of long-acting benzodiazepines. This medication accumulates in a crucial aspect especially with elderly patients. Diazepam results to an extremely quick sedation response and buildup of several metabolites which can cause erratic changes in homeostasis which can disrupt a person’s cognition and physical coordination or balance issues (Fluyau et al., 2018).Q2. Diazepam experiences a significant first-pass effect. What is the first-pass effect, and how can first-pass metabolism be circumvented?> First-pass effect is an event where the drugs get metabolized or absorbed in a certain site of the body that results in a lower concentration of the active medication upon reaching the systemic circulation. It occurs in the liver where the main location of metabolism takes place. First pass effect may also happen in the lungs, vasculature, GI system and other metabolically active tissues in the human body. The most important consideration in first pass effect varies from person to person which play a crucial role in identifying accurate dosing and method of administration (Herman & Santos, 2022). If the first-pass effect is exceptionally prominent in a patient, the drug may require administration via a different route such as administering medications sublingually or orally to avoid or bypass the first-pass metabolism (Herman & Santos, 2022).Q3. What is likely causing the signs of confusion?>Medications with anticholinergic features such as diphenhydramine may predispose geriatric patients with several ill effects. Some elements seen were falls, delirium, cognitive impairment and behavior disturbances. Diphenhydramine is a first-generation histamine 1 receptor antagonist which is consumed for treatment of various conditions such as allergies and cold symptoms. Histamine receptors in the brain play an essential factor in sustenance of wakefulness effect but due to blockage of these receptors caused by diphenhydramine people fall asleep. Diphenhydramine also infiltrates the blood-brain barrier because of the muscarinic and adrenergic receptors causing memory loss, drowsiness, confusion and other cognitive impairments (Dauphinot et al., 2017).Q4. How is warfarin metabolized? Does warfarin cross the placental barrier?> Warfarin is FDA approved drug which is used as a prophylaxis and treatment of numerous health disparities such as venous thrombosis, pulmonary embolus, A-fib, cardiac valve replacement, inherited genetic factors like C and S protein deficiency or Factor V Leiden. It is also consumed to lessen the risk of MI. Warfarin is metabolized in the liver via the cytochrome P450 system by CYP 2C9, 1A2, and 3A4 (StatPearls, 2021). It exhibits its anticoagulation factor through the intrinsic and extrinsic effects in the clotting cascade and hinders with the stimulation of clotting factors by obstructing the function of the vitamin K oxidation-reduction cycle needed for the carboxylation of clotting factors, which then decreases the production of active vitamin K reserves available to act as a cofactor in the development of glutamic acid residues within the clotting elements (StatPearls, 2021).>Warfarin can cross the placental barrier and is considered teratogenic effect on the early stage of conception. It also predisposes the fetus to warfarin embryopathy which happens at eight weeks and can result to serious bleeding during delivery (Nadeem et al., 2021).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?>Metabolism of drugs in children, infants and adults vary due to changes in developmental attributes. Understanding the aspects of drug absorption and transport can assist in formulating of pharmacokinetics (PK) and pediatric dosing accordingly (van Groen et al., 2021). There is a presence of physiological immaturity of organs, systems and metabolic courses in neonates that greatly affect the pharmacokinetics and pharmacodynamics of the medication being given. As children grow older, liver enzymes are able to effectively absorbed or metabolized most medications, because the BMR in children is more high than that of adults, medications are absorbed more quickly. Medication metabolism rates in infants are slower than the metabolism in adults. Drug-metabolizing enzymes in the liver of infants are immature which predispose them to drug toxicity (Ruggiero et al., 2019).Q6. Explain protein binding in the neonate.> Drug-protein binding plays a vital key function in determining the pharmacokinetics of a certain medication. The primary proteins responsible for the binding in plasma are human serum albumin (HSA) and alpha-1-acid glycoprotein (AAG) (Wanat, 2020). Plasma protein binding level in neonates is lower than in adults and will increase accordingly with age. There is relatively low presence of low protein binding and drug binding concentration in neonates than older children and adults which can lead to increased medication potency even on a lower dosage (Zimmerman et al., 2019).ReferencesDauphinot, V., Mouchoux, C., Veillard, S., Delphin-Combe, F.,& Krolak-Salmon, P. (2017). Anticholinergic drugs andfunctional, cognitive impairment and behavioral disturbancesin patients from a memory clinic with subjective cognitive declineor neurocognitive disorders. Alzheimer’s Research & Therapy,9(1), 58. https://doi.org/10.1186/s13195-017-0284-4Fluyau, D., Revadigar, N., & Manobianco, B. E. (2018). Challengesof the pharmacological management of benzodiazepine withdrawal,dependence, and discontinuation. Therapeutic Advances inPsychopharmacology, 147–168.https://doi.org/10.1177/2045125317753340Herman, T.F. & Santos , C. First pass effect. (2022). StatPearls.Treasure Island. StatPearls Publishing.https://www.ncbi.nlm.nih.gov/books/NBK551679Nadeem, S., Khilji, S. A., Ali, F., & Jalal, A. (2021). Continued useof Warfarin in lower dose has safe maternal and neonataloutcomes in pregnant women with prosthetic heart valves.Pakistan Journal of Medical Sciences, 37(4), 933–938.https://doi.org/10.12669/pjms.37.4.3924Ruggiero, A., Ariano, A., Triarico, S., Capozza, M. A., Ferrara,P., & Attinà, G. (2019). Neonatal pharmacology and clinicalimplications. Drugs in context, 8, 212608.https://doi.org/10.7573/dic.212608StatPearls. (2021). Retrieved from https://www.statpearls.com/ArticleLibrary/viewarticle/31296Wanat, K.(2020). Biological barriers, and the influence ofprotein binding on the passage of drugs across them.Mol Biol Rep 47, 3221–3231.https://doi.org/10.1007/s11033-020-05361-2van Groen, B. D., Pilla Reddy, V., Badée, J., Olivares-Morales, A.,Johnson, T. N., Nicolaï, J., Annaert, P., Smits, A., de Wildt, S. N.,Knibbe, C., & de Zwart, L. (2021). Pediatric pharmacokineticsand dose predictions: A report of a satellite meeting to the 10thjuvenile toxicity symposium. Clinical and Translational Science, 14(1),29–35. https://doi.org/10.1111/cts.12843Zimmerman, K. O., Benjamin, D. K., & Becker, M. L. (2019). Neonataltherapeutics: Considerations for dosing. American Journal ofPerinatology, 36(S 02), S18–S21. https://doi.org/10.1055/s-0039-1691772#21. The difficulty for the patient in maintaining her balance after taking diazepam is related to the central nervous system depression caused by the benzodiazepine class of drugs. Benzodiazepines are commonly given for anxiety and insomnia related to anxiety as well as other indications including muscle spasticity and seizures (Rosenthal & Burcham, 2021). With the patient’s advanced age, metabolic clearance of diazepam is slower than in the younger population and may be contributing to her impaired balance as the active metabolites of the drug produces a stronger effect at a higher plasma level (Drenth-van Maanen et al., 2019).2. The first pass effect is drug metabolism by the liver prior to entering the body’s central circulation. Some drugs are rapidly inactivated by liver while some are converted into metabolites that produce the desired effect of the drug. With benzodiazepines the metabolites are pharmacologically active (Rosenthal & Burcham, 2021). The first pass effect of medications can be circumvented through non-oral or parental routes of administration. These include IV, rectal, intranasal, and transdermal routes.3. The most likely cause of the patient’s confusion is related to the diphenhydramine in the over-the-counter cold medication. Histamine-1 antagonists have many adverse reactions including sedation similar to that of alcohol. Non-sedative CNS effects can include dizziness, incoordination, and confusion especially in older patients (Rosenthal & Burcham, 2021). Coupled with the sedative effect, the diphenhydramine is the most likely cause of the patient’s symptoms.4. Warfarin metabolism occurs primarily in the liver by cytochrome P-450. The warfarin metabolites, primarily in the form of warfarin alcohols, are then excreted in the urine with very little of the original form of warfarin left (FDA, n.d.).5. The hepatic metabolism of drugs in children one year and older is similar to adults. In contrast, children under the age of one year have a much slower hepatic metabolism and drug clearance making them susceptible to higher plasma drug levels and weight based dosages must be addressed appropriately (Rosenthal & Burcham, 2021).6. Protein binding in neonates is low relative to that of older children and adults as levels of serum albumin are low in this age group. This leads to increased free levels of drugs in the neonate circulation and increased effects of these drugs (Rosenthal & Burcham, 2021).ReferencesCoumadin tablets (warfarin sodium tablets, USP) crystalline coumadin … www.accessdata.fda.gov. (n.d.). Retrieved May 4, 2022, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/009218s108lbl.pdf/Drenth‐van Maanen, A. C., Wilting, I., & Jansen, P. A. (2019). Prescribing medicines to older people—how to consider the impact of ageing on human organ and body functions. British Journal of Clinical Pharmacology, 86(10), 1921–1930. https://doi.org/10.1111/bcp.14094Rosenthal, L. D., Burchum, J. R., (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants. Elsevier.
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