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

A 75-year-old woman develops symptoms of a cold and buys an over-the-counter cold medication at the grocery store.

Discussion Prompt

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?

A 26-year-old woman who has never been pregnant is seeking preconception care as she is planning to pursue pregnancy in a couple of months. Currently, she has no symptoms to report and on review of body systems, there were no concerns. Her past medical history is significant for a history of rheumatic fever as a child. She subsequently underwent valve replacement with a mechanical heart valve. She is followed by a cardiologist who has already evaluated her cardiac function and she has received clearance from her cardiologist to pursue pregnancy. Records from her cardiologist include a recent cardiac echocardiography report that reveals a normal ejection fraction indicating normal cardiac function.

She has no alterations in her daily activities related to her heart. She has no other significant medical or surgical history. She is a non-smoker, drinks occasionally but has stopped as she is attempting to conceive, and does not use any non-prescription drugs.

Current Medications: Her current medications include only prenatal vitamins, which she has begun in anticipation of pregnancy, and warfarin. She has no known drug allergies.

Vital Signs: On examination, her pulse is 80 beats per minute, blood pressure is 115/70 mm Hg, respiratory rate is 18 breaths per minute, and she is afebrile.

Measurements: Weight = 152 pounds, Height = 5′5 ″, BMI= 25.29

• Q4. How is warfarin metabolized? Does warfarin cross the placental barrier?
• 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?
• Q6. Explain protein binding in the neonate.

Expectations

Initial Post:

• Due: Thursday, 11:59 pm PT
• Length: A minimum of 250 words, not including references
• Citations: At least one high-level scholarly reference in APA from within the last 5 years

Peer Responses:

• Due: Monday, 11:59 pm PT
• Number: A minimum of (2) two peer posts, at least one on a different day than the initial post. Responding to your instructor is not considered a peer response. If the instructor asks you a question, you must answer the question to receive full credit.
• Length: A minimum of 150 words per post, not including references
• Citations: At least one high-level scholarly reference in APA per post from within the last 5 years

Expert Answer and Explanation

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?

The main side effects of diazepam include drowsiness, dizziness, and impaired coordination (Greenblatt et al., 2020). The impaired coordination could be the primary reason why the patient could not maintain her balance.

• Q2. Diazepam experiences a significant first-pass effect. What is the first-pass effect, and how can first-pass metabolism be circumvented?

The first-pass effect refers to the phenomenon in which a significant portion of an orally administered drug is metabolized by the liver before it reaches systemic circulation. First-pass can be circumvented through the use of alternative routes of administration such as intravenous (IV) administration directly delivers the drug into the bloodstream (Greenblatt et al., 2020). Other routes include buccal or sublingual administration, and transdermal patches.

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? 

The confusion and disorientation in the 75-year-old woman is caused by the caused by the presence of diphenhydramine in the over-the-counter cold medication (Grinnell et al., 2022). As an antihistamine medication, diphenhydramine effects on the central nervous system which can also cross the blood-brain barrier and interfere with cognitive function. The sedative effect of the medication is more pronounced for older adults leading to confusion and disorientation.

A 26-year-old woman who has never been pregnant is seeking preconception care as she is planning to pursue pregnancy in a couple of months. Currently, she has no symptoms to report and on review of body systems, there were no concerns…

Current Medications: Her current medications include only prenatal vitamins, which she has begun in anticipation of pregnancy, and warfarin. She has no known drug allergies.

Vital Signs: On examination, her pulse is 80 beats per minute, blood pressure is 115/70 mm Hg, respiratory rate is 18 breaths per minute, and she is afebrile.

Measurements: Weight = 152 pounds, Height = 5′5 ″, BMI= 25.29

• Q4. How is warfarin metabolized? Does warfarin cross the placental barrier?

Warfarin is metabolized primarily in the liver through various enzymes that convert warfarin into inactive metabolites that are then excreted by the kidneys (Grinnell et al., 2022). The warfarin molecules are relatively small in size which make them to cross the placental barrier. However, the transfer is limited and usually considered to be low.

• 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?

The hepatic drug metabolism of children 1 year and older begins to mature and become more similar to that of adults. Enzyme systems, become more developed, leading to improved drug metabolism and clearance (Grinnell et al., 2022). Infants have lower levels of drug-metabolizing enzymes, which can lead to slower drug metabolism and elimination, potentially requiring dose adjustments for certain medications. Adult hepatic drug metabolism, on the other hand, is generally fully developed and efficient.

• Q6. Explain protein binding in the neonate.

Protein binding in the neonate is a crucial pharmacokinetic factor that influences how drugs are distributed and their effects. Neonates often have lower levels of serum proteins, particularly albumin, which is responsible for binding to many drugs (Pyzik et al., 2019). The lower levels of serum proteins results to a higher proportion of drugs in the neonatal bloodstream to remain unbound, or “free.”

References

Greenblatt, D. J., Harmatz, J. S., & Shader, R. I. (2020). Diazepam in the elderly: Looking back, ahead, and at the evidence. Journal of Clinical Psychopharmacology, 40(3), 215-219.

Grinnell, M., Price, K. N., Shah, A., & Butler, D. C. (2022). Antihistamine safety in older adult dermatologic patients. Journal of the American Academy of Dermatology, 87(2), 381-386.

Pyzik, M., Sand, K. M., Hubbard, J. J., Andersen, J. T., Sandlie, I., & Blumberg, R. S. (2019). The neonatal Fc receptor (FcRn): a misnomer?. Frontiers in immunology, 10, 1540.

Alternative Expert Answer

Q1. Explain the cause of this patient’s difficulty in maintaining her balance.

One benzodiazepine (BZD) medication that is frequently recommended to treat anxiety and sleeplessness is diazepam. BZDs are a class of drugs that, in addition to suppressing vestibular responses that could impair a patient’s balance, function as central nervous system depressants (Greenblatt et.al, 2020). BZDs function as GABA-positive allosteric modulators (PAM) by focusing on the GABA-A receptors. When these receptors are coupled together, the channel opens, allowing chloride to enter the cell and reducing neuronal activity.

Q2. Diazepam experiences a significant first-pass effect. What is the first-pass effect, and how can first-pass metabolism be circumvented?

When the body receives a drug concentration that is significantly lower than what was originally taken because of drug metabolism, this is known as the first pass effect in pharmacology. This occurrence occurs after the medicine is consumed; it travels to several locations before being digested at a particular organ before reaching its intended site of action (Jadhav et.al, 2022). The liver is the most often used location for medication metabolism. The lungs, cardiovascular system, gastrointestinal tract, and other bodily parts that are metabolically active may also be included. The healthcare professional may modify the dosage or the administration route, typically intravenously, to avoid the first-pass impact for more efficient clinical use while preserving safety and efficacy.

Q3. What is likely causing the signs of confusion? 

Most over-the-counter cold remedies have antihistamine qualities, which can have major negative effects on those 65 years of age and older. Adverse effects could include delirium and confusion, two cognitive impairments. Antihistamine medications have the potential to have anticholinergic effects, which disrupt the neurotransmitter acetylcholine transmission and result in cognitive loss and confusion (Kennedy et.al, 2020).

Q4. How is warfarin metabolized? Does warfarin cross the placental barrier? 

An FDA-approved medication called warfarin is used to treat and prevent thromboembolic problems that arise from atrial fibrillation and heart valve replacement. Hepatic metabolism of warfarin occurs through the cytochrome P2C9 system. Because this medication has the potential to pass the placental barrier and create problems for the fetus, it is typically contraindicated during pregnancy (Kuppusamy et.al, 2019). But if the expectant mother has a mechanical heart valve, it can be used with close monitoring and assessment..

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?

The physiological differences between children and adults, which impact pharmacokinetics and pharmacodynamics, are significantly influenced by age. Because of their innately limited ability to metabolize medicines, newborns are particularly susceptible to those that are processed in the liver. Hepatic metabolism in children aged one and above is influenced by various factors, including changes in hepatic perfusion, plasma protein binding, and active transport pathways, as well as maturational changes in the expression and activity of drug-metabolizing enzymes (Van Groen et.al, 2021). Intestinal transit time, bile and pancreatic fluid secretion and activity, stomach acidity and emptying time, and other maturational changes in the body may also have an impact on the variations in drug metabolism between newborns and adults..

Q6. Explain protein binding in the neonate.

For a few reasons, including “relatively low serum albumin and competition from endogenous compounds for available binding sites,” drug-protein binding in newborns is still quite embryonic. In neonates, there is a comparatively large concentration of free levels in the systemic circulation due to the fact that drugs undergo extensive protein-binding in adults but not in newborns. In order to guarantee safe use, prescribers must lower dosages of medications that are metabolized by the liver in newborns (Patel & Bussel, 2020). By the time they are 10 to 12 months old, babies should be able to bind proteins at adult levels.

References

Greenblatt, D. J., Harmatz, J. S., & Shader, R. I. (2020). Diazepam in the elderly: Looking back, ahead, and at the evidence. Journal of Clinical Psychopharmacology, 40(3), 215-219. 10.1097/JCP.0000000000001213

Jadhav, A. P., Desai, S. M., Zaidat, O. O., Nogueira, R. G., Jovin, T. G., Haussen, D. C., … & Liebeskind, D. S. (2022). First pass effect with neurothrombectomy for acute ischemic stroke: analysis of the systematic evaluation of patients treated with stroke devices for acute ischemic stroke registry. Stroke, 53(2), e30-e32. https://doi.org/10.1161/STROKEAHA.121.035457

Kennedy, M., Koehl, J., Shenvi, C. L., Greenberg, A., Zurek, O., LaMantia, M., & Lo, A. X. (2020). The agitated older adult in the emergency department: a narrative review of common causes and management strategies. Journal of the American College of Emergency Physicians open, 1(5), 812-823. https://doi.org/10.1002/emp2.12110

Kuppusamy, G., De, A., Jaiswal, A., & Chatterjee, A. (2019). Placenta Barrier and Drug Delivery. Research Journal of Pharmacy and Technology, 12(5), 2545-2552.10.5958/0974-360X.2019.00428.1

Patel, D. D., & Bussel, J. B. (2020). Neonatal Fc receptor in human immunity: Function and role in therapeutic intervention. Journal of Allergy and Clinical Immunology, 146(3), 467-478. https://doi.org/10.1016/j.jaci.2020.07.015

Van Groen, B. D., Nicolaï, J., Kuik, A. C., Van Cruchten, S., Van Peer, E., Smits, A., … & Badée, J. (2021). Ontogeny of hepatic transporters and drug-metabolizing enzymes in humans and in nonclinical species. Pharmacological reviews, 73(2), 597-678. https://doi.org/10.1124/pharmrev.120.000071

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