Case Study: Impact of Patient Factors on Pharmacokinetics and Pharmacodynamics

Case Study 1

LM is an 86-year-old female admitted to the emergency department with delirium. Her spouse is with her and verifies that LM adheres to the medications she is currently prescribed. She does not self-monitor her BP or heart rate at home.

PMH:

  • A Fib diagnosed 1 month ago
  • HTN x 10 years
  • CKD x 5 years
  • Osteoarthritis x 7 years
  • GERD x 20 years

Medications: 

  • Digoxin 0.25 mg QD
  • Metoprolol XL 25mg QD
  • Warfarin 3 mg QD
  • APAP 650 mg TID
  • Omeprazole 20mg QD
  • Multivitamin QD

Allergies: NKDA

Social History:

  • Married to husband for 57 years
  • No smoking, alcohol, limited daily exercise (short walks each morning)

Family History:

None reported

 
Vitals:  Labs:
Wt 113 lbs Ht 5’4” Na+ 138          K+ 4.0
BP 101/58, HR 52 Cl- 99              CO2 27
BUN 33           Cr 1.2
Gluc 109          INR 3.8
Dig 2.4

PE:

Elderly female with altered level of consciousness, no signs of bruising, bleeding, or other injury.

I encourage you to always keep the ADME principles in your mind going forward as you post (particularly metabolism and excretion).

Please remember to use the generic (brand) format as I will begin to deduct points.  I would also like you to start making dosing recommendations in all of your responses were applicable (i.e.   acetaminophen (Tylenol) 650 mg PO q 6 hours).  Remember, for a substantial post, even if you are making a medication recommendation, please have at least 3 sentences and provide a reference as to why you think the recommendation is the best for the patient.    I have been impressed with the discussions thus far so please continue the great work.   Going forward, please try to discuss the “why” behind the statements you make versus just making them (ex:   drug causes kidney dysfunction but how does the drug cause it….renal tubule, loop of Henle damage, etc).

With regards to your application, please be concise and use correct citations.   Please be careful of overusing citations and focus on illustrating the points in your own words.  Also, please ensure, when discussing a disease state, you elaborate on the medications and potential adverse effects.  I am also not a stickler for going over the page requirements in the event it is needed.  Refer to the class rubric for specific grading criteria. A common citation mistake is using commonly abbreviated names.  Such as example is with the CDC.   Per APA formatting, please reference abbreviations in the following manner when citing them (Centers for Disease Control [CDC], 2017).   After you establish this initial citation, you can use (CDC, 2017) for subsequent citations within the paper.

Here are this week’s learning objectives:

  • Analyze the influence of patient factors on pharmacokinetic and pharmacodynamic processes
  • Analyze the impact of changes in pharmacokinetic and pharmacodynamic processes on patient drug therapies
  • Evaluate drug therapy plans for cardiovascular disorders

Here are the assignment objectives and your case is listed in the course announcements:

  • Explain how the factor you selected might influence the pharmacokinetic and pharmacodynamic processes in the patient from the case study you were assigned.
  • Describe how changes in the processes might impact the patient’s recommended drug therapy. Be specific and provide examples.
  • Explain how you might improve the patient’s drug therapy plan and explain why you would make these recommended improvements.

 

Answer

Drug pharmacokinetic and pharmacodynamics processes are highly influenced by patient factors such as age, weight, and medical history. This is especially relevant in geriatric patients like LM, an 86-year-old female with a history of hypertension, chronic kidney disease, and atrial fibrillation. In this discussion, we will analyze the impact of patient factors on pharmacokinetic and pharmacodynamics processes and evaluate how changes in these processes can affect drug therapies for cardiovascular disorders.

In the case of LM, several patient factors may influence her pharmacokinetic and pharmacodynamics processes. As a geriatric patient, LM’s age-related physiological changes may affect drug absorption, distribution, metabolism, and excretion (Rodrigues et al., 2020). These changes include a decrease in organ function, a decrease in lean body mass and an increase in body fat, and changes in drug-receptor density and sensitivity.

Secondly, LM’s medical history, specifically her chronic kidney disease, can affect drug clearance and metabolism. With her creatinine level at 1.2 and elevated BUN level at 33, her kidney function is mildly impaired. This can lead to decreased clearance of certain drugs, including digoxin and warfarin, increasing drug levels and toxicity.

Additionally, LM’s atrial fibrillation and use of multiple cardiovascular drugs (digoxin and metoprolol) may affect the drug’s pharmacodynamics. Specifically, the combination of digoxin and metoprolol can increase the risk of bradycardia and atrioventricular block, given their negative chronotropic effects on the heart, as evidenced by LM’s heart rate of 52 beats per minute (Hendriksen et al., 2022). LM’s atrial fibrillation also requires anticoagulant therapy with warfarin, which increases the risk of bleeding when combined with other medications, as indicated in an elevated INR of 3.8.

Finally, LM’s altered level of consciousness upon admission can further affect any administered drugs’ pharmacokinetic and pharmacodynamics processes. As she cannot self-monitor her blood pressure and heart rate, it is possible that her medications were not appropriately dosed and administered, further exacerbating her delirium. Considering these factors when prescribing and administering medications to geriatric patients is crucial to ensure optimal therapeutic outcomes and prevent adverse drug events.

Impact of Altered Pharmacokinetics and Pharmacodynamics on Drug Therapies

LM is an 86-year-old patient who may be susceptible to age-related declines in organ function. These declines can result in altered drug metabolism and excretion, impacting drug efficacy and increasing the risk of drug toxicity. Due to her chronic kidney disease, LM may experience reduced kidney function, which can affect the clearance of certain drugs like digoxin and warfarin primarily eliminated by the kidneys (Vaidya & Aeddula, 2019). This reduced clearance can lead to a buildup of these drugs in her system, increasing the risk of toxicity, which could contribute to her delirium. Thus, it is essential to consider LM’s age-related changes in organ function when prescribing medications to avoid any adverse effects that may result from altered drug metabolism and excretion.

Altered drug absorption can occur due to various changes in the gastrointestinal tract. Changes in gastrointestinal motility, reduced gastric acidity, and increased intestinal permeability are some factors that can affect the absorption of drugs (Stillhart et al., 2020). For instance, Omeprazole, a proton pump inhibitor, can decrease the absorption of other drugs, such as digoxin. As a result, the therapeutic effects of the drug may reduce. Therefore, it is essential to consider the effects of altered drug absorption while prescribing medication to patients.

Drug-drug interactions occur when combining two or more medications, changing how the body processes drugs. These interactions can alter pharmacokinetic and pharmacodynamics processes, ultimately resulting in altered drug efficacy and an increased risk of adverse effects (Salman et al., 2022). For instance, the simultaneous use of digoxin, metoprolol, and warfarin may raise the risk of bradycardia, hypotension, and bleeding. Additionally, the interaction between APAP and warfarin can heighten the risk of bleeding. Based on the evaluation, medication adjustments may be necessary to optimize drug therapy and reduce the risk of harmful drug interactions.

Evaluating and Improving Drug Therapy Plans for Cardiovascular Disorders

The drug therapy plan for LM’s cardiovascular disorders includes Digoxin 0.25 mg QD, Metoprolol XL 25mg QD, and Warfarin 3 mg QD. Digoxin and Metoprolol XL are used to treat atrial fibrillation and hypertension, respectively, while warfarin is used to prevent blood clots. Each drug’s dosage appears appropriate for the patient’s age, weight, and medical history. However, LM’s current drug therapy plan may need improvement due to her altered level of consciousness and high INR (3.8). Digoxin has a narrow therapeutic index and can cause toxicity, especially in elderly patients with impaired renal function (Cummings & Swoboda, 2019). In LM’s case, her BUN and Cr levels indicate mild to moderate renal impairment.

Additionally, the high INR suggests that the Warfarin dosage may be too high and needs to be adjusted to prevent bleeding complications. Therefore, one recommendation to improve LM’s drug therapy plan is to reduce Digoxin dosage or discontinue it altogether, considering her age, renal function, and altered level of consciousness. Secondly, adjusting the Warfarin dosage to achieve a target INR of 2.0-3.0 to avoid bleeding complications is crucial. This can be achieved by reducing the Warfarin dosage or increasing the frequency of INR monitoring.

Conclusion

In conclusion, patient factors such as age, medical history, organ function, and body composition can significantly influence pharmacokinetic and pharmacodynamics processes. Thus, it is essential to consider these factors when prescribing and administering medications to ensure optimal therapeutic outcomes and prevent adverse drug events. LM’s current drug therapy plan may need adjustment due to her altered level of consciousness and high INR, including reducing the Digoxin dosage or discontinuing it and adjusting the Warfarin dosage to achieve a target INR of 2.0-3.0. With the right drug therapy plan, LM can achieve optimal therapeutic outcomes and improve her overall health.

References

Cummings, E. D., & Swoboda, H. D. (2019, June 4). Digoxin toxicity. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK470568/

Hendriksen, L. C., Omes-Smit, G., Koch, B. C. P., Ikram, M. A., Stricker, B. H., & Visser, L. E. (2022). The sex-based difference in the effect of metoprolol on heart rate and bradycardia in a population-based setting. Journal of Personalized Medicine, 12(6), 870. https://doi.org/10.3390/jpm12060870

Rodrigues, D. A., Herdeiro, M. T., Figueiras, A., Coutinho, P., & Roque, F. (2020). Elderly and polypharmacy: Physiological and cognitive changes. In www.intechopen.com. IntechOpen. http://dx.doi.org/10.5772/intechopen.92122

Salman, M., Munawar, H. S., Latif, K., Akram, M. W., Khan, S. I., & Ullah, F. (2022). Big data management in drug–drug interaction: A modern deep learning approach for smart healthcare. Big Data and Cognitive Computing, 6(1), 30. https://doi.org/10.3390/bdcc6010030

Stillhart, C., Vučićević, K., Augustijns, P., Basit, A. W., Batchelor, H., Flanagan, T. R., Gesquiere, I., Greupink, R., Keszthelyi, D., Koskinen, M., Madla, C. M., Matthys, C., Miljuš, G., Mooij, M. G., Parrott, N., Ungell, A.-L., de Wildt, S. N., Orlu, M., Klein, S., & Müllertz, A. (2020). Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review. European Journal of Pharmaceutical Sciences, 147, 105280. https://doi.org/10.1016/j.ejps.2020.105280

Vaidya, S. R., & Aeddula, N. R. (2019). Chronic renal failure. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK535404/

 

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