Discussion: Pharmacokinetics and Pharmacodynamics

Patient Case

The patient who comes to mind for this discussion is an elderly female admitted to the long-term nursing facility where I worked as a charge nurse many years ago. The patient was admitted to the nursing facility with orders for the GI medication Metoclopramide, which was prescribed for gastroparesis. Discussion: Pharmacokinetics and Pharmacodynamics. Metoclopramide is contraindicated for use in elderly patients due to the risk for extrapyramidal side effects, including tardive dyskinesia; there is increased risk in frail adults and prolonged use (American Geriatrics Society 2019 Beers Criteria Update Expert Panel, 2019). At the time of the admission, the Federal guidelines in place now had not been implemented. When the patient was admitted, she had some physical limitations and health conditions but could participate in her daily living activities actively. The patient ambulated independently with a walker, was independent with toileting and eating, and required supervision with her bathing needs. The patient was alert and oriented with occasional short-term memory loss. I am unable to recall the specific dose of Metoclopramide, but for some reason, this medication did not trigger special monitoring procedures Discussion: Pharmacokinetics and Pharmacodynamics.

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Over time, the patient began to exhibit a decline in her overall health status. She required more assistance with her activities of daily living, and her mental status declined. Initially, the staff attributed her decline to the aging process and possibly behavioral. When the patient started exhibiting repetitive, jerking, gyrating body movements, and abnormal mouth movements, I recalled learning about a possible relationship between Metoclopramide and tardive dyskinesia. I reported my concerns to the nursing supervisor. At the time, the thinking was that tardive dyskinesia was related to antipsychotic use. The doctor assessed the patient, and the medication was discontinued. There was an improvement in her symptoms, but she never returned to her prior level of functioning. The decline could have been due to the aging process, but taking the Metoclopramide for an extended period was not beneficial to her health.

Pharmacokinetics and Pharmacodynamic Factors

Data show that the risk of tardive dyskinesia from Metoclopramide is low, in the range of 0.1% per 1000 patient-years; however, high‐risk groups are elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy, which reduces the thresh‐old for neurological complications (Al-Saffar, Lennernäs, & Hellström, 2019). In my patient, pharmacokinetics that could have altered the expected response include slower elimination resulting in a higher concentration of the drug in her blood. Pharmacodynamic factors involved the drug crossing the blood‐brain barrier and acting in the brain, causing extrapyramidal reactions, including tardive dyskinesia (Al-Saffar, Lennernäs, & Hellström, 2019). My patient’s compounding factors include her age and sex Discussion: Pharmacokinetics and Pharmacodynamics.

Personalized Plan of Care

I would use evidence-based guidelines to plan the care of the patient. Resources such as the Beers Criteria list are available to prevent this type of adverse effect. I would have selected a medication that was not on that list. Geriatric patients are a special population when prescribing medications, as age-related changes impact their bodies’ abilities to metabolize medications. When developing a personalized plan of care, I would consider pharmacokinetic changes in the elderly – altered absorption, changes in drug distribution resulting in increased drug effects, decreased metabolism, and altered excretion of drugs. I would also consider the multiple factors that predispose older adults to adverse drug reactions: drug accumulation secondary to reduced renal clearance, greater severity of illnesses, presence of comorbidities, and increased individual variation secondary to altered pharmacokinetics (Rosenthal & Burchum, 2021).

References

Al-Saffar, A., Lennernäs, H., & Hellström, P. M. (2019). Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited. Neurogastroenterology and Motility : The Official Journal of the European Gastrointestinal Motility Society,, 31(11), e13617. Retrieved from https://doi-org.ezp.waldenulibrary.org/10.1111/nmo.13617

American Geriatrics Society 2019 Beers Criteria Update Expert Panel. (2019). American Geriatrics Society 2019 updated AGS Beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 67(4), 674-694. doi:10.1111/jgs.15767

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s Pharmacotherapeutics for Advanced Practice Nurses and Physician Assistants. Se. Louis: Elsevier, Inc. Discussion: Pharmacokinetics and Pharmacodynamics

Discussion: Pharmacokinetics and Pharmacodynamics

To Prepare

By Day 3 of Week 1

By Day 6 of Week 1

Working not only in the emergency department, but also on the telemetry unit I see things such as respiratory distress, heart failure,  COPD, arrhythmia’s, and renal failure. These are just a few of the things that we as nurses see on a daily basis. One of the biggest cases that stands out to me are my renal failure patients and COPD patients. A certain case that comes to mind is a elderly gentleman that came in with a COPD exacerbation, as well as stage 3 renal failure, the patient was also a diabetic. With this specific case there is a hospitalist, a pulmonologist, a neurologist, cardiologist, and if the patient’s diabetes is not under control then an endocrinologist is also on the case. All of these teams, outside of the hospitalist, looks at their specific area of study so they are constantly  changing medications or “tweaking”  the medication regimen to fix their problem area. With this specific patient the physicians were going back and forth on the dosage of certain medications. The patient’s diuretic dose was changed multiple times during the hospital stay because the pulmonologist would increase the dose due to the fluid from the COPD which is defined as a group of diseases that causes airway blockage and breathing related problems (CDC, 2018). The pulmonologist looks at the patient’s ability to breathe and focuses on what can be done to get the fluid off as quickly as possible, but the nephrologist is going to look at the patient being in renal failure and the kidney’s inability to excrete fluids and medications the way working kidneys do, which could lead to the patient being hyperkalemic, which as we know can cause the patient to start having arrhythmias., if they are not already experiencing them. The nephrologist would then decrease the dosage or change the medication altogether Discussion: Pharmacokinetics and Pharmacodynamics. This patient then developed pneumonia sitting in the bed, while the physicians went back and forth on the dose of the diuretic. At this point the pulmonology team chose to start the patient on low dose steroids and nebulizer treatments, thus increasing the patient’s glucose level, resulting in higher doses of insulin needed, as well as more frequent glucose checks. At the end of the long stay this patient was better, but it took a long time to get this patient all figured out. He was not complelety healed, but he was much better than when he came in and was able to breathe a lot better.

This patient’s pharmacodynamics and pharmacokinetics are clearly effected in multiple ways. First the gentleman’s age could play a role in slowing down the metabolism of medication as well as reabsorption. According to Kinirons and O’Mahoney, aging plays a significant role in the reduction of liver volume, as well as reduction of activity in some cytochrome P450 enzymes (2004). Another factor affecting these things are his different disease processes. The renal failure in itself causes problems with excretion and absorption of medications. The diabetes can cause problems with other body systems that will cause dysfunction with the pharmacodynamics as well as the pharmacokinetics. This patient was also overweight and continued to smoke, with no regard to the advice of the physicians and education to the importance of smoking cessation. The fact that this patient is obese affects the dosage the patient needs of a medication in order for it to be therapeutic, which is extremely concerning, especially if this patient is taking medication that has a narrow therapeutic index (Cheymal, 2000) Discussion: Pharmacokinetics and Pharmacodynamics.

In conclusion, while this patient had a lot of disease processes taking place, the pharmokinetics and pharmacodynamics are majorly affected not only by the underlying diseases, but also by the man’s genetics, obesity, and age, amongst other issues.

Resources:

CDC – COPD Home Page – Chronic Obstructive Pulmonary Disease (COPD). (2018, June 06). Retrieved December 02, 2020, from https://www.cdc.gov/copd/index.html

G;, C. (2000, September). Effects of obesity on pharmacokinetics implications for drug therapy. Retrieved December 02, 2020, from https://pubmed.ncbi.nlm.nih.gov/11020136/ Discussion: Pharmacokinetics and Pharmacodynamics

Kinirons, M., & O’Mahony, M. (2004, May). Drug metabolism and ageing. Retrieved December 02, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884487/

Discussion: Pharmacokinetics and Pharmacodynamics sample 3

Week 1-  Main Discussion Post

Effectual drug therapy is utilized to  fight off  disease, but success is optimized when there is an understanding of a drug’s pharmacokinetic and pharmacodynamic interrelationships (Anker et al., 2018). Pharmacokinetics involves the processes that control a drug’s path through the body and  the concentration of the drug in different body areas (Nagus & Banks, 2018). On the other hand, pharmacodynamics involves the physiological and behavioral results composed by drug molecules that occupy receptors throughout the human body (Nagus & Banks, 2018). Comparable to the idea that every patient acts and functions differently, individual drugs also react in distinctive ways compared with each other. In my clinical experience, there have been several instances when an antibiotic was ordered and administered  and  the desired outcome was not met. For this assignment, I will focus my discussion on an 67 year old patient, who was admitted with a complicated urinary tract infection and had a history of chronic kidney disease stage 5 requiring hemodialysis (CKD-5HD).

 Infections are a major cause of fatality among patients with CKD-5HD; urinary tract infections (UTIs) are common in this patient population (El Nekidy et al., 2020).  In anuric or oliguric patients, UTIs can be problematic to diagnose due to the challenges of obtaining urine samples (El Nekidy et al., 2020). It can take up to two days for patients with CKD-5HD to produce a urine sample, which is generally successfully obtained through catheterization (El Nekidy et al., 2020).  In my particular patient, the urine culture collected grew Escherichia coli. The patient was first treated empirically with ciprofloxacin. Next, a one week follow up urine culture was collected which grew the same organisms. As a result, ciprofloxacin was discontinued and ertapenem was started. A 1000 mg loading dose of ertapenem was first administered followed by 500 mg of the drug  for 4 consecutive dialysis sessions given after dialysis administered through the central venous catheter, which finally resulted in clinical improvement.

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 Creating care plans for patients with CKD-5HD requires specific considerations that are unique to this patient population. Evidence suggests that effective treatment of  UTIs should be done with antibiotics that achieve considerable concentrations in a patient’s urine (El Nekidy et al., 2020). However,  this is not the same in anuric CKD-5HD patients because they are unable to excrete the antibiotics significantly in their urine (El Nekidy et al., 2020).  Unfortunately, renal disease affects the pharmacokinetic parameters of  50% of all essential drugs (Keller & Hann, 2018). Pharmacokinetics assists prescribers to calculate the safest and most appropriate dose adjustment for this specific patient population; pharmacodynamics allows for a quantitative description of the drug’s response (Keller & Hann, 2018). Therefore, when creating a care plan and selecting the most appropriate class and dose of antibiotics  for patients with CKD-5HD,  it is crucial for prescribers and pharmacists to be nephrology trained (El Nekidy et al., 2020) Discussion: Pharmacokinetics and Pharmacodynamics.

 Furthermore, the patient’s age is another factor that needs to be considered when formulating care plans for patients, which may  affect the patient’s pharmacokinetic and pharmacodynamic processes. Many different factors had to be contemplated beforehand when caring for the aforementioned 67 year old patient suffering with a UTI.  Age can create possible pathophysiological changes to disease treatment (Corsonello et al., 2015).  A progressive deterioration in the functional reserve of various organs in the elderly population may affect the pharmacokinetics and/or the pharmacodynamics processes (Corsonello et al., 2015). In addition, alteration in body composition due to advancing age can result in reduced liver mass and perfusion, and reduced renal excretion, which  may also affect either pharmacokinetics or pharmacodynamics (Corsonello et al., 2015)Discussion: Pharmacokinetics and Pharmacodynamics . These issues have  to be taken into account when prescribing antibiotics to older complex patients. Therefore, the effectiveness of a drug and how it is processed in a body can vary in patient’s depending on their age.

References:

Corsonello, A., Abbatecola, A. M., Fusco, S., Luciani, F., Marino, A., Catalano, S., Lattanzio, F.

(2015, January). The impact of drug interactions and polypharmacy on antimicrobial therapy in the elderly. https://www.sciencedirect.com/science/article/pii/S1198743X14000470.

El Nekidy, W. S., Soong, D., Mooty, M., & Ghazi, I. M. (2020). Treatment of recurrent urinary

tract infections in anuric hemodialysis patient, do we really need antimicrobial urinary concentration?. IDCases, 20, e00748. https://doi.org/10.1016/j.idcr.2020.e00748

Keller, F., & Hann, A. (2018). Clinical Pharmacodynamics: Principles of Drug Response and

Alterations in Kidney Disease. Clinical journal of the American Society of Nephrology : CJASN, 13(9), 1413–1420. https://doi.org/10.2215/CJN.10960917

Negus, S. S., & Banks, M. L. (2018). Pharmacokinetic-Pharmacodynamic (PKPD) Analysis with

Drug Discrimination. Current topics in behavioral neurosciences, 39, 245–259. https://doi.org/10.1007/7854_2016_36

Van den Anker, J., Reed, M.D., Allegaert, K. and Kearns, G.L. (2018), Developmental Changes

in Pharmacokinetics and Pharmacodynamics. The Journal of Clinical Pharmacology, 58: S10-S25. https://doi.org/10.1002/jcph.1284  Discussion: Pharmacokinetics and Pharmacodynamics