Discussion: Week 1 A 98-year-old female was brought to the emergency department

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Discussion: Week 1
A 98-year-old female was brought to the emergency department

Discussion: Week 1
A 98-year-old female was brought to the emergency department by her family after finding her on the floor – an unwitnessed fall. The patient has a history of hypertension, hyperlipidemia, stage 3 chronic kidney disease, anxiety, and depression. The patient was on multiple blood pressure medications, statins, and antidepressants. X-rays revealed a bilateral pelvic fracture and the patient was put on a bed rest and prescribed pain medication (Tylenol 650mg and Oxycodone 5mg). Vitals signs were within normal limits, the labs were unremarkable. The patient was admitted to a rehabilitation unit. After a few days on the unit, the patient started declining mentally and changed from being alert and oriented to being confused and then delirious (having visual and audial hallucinations, disturbed sleep, and spontaneous arm movements). The laboratory results continue to be unremarkable. After discussing the case with the patient’s family, the patient was moved to a medical-surgical unit and put on comfort measures only (CMO) program, with all medications being discontinued or changed to prn (as needed). The patient’s mind cleared within a few days, and within a week she stopped hallucinating and became alert and oriented to self, place, and time.
The patient presented in the case study is an example of how drug toxicity has caused delirium in an older adult patient. There are many factors involved that have influenced the pharmacokinetic and pharmacodynamic processes such as genetics, race/ ethnicity, age, gender, environment/ behavior, disease process, and co-morbidities.
Age affects pharmacologic changes of all processes in pharmacokinetics: absorption of the drugs is overall delayed due to decreased gastric pH and gastric acid secretion, decreased intestinal and splanchnic blood flow, decreased gut motility and gastric emptying, decreased hepatic blood flow and increased bioavailability; distribution of the drug can be increased or decreased depending on the type of medication due to decreased organ perfusion blood flow and increased permeability of blood-brain barrier; metabolism is decreased because of decreased hepatic blood flow and decline in liver function; and excretion is slow down due to decline in renal function (Zerah et al., 2020).
Aging affects pharmacodynamics (the effects of drugs on the body) causing either increased pharmacodynamics: increase in half-lives of drugs, increased synergic effect of drugs resulting in adverse effects, or defective homeostatic systems and neurodegenerative disease (leading to polypharmacy and drug interactions) (Zerah et al., 2020).
Polypharmacy was another factor that has influenced the patient’s pharmacokinetic and pharmacodynamic processes. Polypharmacy (simultaneous use of five or more prescriiption drugs) is associated with an increased risk of adverse drug interactions and reduced compliance leading to a “prescribing cascade” and to potentially inappropriate medications (PIMs), falls, altered mental status (delirium), hospitalizations and mortality (Hoel et al., 2021; Nguyen et al., 2023). Risk factors for polypharmacy and PIMs usage include older age, being a woman, and living in rural areas (Nguyen et al., 2023).
Delirium is associated with multiple factors in elderly people but the major factors are considered to be polypharmacy and an imbalance in neurotransmitters (cholinergic deficit or increased dopamine) related to the adverse effects of anticholinergic or dopaminergic drugs (Zerah et al., 2020).
The personalized plan of care for the patient would include analyzing her age, all of her medications, and co-morbidities (such as CKD that affects the elimination of drugs). Of course, it would be very beneficial to have the patient’s genetic profile to utilize the benefits of pharmacogenomics particularly to see how her biomarkers influence disease processes, her response to drugs, or her reaction to drug treatment (Rosenthal & Burchum, 2021). However, it is possible to use other evidence-based well-researched tools/ guidelines to treat the patient and deprescribe high-risk medications such as the Beers criteria and STOPP/START criteria. The Beers criteria contain an extensive list of medications that older adults should avoid or use with caution due to PIMs as well as STOPP/START criteria that identify medications to avoid (STOPP) and potential prescribing omissions (START) in older adults (Hoel et al., 2021; Sampson et al, 2022).
The patient described in the case study was deprescribed slowly from all of her medications: first all the vitamins and supplements, then regular drugs for chronic disease, and, eventually, pain medications. She was later transferred to the assisted living facility where she celebrated her 100-year-old birthday.

References
Hoel, R. W., Giddings Connolly, R. M., & Takahashi, P. Y. (2021). Polypharmacy Management in Older Patients. Mayo Clinic Proceedings, 96(1), 242–256. https://doi.org/10.1016/j.mayocp.2020.06.012Links to an external site.
Nguyen, K., Subramanya, V., & Kulshreshtha, A. (2023). Risk Factors Associated With Polypharmacy and Potentially Inappropriate Medication Use in Ambulatory Care Among the Elderly in the United States: A Cross-Sectional Study. Drugs – Real World Outcomes, 10(3), 357–362. https://doi.org/10.1007/s40801-023-00358-2
Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.
Sampson, E. L., Graham, F., & Teodorczuk, A. (2022). Is There a Role for Medication in Managing Delirium with Dementia? Geriatrics (Basel, Switzerland), 7(5). https://doi.org/10.3390/geriatrics7050114Links to an external site.
Zerah, L., Bihan, K., Kohler, S., & Mariani, L.-L. (2020). Iatrogenesis and neurological manifestations in the elderly. Revue Neurologique, 176(9), 710–723. https://doi.org/10.1016/j.neurol.2019.11.010Links to an external site.
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module One: Initial Discussion Post
Hello, everyone! I’m excited to start this class and expand my pharmacology knowledge. As advanced practice nurses, it’s important for us to have an understanding of not only diseases processes and the impact of certain disorders on the body, but also the impact of pharmacological treatments on the body. The relationship between the body and drugs can be described by pharmacokinetics and pharmacodynamics. Pharmacokinetics is the passage of drugs into the body, through the body, and out of the body. During this journey, the drug passes through four stages, which include absorption (how the drug moves from the site of administration to the site of action), distribution (the journey of the drug through the bloodstream to various tissue throughout the body), metabolism (the process of the drug breaking down), and excretion (the removal of the drug from the body) (Genomind, 2021). Pharmacodynamics refers to the effects that a drug has on one’s body (Marino et al., 2023).
I work at a medication assisted treatment (MAT) clinic, where patients are prescribed Methadone, Suboxone, or Naltrexone. We recently had a 78-year-old male patient establish care at the clinic. He was illicitly using fentanyl and had overdosed. He sought care in hopes of starting Methadone to combat withdrawal symptoms that he was experiencing when trying to cease his illicit fentanyl use. The patient had a knee replacement in 2021 and was prescribed Lisinopril for hypertension. The patient also has a history of alcohol use disorder, but stated that he has been sober from alcohol for 12 years.
Methadone is a long-acting, full opioid agonist, and can be prescribed for chronic pain or opioid use disorder. At the clinic I’m employed at, the usual starting dose of methadone is 30 mg daily. Most patients reach a therapeutic dose around 80 mg daily, but of course, there are patients on both ends of the spectrum. Some patients feel that 30 mg daily is a sufficient dose, while some patients are on a daily dose of 200+ mg daily. Methadone is usually administered in the form of a liquid that’s ingested orally, but some patients are prescribed methadone tablets. Methadone is absorbed by the stomach and is metabolized in the liver. Methadone is eliminated by renal and fecal excretion. The pharmacokinetics of methadone varies from person to person. The activity of CYP3A4 is responsible for methadone bioavailability, and can vary greatly depending on the individual. Some antiretrovirals are CYP3A4 inducers and can decrease the amount of methadone in one’s system, causing them to need a higher dose to prevent withdrawal symptoms. When an individual is pregnant, they often times need a higher dose of methadone due to the quicker metabolization of the medication. Methadone is detectable in plasma approximately 30 minutes after administration and bioavailability varies from 41-76% to 85-95% (Ferrari et al., 2004). Methadone binds to KOR, MOR, and DOR opioid receptors and it’s pharmacodynamic properties, including respiratory depression, analgesia, tolerance, and dependence, are triggered by MOR activation (SciELO, 2015).
Factors that might have influenced pharmacokinetic and pharmacodynamic processes of the identified patient include his age, gender, genetics, and behaviors. In regard to genetics and methadone, those with the D-amino acid oxidase gene may experience a higher methadone plasma concentration, as well as higher occurrence of adverse reactions, such as dry mouth, difficulty with urination, and excessive yawning (Liu et al., 2022). This patient’s behaviors, such as illicit fentanyl use, may cause an increase in sedation and respiratory depression when used with methadone. Fentanyl and methadone are both opioids, so using both in conjunction may increase the patient’s risk of overdose. The patient also endorsed past alcohol use. The use of alcohol and methadone together is dangerous and may be deadly. Using both substances together increases risk of respiratory depression and bradycardia. This patient is 78-years-old. While patients are required to be at least 18-years of age to start methadone, there is not an age maximum. Special considerations should be used when prescribing methadone to individuals aged 65-years or greater, as older adults may have decreased hepatic function which can lead to a reduction of medication clearance. There may be a smaller therapeutic window for adults aged 65-years and older, as decreased hepatic function can lead to a buildup of medication in the body, causing a greater chance of sedation, respiratory depression, and overdose (Wu, 2018). Lastly, methadone dosing does not often differ by gender, but it’s important to keep in mind that studies have shown the decrease in testosterone in males who are on long-term methadone therapy. Men receiving methadone had around a fourth of testosterone levels compared to men who were not on opiates (American Addiction Centers, 2023).
In regard to a treatment plan for this patient, I feel that it would be important to complete a hepatic panel on this patient every three months. As methadone is metabolized in the liver, this patient has a history of alcohol use disorder, and this patient is 78-years-old and liver function declines with age, it would be important to monitor this patient’s liver functions. It would be important for this patient to complete a monthly urine drug screen (UDS) to confirm that the patient is not using illicit substances in conjunction with methadone. At the clinic I’m employed at, we require individuals with a history of alcohol use disorder to complete a breathalyzer prior to dosing to verify that they have not recently consumed alcohol, which could put the patient at an increased risk of respiratory depression or overdose. It would be beneficial to also monitor this patient’s testosterone levels (which could be completed when the patient is having his quarterly hepatic panel checked), as testosterone decreases with age and the use of methadone can cause can a decrease in testosterone. A referral could be placed for this patient to obtain supplemental testosterone therapy if it’s indicated that his testosterone levels are abnormally low. Methadone can cause one’s QTc interval to prolongate, placing the patient at risk of developing an abnormal heart rhythm, such as Torsade’s de Pointes. I would include in this patient’s plan of care to complete an electrocardiogram (EKG) annually, as well as prior to any methadone dose increases (Soroosh et al., 2019). Lastly, as previously mentioned, this patient is on lisinopril for hypertension. It would be important to check in with this patient daily and obtain the patient’s blood pressure when initiating methadone treatment and then following every dose increase, as taking methadone and lisinopril together can lower blood pressure and cause dizziness, hypotension, and fainting.

References
American Addiction Centers. (2023). Opioid use. https://drugabuse.com/opioids/Links to an external site.

Ferrari, A., Coccia, C., Bertolini, A., & Sternieri, E. (2004). Methadone: Metabolism, pharmacokinetics, and interactions. Pharmacological Research, 50(6), 551-559. https://doi.org/10.1016/j.phrs.2004.05.002Links to an external site.

Genomind. (2021). Introduction pharmacokinetics: Four steps in a drug’s journey throughout the body. https://genomind.com/providers/introduction-to-pharmacokinetics-four-steps-in-a-drugs-journey-through-the-body/Links to an external site.

Liu, T., Tsou, H., Chung, R., & Liu, S. (2022). Association of the d-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment. Journal of Human Genetics, 67(5). https://www.researchgate.net/publication/357613451_Association_of_the_D-amino_acid_oxidase_gene_with_methadone_dose_in_heroin_dependent_patients_under_methadone_maintenance_treatmentLinks to an external site.

Marino, M., Jamal, Z., & Zito, P. (2023). Pharmacodynamics. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK507791/Links to an external site.

SciELO. (2015). Revisiting methadone: Pharmacokinetics, pharmacodynamics, and clinical indications. https://www.scielo.br/j/rdor/a/Wn4vdHJL3hrZgv6XrJZk9Rj/#:~:text=Methadone%20is%20an%20opioid%20agonist,triggered%20by%20MOR%20activation%207Links to an external site.

Soroosh, D., Neamatshahi, M., Zarmehri, B, Nakhaee, S., & Mehrpour, O. (2019). Drug-induced prolonged corrected QT interval in patients with methadone and opium overdose. Substance Abuse Treatment, Prevention, and Policy, 14(8). https://substanceabusepolicy.biomedcentral.com/articles/10.1186/s13011-019-0196-3Links to an external site.

Wu, A. (2018). Special considerations for opioid use in elderly patients with chronic pain. U.S. Pharmacist, 43(3), 26-30. https://www.uspharmacist.com/article/special-considerations-for-opioid-use-in-elderly-patients-with-chronic-painLinks to an external site.
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