this are 2 separate discussions, please respond to each with a reference citatio

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this are 2 separate discussions, please respond to each with a reference citation on each response. Respond by suggesting additional patient factors that might have interfered with the pharmacokinetic and pharmacodynamic processes of the patients they described. In addition, suggest how the personalized plan of care might change if the age of the patient were different and/or if the patient had a comorbid condition, such as renal failure, heart failure, or liver failure.
Patient Case
A patient case, from my experience, that comes to mind is a 73-year-old African American woman with a past medical history of hypertension and coronary artery disease. She presented to the emergency
department with confusion and generalized weakness that was concerning for a stroke. Her initial workup ruled out an acute stroke but did reveal hyponatremia with a serum sodium of 123 mEq/L. Her
medication history showed that she was prescribed hydrochlorothiazide (HCTZ), a thiazide diuretic, for control of her hypertension. She was also following a low sodium and low fat diet, as advised by her
primary care provider (PCP).
The patient had been independently managing her activities of daily living and her healthcare with family support for several years, but she had recently begun needing increasingly more help. The patient
had been taking HCTZ for several years without difficulties, prior to this hospitalization. Unfortunately, she had not been able to arrange outpatient visits with her PCP over the course of the coronavirus
disease of 2019 (COVID-19) pandemic. In that time, she had a significant weight loss of about 15 pounds. The weight loss was likely due to decreased appetite associated with the aging process, further
compounded by decreased pleasure eating related to her following a low salt and low fat diet. Her decreased body weight and muscle mass were likely the tipping point for acute hyponatremia, after years of
tolerating HCTZ without incidence.
Thiazide induced hyponatremia (TIH) is defined as serum sodium less than 136 mEq/L in patients taking thiazide diuretics. It is seen in approximately 14% of patients treated with thiazides and can be as
high as 56% in patients greater than 70 years of age. Symptoms of acute hyponatremia include nausea, vomiting, headache, weakness, confusion, and seizures. Patients with chronic hyponatremia or mild
acute hyponatremia may have fatigue, cognitive impairments, gait dysfunction, and falls. Thiazide diuretics are responsible for the highest incidence of drug induced hyponatremia (Liamis et al., 2016).
Factors Influencing Pharmacokinetic and Pharmacodynamic Processes
Pharmacokinetics describes the body’s effects on a drug and pharmacodynamics is how a drug affects the body. Pharmacokinetics and pharmacodynamics are greatly affected by aging in several ways.
Increased gastric emptying time and decreasing gastric blood flow in the elderly can decrease drug absorption. Decreased renal and hepatic function in the elderly population can delay the onset of action,
metabolism, and excretion of medications. Aging’s effects on renal function also decreases glomerular filtration rate (GFR), causing the half-life of medications to be increased (Andres et al, 2019).
Decreased muscle mass in the elderly also affects renal diluting capacity (Liamis et al., 2016).
In relation to thiazide diuretics, decreased muscle mass is labeled as an independent risk factor for developing TIH. People with lower body mass and those with lower total body protein are believed to
have greater serum sodium concentration fluctuations, increasing their risk for TIH. A decrease in GFR is believed to play a role in this. Patients who use thiazide diuretics also have increased stimulation of
anti-diuretic hormone (ADH) due to the decreased extracellular volume. This leads to water retention in the renal tubules and thirst-stimulation. Finally, patients taking a thiazide diuretic and also following a
low sodium diet are found to have a further decrease in serum sodium levels (Liamis et al., 2016).
Personalized Plan of Care
For the above patient, I would stop both the HCTZ and the low salt diet. Going forward, I would follow the Eighth Joint National Committee (JNC 8) guidelines and would start a calcium channel blocker
(CCB) such as amlodipine. The JNC 8 guidelines for management of hypertension in patients of African American decent recommend initiation of a thiazide diuretic or a CCB. The rationale for choosing a
CCB over an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) is that ACEIs had a higher rate of stroke risk and were found to be less effective in reducing blood
pressure in African American patients. Titration of the CCB should continue monthly until a blood pressure goal of <150 mm/Hg systolic and <90 mm/Hg diastolic pressure is reached or until the medication dose is maximized (James et al., 2014). Going forward, she would need both her sodium and her blood pressure monitored. Communication with her PCP would include this plan so that she could have outpatient testing and monitoring arrangements made. She would also need a nutrition consultation, as well as a physical therapy evaluation for rehabilitation potential. Optimizing her nutrition can increase her muscle mass and has also been shown to improve ADLs in elderly patients (Yoshimura et al., 2016). References Andres, T., McGrane, T., McEvoy, M., & Allen, B. (2019). Geriatric pharmacology: An update. Anesthesia Clinics, 37(3), 475-492. James, P., Oparil, S., Carter, B., Cushman, W., Dennison-Himmelfarb, C., Handler, J., Lackland, D., LeFevre, M., MacKenzie, T., Ogedegbe, O., Smith, S., Svetkey, L., Taler, S., Townsend, R., Wright, J., Narva, A., & Ortiz, E. (2014). 2014 Evidence-based guideline for management of high blood pressure in adults. Report from the panel members appointed to the eighth joint national committee (JNC 8). Journal of the American Medical Association, 311(5), 507-520. Liamis, G., Filippatos, T. D., & Elisaf, M. (2016). Thiazide-associated hyponatremia in the elderly: What the clinician needs to know. Journal of Geriatric Cardiology, 13(2), 175-182. Yoshimura, Y., Uchida, K., Jeong, S., & Yamaga, M. (2016). Effects of nutritional supplements on muscle mass and activities of daily living in elderly rehabilitation patients with decreased muscle mass: A randomized control trial. The Journal of Nutrition, Health, and Aging, 20(2), 185-191. #2 Pharmacokinetics and pharmacodynamics Pharmacokinetics is the study of how drugs move through the body, and pharmacodynamics is the study of drugs’ effects on the body and how these effects are produced (Rosenthal & Burchum, 2021). These processes are affected by patient factors such as gender, age, nutrition, and more. In this post, I will describe a clinical case scenario in which pharmacokinetics and pharmacodynamics were affected by patient factors. I will also discuss a plan of care for the patient with these factors in mind. Clinical case scenario: Factors that influence pharmacokinetics and pharmacodynamics One of the most common medications my clinic prescribes for patients with chronic pain is gabapentin. Gabapentin can effectively treat chronic pain, especially neuropathic pain such as post-herpetic neuralgia and peripheral neuropathy (Moore & Gaines, 2019). In one clinical scenario, a female patient in her 80s was prescribed gabapentin for peripheral neuropathy. She also had stage 3 chronic kidney disease (CKD 3), and her body mass index (BMI) was approximately 18. Though she was started on a very low dose of the gabapentin to account for her age and CKD 3, she experienced severe side effects after her first dose, including swelling in her legs and feet, loss of balance, and severe somnolence. Factors that may have influenced this patient’s reaction to gabapentin include advanced age, CKD, and low BMI. CKD can cause delayed renal excretion of drugs, thereby prolonging their effects on the body (Rosenthal & Burchum, 2021). This patient’s advanced age may also have influenced the severity of her adverse reaction to the gabapentin. Older adults have fewer nephrons, which leads to decreased blood filtration, and decreased renal blood flow (Rosenthal & Burchum, 2021). Plan of care Pain management can be quite challenging in patients with CKD. However, the World Health Organization (WHO) created an analgesic ladder for patients with CKD to assist clinicians in determining treatment plans for patients with CKD and chronic pain (Davison, 2019). Gabapentin is the first-line treatment for chronic neuropathic pain in patients with CKD. However, if this therapy is not effective, then the second-line treatment is carbamazepine, and if this is not effective, the third-line treatment is a tricyclic antidepressant such as amitriptyline (Davison, 2019). Following the WHO analgesic ladder, the next line of treatment for the patient in this clinical scenario is to try carbamazepine. I would recommend this patient discontinue the gabapentin and start carbamazepine instead. The WHO analgesic ladder notes that each treatment step should be trialed for 1-4 weeks before adding or changing therapy (Davison, 2019). The patient in this scenario is a classic example of an older adult patient with common comorbidities such as CKD. Prescribers must consider factors that affect pharmacokinetics and pharmacodynamics when determining pharmacological therapies for these types of patients. Evidence-based tools such as the WHO analgesic ladder can assist clinicians in making these treatment decisions. References Davison, S. N. (2019). Clinical Pharmacology Considerations in Pain Management in Patients with Advanced Kidney Failure. Clinical Journal of the American Society of Nephrology: CJASN, 14(6), 917–931. Moore, J., & Gaines, C. (2019). Gabapentin for chronic neuropathic pain in adults. British Journal of Community Nursing, 24(12), 608–609. Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.

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