Advanced Pharmacology: Case Study of an 89-Year-Old Female Patient

Overview

In the modern epoch, it is pertinent to consider age not only as a number but also as a significant determinant of health and well-being. Global population statistics show that the world’s population is aging. In Europe, people over the age of 65 made up 17% of the population in 2010, and this figure is expected to rise to 17.4% by 2060 (Drenth-van Maanen et al., 2020).

Advanced Pharmacology: Case Study of an 89-Year-Old Female Patient

In the United States, the CDC (2022) estimates that people older than 65 years of age represented 16% of the population in 2019, with a projected increase to 21.6% in 2040. The rising aging population has been attributed to (1) lower mortality among the younger population due to improved mother and child care, adequate food, improved hygiene, improved treatment of infectious diseases, and a better politically safe environment, and (2) lower mortality among the elderly due to better prevention and treatment for chronic illnesses such as cardiovascular conditions (Drenth-van Maanen et al., 2020). While aging is a biological process, it is associated with an increase in morbidity and disability.

The provided case scenario of an 89-year-old female patient with multiple comorbidities (hypertension, diabetes, Alzheimer’s disease, osteoarthritis, and hypothyroidism) who is on polypharmacy exemplifies the impact of aging on health and well-being. Except for a low glomerular filtration rate (GFR) of 45 ml/min, the patient’s laboratory results are within normal ranges.

The goal of this paper is to coherently articulate the effect of the patient’s age on the pharmacokinetic and pharmacodynamic processes, with a subsequent emphasis on the impact on the patient’s drug therapy and possible improvements to the therapy plan.

The Patient’s Age and Influence on the Pharmacokinetic and Pharmacodynamic Processes

Aging-related biological changes cause a decline in human organ and body functions. The biological changes may include oxidative stress, telomere shortening, increased lipid peroxidation, altered gene expression, and upregulation of apoptosis, among others.

While pharmacokinetics describes how drugs move into, through, and out of the body (absorption, bioavailability, distribution, metabolism, and excretion), pharmacodynamics describes the biochemical and physiological effects of drugs on the body as well as their mechanisms of action (Grogan & Preuss, 2022; Marino et al., 2022). Due to the altered pharmacokinetic and pharmacodynamic processes in the elderly, physicians may experience difficulty managing drug therapies.

Absorption is the initial process by which a drug moves from the site of administration to systemic circulation. Aging may be associated with decreased blood supply to the gut, decreased gut motility, and delayed gastric emptying, which may delay drug absorption from the gut to the systemic circulation (Drenth-van Maanen et al., 2020), which is especially important for the patient described because she is on multiple oral medications.

Furthermore, because hypochlorhydria is common in older adults, absorption of drugs that require acidic environments, such as NSAIDs, is impaired. Age also influences first-pass metabolism and drug availability. Drenth-van Maanen et al. (2020) define first-pass metabolism as the metabolism of the drug before it reaches the systemic circulation and is dependent on the CYP3A4 enzyme.

The process takes place primarily in the liver, but it can also take place in the intestine. With advancing age, the liver’s mass, blood supply, and CYP3A4 enzymatic activity decline, thus increasing the bioavailability of some drugs and necessitating caution when handling drugs with a very narrow therapeutic index, which can now be initiated at a low dose. On the contrary, first pass activation of several prodrugs, such as ACEIs, may be reduced, resulting in low active drug substance bioavailability.

The ratio of total drug in the body to total drug plasma concentration, or rather, the distribution, is also affected by age. Patients’ body composition changes as they age, with water content decreasing and body fat increasing (Drenth-van Maanen et al., 2020).

As a result, while water-soluble drugs like Metformin and Furosemide, which the patient is taking, will have smaller volumes of distribution, lipid-soluble drugs like Donepezil (a necessity because of its action in the CNS) will have larger volumes of distribution, a longer elimination time, and thus adverse effects will last long after therapy is discontinued (Drenth-van Maanen et al., 2020). Drug metabolism will be reduced due to decreased liver volume, decreased blood supply to the liver, and decreased CYP450 enzymatic capacity.

Finally, due to a smaller fibrotic and atrophic kidney, the final phase of the pharmacokinetic pathway, excretion, will be reduced (Drenth-van Maanen et al., 2020). It is important to note that as the pharmacokinetic processes change, the action of the drugs—biochemical and physiological effects (pharmacodynamics)—also change.

How Changes in the Pharmacokinetic and Pharmacodynamic Processes Impact the Patient’s Recommended Drug Therapy

The reduction in stomach acidity related to old age affects the absorption of drugs that require an acidic medium. The patient is taking Celecoxib for the treatment of her osteoarthritic pain, and to improve absorption, the patient may be advised to take the drugs without a meal, as food has been shown to prolong absorption time and reduce the maximum concentration of the drug in the body (Angeli et al., 2018).

In addition, before taking Metformin, it is recommended that GFR be determined. Because of the reduced muscle mass in the elderly, urea and electrolyte levels may reveal a normal serum creatinine level (Drenth-van Maanen et al., 2020); this is why a GFR should be obtained as an indicator of renal impairment.

Metformin therapy is contraindicated in patients with a GFR of 30 ml/min; additionally, Metformin therapy is not recommended in patients with a GFR of 30-45 ml/kg (Corcoran & Jacobs, 2022). In contrast, a study found that patients with a GFR of 30-60 ml/min could have their Metformin dose halved (Longo et al., 2019), a practice I would consider a viable option for the patient.

Moreover, since the patient already has well-controlled blood sugar levels (101 mg/dl), and is at risk of profound hyperglycemia due to Glyburide therapy, elderly age, renal insufficiency, dementia, and long-term diabetes, some clinicians may consider halving the dosage or withdrawing it, with careful follow-up to determine the reconstitution of a different or same drug later.

How to Improve the Patient’s Drug Therapy Plan and Rationale for the Decisions

To improve the patient’s therapeutic plan, I would employ the following interventions: use of low effective dosages, emphasis on non-pharmacological interventions, pill burden reduction, frequent monitoring, and assigning a caretaker. Low-effective dosages, for example, instead of giving Metformin 500 mg BD, give Metformin 500 mg OD.

The reasoning behind this is that the patient already has well-controlled blood sugar levels, and the GFR is between 30-60 ml/min, a range in which Longo et al. (2019) recommend halving the dosage. Stopping Glyburide therapy is one option for reducing the pill burden, but reducing the dosage by half is also a viable option, intending to reduce the drug’s associated profound hypoglycemia (Hardin & Jacobs, 2022).

Weight loss may be beneficial when considering non-pharmacological options; however, the patient uses a wheelchair, so this may be difficult to achieve. A healthy diet, frequent lifting from the wheelchair to prevent bedsores, and assigning a caregiver who closely reminds her to take her medications and assists her with hygiene and other aspects of daily life will be critical in improving her quality of life.

Conclusion

Older people face multiple problems potentially influencing the beneficial and adverse effects of pharmacotherapy. As a result, physicians face additional challenges when prescribing medications to elderly patients. Therefore, a physician must know the drug’s pharmacokinetics and pharmacodynamics.

One obvious example is the prescription of Celecoxib, whose absorption may be hampered by the aging-related decrease in stomach acidity. This knowledge improves physicians’ competency when dealing with elderly patients. To address the overall issue, adequate information about potential changes in pharmacokinetics and pharmacodynamics in older people must be gathered during drug development.

References

Advanced Pharmacology Assignment Instructions

This is an assignment with an Introduction and Conclusion. Case scenario: LM is an 89-year-old female resident of a long-term care facility which has been experiencing multiple falls, some resulting in injuries such as bruising and skin tears. Over the last six months, her ambulation status has declined from independent to wheelchair level. She complains of pain in her legs when walking more than short distances across the nursing unit.

PMH:

HTN
Alzheimer’s disease
Hypothyroidism
Osteoarthritis
Diabetes
MEDICATIONS:

Amlodipine 10 mg QD
Donepezil 10 mg QHS
Levothyroxine 0.88 mg QAM
Celecoxib 200 mg QD
Furosemide 40 mg QAM
Metformin 500mg, 1 BID
Glyburide 5mg, 1 BID
ALLERGIES: NKA

SOCIAL HISTORY:

Widowed with two adult children living in town, retired photographer and owner of an art supply store

VITALS: LABS:

Weight: 129 lbs TSH 2.45 Free T4 0.98

Height: 64 inches Na 135, K+ 3.8, Cl 99, CO2 25,

BP: Supine = 177/82 Glucose 101, SCr 0.9, BUN 42

HR: 78 bpm WBC 7.0, RBC 4.5, Hgb 11.9, Hct 34.1

Plt 255

Cr: 1.6 UA: Clear

eGFR: 45 ml/min

PE:

HEENT: Normocephalic, no evidence of trauma, PERRLA, EOMI, Dry mucous membranes
CV: RRR
Respiratory: Clear to auscultation bilaterally
Abdomen: Soft, non-tender, no masses or guarding
G/U: Skin intact, assisted with toileting and personal hygiene by staff
Extremities: Bilateral 2+ edema to lower extremities; skin dry, dark bruising, and skin tear to right elbow and forearm
Neuro: Alert and oriented to person only. MMSE 18/30, stable over last 12 months.

PAIN ASSESSMENT:

Faces pain scale: No pain occurs at rest; upon walking, pain is moderate to severe.

Instructions:

Review the Resources for this module and consider the impact of potential pharmacotherapeutics for cardiovascular disorders introduced in the media piece.
Review the case study assigned by your Instructor for this Assignment.
Select one of the following factors: genetics, gender, ethnicity, age, or behavior. (I think age will be a good choice?)
Reflect on how the selected factor might influence the patient’s pharmacokinetic and pharmacodynamic processes.
Consider how pharmacokinetic and pharmacodynamic processes changes might impact the patient’s recommended drug therapy.
Think about how you might improve the patient’s drug therapy plan based on the pharmacokinetic and pharmacodynamic changes. Reflect on whether you would modify the current drug treatment or provide an alternative treatment option for the patient.

By Day 7 of Week 2
Write a 2- to 3-page paper that addresses the following:

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 why you would make these recommended improvements.