Advanced Pharmacology Cardiovascular System
Influence of age on pharmacokinetics and pharmacodynamics.
In geriatrics, the dynamics of drugs are affected differently compared to the young population. Cossart et al. (2021) identify the major disparities, among them being absorption, drug distribution, the metabolism of these drugs, and excretion. These factors can be altered among the elderly because of a change in the biological functions of the elderly organs.
Several pharmacokinetic changes occur in the body, but the prominent ones are a decrease in the renal clearance and secretory capacity as well as impaired hepatic functions (Bleszynska et al., 2022). There may also be a reduction in the protein binding capacity altering the volumes of distribution of different drugs administered to the elderly.
In the liver, the effect of first-pass metabolism is reduced as a result of the reduction in the size of the liver, reduction of blood flow, and decreased CYP enzymes that are involved in metabolism. Therefore, the bioavailability of drugs that go through this metabolism will increase, affecting the organs extensively and may be toxic (Mckeand et al., 2018)
Impact of the above changes on patient’s prescription
Celecoxib is mainly metabolized by the CYP2C9 enzyme in the liver. Because of the factors described above, the elderly are exposed to toxicity because of decreased metabolism of the drug in the liver causing adverse effects on the cardiovascular and the renal systems. If still given, the doses should be reduced and closely monitored. The renal function decreases with an increase in age. Metformin is cleared by the kidneys.
As Clemens et al. (2020) note, when the renal function reduces, less amount of metformin will be removed, this precipitates lactate accumulation which is toxic. Changes in the metabolism of glyburide in the liver, clearing from the kidney, and other pathologies in geriatric patients demand the drug to be monitored and doses adjusted appropriately (Tao et al., 2021).
Adjustment to patient’s medication
Considering the metabolism of amlodipine in the liver, 10mg QD is presumably high and should be adjusted. In geriatric patients, the initial dose of amlodipine is recommended to be 2.5 mg once daily and an optimum dose of 10 mg per day (Khan et al., 2020). I would maintain the dose of donepezil at 10mg QHS. A high dose of donepezil is recommended to improve the cognitive functions among the elderly with Alzheimer’s disease (Kuan et al., 2022). I would also reduce the dose of levothyroxine.
Initial treatment in the elderly should start with levothyroxine given at lower doses than usual. In elderly patients with underlying cardiovascular disease, the recommended initial dose should be 12.5-25 mcg every day. After monitoring, the doses can be increased by 12.5-25 mcg for four to six weeks until the patient is euthyroid (Effraimidis et al., 2022).
The prescribed dosage of celecoxib, 200mg QD, is high. The recommended dose in the elderly is 200mg BD because of the reduced renal function with increased age. Thus, administering high doses of celecoxib would harm the patient (Shin, 2018). One should be cautious when prescribing furosemide since it is excreted slowly among the elderly, hence the need to start the treatment with 20mg daily (Khan et al., 2022). The dose of 40mg QAM is therefore high in this patient. Metformin 500mg 1 BID should be reduced to once per day.
Reduced kidney functions in elderly patients tend to increase the risk of developing adverse effects such as lactic acidosis if metformin is given in high doses. I would discontinue glyburide. In most cases, metformin is indicated in place of glyburide as the first line of diabetes (Clemens et al., 2020).
Błeszyńska, E., Wierucki, Ł., Zdrojewski, T., & Renke, M. (2020). Pharmacological Interactions in the Elderly. Medicina (Kaunas, Lithuania), 56(7), 320. https://doi.org/10.3390/medicina56070320
Clemens, K. K., O’Regan, N., & Rhee, J. J. (2019). Diabetes Management in Older Adults With Chronic Kidney Disease. Current Diabetes Reports, 19(3), 11. https://doi.org/10.1007/s11892-019-1128-3
Cossart, A. R., Isbel, N. M., Scuderi, C., Campbell, S. B., & Staatz, C. E. (2021). Pharmacokinetic and Pharmacodynamic Considerations in Relation to Calcineurin Usage in Elderly Kidney Transplant Recipients. Frontiers in Pharmacology, 12, 635165. https://doi.org/10.3389/fphar.2021.635165
Effraimidis, G., Watt, T., & Feldt-Rasmussen, U. (2021). Levothyroxine Therapy in Elderly Patients With Hypothyroidism. Frontiers in Endocrinology, 12, 641560. https://doi.org/10.3389/fendo.2021.641560
Khan, M. Y., Pandit, S., Ray, S., Mohan, J. C., Srinivas, B. C., Ramakrishnan, S., Mane, A., Mehta, S., & Shah, S. (2020). Effectiveness of Amlodipine on Blood Pressure Control in Hypertensive Patients in India: A Real-World, Retrospective Study from Electronic Medical Records. Drugs – Real World Outcomes, 7(4), 281–293. https://doi.org/10.1007/s40801-020-00211–w
Khan, T. M., Patel, R., & Siddiqui, A. H. (2022). Furosemide. In StatPearls. StatPearls Publishing.
Kuan, Y. C., Huang, K. W., Lin, C. L., Hu, C. J., & Kao, C. H. (2017). Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 79(Pt B), 77–83. https://doi.org/10.1016/j.pnpbp.2017.06.002
McKeand, W., Ermer, J., & Korth-Bradley, J. (2018). Assessment of the Effects of Age and Renal Function on Pharmacokinetics of Bazedoxifene in Postmenopausal Women. Clinical Pharmacology in Drug Development, 7(8), 920–926. https://doi.org/10.1002/cpdd.607
Shin S. (2018). Safety of celecoxib versus traditional nonsteroidal anti-inflammatory drugs in older patients with arthritis. Journal of Pain Research, 11, 3211–3219. https://doi.org/10.2147/JPR.S186000
Tao, Y., E, M., Shi, J., & Zhang, Z. (2021). Sulfonylureas use and fractures risk in elderly patients with type 2 diabetes mellitus: A meta-analysis study. Aging Clinical and Experimental Research, 33(8), 2133–2139. https://doi.org/10.1007/s40520-020-01736-4
Week 2 Assignment Instruction
By Day 7 of Week 2 (by Sunday, 11:59 pm MT)
Write a 2- to 3+ page paper that addresses the following:
- Explain how the factor (i.e. genetics, gender, ethnicity, age or behavior) 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. Would you discontinue any medications, change the dosage, and/or add medications to the patient’s regimen? DISCUSS EACH MEDICATION.
Case study assigned:
LM is an 89-year-old female resident of a long-term care facility who has been experiencing multiple falls, some resulting in injuries such as bruising and skin tears. Over the last 6 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.
- Alzheimer’s disease
- 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
Widowed with 2 adult children living in town, retired photographer and owner of an art supply store
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
Cr: 1.6 UA: Clear
eGFR: 45 ml/min
- 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.
Faces pain scale: No pain occurs at rest, upon walking, pain is moderate to severe