Authors: Alexander Zirulnik MD MPH; Jennifer Koehl PharmD

Edited By: Angel Li, MD, Shan W. Liu MD, SD

Updated: 9/24/2021

Case Study

A 75-year-old female with a past medical history of hypertension, type-2 diabetes mellitus, osteoporosis, and generalized anxiety disorder is brought into the emergency department (ED) by her neighbor who found her on the steps leading up to their apartment building. The patient states that she fell onto her out-stretched hands while ambulating to the front door. She endorses bilateral pain in her upper extremities. She denies any preceding chest pain, shortness of breath, but does endorse some dizziness and gait instability leading up to the fall. She states that lately she has fallen more often. She is intermittently stating that she does not know why she is in the supermarket and appears confused. After you conduct a reassuring physical exam that is only notable for a superficial abrasion to her left palm and some gait instability, you review what medications she takes at home. She provides a medication list that indicates the following: Lisinopril, Metformin, Furosemide, Omeprazole, Lorazepam as needed for anxiety. She states that she has been taking Diphenhydramine for the last month because her allergies have been bothering her. Which of the previous medications may be contributing to the increased falls and confusion for this patient?

Objectives

By the end of this module, the student will be able to: 

1. Understand key biological factors that predispose older adults to adverse drug reactions 
2. Understand the basic steps involved with taking a medication history
3. Define polypharmacy and the purpose of the Beers Criteria
4. Name common medications often encountered in the ED that should be carefully assessed using Beers Criteria

Introduction

Older adults (≥ 65 years of age) make up about one quarter of all patients presenting to the emergency departments across the United States [Ref. 1]. Older adult patients, in comparison to other age groups, often present with more comorbidities and chronic diseases that necessitate extensive management with medications and supplements. Polypharmacy (often defined as 5 or more medications) disproportionately affects older patients and continues to be a leading cause of adverse drug reactions and complications [Ref. 2,3]. In addition to medical comorbidities and polypharmacy, older adults often have cognitive, visual, or hearing impairments that increase the risk of adverse drug events.

Factors Leading to Adverse Drug Reactions in Older Adults

Renal dysfunction

It is estimated that about 14% of the United States population suffers from some form of chronic kidney disease (CKD) [Ref. 4]. A large proportion of those living with CKD are above the age of 65. Renal dysfunction can result from many diseases and age-related changes to the physiology of the kidneys as nephrons decrease resulting in decreased function and ability to metabolize and/or excrete medications. Renal dysfunction plays a large role in the pharmacodynamics of many medications. As the filtration rate and tubular dysfunction worsen, certain drugs accumulate and increase their bioavailability and effect on the body. Special attention needs to be addressed when prescribing medications that are excreted by the kidneys in older patients with comorbid renal dysfunction. Often, medications can still be prescribed to patients with CKD but need to be dosed in accordance with level of renal function. Some medications, like digoxin, can be monitored by drug levels to ensure doses administered are not toxic or harmful to the patient [Ref. 5]. Common medications that should be dose adjusted or avoided in the geriatric population include the following:

Liver dysfunction

As people age, the liver naturally loses some of its ability to metabolize substances. In addition, many chronic conditions affect the liver’s ability to metabolize drugs; such as cirrhosis (alcoholic and non-alcoholic), non-alcoholic fatty liver disease, hepatitis, portal hypertension, and smoking. As the liver loses mass, as is the case in cirrhosis or aging, the first-pass metabolism or clearance of many drugs decreases. This leads to increased bioavailability of the drug in the systemic circulation. Reduced cytochrome P450 activity and decreased hepatic flow associated with aging and many chronic conditions also contribute to increased bioavailability of medications [Ref. 6]. Additionally, a damaged liver produces less protein, leading to increased levels of metabolically active drug for those that are typically highly protein bound (warfarin, phenytoin). Common medications that should be dose adjusted or avoided include the following:

Body Composition

Older adults tend to lose muscle mass and increase total body fat composition leading to an increase in the bioavailability of fat-soluble drugs [Ref. 7]. These body composition changes may lead to an increase in the amount of free drug circulating through the body in addition to a potential decreased duration of action for many drugs.

Medication History

When first assessing any patient in the ED, a provider must ascertain the medications, supplements, and or other substances that a patient may be taking. This is key when assessing any older adult presenting to the ED, especially when presenting with vague complaints such as “fatigue,” “altered mental status,” “dizziness,” or “weakness.” This step not only helps the provider determine if an adverse drug reaction is contributing to the patient’s presentation, but also helps reduce any errors that may arise in transitions of care such as admission to the hospital, discharge to rehabilitation facility, or discharge home [8]. Whenever possible, the patient should be asked directly which medications and supplements they are taking. If needed and possible, due to cognitive impairment or incapacity, a provider should always try to contact the patient’s family members, primary caregiver, or care facility. Often, patients provide healthcare providers with written lists or documentation on their mobile devices. Use caution when relying on an electronic medical record or past documentation to obtain a medication history as these are often not updated, incomplete, and or have incorrect dosing. A detailed medication history should include the following:

• Name of the medication
• The indication for the medication
• The dose of the medication
• How often the medication is taken
• How they take the medication (by mouth, inhaler, per rectum etc.)
• Any non-prescribed medication use (supplements, vitamins, herbal or homeopathic medications)
• Any illicit or recreational substance use
• Do they take their medications every day
• Do they take all their medications independently or not

Polypharmacy & Beers Criteria

Polypharmacy, often defined as taking 5 or more medications, affects older adults more commonly than other age groups. Adverse drug reactions often result from polypharmacy-related errors and are a frequent cause of ED visits by older adults. Beers Criteria is a tool used to identify high risk medications prescribed to older adults with the intent on de-prescribing medications that may lead to adverse drug events [9]. This enables improved medication selection and quality of care while avoiding unnecessary drug costs. Every 3 years, the American Geriatrics Society updates the Beers Criteria list of medications. 

2019 AGS Beers Criteria for Older adults
https://www.pharmacytoday.org/article/S1042-0991(19)31235-6/fulltext 

Common medications that are often encountered in the  ED  that should be carefully considered before use according to the Beers criteria:

Pearls and Pitfalls

• Always review medication lists for older adults to identify any high-risk medications.
• When in doubt if a medication poses any risk to an older adult patient, reference the Beers criteria or a pharmacy colleague. 
• Start low and go slow. Utilize the lowest dose of medications when able and escalate slowly with frequent reassessment.
• Continuously assess the need for medications based on benefit and lifespan to decrease polypharmacy adverse events.
• Instead of adding more medications to treat an older patient’s chief complaint, determine if removing a medication may be helpful.

Case Study Resolution

After further questioning during the medication history, you discover that your patient has been taking Lorazepam 0.5 mg orally every morning instead of as needed and additionally has been taking Diphenhydramine 25 mg orally every morning and night due to worsening seasonal allergies. The patient also tells you that she sometimes forgets when she takes certain medications and may have accidentally taken two doses of Diphenhydramine this morning. Imaging and labs reveal no abnormalities. After observation and oral rehydration her gait instability and mild confusion are resolving. You surmise that these symptoms may have been due to an adverse drug reaction from Diphenhydramine and Lorazepam. You are able to get in touch the patient’s son who lives next door and together with the patient, you counsel them on the side effects of Diphenhydramine and recommend a safer second-generation antihistamine such as Loratadine or Cetirizine for seasonal allergy relief along with a pill box so that she does not take repeat doses of her medications. In addition, you refer her to her primary care physician with the intent on tapering her home Lorazepam with eventual cessation of the medication.

References

1. Samaras N, Chevalley T, Samaras D, Gold G. Older patients in the emergency department: a review. Ann Emerg Med. 2010 Sep;56(3):261-9. doi: 10.1016/j.annemergmed.2010.04.015. PMID: 20619500.
2. Ferner RE and Aronson JK. Communicating information about drug safety. BMJ 2006 Jul 15;333(7559):143-5.
3. Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. Am J Geriatr Pharmacother 2007 Dec;5(4):345-51.
4. U.S. Department of Health and Human Services. (n.d.). Kidney Disease Statistics for the United States. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease. 
5. Whittaker, C. F., Miklich, M. A., Patel, R. S., & Fink, J. C. (2018). Medication Safety Principles and Practice in CKD. Clinical journal of the American Society of Nephrology : CJASN, 13(11), 1738–1746. https://doi.org/10.2215/CJN.00580118
6. Kim, I. H., Kisseleva, T., & Brenner, D. A. (2015). Aging and liver disease. Current opinion in gastroenterology, 31(3), 184–191. https://doi.org/10.1097/MOG.0000000000000176
7. Mangoni, A. A., & Jackson, S. H. (2004). Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. British journal of clinical pharmacology, 57(1), 6–14. https://doi.org/10.1046/j.1365-2125.2003.02007.x
8. Giannini, O., Rizza, N., Pironi, M., Parlato, S., Waldispühl Suter, B., Borella, P., Pagnamenta, A., Fishman, L., & Ceschi, A. (2019). Prevalence, clinical relevance and predictive factors of medication discrepancies revealed by medication reconciliation at hospital admission: prospective study in a Swiss internal medicine ward. BMJ Open, 9(5). https://doi.org/10.1136/bmjopen-2018-026259 
9. American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. (2019). Journal of the American Geriatrics Society, 67(4), 674–694. https://doi.org/10.1111/jgs.15767