Increasing prescription drug use trends in the United States affects patients across all ages, but especially the geriatric patient. As patients age, they are at increased risk for adverse events owing to natural changes in body composition and organ function, increased sensitivity to medications, and a higher chance of adverse events from drug–drug interactions and polypharmacy. Falls are common and can increase morbidity and mortality. To mitigate falls, it is imperative to have a comprehensive approach to screening home medication lists, be aware of and avoid high-risk medications, and deprescribe agents that are potentially inappropriate for this patient population.
Key points
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Geriatric patients are at increased risk for falls owing to prescription medications and polypharmacy.
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Several tools are available to highlight high-risk medications in the geriatric pharmacy.
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Patients with polypharmacy or high-risk medications should be screened for opportunities to remove potentially inappropriate medications, select alternative agents, or adjust doses to improve safety.
Case
Pertinent history: a 70-year-old woman presents for evaluation of a witnessed fall while walking across her living room. Per the spouse, she had no head trauma or loss of consciousness and did not trip on any objects before the fall. Over the past week, she has been suffering from muscle spasm and pain in her lower back for which she was seen in the emergency department. Her spouse noted that she has been less active and more fatigued than usual over the past 2 days.
Past medical history: hypertension, hyperlipidemia, hypothyroidism, chronic kidney disease.
Surgical history: tubal ligation, hernia repair.
Medications: lisinopril 5 mg/d, metoprolol tartrate 25 mg twice daily, atorvastatin 20 mg/d, ezetimibe 10 mg/d, levothyroxine 88 μg daily, tramadol 50 mg every 6 hours as needed for pain, diazepam 10 mg every 8 hours as needed for muscle spasms.
Family history: breast cancer in mother; diabetes and hypertension in sister and father.
S history: drinks 1 to 2 alcoholic beverages per week socially, no tobacco or illicit substance use.
Pertinent physical examination: Height: 60 inches; weight: 50 kg; temperature: 36.7˚C; blood pressure: 128/80 mm Hg; heart rate 85 beats per minutes; respiratory rate 16 breaths per minute; oxygen saturation on room air 98%.
General: slow to respond to questions, fatigued, alert and oriented ×3.
Head, eyes, ears, nose, and throat: pupils equal, round, and reactive to light, mucous membranes slightly dry.
Neck: full range of motion, no pain or tenderness.
Cardiovascular: regular rhythm, no murmurs, rubs, or gallops; all pulses equal.
Pulmonary: clear lungs, no wheezing, rales, or rhonchi.
Abdominal: soft, nontender, nondistended, slow bowel sounds.
Neurologic: 5/5 strength and normal sensation in all 4 extremities, tenderness noted on the lumbar spine.
Musculoskeletal: full range of motion, no edema, no deformities of the extremities.
Skin: small abrasion and bruising to left shin.
Diagnostic testing: A workup for the fall was initiated.
| WBC | 10.4 K/mcL |
|---|---|
| Hgb | 10.6 g/dL |
| Hct | 40.1% |
| Plt | 260 K/mcL |
| Na | 140 mmol/L |
| K | 4.2 mmol/L |
| Cl | 108 mmol/L |
| CO 2 | 23 mmol/L |
| Glucose | 98 mg/dL |
| BUN | 18 mg/dL |
| Creatinine | 1.5 mg/dL |
| Lactate | 1.2 mmol/L |
| Troponin | <0.02 ng/mL |
| Ammonia | 12 mmol/L |
| aPTT | 25 s |
| PT | 1.1 |
| INR | 14.7 s |
Electrocardiogram: normal sinus rhythm, no signs of ischemia or ectopy.
Chest radiograph: normal.
Head computed tomography scan: no acute intracranial abnormalities.
Lumbar spine computed tomography scan : degenerative changes of the lumbar spine, no fracture or dislocation.
Clinical Course
A workup was promptly initiated for her fall, including basic laboratory assessments, coagulation tests, electrocardiogram, and imaging with a chest radiograph and a computed tomography scan of the head and lumbar spine. The only abnormality was her renal function with a calculated creatinine clearance of 28 mL/min, which is consistent with her chronic kidney disease. She had no acute abnormalities on imaging.
Upon further questioning, she recently injured her back while working in her garden. She “did not want an opioid medication” so the emergency department physician started her on tramadol for pain in addition to diazepam for muscle spasms. She had been taking these medications around the clock as prescribed for the past 3 days.
Learning points
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As patients age, they experience changes in their pharmacokinetic and pharmacodynamic responses to medications. This change can increase a patient’s overall sensitivity and the risk of adverse events. Dose adjustments or alternative agent selection may be necessary to mitigate the risk.
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Polypharmacy is commonly defined as the use of five or more medications at a time and taking more medications than clinically appropriate for the patient’s underlying clinical condition.
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Overall prescription numbers have increased by more than 85% in the past two decades disproportionately to the 21% increase in overall US population. The number of patients with polypharmacy also increased from 12.8% to 39.0% during the same time frame. In patients greater than 65 years old, 40% take five to nine medications per day and 18% take more than ten.
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This increase in medication use can be problematic owing to drug–drug interactions, the potential for adverse drug events, added cost, and, most important, increased hospitalization and mortality. ,
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Several tools are available to help avoid inappropriate medications therapy and polypharmacy in the geriatric patient.
Physiology and Pathophysiology
With advancing age, patients experience several changes with respect to pharmacokinetics and pharmacodynamics that generally cause medications to be more potent and have a longer duration of action than predicted compared with their younger counterparts. ( Table 1 ).
| Pharmacokinetic/Pharmacodynamic Change | Effect on Medications | Medication Examples |
|---|---|---|
| Decreased muscle mass and circulating plasma proteins | Highly protein-bound medications may have increased serum concentrations. | Verapamil, haloperidol, propranolol |
| Increased total body fat | Lipophilic medications may have lower plasma concentrations and prolonged duration of effect. | Diazepam, midazolam, lorazepam |
| Decreased water concentration | Hydrophilic medications may have increased plasma concentrations and effect. | Lithium, digoxin |
| Decreased renal function | Decreased clearance of medication eliminated by the kidneys. | Sulfamethoxazole-trimethoprim, ciprofloxacin, apixaban, rivaroxaban, enoxaparin, tramadol, gabapentin, famotidine |
| Decreased hepatic CYP enzyme capacity and lower hepatic blood flow | Reduced clearance of medication metabolized by CYP enzymes or cleared by the liver including first pass metabolism. Decreased conversion of prodrugs. | Propranolol, verapamil, theophylline, risperidone, carbamazepine |
Renal insufficiency
Chronic kidney disease is prevalent in 15% (37 million people) of the US adult population and is more common in persons aged 65 or older. Many medications with renal clearance require adjustment for chronic kidney disease to prevent adverse events and/or accumulation of the medication.
Creatinine clearance as calculated by the Cockcroft-Gault equation is the gold standard for assessing renal function as it relates to medication safety. Most package insert dose adjustments are based on this formula. Most medications cleared by the kidneys do not require dose adjustment until the creatinine clearance is less than 60 mL/min. Each medication should be checked with a reliable drug reference as the cutoffs vary.
Cockcroft-Gault equation for creatinine clearance:
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