A complex question: Why age is more than a number
For clinical and administrative purposes in the United States, an individual is often considered elderly at age 65, aligning with eligibility for Medicare benefits. However, when it comes to the safety and efficacy of medications, this chronological age is merely a starting point. A 65-year-old with multiple chronic conditions may have more significant medication risks than an 85-year-old in robust health. The true determinant is biological aging, which causes physiological changes that impact how the body processes drugs.
Age-related changes affecting medications
As we age, a number of physiological shifts occur that alter how the body handles medications. These changes fall under the two main branches of pharmacology: pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body).
Pharmacokinetic changes
- Absorption: Changes in the gastrointestinal tract, such as decreased gastric acid secretion and delayed stomach emptying, can affect how quickly drugs enter the bloodstream. While overall absorption may not change significantly, the rate can be altered. For example, drugs requiring an acidic environment for dissolution, like ketoconazole, may be poorly absorbed.
- Distribution: Body composition changes significantly with age, typically involving a decrease in total body water and lean body mass, alongside an increase in body fat. This alters the volume of distribution for different types of drugs:
- Water-soluble drugs (e.g., digoxin, lithium) have a smaller volume of distribution, leading to higher plasma concentrations and a greater risk of toxicity at standard doses.
- Fat-soluble drugs (e.g., diazepam) have a larger volume of distribution. They accumulate in fatty tissues and have a prolonged half-life, increasing the duration of action and risk of residual effects.
- Metabolism: The liver's ability to metabolize drugs often declines with age, largely due to reduced liver blood flow and volume. This is particularly true for drugs that undergo significant 'first-pass metabolism,' where a portion of the drug is metabolized by the liver before it can enter the bloodstream. Medications like propranolol and metoclopramide can have increased bioavailability, requiring lower starting doses.
- Elimination: Kidney function typically decreases with age, affecting the elimination of many medications. Because drugs are cleared more slowly, they can accumulate to toxic levels. This is a critical factor for medications with a narrow therapeutic index, such as digoxin or some antibiotics. A normal serum creatinine level in an older adult can be misleading, as their reduced muscle mass means less creatinine is produced, masking a decline in kidney function.
Pharmacodynamic changes
Pharmacodynamic changes mean older adults can have an altered sensitivity to a drug's effects. This can be an increased sensitivity (making the drug more potent) or a decreased sensitivity (making it less effective). For instance, older adults often have heightened sensitivity to central nervous system drugs like benzodiazepines, which can increase the risk of sedation and falls. Conversely, they may show a blunted response to beta-blockers, requiring careful dose titration to achieve the desired effect.
Tools and strategies for safe medication management
Given the complexities of age-related drug response, personalized care is essential. Several tools and strategies help healthcare professionals and patients manage medications safely.
The Beers Criteria
The American Geriatrics Society (AGS) Beers Criteria is a widely used resource listing potentially inappropriate medications (PIMs) for older adults. Updated regularly, the list guides healthcare providers in identifying medications that should be avoided or used with caution in geriatric patients, balancing risks against benefits. Categories include:
- Drugs to avoid: Medications with a high risk of adverse effects in older adults (e.g., certain anticholinergics and long-acting benzodiazepines).
- Drugs to use with caution: Medications that may be appropriate in some circumstances but require close monitoring.
- Drug-disease interactions: Certain medications can worsen common conditions in older adults (e.g., NSAIDs worsening heart failure).
- Drug-drug interactions: Lists combinations of medications that can be particularly harmful when used together.
- Dose adjustment based on kidney function: Reminds providers to adjust dosages for medications cleared by the kidneys.
Medication reconciliation and review
Regular medication reviews are critical, especially for older adults with polypharmacy—the use of multiple medications. A proper review involves consolidating all medications (prescription, over-the-counter, and supplements) to identify discrepancies, eliminate unnecessary drugs, and simplify complex regimens. A "brown bag" review, where the patient brings all medications to an appointment, is a highly effective method.
Deprescribing
Deprescribing is the process of tapering, reducing, or stopping medications to minimize harm and manage polypharmacy. It is a systematic process that prioritizes patient preferences and goals. For example, deprescribing a benzodiazepine in an older patient might reduce the risk of falls and cognitive impairment.
Comparison of medication response in younger vs. older adults
| Feature | Younger Adults (e.g., 25 years) | Older Adults (e.g., 75 years) |
|---|---|---|
| Body Composition | Higher lean muscle mass, more total body water. | Lower lean muscle mass, less total body water, higher body fat percentage. |
| Liver Function | Higher liver blood flow and enzymatic activity. | Decreased liver blood flow and enzymatic activity, particularly Phase I metabolism. |
| Kidney Function | Higher glomerular filtration rate (GFR). | Declining GFR, leading to reduced drug clearance. |
| Pharmacokinetics | Shorter half-life for fat-soluble drugs; longer for water-soluble. | Longer half-life for fat-soluble drugs; higher plasma concentrations for water-soluble. |
| Pharmacodynamics | Standard sensitivity to many drugs. | Altered sensitivity (often increased) to certain drug classes like CNS drugs and anticoagulants. |
| Polypharmacy Risk | Lower risk; fewer chronic conditions. | High risk; more chronic diseases and specialists prescribing. |
| Side Effect Risk | Lower overall risk. | Higher risk of adverse drug events (ADEs), which can mimic or worsen other conditions. |
Conclusion: A personalized approach is key
While the chronological age of 65 is a common reference point for categorizing older adults, it is a poor indicator for medication management alone. The physiological changes that accompany biological aging—namely altered pharmacokinetics and pharmacodynamics—are what truly matter. These changes necessitate a personalized, cautious approach to prescribing and managing medications for older adults. Tools like the Beers Criteria, regular medication reviews, and deprescribing protocols are invaluable for mitigating the increased risk of adverse drug events and improving overall health outcomes in the geriatric population. Ultimately, safe medication use is a team effort involving patients, caregivers, and informed healthcare providers who prioritize individual patient needs over a simple number.
