Why Are Older Adults More Susceptible to Adverse Reactions?
Instead of being less susceptible, older adults face a higher risk of adverse drug reactions (ADRs) for several interconnected reasons. The aging process involves complex changes in the body that alter how medications are absorbed, distributed, metabolized, and eliminated. This is further compounded by the presence of multiple chronic conditions and the use of numerous medications, a phenomenon known as polypharmacy.
Age-Related Physiological Changes
Pharmacokinetics describes how the body affects a drug, covering its absorption, distribution, metabolism, and excretion. Pharmacodynamics refers to how the drug affects the body. Both are altered in older adults, increasing the risk of adverse reactions.
- Altered Drug Distribution: With age, body composition shifts, with an increase in body fat and a decrease in total body water and lean muscle mass. This has different effects on medication distribution:
- Lipid-soluble drugs: Medications stored in fat (e.g., diazepam, some antidepressants) have a larger volume of distribution and a longer half-life, meaning they stay in the body longer and can accumulate to toxic levels.
- Water-soluble drugs: These drugs (e.g., digoxin, lithium) have a smaller volume of distribution, leading to higher plasma concentrations and a greater risk of toxic effects at standard doses.
- Slower Metabolism and Excretion: The liver and kidneys play crucial roles in breaking down and removing drugs from the body. Their efficiency often declines with age.
- Reduced Liver Function: Decreased liver mass and blood flow slow down drug metabolism, especially for drugs metabolized by Phase I enzymes.
- Reduced Kidney Function: Glomerular filtration rate (GFR) steadily decreases with age, impairing the kidneys' ability to excrete drugs and increasing the risk of drug accumulation and toxicity.
- Increased Drug Sensitivity: Older patients can have an exaggerated response to certain medications even at normal plasma concentrations due to changes in receptor affinity and homeostatic mechanisms. For instance, older adults are more sensitive to central nervous system (CNS) depressants like benzodiazepines, which increases the risk of sedation, falls, and confusion.
The Risks of Polypharmacy and Comorbidities
Older adults often have multiple chronic diseases, which leads to polypharmacy—the regular use of multiple medications, typically five or more. This creates a complex and hazardous medication regimen.
- Drug-Drug Interactions: The more medications a patient takes, the higher the chance of a drug-drug interaction. One medication can affect how another is metabolized or eliminated, leading to higher drug levels and potential toxicity.
- Drug-Disease Interactions: A medication prescribed for one condition might exacerbate another pre-existing condition. For example, a nonsteroidal anti-inflammatory drug (NSAID) prescribed for arthritis could worsen heart failure or kidney disease.
- Prescribing Cascades: This occurs when a new medication is prescribed to treat a new symptom, which is actually an adverse effect of another medication. The cycle can continue, leading to an increasing and often unnecessary medication burden.
Practical Steps to Mitigate Adverse Reactions
Comparison of Adverse Reaction Factors in Older vs. Younger Adults
| Feature | Older Adults (65+) | Younger Adults (<65) |
|---|---|---|
| Incidence of ADRs | Significantly higher | Lower |
| Hospitalizations due to ADRs | 4 to 7 times higher; often more serious | Lower rates |
| Polypharmacy Risk | High; use of 5+ meds is common | Lower; typically fewer chronic conditions |
| Drug Metabolism (Liver) | Often decreased efficiency | Generally robust |
| Drug Excretion (Kidneys) | Decreased GFR common | Generally robust |
| Drug Sensitivity | Often increased, especially for CNS drugs | Less sensitive |
| Common Drug Classes Involved | Anticoagulants, cardiovascular drugs, psychotropics | Varies; fewer complex interactions |
Strategies to Reduce Risk in Older Patients
- Comprehensive Medication Review: Healthcare providers should regularly and systematically review all medications, including prescriptions, over-the-counter drugs, and supplements. This can identify discontinued, inappropriate, or conflicting medications.
- Deprescribing: A careful, systematic process of reducing or stopping unnecessary or potentially harmful medications is crucial. This is especially important for drugs listed on tools like the Beers Criteria, which identify medications that are potentially inappropriate for older adults.
- Lower Doses and Slower Titration: For many medications, especially those that act on the central nervous system or have narrow therapeutic windows, starting at a lower dose and increasing it gradually is recommended for older patients.
- Patient Education and Engagement: Patients and caregivers should be educated on how to recognize potential adverse effects. Encouraging patients to be active participants in their medication management, such as using a pill box or calendar, can improve adherence and safety.
- Monitoring: Regular monitoring of organ function (e.g., using creatinine clearance to estimate GFR instead of serum creatinine) is vital for older adults, as lab values may be misleading. For medications with a narrow therapeutic index, monitoring blood levels can prevent toxicity.
Conclusion
Contrary to the idea that older adults are less likely to experience adverse reactions, they are, in fact, at a significantly higher risk compared to younger patients. This vulnerability is not a simple consequence of age but results from a complex interplay of physiological changes, multiple chronic conditions, and the often unavoidable necessity of polypharmacy. The altered pharmacokinetics and pharmacodynamics in older bodies, coupled with an increased potential for drug-drug and drug-disease interactions, make them a special population in pharmacological terms. By implementing proactive strategies such as regular medication reviews, deprescribing, and close monitoring, healthcare providers can mitigate these risks and improve patient safety and outcomes. Education and close communication with patients and their caregivers are also indispensable tools in preventing adverse drug events in this vulnerable population.
