Which of the following factors increases the risk of adverse drug reactions (ADRs) in older adults?

Oct 14, 2025 5 min read •

Geriatrics Pharmacology Patient Safety

It is estimated that up to 30% of all hospital admissions for people aged 65 and over are medication-related, and approximately half of these could be prevented. This highlights the critical importance of understanding which of the following factors increases the risk of adverse drug reactions (ADRs) in older adults, including physiological changes, polypharmacy, and multiple chronic conditions.

Quick Summary

Several factors raise the risk of adverse drug reactions (ADRs) in older adults, such as changes in drug metabolism and clearance due to aging, the use of multiple medications (polypharmacy), and the presence of coexisting chronic diseases (multimorbidity). Other contributing factors include genetic predisposition, cognitive impairment, and specific geriatric syndromes like falls and delirium.

Key Points

Altered Pharmacokinetics: Age-related changes in organ function, such as reduced kidney and liver clearance, can cause drugs to accumulate in the body, increasing the risk of adverse effects.
Polypharmacy: Taking multiple medications (often defined as five or more) for coexisting conditions significantly raises the risk of drug-drug interactions and adverse reactions.
Multimorbidity: The presence of multiple chronic diseases can lead to drug-disease interactions and exacerbate underlying health problems, further complicating medication management.
Altered Pharmacodynamics: Older adults can have increased sensitivity to some drugs due to changes in receptor function and homeostatic mechanisms, leading to heightened effects even at therapeutic doses.
Cognitive and Functional Impairments: Conditions like dementia, poor vision, or difficulty handling medication can increase the likelihood of medication errors and non-adherence, resulting in adverse events.
Geriatric Syndromes: Symptoms of ADRs, such as falls, delirium, and cognitive decline, can mimic or worsen common geriatric syndromes, making them harder to detect and properly diagnose.
Narrow Therapeutic Index Drugs: Medications with a narrow therapeutic range, such as digoxin or warfarin, pose a greater risk of toxicity in older adults due to age-related physiological changes.

Age-Related Changes in Drug Metabolism

As individuals age, their bodies undergo physiological changes that significantly affect how they process medications. These changes, also known as altered pharmacokinetics and pharmacodynamics, are a primary reason for the increased risk of adverse drug reactions (ADRs) in older adults. These changes are not uniform and vary greatly among individuals, which adds to the complexity of prescribing medication for this population.

Impact on Pharmacokinetics (ADME)

Pharmacokinetics is the study of how drugs move through the body—specifically, their Absorption, Distribution, Metabolism, and Excretion (ADME). In older adults, age-related changes can affect all four of these processes:

Absorption: While changes in drug absorption due to aging are generally not considered clinically significant, certain factors can play a role. For example, reduced gastric acid production and slower gastric emptying can alter the absorption of some drugs.
Distribution: Older adults typically have a higher percentage of body fat and a lower proportion of total body water and muscle mass. This shift affects the distribution of drugs throughout the body. Fat-soluble drugs (e.g., diazepam) may have a larger volume of distribution and a prolonged half-life, while water-soluble drugs (e.g., digoxin) may have a smaller volume and reach higher plasma concentrations.
Metabolism: The liver's ability to metabolize drugs can decline with age due to decreased liver mass and reduced blood flow. This particularly impacts drugs that are processed by Phase 1 (oxidation) pathways. The activity of cytochrome P450 (CYP) enzymes, which are crucial for drug metabolism, can also be affected, potentially leading to drug accumulation and higher-than-intended drug levels.
Excretion: Kidney function, measured by glomerular filtration rate (GFR), also declines with age. This reduces the body's ability to excrete drugs that are cleared by the kidneys, increasing the risk of drug accumulation and toxicity, especially for medications with a narrow therapeutic index.

Impact on Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body. Older adults can have altered pharmacodynamic responses, meaning they may be more sensitive or less sensitive to a drug's effects at a given concentration. For instance, older adults may be more sensitive to the central nervous system effects of drugs like benzodiazepines and opioids, leading to increased sedation or confusion. Conversely, they may have a blunted response to some cardiovascular medications, requiring careful dose adjustments.

The Role of Polypharmacy

One of the most significant risk factors for ADRs in older adults is polypharmacy, often defined as the regular use of five or more medications. The higher the number of medications taken, the higher the risk of experiencing adverse effects. For example, the risk of an ADR may increase dramatically with the number of medications: up to 13% for two medications, 58% for five, and over 80% for seven or more.

Risks associated with polypharmacy

Drug-Drug Interactions: Taking multiple medications increases the likelihood of interactions between them, altering their effectiveness or causing unexpected side effects.
Prescribing Cascade: An ADR can be mistaken for a new medical condition, leading a clinician to prescribe another medication to treat the side effect. This creates a cycle of prescribing that further increases the risk of more ADRs.
Medication Non-Adherence: Complex medication regimens can be difficult for older adults to manage, leading to missed or incorrect doses. This can be due to forgetfulness, confusion, or difficulty handling pill bottles, especially with cognitive or sensory impairments.

Chronic Diseases and Multimorbidity

As people age, they often develop multiple chronic health conditions, a state known as multimorbidity. The risk of ADRs increases with the number of chronic diseases present.

Multimorbidity-Related Factors

Drug-Disease Interactions: A medication used to treat one condition might exacerbate another. For example, a beta-blocker prescribed for a cardiovascular condition could worsen symptoms in a patient with asthma.
Organ Dysfunction: Chronic conditions, particularly those affecting the kidneys or liver, can impair the body's ability to metabolize and clear drugs. Since these organs are crucial for drug elimination, their dysfunction significantly increases the risk of toxicity.

Geriatric Syndromes and Impairments

Geriatric syndromes are common health conditions in older adults that can be both a cause and a consequence of ADRs. These syndromes include falls, delirium, and cognitive impairment.

Falls: Many medications, such as sedatives, antidepressants, and antihypertensives, can increase the risk of falls due to side effects like dizziness, sedation, and orthostatic hypotension.
Delirium: Drugs with anticholinergic properties, sedatives, and opioids can precipitate or worsen delirium, a state of acute confusion that is often an unrecognized ADR in older adults.
Cognitive Impairment: Patients with cognitive issues, such as dementia, may have trouble managing their medications correctly, increasing the risk of errors. Cognitive and sensory impairments can also lead to underreporting of ADRs.

Comparison of Key Risk Factors


Feature	Age-Related Physiological Changes	Polypharmacy	Chronic Diseases (Multimorbidity)
Mechanism	Altered pharmacokinetics and pharmacodynamics (e.g., reduced renal/hepatic function, altered drug sensitivity).	Increased number of medications leading to higher risk of drug-drug interactions.	Drug-disease interactions; impaired organ function from disease states.
Associated Risks	Drug accumulation, prolonged drug effects, increased sensitivity to some drug classes.	Higher chance of drug interactions, prescribing cascades, medication non-adherence.	Organ failure contributing to poor drug clearance; drugs for one condition worsening another.
Likely ADRs	Sedation with CNS drugs, bleeding with warfarin, digoxin toxicity, etc..	Gastrointestinal bleeding with NSAIDs and anticoagulants, cognitive impairment, falls.	Heart failure exacerbation, worsening asthma, hypoglycemic episodes.
Detection Challenge	Variable presentation, often mistaken for normal aging or disease progression.	Requires careful medication reconciliation and review of all prescribed drugs, OTCs, and supplements.	Symptoms can overlap with underlying chronic conditions, making causality hard to determine.
Mitigation Strategy	Start with low doses, titrate slowly, and monitor closely. Consider drugs with simpler metabolism.	Deprescribing, medication reviews, simplifying medication schedules.	Comprehensive geriatric assessment, careful consideration of drug-disease interactions.

Conclusion

Several interconnected factors contribute to the heightened risk of adverse drug reactions in older adults. Foremost among these is the aging process itself, which changes how the body absorbs, distributes, metabolizes, and excretes medications. This is compounded by polypharmacy, the use of multiple medications, which dramatically increases the likelihood of harmful drug interactions. Furthermore, the presence of multiple chronic diseases and the development of geriatric syndromes like falls and delirium significantly amplify the risk. A holistic approach that includes careful prescribing practices, regular medication reviews, and considering the patient's overall health and functional status is essential for preventing these avoidable harms. By recognizing and proactively addressing these factors, healthcare providers can improve medication safety and enhance the quality of life for older adults.

Authoritative Sources

Health in Aging Foundation: A resource providing health information and aging tips for older adults and caregivers.
The Merck Manuals, Geriatrics Section: A comprehensive medical reference with detailed information on pharmacologic therapy in older adults.
National Institute on Aging: A reputable source for news and information on polypharmacy and deprescribing.

Frequently Asked Questions

Polypharmacy is the regular use of multiple medications, typically five or more. It is a major risk factor for older adults because it increases the likelihood of harmful drug-drug interactions, complicates medication regimens, and can lead to overmedication and increased side effects.

As we age, both kidney and liver function can decline. Since these organs are responsible for metabolizing and clearing drugs from the body, their reduced efficiency can cause medications to build up to toxic levels, increasing the risk of adverse reactions.

Yes, chronic diseases, a condition known as multimorbidity, increase the risk of ADRs. The risk rises with the number of coexisting diseases. This can be due to drug-disease interactions, where a medication for one condition negatively affects another, or because certain diseases impair drug metabolism.

Common signs of an ADR in older adults can be non-specific and easily mistaken for other conditions. They include confusion, drowsiness, falls, dizziness, gastrointestinal problems, and cognitive decline. These symptoms often mimic or worsen existing geriatric syndromes.

Certain medications, such as those with strong anticholinergic effects, opioids, and sedatives, should be used with caution or avoided in older adults due to increased sensitivity and a higher risk of adverse effects like falls and confusion. Tools like the Beers Criteria help identify potentially inappropriate medications for this age group.

Older adults can experience altered pharmacodynamic responses, meaning their bodies may have a different, often heightened, reaction to drugs. For instance, they may feel stronger sedative effects from medications like morphine, even at standard doses, due to changes in the central nervous system.

Strategies to improve medication management include regular medication reviews, simplifying complex regimens, and deprescribing (reducing or stopping unnecessary medications). Enhanced communication between healthcare providers, patients, and caregivers is crucial for preventing medication errors and identifying potential ADRs early.

References

Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice. Always consult a qualified healthcare provider regarding personal health decisions.