Which combination places older adults at a higher risk for adverse drug events?

According to the Centers for Disease Control and Prevention, older adults account for a disproportionate number of emergency hospitalizations for adverse drug events (ADEs), with unintentional overdoses being a leading cause. Knowing which combination places older adults at a higher risk for adverse drug events is crucial for minimizing these risks and promoting safer medication practices.

Quick Summary

The combination of polypharmacy (taking five or more medications) and central nervous system (CNS)-active drugs, such as opioids and benzodiazepines, presents a significantly higher risk for adverse drug events in older adults due to age-related changes in metabolism and increased sedation effects. These effects are further compounded by multiple prescribers and the use of over-the-counter medications.

Key Points

• Polypharmacy is a leading risk factor: Taking five or more medications, a condition known as polypharmacy, drastically increases the risk of adverse drug events and dangerous drug interactions in older adults.

• CNS-active drug combinations are highly dangerous: The combination of central nervous system (CNS) depressants like opioids and benzodiazepines creates additive sedative effects, significantly raising the risk of respiratory depression, falls, and overdose.

• Age-related changes in metabolism increase drug toxicity: Decreased kidney and liver function in older adults can slow drug clearance, allowing medications to build up to toxic levels and cause adverse effects.

• Anticholinergic burden carries specific risks: The cumulative effect of multiple medications with anticholinergic properties can impair cognitive function, cause urinary retention, and increase the risk of falls.

• Communication and medication review are vital: To mitigate risks, older adults should use a single pharmacy and ensure all healthcare providers are aware of their complete medication list, including over-the-counter drugs and supplements.

• Deprescribing is a critical strategy: Healthcare providers can reduce unnecessary risk by proactively discontinuing medications or adjusting dosages when the potential harms outweigh the benefits, a process known as deprescribing.

Understanding the Increased Risk in Older Adults

Older adults are uniquely susceptible to adverse drug events (ADEs) due to several physiological and systemic factors. As the body ages, changes occur in how it absorbs, distributes, metabolizes, and excretes medications—a process known as pharmacokinetics. Renal and hepatic functions can decline, causing drugs to stay in the system longer and accumulate to toxic levels. Additionally, age-related changes in pharmacodynamics—how a drug affects the body—can make older adults more sensitive to a medication's effects, especially those affecting the central nervous system.

Beyond biological changes, systemic issues contribute significantly. The prevalence of multimorbidity, or multiple chronic conditions, means older adults often require multiple medications simultaneously, a situation known as polypharmacy. Each additional medication increases the risk of dangerous drug-drug interactions exponentially. Complex medication regimens are also difficult to manage, increasing the likelihood of errors, non-adherence, or unintentional overdoses. The use of multiple prescribers who may be unaware of the full medication list is another critical risk factor.

The Dangers of Polypharmacy

Polypharmacy, defined as the routine use of five or more medications, is a widespread issue in senior care. While often necessary to manage complex health needs, it creates a web of potential interactions that are difficult to predict and manage. A prescribing cascade is a dangerous cycle where a new drug is prescribed to treat the side effects of another drug, with the side effect mistakenly identified as a new medical condition. Common symptoms of polypharmacy-related ADEs, such as dizziness, confusion, and fatigue, are often incorrectly attributed to the aging process itself rather than the medication regimen. This can lead to further unnecessary prescriptions, exacerbating the problem.

High-Risk Drug Combinations to Avoid

Certain classes of drugs, particularly when combined, pose an elevated risk for serious adverse events in older adults:

• Opioids and Benzodiazepines: This combination is notoriously dangerous due to its additive sedative effects. Both classes act on the central nervous system (CNS) and can cause severe drowsiness, respiratory depression, and increased risk of falls and confusion. This combination significantly increases the risk of life-threatening overdose.
• Multiple Anticholinergic Medications: Many common medications, including some antidepressants, antihistamines, and bladder control drugs, have anticholinergic properties. Using multiple anticholinergics can lead to confusion, constipation, urinary retention, and increased fall risk due to dizziness and blurred vision.
• Anticoagulants and NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, when combined with blood thinners such as warfarin, can dramatically increase the risk of gastrointestinal bleeding. This synergistic toxicity is far greater than the risk from either drug alone.
• Antidiabetics and Other Meds: Combining hypoglycemic agents (like insulin or sulfonylureas) with other drugs can lead to dangerous hypoglycemia (low blood sugar). Unintentional overdoses of insulin and other oral hypoglycemic agents are a major cause of emergency hospitalizations for ADEs in older adults.

Strategies for Safer Medication Management

Minimizing the risk of ADEs requires a proactive approach from both healthcare providers and older adults or their caregivers. Deprescribing—the intentional discontinuation of unnecessary or harmful medications—is a critical strategy.

1. Comprehensive Medication Review: Bring all medications, including over-the-counter drugs, vitamins, and supplements, to every doctor's appointment. This allows healthcare providers to perform a "brown bag review" to identify redundancies, expired medications, and potential interactions.
2. Use Screening Tools: Doctors can use validated tools like the American Geriatrics Society (AGS) Beers Criteria and the STOPP/START criteria to identify potentially inappropriate medications and areas for deprescribing.
3. Use a Single Pharmacy: Filling all prescriptions at one pharmacy helps ensure the pharmacist has a complete record and can perform drug interaction checks.
4. Simplify Dosing Schedules: Simplifying complex medication schedules can help improve adherence and reduce the risk of errors.
5. Monitor for Side Effects: Be vigilant for new or worsening symptoms after a medication change, as these may be signs of an ADE. Report any concerns to a healthcare provider.

Medication Risk Factors in Older Adults: A Comparison

Risk Factor	Description	Impact on ADE Risk	Common Examples of Impacted Drugs
Polypharmacy	Taking five or more medications regularly.	Drastically increases risk of drug-drug interactions and medication errors; higher chance of hospitalization.	CNS drugs, anticoagulants, NSAIDs
Central Nervous System (CNS) Depressants	Combining drugs that affect the brain, such as opioids, benzodiazepines, and some antidepressants.	Additive sedative effects lead to confusion, dizziness, impaired balance, and higher risk of falls and respiratory depression.	Opioids, benzodiazepines, tricyclic antidepressants
Altered Pharmacokinetics	Age-related decline in kidney and liver function.	Leads to slower drug clearance, accumulation of medication, and higher risk of toxicity.	Digoxin, warfarin, benzodiazepines
Anticholinergic Burden	Combining multiple medications with anticholinergic side effects.	Cumulative effects increase risk of cognitive impairment, urinary retention, and constipation.	Certain antidepressants, antihistamines, and bladder medications
Multiple Prescribers	Seeing multiple doctors who are not communicating with one another.	Lack of oversight increases risk of prescribing duplications and harmful interactions; each additional prescriber raises ADE risk by 30%.	All medications

Communicating with Your Healthcare Providers

Effective communication is the cornerstone of preventing ADEs. Older adults, along with their caregivers, should actively participate in their healthcare decisions. When discussing a new medication, ask about potential side effects and how it might interact with existing prescriptions, over-the-counter remedies, and supplements. For those with multiple chronic conditions, it's beneficial to have one primary care physician who coordinates all care and has the most complete picture of the patient's health.

For more in-depth information and resources on medication management for seniors, consult authoritative sources like the National Institute on Aging.

The Takeaway

Managing medications can be complex, but being aware of the specific risks associated with certain drug combinations can significantly improve safety outcomes for older adults. The combined effects of polypharmacy and CNS-active drugs, along with age-related physiological changes, pose the most significant threat. Regular medication reviews, open communication, and careful monitoring are essential steps toward safer and healthier aging. Prioritizing medication safety is not just about avoiding harm—it's about enhancing the overall quality of life for older adults.

Frequently Asked Questions

What is polypharmacy and why is it a risk for older adults?

Polypharmacy is the use of five or more medications simultaneously. It increases the risk for older adults because it raises the probability of harmful drug-drug interactions, complicates medication management, and increases the chance of medication errors and unintentional overdoses.

Why are combinations of opioids and benzodiazepines so dangerous for seniors?

Opioids and benzodiazepines are both CNS depressants. When combined, their sedative effects are amplified, leading to excessive drowsiness, impaired balance, slowed breathing, and a significantly higher risk of falls, injury, and fatal overdose.

How do age-related body changes affect medication safety?

As the body ages, changes in organ function, particularly the kidneys and liver, can slow down the metabolism and excretion of drugs. This means medications can accumulate in the body to toxic levels, even at what would be considered a normal dose for a younger person.

What is a prescribing cascade?

A prescribing cascade occurs when an adverse drug reaction is misinterpreted as a new medical condition, leading to the prescription of another medication to treat the side effect. This creates a vicious cycle of unnecessary medication and compounded side effects.

What are anticholinergic medications and why should seniors be cautious?

Anticholinergic medications block acetylcholine, a neurotransmitter, affecting the brain and other organs. Many common drugs have these properties, and cumulative exposure can cause side effects like confusion, memory problems, urinary retention, and increased fall risk in older adults.

How can caregivers and older adults help prevent adverse drug events?

Caregivers and older adults can help prevent ADEs by keeping an accurate and complete medication list, including all OTCs and supplements, and sharing it with every doctor. Using a single pharmacy and monitoring for new side effects are also important steps.

What is deprescribing?

Deprescribing is the process of identifying and safely stopping or reducing medications that are no longer necessary or may be causing harm. It helps to simplify a regimen and improve the patient's overall health and quality of life.