Why are older adults likely to experience more problems with relatively small amounts of medications?

According to the Centers for Disease Control and Prevention, older patients are twice as likely to visit the emergency room due to adverse drug events. The key reason for this vulnerability is that an aging body processes medications differently, making older adults likely to experience more problems with relatively small amounts of medication.

Quick Summary

Age-related physiological changes affect how the body absorbs, distributes, metabolizes, and excretes drugs, causing medications to build up to higher, potentially toxic, levels. Changes in body composition, declining liver and kidney function, and increased drug sensitivity all contribute to this heightened risk, which is often exacerbated by polypharmacy.

Key Points

• Altered Pharmacokinetics: Age-related changes in absorption, distribution, metabolism, and excretion cause medications to behave differently in an older person's body.

• Reduced Organ Function: A decline in kidney and liver function is a primary reason drugs are cleared more slowly, leading to accumulation and higher concentrations in the body.

• Increased Drug Sensitivity: Older adults have heightened sensitivity to many drugs, particularly those affecting the central nervous system and cardiovascular system, resulting in stronger effects and more side effects.

• Body Composition Changes: With less total body water and more fat tissue, fat-soluble drugs accumulate more and water-soluble drugs become more concentrated.

• Polypharmacy Risks: Taking multiple medications increases the risk of adverse drug-drug interactions and side effects, amplifying the danger posed by altered drug processing.

• Importance of Vigilance: Proper medication management, including regular reviews by a healthcare provider and maintaining a comprehensive medication list, is critical to minimizing risks.

Understanding Pharmacokinetics: What the Body Does to the Drug

Pharmacokinetics describes how a drug moves through the body, from absorption to eventual excretion. In older adults, age-related changes significantly alter this process, causing even small doses of medication to have a magnified and prolonged effect. This can increase the risk of side effects and adverse reactions.

Altered Absorption

While absorption changes are often not clinically significant, there are some factors at play:

• Slower Gastric Motility: Slower stomach emptying can affect the rate at which some drugs are absorbed.
• Decreased Splanchnic Blood Flow: A reduction in blood flow to the digestive tract can impact drug uptake.
• Reduced Gastric Acid: A decrease in stomach acid, more common with age, can affect the absorption of certain medications.

Changes in Drug Distribution

As the body ages, its composition changes, with a decrease in total body water and lean body mass and an increase in fat tissue. These changes dramatically affect how drugs are distributed throughout the body.

• Water-Soluble Drugs: Medications like digoxin and lithium distribute in a smaller volume of water, leading to higher concentrations in the bloodstream.
• Fat-Soluble Drugs: Medications like diazepam and other benzodiazepines accumulate in the increased fat tissue, which can prolong their half-life and increase the risk of toxicity.
• Protein Binding: Reduced serum albumin levels, often seen in older adults due to malnutrition or illness, mean there are fewer proteins for drugs to bind to. This increases the concentration of active, or "free," drug in the bloodstream, raising the risk of toxic effects for highly protein-bound medications like warfarin and phenytoin.

Impaired Metabolism

The liver's ability to metabolize drugs declines with age due to decreased liver size and reduced blood flow. This means drugs are processed more slowly and stay in the body longer.

• First-Pass Metabolism: For drugs that are significantly metabolized by the liver before entering circulation (first-pass metabolism), a diminished liver function leads to higher systemic drug levels.
• Phase I and Phase II Metabolism: The liver's two-phase detoxification system is also affected. Phase I metabolism (oxidation) is generally more impacted by age, while Phase II (conjugation) is more stable. For this reason, healthcare providers often prefer drugs metabolized via the more stable Phase II pathway, such as lorazepam, over those reliant on Phase I, like diazepam.

Slowed Excretion

Kidney function typically declines with age, with a reduction in glomerular filtration rate (GFR). Since the kidneys are responsible for clearing many drugs from the body, this reduction in function means drugs are eliminated more slowly, leading to drug accumulation and potential toxicity.

Understanding Pharmacodynamics: What the Drug Does to the Body

Pharmacodynamics is the study of how drugs affect the body. In older adults, changes in organ systems and receptor sensitivity can increase a person's response to a drug, leading to a greater effect—both therapeutic and adverse—even at the same blood concentration as a younger person.

Increased Central Nervous System (CNS) Sensitivity

Many drugs that act on the brain and nervous system, such as sedatives, antidepressants, and opioids, can cause stronger effects in older adults. This can result in increased drowsiness, dizziness, confusion, and a higher risk of falls.

Altered Cardiovascular Response

Older adults have a reduced ability to compensate for changes in blood pressure due to medications. This can lead to significant drops in blood pressure (orthostatic hypotension) when standing, increasing the risk of dizziness and falls.

The Challenge of Polypharmacy and Drug Interactions

Older adults often manage multiple chronic conditions and take several medications simultaneously—a phenomenon known as polypharmacy. This significantly increases the risk of adverse drug reactions and dangerous drug-drug interactions, where one medication can affect how another is processed in the body.

Comparison of Drug Processing by Age

Process	Young Adults	Older Adults
Body Composition	Higher lean body mass and total body water, lower fat.	Lower lean body mass and total body water, higher fat.
Drug Distribution	Water-soluble drugs are more diluted; fat-soluble drugs have smaller storage.	Water-soluble drugs become more concentrated; fat-soluble drugs have increased volume and longer half-life.
Liver Metabolism	Robust liver function and blood flow efficiently metabolize drugs.	Decreased liver mass and blood flow slow drug metabolism.
Kidney Excretion	Efficient renal clearance rapidly removes drugs from the body.	Declining kidney function and GFR slow drug elimination.
Drug Sensitivity	Standard therapeutic response to drugs.	Increased sensitivity, especially to CNS and cardiovascular drugs.

Best Practices for Senior Medication Management

For older adults and their caregivers, understanding these challenges is the first step toward safer medication use. Collaborative medication management is key to minimizing risks.

1. Keep a Comprehensive List: Maintain a complete and updated list of all medications, including prescriptions, over-the-counter drugs, vitamins, and supplements. Share this list with every healthcare provider.
2. Use a Single Pharmacy: Filling all prescriptions at one pharmacy allows the pharmacist to monitor for potential drug interactions and side effects.
3. Regular Medication Reviews: Schedule regular reviews with a healthcare professional to reassess medication needs and simplify the regimen. This process, known as 'deprescribing,' is a critical way to reduce the risks associated with polypharmacy.
4. Start Low, Go Slow: A core principle in geriatric medicine is to start with the lowest possible dose and increase it gradually based on the patient's response.
5. Be Aware of High-Risk Medications: Certain medications, such as benzodiazepines, anticholinergics, and NSAIDs, are known to pose higher risks for older adults. The American Geriatrics Society Beers Criteria provides a list of potentially inappropriate medications for seniors.

Conclusion

Older adults' heightened sensitivity to medication is a complex issue driven by physiological changes in pharmacokinetics and pharmacodynamics. Reduced kidney and liver function, altered body composition, and increased receptor sensitivity cause medications to build up in the body and produce stronger effects. Combined with the prevalence of polypharmacy, these factors create a significant risk for adverse drug reactions, even at seemingly small doses. Proactive medication management, including regular reviews and communication with healthcare providers, is essential for ensuring medication safety and promoting healthy aging.

Frequently Asked Questions

What is the primary reason why older adults are more susceptible to medication problems?

The primary reason is the body's altered ability to process drugs due to age-related changes, particularly a decline in liver and kidney function. This leads to medications staying in the body longer and accumulating to higher, potentially toxic, levels.

How does reduced kidney function affect medication in older adults?

As kidney function declines with age, the body's ability to filter and excrete drugs from the bloodstream is reduced. This can cause medications that are primarily eliminated by the kidneys to build up to toxic levels, especially those with a narrow therapeutic index.

What does 'polypharmacy' mean and how does it increase medication risks for seniors?

Polypharmacy is the use of multiple medications at the same time. It increases medication risks for older adults by heightening the potential for dangerous drug-drug interactions, adverse side effects, and issues with adherence.

Why are medications that affect the brain, like sleeping pills, riskier for older adults?

Older adults have an increased sensitivity to drugs that act on the central nervous system, such as sleeping pills and tranquilizers. This can lead to enhanced side effects like drowsiness, confusion, and a greater risk of falls, even at normal doses.

How do changes in body fat and water impact medication in seniors?

With age, older adults tend to have more body fat and less total body water. This means water-soluble medications become more concentrated, and fat-soluble medications accumulate in the body's fatty tissues, prolonging their effect and increasing toxicity risk.

What is the "start low, go slow" approach to medication for seniors?

"Start low, go slow" is a prescribing principle in geriatric medicine where healthcare providers begin with a lower-than-normal dose for an older patient and gradually increase it. This helps manage the patient's response and minimize side effects while still achieving the desired therapeutic effect.

What is the Beers Criteria and how can it help manage medication risks for seniors?

The Beers Criteria is a list developed by the American Geriatrics Society that identifies potentially inappropriate medications for older adults. It serves as a guide for healthcare professionals to help avoid drugs that may pose higher risks than benefits in this population.