Understanding What are the Age-Related Changes Affecting Medications?

Older adults are twice as likely to experience medication side effects, often due to significant physiological changes. Understanding what are the age-related changes affecting medications is crucial for managing health and preventing adverse effects.

Quick Summary

The body's absorption, distribution, metabolism, and elimination of drugs are all altered with age, leading to increased drug concentrations, prolonged effects, and a higher risk of adverse reactions. These shifts require careful medication management, dose adjustments, and regular professional review to ensure safety and effectiveness.

Key Points

• Body Composition Shifts: Increased body fat and decreased total body water change how drugs are distributed, concentrating water-soluble drugs and prolonging the effects of fat-soluble drugs.

• Slower Metabolism: Reduced liver function and blood flow can increase the bioavailability of some oral drugs and prolong their clearance.

• Reduced Renal Function: The kidneys' filtering capacity naturally declines with age, leading to the accumulation of many drugs and a higher risk of toxicity.

• Increased Drug Sensitivity: Older adults often have a heightened sensitivity to certain medications, meaning lower doses may be needed to achieve the desired effect while minimizing side effects.

• Polypharmacy Risk: Taking multiple medications (polypharmacy) is more common with age and increases the likelihood of dangerous drug interactions and adverse effects.

• Need for Monitoring: Due to these changes, close monitoring, regular medication reviews, and communication with healthcare providers are essential for medication safety.

Introduction to Pharmacokinetics in Aging

As the body ages, a cascade of physiological changes occurs that can profoundly impact how medications work. These shifts affect pharmacokinetics, the study of how a drug moves through the body, which involves four key processes: absorption, distribution, metabolism, and elimination. For older adults, these changes can alter a drug's effectiveness, increase the risk of side effects, and make managing complex medication regimens challenging. Recognizing these changes is the first step toward safe and effective medication use.

Age-Related Changes in Drug Absorption

While the gastrointestinal tract has a large functional reserve, certain age-related changes can affect drug absorption, though these are often less clinically significant than other factors.

• Decreased Gastric Acid Production: A reduction in stomach acid can impair the absorption of some drugs that require an acidic environment to dissolve properly, such as calcium carbonate.
• Slower Gastric Motility: Slower movement through the digestive tract can delay the onset of action for some medications.
• Underlying Conditions and Medications: The presence of conditions like atrophic gastritis or the use of medications such as proton pump inhibitors can increase gastric pH, further altering absorption.

How Aging Affects Drug Distribution

Body composition undergoes a significant shift with age, directly influencing how drugs are distributed throughout the body.

• Decreased Total Body Water: As lean body mass and total body water decrease, water-soluble drugs like digoxin and lithium have a smaller volume of distribution. This can lead to higher-than-expected drug concentrations in the bloodstream, increasing the risk of toxicity.
• Increased Body Fat: The proportion of body fat generally increases with age. This expands the volume of distribution for lipid-soluble drugs like diazepam, causing them to accumulate in fat tissue. This accumulation can prolong the drug's half-life, leading to extended effects and a greater risk of toxicity with repeated dosing.
• Decreased Serum Albumin: Malnutrition or acute illness can lead to lower levels of serum albumin, the protein that binds to many drugs in the bloodstream. With fewer binding sites available, the concentration of active, unbound drug increases, potentially leading to toxic effects for highly protein-bound medications like phenytoin and warfarin.

Impact on Drug Metabolism and Excretion

Metabolism, primarily in the liver, and excretion, mainly by the kidneys, are the body's primary mechanisms for breaking down and removing drugs. Both processes decline with age.

Changes in Hepatic Metabolism

• Reduced Hepatic Blood Flow: Liver blood flow decreases with age, which reduces the liver's ability to metabolize certain drugs, especially those with a high first-pass metabolism.
• Altered Enzyme Activity: While some liver enzyme (Phase I) activity may decline, the effects can be variable. Phase II metabolic processes, such as glucuronidation, are generally more stable, which is why drugs metabolized by this pathway are often preferred for older adults.

Changes in Renal Excretion

• Decreased Glomerular Filtration Rate (GFR): The GFR, a measure of kidney function, declines progressively with age. This reduces the kidneys' ability to filter and eliminate drugs from the body.
• Misleading Creatinine Levels: Standard creatinine tests can be misleading in older adults because they have less muscle mass, which leads to lower creatinine production. This can make estimated kidney function appear normal even when it is not, increasing the risk of drug accumulation and toxicity for renally excreted drugs.

Altered Pharmacodynamics and Drug Sensitivity

Pharmacodynamics refers to a drug's effect on the body. With age, the body's response to drugs can change, increasing sensitivity to certain classes of medications. This means that a standard dose for a younger adult can have a much stronger, potentially adverse, effect on an older adult. Examples include an increased sensitivity to the sedative effects of benzodiazepines and the pain-relieving effects of opioids.

The Dangers of Polypharmacy

Many older adults take multiple medications for various conditions, a practice known as polypharmacy. This increases the risk of drug-drug and drug-disease interactions, compounding the challenges posed by age-related physiological changes. This can lead to a 'prescribing cascade,' where side effects from one medication are misinterpreted as a new medical condition and treated with another unnecessary drug.

Comparison: Drug Effects in Younger vs. Older Adults

Feature	Younger Adult	Older Adult
Body Composition	Higher lean body mass, higher total body water	Lower lean body mass, lower total body water; higher body fat
Drug Distribution	Water-soluble drugs distributed broadly; lipid-soluble drugs less sequestered	Water-soluble drugs have higher plasma concentration; lipid-soluble drugs accumulate in fat tissue
Drug Metabolism	More robust liver function and metabolic enzyme activity	Reduced hepatic blood flow and potentially decreased Phase I enzyme activity
Drug Excretion	Efficient renal clearance via GFR	Reduced renal clearance, increasing risk of drug accumulation
Drug Sensitivity	Standardized response to drugs	Increased sensitivity to certain drug classes (e.g., CNS depressants)
Risk of Side Effects	Lower, often more predictable	Higher due to altered pharmacokinetics and polypharmacy

Strategies for Safe Medication Management

1. Maintain a Comprehensive Medication List: Keep a list of all medications, including prescriptions, over-the-counter drugs, vitamins, and herbal supplements. Update it regularly and share with all healthcare providers.
2. Use a Single Pharmacy: Filling all prescriptions at one pharmacy allows the pharmacist to monitor for potentially harmful drug interactions.
3. Ask Questions: Always ask your doctor or pharmacist about a new medication's purpose, proper dosage, potential side effects, and what to do if you miss a dose.
4. Avoid Prescribing Cascades: Be mindful if a new symptom appears after starting a new medication. It could be a side effect, and adding another medication to treat it could be inappropriate.
5. Explore Deprescribing: In consultation with a healthcare provider, consider whether some medications are still necessary, especially those started years ago for a condition that has since resolved or changed.
6. Use Memory Aids: Utilize pill organizers, smartphone reminders, or medication schedules to stay on track, especially with complex regimens.

Conclusion

The physiological changes that accompany aging have a profound and interconnected effect on how medications are processed by the body. From shifts in body composition that alter drug distribution to declines in liver and kidney function that impede metabolism and excretion, these factors necessitate a more cautious and individualized approach to medication management. Open communication with healthcare providers, regular medication reviews, and informed self-management are vital to navigating these changes, ensuring that medications remain a source of health and not harm.

For more detailed information on managing medications as you age, visit the official FDA resource on the topic: As You Age: You and Your Medicines.

Frequently Asked Questions

What is the biggest risk for older adults taking medication?

The biggest risk is the potential for adverse drug reactions (ADRs). Age-related changes can cause medications to linger in the body longer, increasing concentrations and the chances of a harmful side effect or interaction, especially with polypharmacy.

How does reduced kidney function affect medications in seniors?

Reduced kidney function, which is common with age, impairs the body's ability to excrete drugs. This can cause drugs to accumulate to toxic levels, especially those primarily eliminated by the kidneys, such as digoxin and certain antibiotics.

Why do some medications cause more side effects in older people?

Older people may experience more side effects because of increased sensitivity to certain drugs (pharmacodynamics) and altered metabolism and excretion (pharmacokinetics). These factors mean a drug may have a stronger or longer-lasting effect than intended.

Is it true that a senior’s smaller muscle mass affects medication?

Yes. Lower muscle mass leads to lower creatinine production, a substance used to estimate kidney function. This can cause doctors to overestimate kidney function, potentially leading to medication dosages that are too high.

What is 'start low and go slow' in senior medication management?

'Start low and go slow' is a prescribing principle for older adults. It means beginning with the lowest effective dose of a medication and increasing it gradually, as needed, to minimize the risk of adverse effects.

How can I tell if a new symptom is a medication side effect?

Be suspicious if a new symptom, such as confusion, dizziness, or a change in mood, appears after starting a new medication or changing a dose. You should assume it's medication-related until proven otherwise and discuss it with a doctor.

What role does a pharmacist play in managing senior medications?

Pharmacists are crucial. They can perform medication reviews to check for potential drug interactions, educate patients on how to take medications properly, and help simplify complex regimens, especially if you use a single pharmacy.