What are physiological changes of aging that impact medication administration?

Oct 28, 2025 3 min read •

Geriatrics Pharmacology Patient Safety

According to the FDA, older adults are more susceptible to adverse drug reactions and harmful drug interactions due to normal body changes. Understanding what are physiological changes of aging that impact medication administration is crucial for ensuring medication safety and efficacy in this population, as declining organ function and altered body composition affect how the body handles drugs.

Quick Summary

Age-related physiological changes significantly alter how the body processes medications, impacting absorption, distribution, metabolism, and excretion. These changes can increase the risk of toxicity and reduce drug effectiveness, making individualized dosing and careful monitoring essential for older adults.

Key Points

Altered Pharmacokinetics: Aging changes how drugs are absorbed, distributed, metabolized, and excreted, altering therapeutic effects and risks.
Renal Function Decline: A reduced glomerular filtration rate (GFR) with age is a primary factor leading to slower drug clearance and a higher risk of toxicity from renally excreted drugs.
Body Composition Shifts: Increased body fat and decreased total body water alter drug distribution, causing lipid-soluble drugs to accumulate and water-soluble drugs to reach higher concentrations.
Increased Drug Sensitivity: Changes in drug receptors and homeostatic mechanisms can increase an older adult's sensitivity to certain medications, such as central nervous system depressants, raising the risk of side effects like confusion and falls.
Impaired Hepatic Metabolism: Decreased liver blood flow and enzyme activity can impair the metabolism of certain drugs, particularly those with high first-pass metabolism, leading to increased bioavailability and higher plasma concentrations.
Clinical Dosing Strategy: A "start low and go slow" dosing approach is crucial to accommodate age-related changes and minimize adverse drug reactions.

Age-Related Changes in Pharmacokinetics: The Body’s Handling of Drugs

Pharmacokinetics describes how the body absorbs, distributes, metabolizes, and excretes a drug. With age, physiological changes alter each of these processes, leading to significant implications for medication administration and safety.

Absorption

Changes in the gastrointestinal system, such as decreased gastric acidity, slowed gastric emptying, and reduced splanchnic blood flow, can affect drug absorption, potentially altering the timing and rate of absorption for some medications.

Distribution

Age-related shifts in body composition significantly alter how drugs are distributed. Increased body fat and decreased total body water can lead to a larger volume of distribution for lipid-soluble drugs and a smaller volume of distribution for water-soluble drugs, impacting drug half-life and plasma concentrations. Decreased serum albumin can also result in a higher free fraction of highly protein-bound drugs, increasing the risk of adverse effects.

Metabolism

Drug metabolism primarily occurs in the liver. Reduced hepatic blood flow and altered enzyme activity, particularly in Phase I oxidation, can decrease the metabolism and clearance of certain drugs. Phase II conjugation reactions tend to be less affected by age.

Excretion

Kidney function naturally declines with age, significantly influencing drug excretion. A decreased Glomerular Filtration Rate (GFR) reduces the kidneys’ ability to filter drugs, potentially causing renally excreted medications to accumulate to toxic levels. Creatinine clearance is a more accurate indicator of renal function in older adults than serum creatinine alone due to reduced muscle mass.

Impact of Pharmacodynamic Changes

Pharmacodynamics, how a drug affects the body, also changes with age. Older adults may experience increased sensitivity to certain drugs, particularly those acting on the central nervous system, raising the risk of side effects like sedation and confusion. Alterations in drug receptor function can also affect drug effectiveness or increase side effect risks.

Comparison of Pharmacokinetic Changes by Drug Solubility


Feature	Water-Soluble (Hydrophilic) Drugs	Lipid-Soluble (Lipophilic) Drugs
Effect of Age-Related Change	Reduced total body water leads to a smaller volume of distribution (Vd).	Increased body fat leads to a larger volume of distribution (Vd).
Plasma Concentration	Higher plasma concentrations for a given dose due to smaller Vd.	Potential for accumulation in fat stores, leading to erratic release and variable plasma levels.
Half-Life	Elimination half-life may be prolonged due to reduced renal clearance.	Elimination half-life is often significantly prolonged due to fat accumulation and slower release.
Risk Factor	Higher risk of acute toxicity, especially with narrow therapeutic index drugs.	Higher risk of chronic toxicity due to drug accumulation over time.
Clinical Example	Digoxin, Lithium, Aminoglycosides.	Diazepam, Amitriptyline.

Best Practices for Clinicians and Caregivers

Given these physiological changes, it is essential to tailor medication management for older adults, often employing a "start low and go slow" approach to dosing and careful monitoring. Addressing adherence challenges is also important.

Conclusion

Aging affects how the body handles medications at every stage. Declining organ function, changes in body composition, and altered drug sensitivity necessitate a personalized approach to medication administration to optimize benefits and minimize harm in geriatric care. Continuous assessment and communication are key to safe and effective drug regimens as individuals age.

For more detailed guidance on medication safety in older adults, the National Institute on Aging provides additional resources.

Frequently Asked Questions

Aging can cause a decrease in gastric acid, slower gastric emptying, and reduced blood flow to the digestive tract, which may delay drug absorption or slightly decrease the bioavailability of certain medications. However, these changes are often less clinically significant than other age-related factors.

With age, the body has a higher percentage of fat and less total body water. This means lipid-soluble drugs are stored in fat for longer, increasing their half-life, while water-soluble drugs have a smaller distribution volume, leading to higher drug concentrations in the blood.

The liver is the main site for drug metabolism. As liver size and blood flow decrease with age, so does the efficiency of metabolism, potentially leading to drug accumulation and toxicity, especially for drugs that undergo extensive first-pass metabolism.

Reduced kidney function, indicated by a lower glomerular filtration rate (GFR), is common in aging and is the most significant factor affecting drug elimination. It causes renally excreted drugs to build up in the body, increasing the risk of adverse effects.

Pharmacokinetics (PK) describes how the body processes a drug (absorption, distribution, metabolism, excretion), while pharmacodynamics (PD) describes a drug’s effect on the body. Both are altered with age; for example, a slower metabolism (PK) can increase a drug's concentration, while a heightened receptor sensitivity (PD) can amplify its effect.

Older adults generally require lower medication doses due to a combination of slower drug clearance (leading to higher drug concentrations) and an increased sensitivity to a drug's effects. The "start low, go slow" approach minimizes the risk of toxicity and adverse reactions.

Yes, polypharmacy, or the use of multiple medications, is more common in older adults and increases the risk of drug-drug interactions. These interactions can further affect drug metabolism, clearance, and increase the risk of adverse drug reactions.

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.