How Aging Affects Pharmacokinetics
As people get older, the way their bodies handle drugs changes. This process is known as pharmacokinetics, which encompasses how a medication is absorbed, distributed, metabolized, and excreted. In older adults, physiological changes can profoundly affect each of these stages, often leading to a greater potential for drug toxicity and adverse drug events (ADEs).
Absorption: Minimal but Potential Changes
Though aging itself does not dramatically change how most medications are absorbed, several age-related factors can have an effect.
- Decreased Gastric Acidity: Reduced stomach acid can impair the absorption of certain drugs, such as calcium carbonate. For drugs that need an acidic environment to dissolve, this can mean a less effective dose.
- Delayed Gastric Emptying: Slower stomach motility can delay a drug’s movement into the small intestine, slowing the onset of action for medications like acetaminophen.
- Splanchnic Blood Flow: A modest reduction in blood flow to the digestive tract can also slightly impact absorption rates, though this is not usually clinically significant on its own.
Distribution: Changes in Body Composition
Body composition changes are one of the most significant factors altering drug distribution in older adults.
- Increased Body Fat: Older adults tend to have a higher ratio of body fat to lean muscle mass and total body water. This means that fat-soluble (lipophilic) drugs, such as diazepam, can accumulate more extensively in fatty tissues. This storage can prolong the drug’s half-life and lead to higher concentrations and potential toxicity.
- Decreased Total Body Water: Conversely, a reduction in total body water and lean mass means that water-soluble (hydrophilic) drugs, like digoxin and lithium, have a smaller volume in which to dissolve. This can lead to higher plasma concentrations and an increased risk of toxic effects.
- Reduced Serum Albumin: Malnutrition or illness can decrease serum albumin levels, a protein that binds to certain drugs in the blood. When there is less albumin available, a higher concentration of unbound (free) drug circulates, increasing its activity and the risk of toxic side effects, particularly for highly protein-bound drugs like warfarin.
Metabolism: Reduced Liver Function
The liver’s ability to process and break down medications (metabolism) decreases with age, primarily due to reduced liver size and blood flow.
- Lower Hepatic Blood Flow: With age, hepatic blood flow can decrease by as much as 40%, slowing down the metabolism of drugs with a high liver extraction ratio. This means a standard dose of such a drug can result in much higher circulating concentrations in an older adult.
- First-Pass Metabolism: This occurs when an orally administered drug is metabolized by the liver before it reaches systemic circulation. A reduction in this effect can significantly increase the bioavailability of certain medications, such as opioids, leading to greater potency and higher risk of adverse effects.
Excretion: Declining Renal Function
Kidney function, particularly the glomerular filtration rate (GFR), declines progressively with age, even in healthy adults. This is arguably the most important factor in altered drug elimination in the elderly.
- Reduced GFR: The rate at which the kidneys filter waste products from the blood decreases, leading to a prolonged half-life for many drugs that are excreted by the kidneys. This accumulation can lead to toxic levels if not addressed with appropriate dose adjustments.
- Unreliable Indicators: Standard measures of renal function, like serum creatinine, can be misleading in older adults. Reduced muscle mass and physical activity lead to lower creatinine production, so what appears to be a normal serum creatinine level may mask a significantly reduced GFR.
Pharmacodynamics: Altered Drug Sensitivity
Beyond pharmacokinetic changes, older adults can also experience altered pharmacodynamics—the body's response to a drug. These changes often involve increased sensitivity to medications, meaning lower doses may be needed to achieve the desired therapeutic effect, and side effects can be more pronounced.
- Increased Central Nervous System (CNS) Sensitivity: Older adults often have a heightened sensitivity to drugs that affect the brain, such as benzodiazepines and anticholinergics. This can result in greater sedation, confusion, and an increased risk of falls.
- Reduced Homeostatic Capacity: Aging can reduce the body's ability to maintain a stable internal environment (homeostasis). This means an older person's body may struggle to counteract a drug's effect, making adverse reactions more likely.
Comparison of Pharmacokinetic Changes in Younger vs. Older Adults
| Pharmacokinetic Parameter | Younger Adults | Older Adults | Effect on Medication |
|---|---|---|---|
| Body Composition | Higher lean body mass and total body water; lower body fat. | Lower lean body mass and total body water; higher body fat. | Increases volume of distribution for fat-soluble drugs and decreases it for water-soluble drugs, altering concentrations. |
| Liver Metabolism | Higher hepatic blood flow and liver mass; higher activity of Phase I enzymes. | Reduced hepatic blood flow and liver mass; decreased Phase I enzyme activity. | Slower metabolism and clearance, increasing bioavailability and risk of toxicity. |
| Renal Excretion | Higher glomerular filtration rate (GFR) and renal blood flow. | Reduced GFR and renal blood flow (starts to decline after age 30). | Prolonged drug half-life and delayed clearance, increasing risk of drug accumulation and toxicity. |
| Drug-Protein Binding | Generally stable serum albumin levels. | Lower serum albumin levels possible, especially with malnutrition or illness. | Increases the concentration of unbound, active drug in the blood for highly protein-bound medications, increasing effects and potential toxicity. |
| CNS Sensitivity | Lower sensitivity to certain drug classes (e.g., sedatives). | Increased sensitivity to CNS-active drugs. | Greater risk of sedation, confusion, and falls from CNS-active medications. |
Managing Medications for Older Adults
Given the complex changes that occur with age, safe and effective medication management for older adults is paramount. The axiom “start low and go slow” is a guiding principle for many prescribers.
- Regular Medication Reviews (Deprescribing): This involves periodically assessing and potentially discontinuing medications that are no longer necessary or beneficial, or that pose a higher risk than benefit.
- Comprehensive Medication List: Maintain an up-to-date list of all medications, including prescriptions, over-the-counter drugs, vitamins, and supplements. This helps providers identify potential drug-drug or drug-disease interactions.
- Use One Pharmacy: Using a single pharmacy allows the pharmacist to monitor for harmful drug-drug interactions.
- Adherence Aids: Utilizing a pillbox, creating a medication schedule, and setting reminders can help older adults remember to take their medications correctly.
- Proper Storage: Storing medications correctly and checking expiration dates helps ensure their efficacy and safety.
- Education and Communication: Educating the patient and family about the purpose of each medication and potential side effects is crucial. Open communication with healthcare providers can lead to better outcomes.
Conclusion
Aging brings about a series of normal physiological changes that significantly impact how the body processes medications. These alterations, affecting drug absorption, distribution, metabolism, and excretion, can increase the risk of adverse drug reactions and toxicity in older adults. By understanding these age-related changes, healthcare professionals and caregivers can implement strategies to manage medications more safely and effectively. Careful dose adjustment, regular medication reviews, and vigilant monitoring are essential to ensure that medications provide maximum therapeutic benefit with minimal risk, contributing to the overall health and well-being of the aging population.
Authoritative Outbound Link
For more information on drug safety in older adults, visit the National Institute on Aging's resource page: The Dangers of Polypharmacy and the Case for Deprescribing in Older Adults.
