Understanding Pharmacokinetics: What the Body Does to the Drug
Pharmacokinetics describes how the body absorbs, distributes, metabolizes, and excretes a drug. Each of these stages is significantly altered in older adults, impacting a medication's effect [2, 6].
Altered Drug Absorption
While absorption itself remains relatively stable in most healthy older adults, several age-related factors can subtly influence it, including reduced blood flow to the digestive tract and a higher gastric pH [2, 6]. Certain medications commonly used by seniors can also change gastric pH, altering how well other drugs are absorbed [2].
Changes in Drug Distribution
As people age, body composition shifts, which has a major impact on drug distribution [2, 6]. Older adults tend to have a higher proportion of body fat and less lean muscle mass and total body water [2, 6]. This means medications that dissolve in fat (lipophilic) accumulate more easily, prolonging their effect, while water-soluble drugs (hydrophilic) have a smaller volume to distribute in, leading to higher concentrations [2, 6]. A decrease in serum albumin, often seen in older adults, also means less protein binding for certain drugs, leaving more active drug in the bloodstream and increasing potency and toxicity risk [2, 6].
Slower Metabolism in the Liver
Metabolism, primarily in the liver, slows down with age due to decreased liver mass and hepatic blood flow [2, 6]. The liver's ability to perform Phase I metabolic reactions is often reduced, and first-pass metabolism declines [2, 6]. However, Phase II reactions are generally less affected [2, 6]. This slower metabolism means drugs remain in the system longer, potentially requiring lower doses [2, 6].
Reduced Kidney Function and Excretion
Normal aging is associated with a progressive decline in kidney function, including a reduced glomerular filtration rate (GFR) [2, 6]. This leads to slower clearance of renally excreted drugs, causing accumulation and potential toxicity, especially for drugs with a narrow therapeutic index [2, 6]. Serum creatinine levels can be misleading in older adults due to less muscle mass, necessitating estimated GFR for accurate dosing [2, 6].
Understanding Pharmacodynamics: What the Drug Does to the Body
Pharmacodynamics refers to how a drug affects the body. Older adults experience altered tissue sensitivity and impaired homeostatic mechanisms [2, 6].
Increased Sensitivity of Receptors
Some tissues and receptors become more sensitive with age. Older adults often show increased sensitivity to central nervous system (CNS) drugs like sedatives and opioids, leading to exaggerated effects [2, 6]. They may also have altered responses to cardiovascular drugs [2, 6].
Impaired Homeostatic Responses
Homeostatic mechanisms are less efficient in older adults, worsening medication side effects [2, 6]. Examples include weaker baroreceptor reflexes exacerbating drug-induced postural hypotension [2, 6].
The Impact of Polypharmacy
Polypharmacy, the use of multiple medications, is a major factor complicating drug sensitivity [2, 3]. Taking multiple drugs dramatically increases the risk of drug-drug interactions and can lead to a prescribing cascade, where a new drug treats a symptom caused by an existing medication [2, 3].
Comparing Drug Response: Elderly vs. Younger Adults
| Factor | Younger Adults | Elderly Adults |
|---|---|---|
| Body Composition | Higher lean body mass and total body water, lower body fat. | Lower lean body mass and total body water, higher body fat [2, 6]. |
| Drug Distribution | Lower volume of distribution for lipophilic drugs; higher for hydrophilic drugs. | Higher volume of distribution for lipophilic drugs; lower for hydrophilic drugs [2, 6]. |
| Liver Metabolism | Robust hepatic blood flow and Phase I enzyme activity. | Reduced hepatic blood flow and Phase I enzyme activity [2, 6]. |
| Kidney Excretion | Efficient renal clearance, stable GFR. | Reduced renal clearance, declining GFR [2, 6]. |
| CNS Sensitivity | Standard sensitivity to CNS-acting drugs. | Increased sensitivity, greater risk of CNS side effects [2, 6]. |
| Protein Binding | Generally higher serum albumin levels. | Lower serum albumin levels due to illness or malnutrition [2, 6]. |
Navigating Medication Safety for Seniors
Given these physiological changes, medication management for older adults requires caution [1, 5].
- Start Low and Go Slow: Begin with a low dose and increase gradually while monitoring the patient's response [1, 5].
- Regular Medication Review: Healthcare providers should regularly review all medications, including over-the-counter drugs and supplements [1, 5].
- Monitor for Adverse Effects: It's crucial to identify new symptoms that might be medication side effects [1, 5].
- Simplify Regimens: Simplifying complex medication schedules can improve adherence and safety [1, 5].
For more detailed guidance on medication safety, the FDA offers several safety tips for older adults [4].
Conclusion
An aging body's interaction with pharmaceuticals is different from a younger person's [2, 5]. Altered pharmacokinetics, including changes in distribution, metabolism, and excretion, combined with altered pharmacodynamics like increased receptor sensitivity, explain why elderly are more sensitive to drugs [2, 6]. Understanding these changes is vital for promoting safe and effective medication use, better health outcomes, and a higher quality of life in the older population [1, 5]. This emphasizes the need for personalized dosing and vigilant monitoring [1, 5].
