Question

Elderly persons may have altered drug disposition because of (A) a markedly reduced absorption of many drugs. (B) higher volumes of distribution for water-soluble drugs. (C) an accelerated renal excretion of ionized drugs. (D) an increased permeability of the blood-brain barrier. (E) a reduced capacity to oxidize drugs.

Short answer

The correct answer is (E) a reduced capacity to oxidize drugs.

Step-by-step solution

Understanding Drug Disposition

Drug disposition encompasses the absorption, distribution, metabolism, and excretion of drugs. Elderly individuals often experience changes in these processes due to physiological aging.

Examining Each Choice

We must examine each option to see how it relates to drug disposition in the elderly: - **Option A**: Contrary to markedly reduced absorption, most elderly maintain normal absorption levels. - **Option B**: Elderly often have lower volumes of distribution for water-soluble drugs due to decreased body water. - **Option C**: Renal excretion is slower in elderly due to reduced kidney function, not accelerated. - **Option D**: Blood-brain barrier permeability typically decreases with age, not increases. - **Option E**: Aging is often associated with a reduced capacity to metabolize drugs, particularly affecting oxidative metabolism.

Identifying the Correct Answer

Among the given options, only Option E corresponds to a known change in elderly drug disposition. With age, the liver's ability to carry out oxidation reactions necessary for drug metabolism decreases.

Conclusion

The reduced capacity to oxidize drugs in elderly individuals reflects a slower phase I metabolism, which can lead to changes in drug efficacy and potential side effects.

Key concepts

Drug Absorption in the Elderly

As people age, their bodies undergo numerous changes, and one area significantly affected is drug absorption. While it might be assumed that elderly individuals experience a markedly reduced absorption of drugs, this is not entirely accurate. In reality, most elderly people maintain similar drug absorption levels to younger adults. Several factors influence this process:

• Gastric pH levels: As people age, their stomach produces less acid, leading to higher gastric pH. However, this alteration has a minimal impact on drug absorption for most medications.
• Gastrointestinal motility: Aging can slow down the digestive tract's movement, potentially affecting drug absorption times. But overall absorption remains largely unchanged.
• Surface area of absorption: With aging, the surface area available for drug absorption in the intestines can decrease, but the body usually compensates for these changes, maintaining adequate absorption rates for many drugs.

Understanding these nuances is crucial for optimizing pharmacotherapy in the elderly.

Drug Metabolism in Aging

Drug metabolism is the process by which the body transforms and breaks down medicines, usually in the liver. As individuals grow older, this process can be significantly affected. Particularly, the liver's capacity to oxidize drugs decreases with age. Here are some key points about drug metabolism in the elderly:

• Reduced liver size: The liver usually shrinks with age, leading to diminished blood flow and a lower metabolic rate.
• Phase I reactions: These involve oxidation, reduction, and hydrolysis. Their efficiency notably declines, causing slower drug clearance.
• Phase II reactions: Processes such as glucuronidation often remain relatively stable, not experiencing as much decline.

This reduction in drug metabolism can increase the risk of drug accumulation, necessitating adjustments in dosing and careful monitoring.

Volume of Distribution

Volume of distribution describes how a drug spreads in the body. Water-soluble drugs have a different volume of distribution in elderly individuals due to aging-related body composition changes. Key factors influencing this include:

• Decreased body water: Older adults typically have less body water, leading to lower volumes of distribution for these drugs, as there's less fluid available to carry them.
• Increased body fat: Contrary to water-soluble drugs, lipid-soluble drugs may see larger volumes of distribution, as older individuals generally have more body fat.
• Protein binding changes: Aging may also affect the plasma protein binding of drugs, influencing how widely drugs circulate through the bloodstream.

These adjustments are essential for tailoring medication regimens to ensure both efficacy and safety.

Renal Excretion Changes

Renal excretion, the process by which the kidneys remove drugs from the body, changes markedly as we age. This decline primarily occurs because of reduced kidney function in older adults. Important considerations include:

• Decreased glomerular filtration rate (GFR): With aging, GFR often decreases, reflecting less efficient kidney filtering.
• Tubular function: Tubular secretion and reabsorption also become less effective, impacting drug clearance.
• Potential for drug accumulation: Poorer excretion can lead to higher drug levels, increasing the risk of side effects and toxicity. Thus, dosage adjustments and monitoring renal function in the elderly are essential.

This knowledge is pivotal for preventing adverse drug reactions in the elderly population.

Blood-Brain Barrier Permeability in the Elderly

The blood-brain barrier (BBB) is a selective barrier that protects the brain from potentially harmful substances. Its permeability can change with age, though typically, it becomes less permeable rather than more. Some factors that influence BBB permeability include:

• Barrier integrity: Aging may lead to a weakening of the barrier, yet the predominant consensus is reduced permeability, which can alter drug delivery to the brain.
• Transport mechanisms: The efficiency of transporters that move drugs across the BBB can decrease, influencing drug effectiveness.
• Neurodegenerative changes: Conditions such as Alzheimer's might further impact the BBB, altering drug permeability uniquely for each individual.

An understanding of these changes is crucial for managing neurological and psychiatric conditions in the elderly effectively.