Understanding What Age-Related Physiological Changes Increase the Risk of Adverse Drug Reactions?

Recent studies suggest that up to one in three hospital admissions for older adults may be medication-related. This underscores the critical need for seniors, caregivers, and healthcare professionals to understand what age-related physiological changes increase the risk of adverse drug reactions, ensuring safer and more effective medication management.

Quick Summary

Reduced kidney and liver function, altered body composition (less water, more fat), and increased sensitivity of target receptors are primary age-related physiological shifts elevating adverse drug reaction risks in older adults, alongside conditions like polypharmacy and multimorbidity.

Key Points

• Reduced Kidney and Liver Function: With age, the kidneys and liver become less efficient, impairing the body's ability to eliminate medications, which can lead to toxic drug levels.

• Altered Body Composition: Older adults typically have less total body water and more body fat, which affects how drugs are distributed and can increase the concentration of certain medications.

• Increased Drug Sensitivity: Changes in the central nervous system and a diminished ability to maintain homeostasis make older adults more sensitive to the effects of many drugs, including opioids and sedatives.

• Impact of Polypharmacy: Taking multiple medications simultaneously, a common practice for older adults, significantly increases the risk of dangerous drug-drug interactions.

• Delayed Drug Effects: Slower gastrointestinal motility can delay medication absorption, altering the timing and effectiveness of treatments.

• Risk of Cognitive Side Effects: Many medications can cause confusion or delirium in older adults due to increased brain sensitivity, which can be mistaken for other age-related conditions.

Introduction

As the body ages, a cascade of physiological changes affects how it processes and responds to medications. These shifts in drug absorption, distribution, metabolism, and excretion—collectively known as pharmacokinetics—can significantly alter a medication's effectiveness and increase the likelihood of adverse drug reactions (ADRs). While the risk factors for ADRs are numerous, they are particularly pronounced in older adults, a population that often manages multiple chronic conditions with multiple medications, a practice known as polypharmacy.

Age-Related Changes in Drug Pharmacokinetics

The journey of a drug through the body, from the moment it is taken to its final elimination, is known as pharmacokinetics. Aging modifies each of these steps, creating a unique pharmacological profile for older individuals that differs markedly from younger adults.

Alterations in Absorption

Drug absorption is the process by which a medication enters the bloodstream. In older adults, several factors can alter this process:

• Increased Gastric pH: The stomach's acidity tends to decrease with age, affecting the breakdown and absorption of certain medications that require an acidic environment to dissolve properly.
• Delayed Gastric Emptying: Slower stomach motility can delay a drug's entry into the small intestine, where most absorption occurs, potentially delaying the onset of action for some medications.
• Slower Intestinal Motility: A general slowing of the digestive tract can affect the rate at which some drugs are absorbed. For certain drugs, this can prolong their effects and increase exposure time, potentially leading to adverse effects.

Changes in Distribution

Drug distribution refers to how a drug spreads throughout the body's tissues and fluids. Key age-related shifts in body composition alter this process:

• Increased Body Fat, Decreased Total Body Water: With age, the proportion of body fat increases, while total body water decreases. This has a significant impact on drug levels:
  • Fat-soluble drugs: Medications that dissolve in fat, such as diazepam and many antidepressants, accumulate in the increased fat tissue, prolonging their half-life and increasing the risk of toxicity.
  • Water-soluble drugs: Medications that dissolve in water, like digoxin and some antibiotics, have a smaller volume of distribution. This can lead to higher, potentially toxic, drug concentrations in the bloodstream.
• Reduced Serum Albumin: Decreased liver function or malnutrition can lead to lower levels of serum albumin, a protein that binds to many drugs in the bloodstream. Since only the unbound, or 'free,' portion of a drug is active, a drop in albumin can lead to higher concentrations of the active drug, increasing the risk of toxic effects.

Declining Liver and Kidney Function

The liver and kidneys are the body's primary organs for drug metabolism and excretion. Their age-related decline is a major contributor to increased ADR risk.

• Decreased Liver Metabolism: The liver's ability to metabolize drugs decreases with age due to reduced blood flow and a decline in the size and efficiency of liver cells. This means drugs are broken down more slowly, staying in the body longer and increasing the risk of accumulation and toxicity. Some examples include certain antiarrhythmics, antidepressants, and benzodiazepines.
• Reduced Kidney Excretion: Renal function steadily declines after age 35 to 40, with a reported 40% reduction in functioning nephrons by the eighth decade of life. This impairs the body's ability to excrete drugs and their metabolites, especially water-soluble drugs eliminated primarily through the kidneys. Medications like metformin, certain antibiotics, and digoxin require careful monitoring in older adults with reduced kidney function.

Altered Pharmacodynamics and Drug Sensitivity

Beyond changes in how the body handles drugs (pharmacokinetics), aging also alters how drugs affect the body (pharmacodynamics). Older adults often exhibit an increased sensitivity to certain medications, even at normal blood levels.

• Central Nervous System (CNS) Effects: Older adults are more sensitive to CNS-acting drugs, such as opioids, benzodiazepines, and sedatives. This can lead to exaggerated effects like sedation, confusion, and cognitive impairment.
• Reduced Homeostatic Reserve: The body's ability to maintain a stable internal environment (homeostasis) diminishes with age. This makes older adults more susceptible to the side effects of medications that impact physiological systems. For example, the risk of orthostatic hypotension (a drop in blood pressure upon standing) is higher in older adults taking antihypertensives because of attenuated baroreceptor reflexes.

Comparison of Pharmacological Differences

Feature	Younger Adults	Older Adults
Body Composition	Higher percentage of water, lower percentage of fat.	Lower percentage of water, higher percentage of fat.
Drug Distribution	Faster and more widespread distribution of water-soluble drugs.	Water-soluble drugs reach higher concentrations due to less dilution. Fat-soluble drugs accumulate in increased fat tissue.
Liver Function	Higher liver blood flow and metabolic enzyme activity.	Reduced liver blood flow and metabolic enzyme activity, leading to slower drug clearance.
Kidney Function	Efficient glomerular filtration rate (GFR).	Declining GFR and fewer functional nephrons, leading to slower drug excretion.
Drug Sensitivity	Standard pharmacological response.	Often increased sensitivity, especially to CNS-acting drugs.
Risk of ADRs	Lower.	Higher, with potential for more severe outcomes.

The Role of Polypharmacy and Multimorbidity

It is important to note that the isolated physiological changes of aging are often compounded by other clinical realities for seniors. The presence of multiple chronic diseases (multimorbidity) and the subsequent use of multiple medications (polypharmacy) significantly amplify the risk of ADRs. Drug-drug interactions can occur when one medication alters the effect of another, and drug-disease interactions can happen when a drug used for one condition worsens another existing condition. For a deeper look into this topic, you can read more in a comprehensive narrative review of adverse drug reactions in older adults published by the journal Clinical Interventions in Aging [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149349/].

Conclusion

The physiological changes of aging, including shifts in body composition, declining liver and kidney function, and altered drug sensitivity, create a perfect storm for an increased risk of adverse drug reactions. Recognizing these underlying factors is the first step toward better medication management. By taking a holistic approach that considers an individual's unique health profile, healthcare providers and patients can collaborate to optimize therapeutic regimens, minimize risks, and improve quality of life throughout the aging process.

Frequently Asked Questions

How does reduced kidney function affect medication in older adults?

Reduced kidney function means that medications and their byproducts are cleared from the body more slowly. This can lead to a buildup of the drug to potentially toxic levels, requiring dosage adjustments for many common medications.

What is polypharmacy, and how does it relate to the risk of adverse drug reactions?

Polypharmacy refers to the use of multiple medications at once. In older adults, this significantly increases the risk of drug-drug interactions, where one drug's effect is altered by another, potentially leading to a higher risk of adverse reactions.

How does increased body fat in older adults impact medication?

With more body fat and less water, fat-soluble medications can accumulate in fat tissue, increasing their half-life and duration of action. Conversely, water-soluble drugs become more concentrated in the bloodstream, raising the risk of toxicity.

Why are older adults more sensitive to certain drugs like sedatives?

Older adults can experience altered pharmacodynamics, meaning their bodies respond differently to drugs. Decreased nerve function and a reduced ability to compensate for changes can increase sensitivity to central nervous system depressants, leading to greater sedation or confusion.

Are there specific types of medications that are more likely to cause adverse drug reactions in seniors?

Yes. Medications acting on the central nervous system (e.g., sedatives, antipsychotics), cardiovascular drugs, and those with a narrow therapeutic window (like digoxin or warfarin) are particularly prone to causing adverse reactions in older adults.

What is the role of the liver in increasing adverse drug reactions in the elderly?

As the liver's size and blood flow decrease with age, its capacity to metabolize and break down drugs is reduced. This leads to slower drug clearance and a higher risk of drug accumulation and toxicity.

What can patients and caregivers do to mitigate the risk of adverse drug reactions?

Seniors and their caregivers should regularly review all medications, including over-the-counter drugs, with a healthcare provider. Starting with lower doses, monitoring for side effects, and simplifying medication regimens are also key preventive strategies.