The Aging Body, the Changing Drug: A Pharmacological Guide for Geriatric Care

Abstract

The aging process leads to significant physiological changes that have a profound impact on how the body handles medications. These changes affect both pharmacokinetics (absorption, distribution, metabolism, and excretion) and pharmacodynamics (drug effects), thereby increasing the risk of adverse drug events (ADEs) and therapeutic failures in older adults. This article explores the key age-related physiological alterations and their influence on drug responses. It provides clinical guidelines for healthcare providers in terms of how to titrate drug dosages, choose medications, and monitor patients effectively to optimize pharmacotherapy and improve patient safety among the older population.

Introduction

The global population is aging rapidly, and the number of older adults requiring pharmacotherapy for various health conditions is increasing. However, prescribing medications to older adults poses unique challenges because of the physiological changes associated with aging. These changes affect all aspects of drug handling within the body, from absorption to elimination, and can significantly alter drug responses. Older adults are more susceptible to these adverse drug events, drug interactions, and therapeutic failures. Understanding the pharmacology of aging will help healthcare professionals optimize medication management in this vulnerable population concerning safety. This article explores key age-related physiological changes, and their influence on pharmacokinetics and pharmacodynamics, and provides practical recommendations for adjusting dosages and monitoring for ADEs in older adults.

Literature Review

A substantial body of literature has documented the age-related changes in pharmacokinetics and pharmacodynamics. Key findings include:  

• Changes in Absorption: Gastric acid production decreases with age, which can affect the absorption of certain drugs. Reduced gastric emptying and gastrointestinal motility can also alter drug absorption rates.  

• Changes in Distribution: Body composition changes with age, including a decrease in lean body mass and an increase in body fat. This can affect the distribution of lipophilic and hydrophilic drugs. Decreased serum albumin levels can also affect drug binding and distribution.  

• Changes in Metabolism: Hepatic function declines with age, reducing the activity of drug-metabolizing enzymes, particularly cytochrome P450 enzymes. This can lead to decreased drug clearance and increased drug levels.  

• Changes in Excretion: Renal function declines with age, significantly impacting the elimination of many drugs. This is a crucial consideration for drugs that are primarily excreted by the kidneys.  

• Changes in Pharmacodynamics: Age-related changes in receptor sensitivity, signal transduction pathways, and homeostatic mechanisms can alter drug effects. Older adults may be more sensitive to certain drugs, such as benzodiazepines and opioids, and more resistant to others.  

Studies have also highlighted the increased risk of ADEs in older adults, particularly those taking multiple medications (polypharmacy). Research has shown that medication errors, drug interactions, and inappropriate prescribing are common contributors to ADEs in this population.  

Age-Related Physiological Changes and Their Impact on Pharmacokinetics

• Absorption:

  • Decreased gastric acid production can reduce the absorption of drugs requiring an acidic environment for dissolution.

  • Reduced gastric emptying and gastrointestinal motility can delay drug absorption.  

  • Decreased splanchnic blood flow can also affect drug absorption.  

• Distribution:

  • Decreased lean body mass and increased body fat can alter the volume of distribution of drugs. Lipophilic drugs may have a larger volume of distribution, leading to prolonged effects, while hydrophilic drugs may have a smaller volume of distribution, leading to higher initial concentrations.  

  • Decreased serum albumin levels can reduce drug binding, leading to increased free drug concentrations and potentially increased drug effects or toxicity.  

• Metabolism:

  • Reduced hepatic blood flow and decreased activity of drug-metabolizing enzymes, particularly cytochrome P450 enzymes, can decrease drug clearance and prolong drug half-life, leading to accumulation and increased risk of toxicity.  

• Excretion:

  • Decreased renal function, as measured by glomerular filtration rate (GFR), is a major factor affecting drug elimination in older adults. This can lead to the accumulation of really excreted drugs and an increased risk of ADEs.  

Age-Related Changes and Their Impact on Pharmacodynamics

• Changes in Receptor Sensitivity: Older adults may exhibit increased sensitivity to certain drugs (e.g., benzodiazepines, opioids) due to changes in receptor number or affinity.

• Changes in Homeostatic Mechanisms: Age-related decline in physiological reserves can impair the body's ability to compensate for drug effects, increasing the risk of adverse events such as orthostatic hypotension or electrolyte imbalances.  

• Changes in Signal Transduction: Alterations in intracellular signaling pathways can affect drug responses.

Practical Guidance for Pharmacotherapy in Older Adults

• Start Low, Go Slow: Initiate drug therapy at lower doses than typically used in younger adults and titrate slowly based on clinical response and tolerability.  

• Consider Drug Interactions: Be vigilant about potential drug interactions, especially in patients taking multiple medications. Utilize drug interaction databases and consult with pharmacists when necessary.

• Monitor Renal and Hepatic Function: Regularly assess renal and hepatic function to guide drug dosage adjustments. Use estimated GFR (eGFR) to assess renal function and adjust doses of renally excreted drugs accordingly.

• Simplify Medication Regimens: Minimize the number of medications and simplify dosing schedules to improve adherence.  

• Regularly Review Medications: Conduct regular medication reviews to identify unnecessary medications, potential drug interactions, and ADEs.  

• Educate Patients and Caregivers: Provide clear instructions about medication use, potential side effects, and the importance of adherence.

• Consider Non-Pharmacological Alternatives: Explore non-pharmacological approaches, such as lifestyle modifications or physical therapy, whenever possible.

Specific Drug Classes of Concern in Older Adults

• Benzodiazepines: Increased risk of falls, cognitive impairment, and over-sedation.

• Opioids: Increased risk of respiratory depression, constipation, and cognitive impairment.

• Anticholinergics: Increased risk of cognitive impairment, constipation, urinary retention, and blurred vision.

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Increased risk of gastrointestinal bleeding, renal impairment, and cardiovascular events.  

The Role of Geriatric Assessment

A comprehensive geriatric assessment, including an evaluation of functional status, cognitive function, and comorbidities, is essential for optimizing pharmacotherapy in older adults.  

Conclusion

The pharmacology of aging is complex but very crucial for healthcare providers who care for older adults. Understanding the changes in physiology associated with aging can impact drug response allowing clinicians to optimize medication management, minimize adverse drug events, and improve outcomes for patients. This is the practical guidance that should be implemented in a patient, starting low and going slow, consideration of drug interactions, monitoring of organ function, and simplification of medication regimens, for safe and effective pharmacotherapy in the geriatric population.