Age-Related Pharmacokinetic Changes: What the Body Does to the Drug
Pharmacokinetics describes the movement of drugs through the body, covering four main processes: absorption, distribution, metabolism, and excretion (ADME). With age, various physiological changes occur that can alter each of these steps, leading to different drug concentrations and effects compared to younger individuals.
Absorption
While often less significant than other factors, some age-related changes can affect drug absorption. Factors such as decreased gastrointestinal blood flow, increased gastric pH, and slower gastric motility can alter how and when a drug enters the bloodstream. For most passively absorbed drugs, the clinical impact is minimal. However, for certain medications, such as calcium carbonate which requires an acidic environment, absorption can be impaired.
Distribution
As people age, body composition shifts significantly, with a decrease in total body water and lean muscle mass and an increase in body fat. This change directly influences how drugs are distributed throughout the body:
- Water-soluble drugs: Medications that dissolve in water, like digoxin and lithium, have a reduced volume of distribution due to less total body water. This results in higher concentrations of the drug in the blood, increasing the risk of toxicity if not properly dosed.
- Fat-soluble drugs: Medications that dissolve in fat, like diazepam, have an increased volume of distribution due to higher body fat percentages. This means the drug can accumulate in fat tissue, prolonging its half-life and duration of action, which increases the risk of residual effects.
Metabolism
Most drug metabolism occurs in the liver, and the liver's ability to process medications declines with age. Reduced liver size and hepatic blood flow can decrease the metabolic rate, particularly for drugs that undergo significant first-pass metabolism. This can increase the bioavailability of certain medications, leading to higher active drug concentrations in the body.
Excretion
The kidneys' ability to excrete drugs and waste products diminishes with age, a key factor in drug clearance. The glomerular filtration rate (GFR) typically decreases after middle age. This can cause medications that are primarily eliminated by the kidneys, such as certain antibiotics and digoxin, to build up to toxic levels if dosages are not adjusted. Importantly, a patient's serum creatinine level alone is an unreliable indicator of renal function in older adults due to the age-related loss of muscle mass.
Age-Related Pharmacodynamic Changes: What the Drug Does to the Body
Pharmacodynamics refers to how a drug affects the body. As people age, changes at the cellular and receptor level can alter the body's sensitivity to medications, making older adults more vulnerable to their effects.
Altered Receptor Sensitivity
Many physiological systems experience altered receptor function with age. For instance, older adults often have diminished sensitivity in their cardiac beta-adrenergic receptors, affecting their response to certain cardiovascular drugs. Conversely, they may have an increased sensitivity to drugs affecting the central nervous system, such as benzodiazepines and opioids, leading to greater sedation and confusion at lower doses.
Impaired Homeostatic Mechanisms
Ageing can weaken the body's homeostatic mechanisms, such as blood pressure regulation and temperature control. This impaired ability to respond to physiological stress means that medications can cause a more pronounced effect. For example, some blood pressure medications may cause a much larger drop in blood pressure in older adults, increasing the risk of dizziness and falls.
Polypharmacy and Drug Interactions in Older Adults
Polypharmacy, the regular use of multiple medications (typically five or more), is a serious concern in older adults. The high prevalence of chronic conditions in this population often necessitates multiple prescriptions, increasing the risk of adverse drug events (ADEs), which account for almost 30% of all hospital admissions.
Increased Risk of Interactions
With each additional medication, the likelihood of a drug-drug interaction rises significantly. These interactions can:
- Amplify the effects of a drug, potentially leading to toxicity.
- Diminish a drug's effectiveness.
- Cause unintended side effects.
The Beers Criteria
To help mitigate these risks, the American Geriatrics Society developed the Beers Criteria, a list of potentially inappropriate medications for older adults. It highlights drugs that may pose unnecessary risk, such as certain anticholinergics and long-acting benzodiazepines, which can cause confusion, sedation, and an increased risk of falls.
Understanding the Impact: A Comparison
To illustrate the practical effects of these changes, consider the difference in medication response between a young adult and an older adult.
| Aspect | Younger Adult | Older Adult |
|---|---|---|
| Body Composition | Higher lean body mass, lower body fat, more total body water. | Lower lean body mass, higher body fat, less total body water. |
| Drug Distribution | Higher concentrations of fat-soluble drugs, lower concentrations of water-soluble drugs. | Accumulation of fat-soluble drugs (prolonged action); higher plasma concentrations of water-soluble drugs (higher risk of toxicity). |
| Liver Metabolism | Robust metabolic capacity and first-pass effect. | Reduced liver size and blood flow, leading to slower drug metabolism and increased bioavailability. |
| Kidney Excretion | Efficient renal clearance, reliable creatinine levels as a proxy for function. | Declining renal function (GFR), requiring careful dosage adjustments; creatinine less reliable indicator. |
| Drug Sensitivity | Standard receptor sensitivity and faster homeostatic responses. | Increased sensitivity to certain drug classes, impaired compensatory homeostatic mechanisms. |
| Risk of ADEs | Lower risk due to efficient processing and clearance. | Higher risk due to slower processing, potential accumulation, and increased sensitivity. |
Conclusion: Navigating Medication Safely with Age
How age affects medicine is a multi-faceted issue that highlights the need for a personalized and cautious approach to prescribing and managing drugs. As the body undergoes changes in pharmacokinetics and pharmacodynamics, older adults become more susceptible to adverse drug reactions and complex interactions, particularly in the context of polypharmacy. For patients and caregivers, clear communication with healthcare providers and a thorough understanding of all medications, including over-the-counter and supplements, are paramount. Regularly reviewing medication regimens, considering deprescribing unnecessary or inappropriate medications, and monitoring for subtle side effects are essential strategies for ensuring medication safety as one ages. For a deeper understanding of medication safety in older adults, refer to the resources from the National Institute on Aging.
Proactive Medication Management in Older Adults
- Maintain a Comprehensive Medication List: Always keep an updated list of all prescription and over-the-counter medications, as well as any vitamins, supplements, and herbal products. This provides healthcare providers with a complete picture to prevent dangerous interactions.
- Prioritize Medication Reviews: Conduct regular medication reviews with your doctor or pharmacist to assess the necessity and appropriateness of all drugs. Ask if any medications can be simplified or discontinued.
- Start Low, Go Slow: Discuss the potential for lower dosages with your healthcare provider. Due to slower metabolism and clearance, older adults often require lower doses than younger individuals to achieve the same therapeutic effect with less risk of toxicity.
- Understand Side Effects: Be aware of potential side effects and how they may manifest differently with age, such as increased confusion or dizziness from CNS-active drugs. Report any new or worsening symptoms to your doctor immediately.
- Use One Pharmacy: Using a single pharmacy allows the pharmacist to better monitor for potential drug-drug interactions and ensure consistency in your medication regimen.
What are common issues related to age and medication?
Common issues include polypharmacy (taking multiple medications), a higher risk of side effects, drug-drug and drug-disease interactions, and medication non-adherence due to complex schedules or cognitive impairment.
Why do older adults often require lower medication dosages?
Older adults often need lower doses because age-related changes in body composition, liver metabolism, and kidney function can cause drugs to stay in the body longer and accumulate to potentially toxic levels.
What is polypharmacy and why is it risky for older adults?
Polypharmacy is the regular use of multiple medications, typically five or more. It is risky because it increases the chance of adverse drug reactions, drug interactions, falls, and cognitive impairment.
How does decreased kidney function affect medication?
As kidney function declines with age, the body's ability to excrete drugs is reduced. This can cause drugs that are eliminated by the kidneys to build up in the system, potentially leading to toxic effects if dosages are not adjusted.
What role do changes in body fat and water play in drug effects?
As body fat increases and total body water decreases with age, the distribution of medications changes. Water-soluble drugs become more concentrated in the blood, while fat-soluble drugs accumulate in body fat, extending their half-life and duration of action.
What are the Beers Criteria?
The Beers Criteria is a list of potentially inappropriate medications for older adults developed by the American Geriatrics Society. It helps healthcare providers identify drugs that may pose unnecessary risk due to age-related changes and comorbidities.
What can I do to ensure my medications are safe as I age?
Always maintain an up-to-date list of all medications, including supplements, and review it regularly with your doctor. Use a single pharmacy, report any new symptoms, and ask questions about your medication regimen to ensure safety.
How does age affect medicine absorption and metabolism?
While the impact on absorption is often minor, age-related declines in liver size and blood flow lead to slower metabolism, particularly for drugs with a high first-pass effect. This can increase drug bioavailability and potentially cause higher concentrations in the body.
