Module 4: Drug Therapy in Older Adults Flashcards
Facts
Disproportionately high prescription drug use
exists in the older adult population (65 years and
older)
Older adult patients experience more adverse
drug reactions and drug-drug interactions than
younger patients do
Excessive prescribing
Poor adherence
Physical Changes in Older Adults - Pharmacokinetics
Pharmacokinetic Changes in Older Adults:
Absorption: Changes in gastric pH and slowed gastric emptying can affect drug absorption. Decreased gastrointestinal motility and blood flow may also alter the rate and extent of drug absorption.
Distribution: There is an increase in body fat and a decrease in lean body mass and total body water. This affects the volume of distribution for lipophilic (fat-soluble) and hydrophilic (water-soluble) drugs, respectively. Decreased serum albumin can affect the binding of drugs, increasing the free (active) drug concentration.
Metabolism: Liver mass and blood flow decrease with age, which can reduce the hepatic metabolism of drugs, prolonging their half-life and increasing the risk of accumulation and toxicity.
Excretion: Renal function declines with age, affecting the elimination of drugs that are renally excreted. Creatinine clearance (CrCl) is a more accurate measure of renal function than serum creatinine levels in the elderly due to decreased muscle mass.
Pharmacodynamic
Pharmacodynamic Changes in Older Adults:
Altered Drug Sensitivity: There may be an increased or decreased sensitivity to various drugs, partly due to changes in receptor numbers, affinity, and post-receptor mechanisms. For example, older adults may be more sensitive to anticoagulants, opioids, and sedatives.
Homeostatic Regulation: The body’s ability to maintain homeostasis diminishes, making older adults more susceptible to the effects of drugs that alter physiological parameters like blood pressure, glucose levels, and electrolyte balance.
Higher Risk for Adverse Drug Reactions
Adverse Drug Reactions and Drug Interactions:
Older adults are at higher risk for adverse drug reactions (ADRs) due to polypharmacy, comorbidities, and the aforementioned pharmacokinetic and pharmacodynamic changes. ADRs can range from mild (e.g., dry mouth, constipation) to severe (e.g., falls, bleeding, renal failure).
Drug-drug interactions are more common due to the number of medications typically prescribed. Interactions can lead to reduced efficacy of medications or increased risk of ADRs.
Promoting Adherence
Promoting Adherence:
Simplify Regimens: Use the least number of medications and doses per day to manage conditions effectively.
Educate: Provide clear, accessible information about each medication, its purpose, how and when to take it, and possible side effects.
Use of Aids: Recommend the use of pill organizers, medication dispensing systems, or electronic reminders to help with adherence.
Regular Review: Conduct regular medication reviews to reassess the need for each medication, adjust dosages, and discontinue unnecessary medications.
Involve Caregivers: Engage family members or caregivers in the medication management process, especially for patients with cognitive impairment or those who require assistance with medication administration.
Rate of Absorption with Age
Altered gastrointestinal absorption is not a major
factor in drug sensitivity
The percentage of an oral dose that is absorbed
does not change with age
The rate of absorption may slow with age
Delayed gastric emptying and reduced
splanchnic blood flow also occur
Changes in Body Composition with Aging + Effects on Drugs
Increased Percentage of Body Fat
Implication: Fat tissue serves as a storage depot for lipid-soluble drugs, extending their duration of action and half-life. This can lead to drug accumulation and increased risk of toxicity over time.
Examples: Sedatives, anesthetics, and some antidepressants are lipid-soluble and can have prolonged effects in individuals with higher body fat percentages.
Decreased Percentage of Lean Body Mass
Implication: A decrease in lean body mass reduces the distribution volume for water-soluble drugs, potentially leading to higher plasma concentrations and more intense effects for a given dose. This necessitates careful dosing and monitoring to avoid drug toxicity.
Examples: Drugs with a primarily water-soluble distribution, such as digoxin, may require dose adjustments based on lean body mass rather than total body weight.
Decreased Total Body Water
Implication: The reduction in total body water decreases the volume of distribution for hydrophilic (water-soluble) drugs, resulting in higher plasma concentrations and potentially more pronounced drug effects. This is particularly relevant for medications that are excreted renally or have narrow therapeutic windows.
Examples: Medications like lithium (used for bipolar disorder) and aminoglycoside antibiotics, which are water-soluble, may have increased concentrations and risk of toxicity.
Reduced Concentration of Serum Albumin
Implication: Serum albumin is a primary protein responsible for the binding of many drugs in the bloodstream. A decrease in albumin levels, which can occur due to malnutrition or liver disease, increases the fraction of unbound (free) drug, enhancing its pharmacological activity and risk of adverse effects.
Examples: Warfarin, a commonly used anticoagulant, is highly protein-bound. Reduced albumin levels can increase the free fraction of warfarin, necessitating careful monitoring of coagulation parameters to avoid bleeding complications.
Clinical Considerations for Managing Older Adults:
Individualized Dosing: Consideration of the patient’s body composition and nutritional status is essential when determining drug dosages to avoid underdosing or overdosing.
Monitoring: Regular monitoring of drug levels, especially for medications with narrow therapeutic indices, is crucial to ensure they remain within the therapeutic range.
Nutritional Support: Addressing nutritional deficiencies can help improve albumin levels and overall drug metabolism and elimination.
Polypharmacy Management: Given the altered pharmacokinetics in older adults, a thorough review of all medications is necessary to minimize the risk of drug-drug interactions and adverse effects.
Hepatic Metabolism of Drugs
Changes in Hepatic Metabolism with Age:
Reduced Hepatic Blood Flow: The liver receives a significant proportion of its blood supply from the portal vein, which carries blood from the gastrointestinal tract. With aging, there is a decrease in blood flow through the liver, which can slow the rate at which drugs are delivered to the liver for metabolism.
Decreased Liver Mass: Liver size and mass decrease with age, which can reduce the overall metabolic capacity of the liver. This reduction in liver mass contributes to the decreased metabolism of drugs.
Diminished Activity of Hepatic Enzymes: The liver contains numerous enzymes responsible for drug metabolism, primarily through the cytochrome P450 (CYP) system. Aging can lead to a decrease in the activity of some of these enzymes, affecting the metabolism of drugs that are substrates for these enzymes.
Implications for Drug Therapy:
Increased Half-Lives of Drugs: Due to the decreased rate of hepatic metabolism, the half-lives of some drugs may be prolonged in older adults. This can lead to drug accumulation and increased risk of adverse effects, particularly for medications with narrow therapeutic windows.
Prolonged Drug Responses: The pharmacological effects of some drugs may be prolonged due to slower metabolism, requiring adjustments in dosing frequency to avoid toxicity.
Enhanced Responses to Oral Drugs: Many orally administered drugs undergo significant first-pass metabolism in the liver, where a portion of the drug is metabolized before reaching systemic circulation. With reduced hepatic metabolism, a greater proportion of the drug may bypass first-pass metabolism and reach systemic circulation, potentially enhancing the drug’s pharmacological effects. This is particularly relevant for drugs with a high first-pass effect.
Clinical Considerations:
Individualized Dosing: Starting with lower doses and titrating slowly (“start low, go slow”) can help avoid adverse effects due to prolonged drug half-lives and enhanced drug responses.
Monitoring for Adverse Effects: Regular monitoring for signs of drug toxicity and adverse reactions is crucial, especially when initiating or adjusting the dosages of medications known to have significant hepatic metabolism.
Reviewing Medication Regimens: Periodic review of the patient’s medication regimen is important to assess the need for continued therapy, adjust dosages, and discontinue unnecessary medications, thereby minimizing the risk of polypharmacy and adverse drug interactions.
Excretion Changes - Changes in Renal Function
Changes in Renal Function:
Renal Blood Flow: There is a gradual decrease in renal blood flow with age, which can reduce the kidneys’ ability to filter blood effectively.
Glomerular Filtration Rate (GFR): The GFR, a critical measure of kidney function, declines. This reduction is due to factors such as a decrease in the size of the kidneys, loss of glomeruli, and sclerosis of the remaining glomeruli.
Active Tubular Secretion: The efficiency of active tubular secretion, a process by which substances are actively transported from the blood into the tubular urine, also diminishes with age. This affects the excretion of certain drugs and their metabolites.
Number of Nephrons: There is a reduction in the number of functioning nephrons, the basic structural and functional units of the kidney, which contributes to the overall decline in renal function.
Excretion Changes - Implications for Drug therapy
Implications for Drug Therapy:
Drug Accumulation: Due to reduced renal excretion, drugs and their metabolites can accumulate in the body, leading to increased risk of toxicity. This is particularly concerning for drugs that are primarily eliminated by the kidneys.
Adverse Drug Reactions (ADRs): Older adults are at a higher risk for ADRs due to drug accumulation. ADRs can range from mild (e.g., gastrointestinal upset) to severe (e.g., renal failure, electrolyte imbalances, ototoxicity with certain antibiotics).
Dosage Adjustments: Many medications require dose adjustments based on the patient’s renal function, often guided by the estimated GFR (eGFR). Drugs with narrow therapeutic windows require careful monitoring and dosage individualization
Assessing Renal Function
Clinical Considerations:
Assessment of Renal Function: Regular assessment of renal function using markers such as serum creatinine and eGFR calculations is essential for detecting declines in renal function and adjusting drug dosages accordingly.
Selection of Medications: Consideration of the renal excretion pathway for each medication and the potential need for alternative drugs with non-renal elimination routes in patients with significant renal impairment.
Monitoring for Toxicity: Vigilant monitoring for signs of drug toxicity, especially for renally-cleared medications, and adjusting therapy as needed to prevent ADRs.
Patient Education: Educating patients and caregivers about the importance of medication adherence, potential side effects, and the need for regular monitoring of renal function.
Renal function should be assessed with drugs
that are eliminated primarily by the kidneys
In patients who are older adults:
Use creatinine clearance rather than serum creatinine
to assess this, because lean muscle mass (source of
creatinine) declines in parallel with kidney function
Creatinine levels may be normal even though kidney
function is greatly reduced
Pharmacodynamics in Older Adults
Alterations in receptor properties may underlie
altered sensitivity to some drugs
Drugs with more intense effects in older adults
* Warfarin and certain central nervous system depressants
Beta blockers less effective in older adults, even in
the same concentrations
* Reduction in number of beta receptors
* Reduction in the affinity of beta receptors for beta-receptor blocking agents
Adverse Drug Reactions in the Elderly
Seven times more likely in the elderly
Account for 16% of hospital admissions
Account for 50% of all medication-related deaths
Majority are dose related rather than
idiosyncratic
Symptoms in older adults often nonspecific
May include dizziness and cognitive impairment
