Podcast
Questions and Answers
A patient with a creatinine clearance (CrCl) of 10 is likely to require what adjustment to their drug dose?
A patient with a creatinine clearance (CrCl) of 10 is likely to require what adjustment to their drug dose?
In older adults, a decrease in liver blood flow can lead to which of the following pharmacokinetic changes?
In older adults, a decrease in liver blood flow can lead to which of the following pharmacokinetic changes?
A reduction in liver size in older adults can lead to which effect on drug pharmacokinetics?
A reduction in liver size in older adults can lead to which effect on drug pharmacokinetics?
Why is it important to calculate both CrCl and eGFR when dosing drugs in older patients?
Why is it important to calculate both CrCl and eGFR when dosing drugs in older patients?
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Which of the following statements is MOST accurate regarding drug metabolism in older adults?
Which of the following statements is MOST accurate regarding drug metabolism in older adults?
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What is one of the most common consequences of reduced drug elimination in older adults?
What is one of the most common consequences of reduced drug elimination in older adults?
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When adjusting drug dosages for older adults, what is generally recommended as an approach?
When adjusting drug dosages for older adults, what is generally recommended as an approach?
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What is the relationship between aging and pharmacodynamics?
What is the relationship between aging and pharmacodynamics?
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What is the primary route of elimination for most medications through the kidneys?
What is the primary route of elimination for most medications through the kidneys?
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Which of the following is true regarding the methods to assess renal function?
Which of the following is true regarding the methods to assess renal function?
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What is an approximate average eGFR for a healthy young adult?
What is an approximate average eGFR for a healthy young adult?
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According to the content, what factor should be considered when making renal dose adjustments?
According to the content, what factor should be considered when making renal dose adjustments?
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What is a key difference between the Cockcroft-Gault (CrCl) and CKD-EPI (eGFR) equations in the context of drug dosing?
What is a key difference between the Cockcroft-Gault (CrCl) and CKD-EPI (eGFR) equations in the context of drug dosing?
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Which of the following statements is TRUE about the use of CrCl and eGFR in renal dosing?
Which of the following statements is TRUE about the use of CrCl and eGFR in renal dosing?
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A 65-year old patient has an average eGFR of 55mL/min. Which of the following statements best explains this?
A 65-year old patient has an average eGFR of 55mL/min. Which of the following statements best explains this?
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What type of drugs are most likely to be affected by decreased kidney function?
What type of drugs are most likely to be affected by decreased kidney function?
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What is the prescribing cascade?
What is the prescribing cascade?
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According to the information provided, which of the following is considered a risk factor for adverse drug events?
According to the information provided, which of the following is considered a risk factor for adverse drug events?
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When initiating drug therapy for an older patient, what is the recommended approach?
When initiating drug therapy for an older patient, what is the recommended approach?
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What does 'deprescribing' refer to in the context of prescribing for older adults?
What does 'deprescribing' refer to in the context of prescribing for older adults?
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According to the information, what is the minimum number of concurrent medications that can be considered a risk factor for adverse drug events?
According to the information, what is the minimum number of concurrent medications that can be considered a risk factor for adverse drug events?
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Study Notes
Drug Dosing in Special Populations
- Presentation by Gretchen Ray, PharmD, PhC, BCACP, CDCES, Associate Professor, UNM College of Pharmacy
- Date: January 17, 2025
Objectives
- Describe how renal and hepatic disease alter drug elimination/metabolism
- Accurately calculate CrCl and eGFR for renal function
- Adjust medication doses using CrCl and eGFR, referencing Lexi-Drug
- Define lab tests and clinical symptoms for Child-Pugh score calculation
- Provide general recommendations for hepatic-related dose reduction based on Child-Pugh score
- Describe pharmacokinetic and pharmacodynamic changes in geriatric populations
- Identify adverse drug event risk factors in geriatrics and mitigation strategies
Renal Disease
- Kidney disease reduces drug elimination
- Water-soluble drugs are primarily eliminated by the kidneys via glomerular filtration.
- Kidney function measured by glomerular filtration rate (GFR)
- Average young adult eGFR: 120-140 mL/min
- Average 65-year-old eGFR: 50-60 mL/min
Renal Function Assessment Equations
- Cockcroft-Gault: calculates creatinine clearance (CrCl)
- CrCl = (140-age)×BW / (72×SCr) (×0.85 if female)
- CKD-EPI: calculates estimated GFR (eGFR)
- Recommended by the National Kidney Foundation
- eGFRcr = 142 x min(Scr/k, 1) ^ 1.200 x max(Scr/k, 1) ^ -1.200 x 0.9938Age x 1.012 [if female]
- Recommended by the National Kidney Foundation
Renal Function Considerations
- CrCl developed for drug dosing.
- Accurate CrCl calculation requires ideal, actual, or adjusted patient weight.
- Prior to 2010, drug renal dosing primarily relied on CrCl
- eGFR calculated since 2010 frequently replaces CrCl calculations for renal drug dosing.
- CrCl and eGFR are not interchangeable
Renal Dose Adjustment Considerations
- Overdosing consequences when CrCl or eGFR is below 60 mL/min
- Underdosing consequences (goal of therapy: cure vs symptom management)
- Dosage range of the drug
Tools for Renal Function Calculation
- Global RPh (www.globalrph.com)
- Multiple creatinine clearance calculators
- National Kidney Foundation (https://www.kidney.org/professionals/KDOQI/gfr)
- Professionals GFR Calculator
- FAQs
- MD Calc (www.mdcalc.com)
Hepatic Disease
- Most lipid-soluble drugs are metabolized by the liver
- Hepatitis: Liver inflammation, reducing hepatocyte function, and causing potential mild, transient decrease in drug metabolism.
- Cirrhosis: Permanent loss of functional hepatocytes; reduced intrinsic clearance and reduced hepatic blood flow reduce the delivery of drugs to functioning parts of the liver.
Liver Function Assessment: Child-Pugh Score
- No single lab test to assess liver function
- The Child-Pugh score uses 5 lab tests/ clinical symptoms to evaluate liver metabolic ability
- Includes serum albumin, total bilirubin, prothrombin time, ascites, and hepatic encephalopathy.
Hepatic Dose Adjustment
- If a drug is ≥ 60% hepatically metabolized, dose reduction is often required in patients with hepatic impairment.
- Typical recommendations:
- CP Score 8–9: ~25% dose decrease
- CP Score >10: ~50% dose decrease
- Consult Lexidrug or other databases for hepatic dosing adjustments.
- Clinical reasoning based on the Child-Pugh score is advised.
Drug Dosing in Geriatrics
- Aging affects drug metabolism (liver is common site of drug metabolism )
- Decrease in liver blood flow reduces first-pass effect, increases bioavailability.
- Decreased liver size and reduced metabolizing enzymes impacts drug clearance and half-life.
- Reduced lean body mass results in lower creatinine production and lower GFR (glomerular filtration rate).
- CrCl and eGFR should be calculated for older patients.
Pharmacodynamics in Geriatrics
- Time course and intensity of drug effects vary greatly with age
- Medication use in older adults: follow 2023 Beers Criteria update for inappropriate and potentially risky medications.
Adverse Drug Events (ADE) Prescribing Cascade
- Adverse drug effects can be misinterpreted as new medical conditions.
- Subsequent drug therapies may exacerbate the issue leading to a cascade of complications.
Risk Factors for ADEs in Geriatric Patients
- 6 or more concurrent chronic conditions
- 12 or more doses of drugs/day
- 9 or more medications
- Prior adverse drug reaction
- Low body weight or BMI
- Age 85
- Estimated CrCl <50 mL/min
Principles of Prescribing for Older Patients
- Start with low doses
- Slowly titrate upward, as tolerated by the patient
- Avoid starting multiple new medications simultaneously
- Consider deprescribing medications if they are no longer necessary
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Description
This quiz focuses on the pharmacological considerations for drug dosing in special populations, particularly in relation to renal and hepatic diseases. Participants will learn to calculate renal function metrics and adjust medication dosages appropriately. The content also addresses pharmacokinetics in geriatrics and strategies to mitigate adverse drug events.
