Podcast
Questions and Answers
Which of the following is the primary route of elimination for most water-soluble drugs?
Which of the following is the primary route of elimination for most water-soluble drugs?
What is the approximate average eGFR (estimated Glomerular Filtration Rate) in a healthy young adult?
What is the approximate average eGFR (estimated Glomerular Filtration Rate) in a healthy young adult?
Which equation is specifically designed to assess renal function for the purpose of drug dosing?
Which equation is specifically designed to assess renal function for the purpose of drug dosing?
For accurate calculation of Creatinine Clearance (CrCl) using the Cockcroft-Gault equation, which patient weight should be used?
For accurate calculation of Creatinine Clearance (CrCl) using the Cockcroft-Gault equation, which patient weight should be used?
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What primary purpose was the CKD-EPI equation developed for?
What primary purpose was the CKD-EPI equation developed for?
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Prior to 2010, what was the primary method used to determine renal dosing adjustments for drugs?
Prior to 2010, what was the primary method used to determine renal dosing adjustments for drugs?
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Why is it crucial to consider the potential consequences of overdosing a drug when making renal dose adjustments?
Why is it crucial to consider the potential consequences of overdosing a drug when making renal dose adjustments?
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Which of the following best describes the relationship between CrCl and eGFR?
Which of the following best describes the relationship between CrCl and eGFR?
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What is the primary concern related to adverse drug effects in older patients, as indicated by the prescribing cascade?
What is the primary concern related to adverse drug effects in older patients, as indicated by the prescribing cascade?
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Which of the following is a key principle when prescribing for older patients?
Which of the following is a key principle when prescribing for older patients?
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What factor contributes to a higher risk of adverse drug events in elderly patients?
What factor contributes to a higher risk of adverse drug events in elderly patients?
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Which approach to medication management is recommended for older adults to improve safety?
Which approach to medication management is recommended for older adults to improve safety?
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What is a common risk factor for adverse drug effects related to kidney function in older adults?
What is a common risk factor for adverse drug effects related to kidney function in older adults?
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What is the primary reason for starting with a reduced drug dosage in older patients?
What is the primary reason for starting with a reduced drug dosage in older patients?
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How does aging impact the pharmacokinetics of drugs in older adults?
How does aging impact the pharmacokinetics of drugs in older adults?
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Which of the following is NOT a factor contributing to reduced renal function in older adults?
Which of the following is NOT a factor contributing to reduced renal function in older adults?
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Why is it important to calculate creatinine clearance (CrCl) and estimated glomerular filtration rate (eGFR) when dosing drugs in older patients?
Why is it important to calculate creatinine clearance (CrCl) and estimated glomerular filtration rate (eGFR) when dosing drugs in older patients?
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What is the primary site of drug metabolism in the body?
What is the primary site of drug metabolism in the body?
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What is the effect of decreased liver blood flow in older adults?
What is the effect of decreased liver blood flow in older adults?
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How does age affect drug pharmacodynamics?
How does age affect drug pharmacodynamics?
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Study Notes
Drug Dosing in Special Populations
- The presentation discusses drug dosing considerations for special populations, focusing on renal and hepatic disease, as well as geriatrics.
- Objectives include describing how renal and hepatic disease affect drug elimination/metabolism, accurately calculating renal function using CrCl and eGFR, adjusting medication dosages using those measurements and reference materials, defining lab tests/symptoms for Child-Pugh score calculation, and describing pharmacokinetic/pharmacodynamic changes in geriatric populations.
Renal Disease
- Kidney disease reduces the elimination of most drugs.
- Primarily, glomerular filtration is the route for eliminating most medications.
- Kidney function is measured by the glomerular filtration rate (GFR).
- Average GFR in healthy young adults is ~120-140 mL/min.
- By age 65, average GFR is ~50-60 mL/min.
Renal Drug Elimination Calculations
- Cockcroft-Gault equation calculates creatinine clearance (CrCl):
- CrCl = (140 - age) × weight (kg) / (72 × serum creatinine (mg/dL)) × 0.85 (if female).
- CKD-EPI equation, recommended by the National Kidney Foundation, calculates estimated GFR (eGFR).
- eGFRcr = 142 x min(Scr/k, 1)^a x max(Scr/k, 1)-1.200 x 0.9938Age x 1.012 [if female].
CrCl vs. eGFR
- CrCl was the standard for drug dosing until 2010.
- Now, many drugs use eGFR for renal dosing.
- CrCl and eGFR are not interchangeable.
Considerations for Renal Dose Adjustments
- Overdosing consequences should be considered.
- Underdosing consequences depend on therapeutic goals (cure vs. symptom management)
- Always assess the drug's dosing range.
- Dosing adjustments usually start when CrCl or eGFR is <60 mL/min.
Tools for Renal Function Calculation
- Global RPh (www.globalrph.com)
- National Kidney Foundation calculators.
- MD Calc (www.mdcalc.com)
Hepatic Disease
- Lipidsoluble drugs are primarily metabolized by the liver.
- Hepatitis is liver inflammation, decreasing the liver's functional ability.
- Mild cases of hepatitis temporarily decrease metabolization.
- Cirrhosis is a permanent loss of liver function caused by loss of hepatocytes.
- Reduced liver blood flow limits drug delivery.
Determining Hepatic Function: Child-Pugh Score
- There's no single test to assess liver function.
- The Child-Pugh score is used to estimate hepatic function.
- It combines lab values and clinical symptoms (serum albumin, total bilirubin, prothrombin time, ascites and hepatic encephalopathy).
- The score classifies severity, affecting how a drug is metabolized
Dose Adjustments in Hepatic Disease
- Drugs metabolized ≥60% by the liver may require reduced doses.
- Clinical judgment is often needed, as well as using dosing recommendations from reference materials.
- Typical recommendations:
- C-P Score 8-9: decrease dose ~25%
- C-P Score >10: decrease dose ~50%
Drug Dosing in Geriatrics
- Aging affects drug metabolism, frequently impacting drug elimination via the kidney.
- Reduced elimination can lead to drug accumulation and toxicity.
- Lower GFR and reduced lean body mass (affecting creatinine production) are among the contributing factors for reduced clearance in the elderly.
- Creatinine may seem normal, while actual clearance is reduced.
Aging and Metabolism
- Liver is the primary site for drug metabolism.
- Decreased liver blood flow and reduced size increase bioavailability and reduce first pass metabolism.
- Reduced metabolizing enzymes result in decreased clearance and prolonged half-life (t1/2)
- Lower doses are usually recommended for the elderly
Pharmacodynamics in Geriatrics
- Time course and intensity of drug effects may change with aging; these changes vary significantly amongst individuals.
- The 2023 updated Beers Criteria classifies inappropriate medications for use in older adults, aiding in the proper drug selection and preventing potential adverse effects.
Adverse Drug Events (ADEs) Prescribing Cascade
- An adverse effect from a drug can be misinterpreted as a new medical condition.
- This misdiagnosis could lead to prescribing another drug, further perpetuating the cycle of adverse effects.
Risk Factors for ADEs in Geriatrics
- Multiple chronic conditions (>6)
- High daily drug doses (>12)
- Numerous medications (>9)
- Prior adverse drug reactions
- Low body weight/mass index
- Age ≥ 85
- Low CrCl (<50 mL/min)
Principles of Prescribing for Older Patients
- Start low, slow increases as appropriate.
- Avoid prescribing multiple new drugs at once.
- Consider deprescribing (removal/lowering doses of unnecessary drugs).
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Description
This quiz explores drug dosing considerations for populations with renal and hepatic diseases, focusing on pharmacokinetics in geriatrics. Learn how to calculate renal function and adjust medication dosages based on clinical measurements. Prepare to understand the implications of kidney health on medication efficacy.
