Drug Dosing in Special Populations

Drug Dosing in Special Populations

• Renal disease and hepatic disease can alter drug elimination or metabolism.
• Accurately calculate CrCl (Creatinine Clearance) and eGFR (estimated glomerular filtration rate) to adjust medication doses. Use reference resources such as Lexidrug.
• Define lab tests and clinical symptoms for Child-Pugh score calculation, which assists in hepatic-related dose adjustments.
• Provide generalized recommendations for hepatic dose reduction based on Child-Pugh score.
• Describe pharmacokinetic and pharmacodynamic changes in a geriatric population.
• Identify risk factors for adverse drug events (ADEs) in older adults and strategies to minimize the risk.

Renal Disease

• Kidney disease reduces the elimination of most drugs.
• Glomerular filtration is the primary method of renal drug elimination.
• Kidney function assessment utilizes glomerular filtration rate (GFR).
• Average GFR in a young adult is 120-140 mL/min. By age 65, average GFR decreases to 50-60 mL/min.

Equations to Assess Renal Function

• Cockcroft-Gault equation: used to measure creatinine clearance (CrCl).
  • CrCl = (140 - age) × weight (×0.85 if female) / 72 × serum creatinine
• CKD-EPI equation: The National Kidney Foundation recommends this for eGFR calculation.
  • eGFR calculation uses the formula: eGFR_cr = 142 x min(Scr/k, 1)^a x max(Scr/k, 1)^-1.200 x 0.9938^Age x 1.012 [if female]
  • This is an updated recommendation to estimate GFR since 2010

CrCl and eGFR

• CrCl was historically the primary method for renal drug dosing.
• Since 2010, eGFR from the CKD-EPI equation frequently used.
• CrCl and eGFR measurements are not interchangeable.

What to Consider When Making Renal Dose Adjustments

• Recognize the consequences of overdosing and underdosing in patients with impaired renal function.
• Use the goal of therapy as a guide (cure versus symptom management).
• Know the drug dosage range.
• Dose adjustments usually occur when CrCl or eGFR is less than 60 mL/min.

Tools for Calculating Renal Function

• Global RPh website
• National Kidney Foundation online tools
• MDCalc website

Practice Example

• A 67-year-old female with diabetes, neuropathy, and serum creatinine (SCr) of 1.5 is taking gabapentin.
• The example involves calculating CrCl and eGFR to determine appropriate dosages.

Hepatic Disease

• Most lipid-soluble drugs are metabolized by the liver.
• Hepatitis results in liver inflammation, which diminishes hepatocyte function and can temporarily lower drug metabolism.
• Cirrhosis is the permanent loss of functional hepatocytes.
• Reduced liver blood flow decreases drug delivery and ultimately effects drug metabolism.

Determination of Hepatic Function: Child-Pugh Score

• The Child-Pugh score evaluates liver function.
• The score combines various lab tests and clinical symptoms, including serum albumin, bilirubin, and prothrombin time.

Dose Adjustments in Hepatic Disease

• If a drug is metabolized by the liver at or greater than 60% of total metabolism.
• Typical recommendations for dose reductions vary based on Child-Pugh score. (e.g., C-P Score 8-9: -25%; C-P Score >10: -50%).
• Use medication database tools (e.g., Lexidrug) for guidance.
• Clinical reasoning is important when making dose adjustments based on the Child-Pugh score.

Drug Dosing in Geriatrics

Aging and Metabolism

• The liver is the primary location for drug metabolism.
• Decline in liver blood flow with age increases bioavailability of a drug. This reduced first-pass metabolism can lead to a higher concentration of the parent drug in the systemic circulation.
• Age-related changes in liver size and metabolic enzyme activity decrease drug clearance. This can lead to a longer half-life of a drug.

Aging and Drug Elimination

• Most drugs are excreted via the kidneys. Age-related kidney function decline reduces elimination rates, potentially resulting in drug accumulation and toxicity.
• Reduced lean body mass decreases creatinine production, which is further reflected in lower eGFR.
• Scr may not consistently reflect this reduction as it may appear normal.

Pharmacodynamics

• Time course and intensity of a drug's effect can change with aging.
• Medication utilization in the elderly is important to consider (e.g. Beers Criteria)

ADE Prescribing Cascade

• Adverse drug effects are misinterpreted as new conditions and initiate a cascade.

Risk Factors for Adverse Drug Events

• Multiple chronic conditions increase ADE risk.
• Increased pill burden (larger quantity of drugs taken each day).
• Prior adverse reactions to drugs.
• Low BMI/body weight.
• Age 85 or older.
• Estimated CrCl < 50 mL/min

Principles of Prescribing for Older Patients

• Start with low doses and titrate slowly, carefully observing patient response.
• Avoid starting multiple medications at once.
• Consider deprescribing (discontinuing) medications when appropriate.