Drug Dosing in Special Populations

Drug Dosing in Special Populations

• Presentation focused on adjusting drug dosages for specific patient groups.
• Topics included renal and hepatic disease, as well as geriatric considerations.

Renal Disease

• Kidney disease affects drug elimination of most medications.
• Most water-soluble drugs are excreted by the kidney through glomerular filtration.
• Kidney function is measured by glomerular filtration rate (GFR).
• Average GFR in young, healthy adults is ~120-140 mL/min.
• By age 65, average GFR declines to ~50-60 mL/min.
• Equations like Cockcroft-Gault and CKD-EPI are used to calculate creatinine clearance (CrCl) and eGFR, respectively.
• CrCl = (140-age) × BW/(72×SCr) × 0.85(if female).
• eGFR values are recommended by the National Kidney Foundation to calculate kidney function.
• CrCl and eGFR should not be used interchangeably.
• Dosing adjustments are needed when CrCl or eGFR decreases to below 60 mL/min.
• Factors to consider when making renal dose adjustments include; consequences of overdosing, under-dosing, goal of therapy and dosing range of the drug.
• Tools for calculating renal function include Global RPh, calculators (multiple Creatinine Clearance Methods) and National Kidney Foundation calculator tools and MD Calc.

Hepatic Disease

• Most lipid-soluble drugs are metabolized by the liver.
• Hepatitis, an inflammation of the liver, reduces the liver's ability to metabolize drugs transiently.
• Cirrhosis permanently damages the liver, reducing its functional capacity and blood flow to the liver.
• Decreased blood flow to the liver reduces drug delivery to functioning hepatocytes.
• Child-Pugh score uses lab tests (albumin, bilirubin, prothrombin time) and clinical symptoms (ascites, hepatic encephalopathy) to evaluate liver function.
• Severity of cirrhosis is classified by the Child-Pugh score, with scoring systems used to categorize the level of liver damage.
• For drugs that are ≥60% metabolized by the liver, adjustments may include decreasing the dose by 25% for Child-Pugh scores between 8-9, or 50% if the score is above 10.

Geriatric Considerations

• Aging affects various aspects of drug metabolism and elimination.
• Older adults, sometimes exhibit a decrease in liver blood flow.
• A decrease in cardiac function also results in a decrease in liver blood flow, reducing drug delivery to the liver.
• Older adults typically have a reduced liver size.
• Older adults also may experience a reduction in the amount of enzymes necessary for drug metabolism in the liver.
• Age-related changes can also lead to lower GFR.
• Creatinine Production is also reduced with age.
• Factors to consider that can cause adverse drug events include; prior adverse drug reactions, low body weight or body mass index, age 85 and older and estimated CrCl less than 50ml/min.
• Lower CrCl and GFR values (less than 60 ml/min) for elderly adults may cause adverse effects.
• Principles for prescribing medications to older adults include; starting with low doses, slowly titrating to the necessary dose, avoid starting multiple drugs at once and consider deprescribing.

Practice Example

• A 67-year-old female taking gabapentin for neuropathy with other medical conditions is used as an example.
• Practical application of the principles discussed above.

Additional information

• Adverse drug events (ADEs) can arise from drug interactions, use of multiple drugs, or inappropriate dosages.
• A cascade, where one ADE prompts the use of further drugs, can lead to a chain of additional ADEs.
• General guidelines to avoid adverse effects for elderly patients include lower starting doses, slow increases in medications, avoiding starting several drugs at once, and considering deprescribing.