Drug Dosing Flashcards
What patients require assessment of drug dosing
- Medical History
CKD
Diabetes
Hypertension
Age
Vascular Disease
What patients require assessment of drug dosing
- Drugs
Nephrotoxic drugs
Drugs that require significant renal excretion
Why do we assess drug dosing in renal impairment
Prevent toxic effects
Prevent kidney damage
CKD and ADME
Absorption
- Edematous (Fluid swollen) GI tract reduces absorption
Distribution
- Reduced protein binding = Increase Vd
–> Phenytoin
- Altered tissue binding = Less affinity for binding sites = Decrease Vd
–> Digoxin
Metabolism
- Reduced metabolism from uremic toxins
Excretion
- Reduced excretion of drugs that are renally eliminated
How do we assess kidney function
Creatinine is the best estimate of GFR
- Almost all is exclusively eliminated by glomerular filtration
What affects serum creatinine
Age
Weight
Malnutrition
Amputation
Biological Sex
Muscle Wasting
Hydration
Serum Creatinine in Elderly
Will be reduced due to low muscle mass
- Produces less creatinine
Different BMI Classes
- Classification
- Which weight to use
Underweight (<18.5)
- Use Actual Body Weight (ABD)
Normal Weight (18.5-24.9)
- Use Ideal Body Weight (IBW)
Overweight (>25)
- Use Adjusted Dosing Weight (DW)
Cockcroft-Gault Equation and the different body weights
IBW will underestimate CrCl
ABW will overestimate CrCl
DW improves accuracy
No standard in assessing obese patients
What do we use eGFR for
Identifying the stage of Kidney Dysfunction
- Mainly used for initial information about kidney function
Cockcroft-Gault vs eGFR
Cockcroft-Gault is used to validate drug dosing
eGFR has to much variability and can result in different dosing recommendations
Calculating Cockcroft-Gault for Transgender Patients
If patient has been on hormone therapy for longer than 6 months use the gender they are transition into instead of biological sex
Steps to adjusting dose
- Review patient history, demographic, clinical history. Then obtain eGFR from lab with serum creatinine
- Calculate creatinine clearance (Use either appropriate weight or no weight)
- Review current medications, determine which drugs need to be altered
- Use drug dosing references to determine appropriate dosage
- If appropriate empirically adjust the dose/interval - Monitor for response and adverse effects
- Revise regimen based on response
Questions to ask when considering drug dosing
- Is an immediate effect required?
- Is drug effective/safe for patient with renal failure
- Is drug nephrotoxic
- Is drug >50% renally eliminated
- Dose the drug have toxic metabolies
- Are there other options besides dose adjustment
Drug Classes that require Dosage Adjustment in CKD
Anticoagulants
Anti-hyperglycemic agents
Antimicrobials and related agents
Centrally Acting Drugs (Opioids, Gabapentin)
Cardiac Drugs
GI Drugs
What do we have to consider for dialyzed drugs
Molecular Weight
Protein Binding
Volume of Distribution
Water Solubility
Dialysis Membrane
Blood/Dialysate Flow Rate
Molecular Weight Impact on Clearance
Larger the molecule the lower the clearance
Protein Binding Impact on Clearance
The more protein binding the lower the clearance
Volume of Distribution Impact on Clearance
The more Volume Distribution the lower the clearance
Water Solubility
The higher the water solubility the greater the clearing
Dialysis Membrane
Pore size, surface area, and geometry can affect clearance
High flux membrane (larger pores) can clear higher molecular weight drugs
Blood/Dialysate flow rate Impact on Clearance
Increases with blood flow rates, greater dialysis rates can increase clearance
