16. CPK & KIDNEY Flashcards
(22 cards)
Explain how the fe of a drug predicts the need for dosage adjustment for patients with renal impairment
The doses of drugs with fe ≥ 0.5 (50% or more renally cleared) should usually be reduced in patients with renal disease
Higher fe = more drug excreted renally → needs more dosage adjustment in pts with renal disease
What does a low “Q” indicate?
a greater change in the dosing regimen is needed
Explain how CKD impacts bioavailability
- Alterations in intestinal or hepatic drug metabolism
- Alterations in uptake or efflux transporters
List variables that impact distribution in patients with CKD
- Vd: fluid volume
- Vp: plasma volume
- fu,t: tissue binding
- fu: protein binding
Describe the change in Vd for patients with CKD
increased fluid volume
Describe the change in Vp for patients with CKD
increased due to fluid overload
Describe the change in tissue binding (fu,t) for patients with CKD
Decreased tissue binding
Describe the change in protein binding (fu) for patients with CKD
generally increased:
- changes to albumin binding sites & reduced albumin
- accumulation of competing metabolites
- accumulation of endogenous inhibitors of binding
Describe the changes in metabolism due to CKD
- No overwhelming changes due to renal disease
- AVOID drugs that cause metabolite accumulation in pts with renal disease
Describe the changes in excretion due to CKD
Drug excretion markedly reduced (reduced renal Cl)
Describe the “intact nephron hypothesis”
Suggests that all renal drug elimination processes decline in parallel:
Glomerular filtration
Renal tubular secretion
Reabsorption
What weight should be used to calculate CrCl for a patient whose TBW < IBW?
TBW
What weight should be used to calculate CrCl for a patient whose TBW ~ IBW?
Use TBW or IBW
(they’re basically the same number)
What weight should be used to calculate CrCl for a patient whose TBW > IBW?
Use AdjBW
typically BMI is also 25+
What is the conversion factor for inches -> meters?
0.0254 m = 1 inch
List the assumptions that underlie the application of renal function estimation in dosage regimen adjustment for patients with renal disease
- Linear PK
- Drug does not follow non-linear PKs
- ClCr is an accurate assessment of renal function and Cl declines linearly with ClCr
- No changes in drug metabolism, metabolite formation, or absorption
- Unaltered drug absorption, protein binding, and ClNR
- No changes in drug response
What is the fraction of drug excreted unchanged?
fe
Ratio of the amount of drug excreted unchanged (Ae0-inf) in the urine to the fraction of drug absorbed (FD)
What equations can you use to estimated fe?
Ke/Kel
ClR/Cl
List assumptions made when using Q to calculate dosage adjustment
- ClCr is an accurate assessment of renal function and Cl declines linearly with ClCr
- Drug does NOT follow non-linear PKs
- Unaltered drug absorption, protein binding and ClNR
List the steps for adjusting pt dose using Q (dosage adjustment factor)
- Solve for KF
- Solve for Q using given fe
- Calculate the new dose/interval using Q
- Choose most practical dosing regimen
What are the options for changing a dosing regimen?
- Reduce dose & maintain dosing interval
- Extend the dosing interval & maintain dose
- Adjust both the dose & the dosing interval
What is the preferred option for changing a dosing regimen for pts with renal disease?
Extend the dosing interval & maintain dose
