Dosage Adjustment: Renal Disease Flashcards
What are do the kidneys regulate?
- Body fluids
- Electrolyte balance
- Removal of metabolic waste
- Drug excretion from the body
What occurs during uremia?
- Decreased GFR and/or active secretion
- Leads to decreased in Clr and increased elimination t1/2
What PK processes and PD of drugs are altered by renal impairment?
- Drug distribution (Vd and protein binding)
- Drug elimination (biotransformation and renal excretion)
- Therapeutic and toxic responses may be altered as a result of changes in receptors sensitivity at the site of drug action
What PK parameters are changed in uremic patients?
F, Vd, and Cl
Why is F changed in CKD patients?
Exhibit pathophysiological changes in GIT that can impact drug absorption
How can F decrease from CKD?
- Increased gastric pH an to a lesser extent decreased GI motility
- Altered drug absorption in concomitant cirrhosis or CHF
How can F increase from CKD?
- High ER drugs
- Decreased in first pass metabolism
What can cause a decease in CLt fromm CKD?
CLr decreases due to decreasing GFR and secretion
CLh decreases from intrinsic clearance
What does Vd change from renal impairment?
- Changes in plasma protein binding
- Protein binding of many acidic drugs
Why are changes in plasma protein binding alone will not have a significant clinical implications?
An increase in the fraction of unbound drug may result in a corresponding increase in Vd and Cl resulting in a no net change in plasma drug concentrations
Is there more acidic drug protein binding for renal impairment?
Decrease in patients due to hypoalbuminemia
What are examples of drugs that undergo acidic protein binding?
- Penicillin
- Cephalosporin
- Aminoglycosides
- Furosemide
- Phenytoin
What type of drugs are less affected by CKD?
Weak basic drugs from AAG
What components should be a adjusted for renal impairment?
- LD based on Vd
- Maintenance dose based on Cl
- For drugs that are eliminated primarily by metabolism or biliary secretion, uremia may not alter PK sufficiently to warrant dosage adjustment
How does LD change from CKD?
Vd is not significantly altered, thus the LD is the same in uremic and normal renal patients
What do most dose adjustment methods assume?
After multiple doses, either oral, or IV bolus or infusion, the therapeutic drug concentrations in uremic (renal) patients is the same as that required in patients with normal renal function.
How do you calculate uremic patient if the dosing interval and F are unchanged using clearance?
How do you calculate uremic CLtotal?
We need to know renal (CLrenal), non-renal (CLnon-renal) clearances and the creatinine clearance (CLcr) both in normal and uremic patient.
How do you calculate clearance ratio of uremic and normal?
Describe the Drug A slope
- Is eliminated by both renal (CLRenal) and non-renal (CLNon-Renal).
- The y-intercept is the CLNon-Renal = 60 mL/min.
- CLRenal = (Slope of the line A) * (CLcr)
Describe Drug B slope
Is eliminated ONLY via the renal pathway, as the non-renal clearance, the y-intercept, is zero for this drug (CLNon-Renal = 0 mL/min).
Describe Drug C slope
- Is NOT eliminated by the renal pathway at all (as the slope is zero, CLRenal = 0 * CLcr = 0).
- Rather elimination is by the non-renal pathway (CLNon-Renal = 25 mL/min).
- Therefore, the clearance of drug C is not affected by the magnitude of creatinine clearance (CLCR).
How do you calculate uremic dose using k?
How do you calculate k ratio?
What is the purpose for nomogram method?
- Use in estimating dosage regimens in uremic patients
- Classifies drug (A-L) based on ratios of rate constant (k) in uremic and normal patients
- Provides an estimate of the ratio of the uremic elimination rate constant (kuremic) to the normal elimination rate constant (knormal) on the basis of CLcr
What do we do a dosage adjustment based on dosing interval?
