Pharmacology 2: Renal Dosing Flashcards
What is the importance of dosing medications based on renal function?
- Avoid accumulation of drug and/or active metabolites
- Optimize pharmacologic effort
- Provide cost-effective therapy (reduced dose with equivalent efficacy
What are some examples of non-renal elimination?
Liver, feces, sweat
What are 3 factors in renal elimination?
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
What does the GFR represent?
The functional status of the kindeys (as renal mass decreases secondary to aging or disease) there is a progressive decrease in GFR
What is a normal GFR?
120 ml/min
For medications that require adjustments in kidney disease, what is the GFR when you would do this?
Below 50-60 (this is where the drug will begin to accumulate)
What is the GFR in stage 1 kidney disease?
Greater or equal to 90
What is the GFR in stage 2 kidney disease?
60-89
What is the GFR in stage 3 kidney disease?
30-59
What is the GFR in stage 4 kidney disease?
15-29
What is the GFR in stage 5 kidney disease?
Under 15 or dialysis
What are the drug characteristics that are predictive of a need to modify dosing in patients with renal disease?
- Potential change in volume of distribution
- % renal clearance
- Poor removal by dialysis
- Potential for adverse response
What are 3 situations where there might be a potential change in the volume of distribution?
- Acidic drugs (increase BUN and excrete N leading to uremia which will displace acidic drugs from their binding sites)
- Highly protein bound drugs (over 90%)
- Small volume of distribution
What are 2 examples of acidic drugs?
Phenytoin and warfarin
If a drug is bound to protein is it pharmacologically active?
NO..in renal patients, they usually have low protein stores and produce less albumin causing more active drug because not as much is bound to protein
What is the % cutoff of amount of a dose eliminate unchanged in urine where you worry about renal dosing?
30%
What are 2 features of a drug what can result in poor removal by dialysis?
- Highly protein bound (because it can’t cross the dialysis membrane)
- Large volume of distribution
What 2 drugs specifically do we worry about with potential for adverse response related to issues with renal clearance?
- Digoxin
- Aminoglycosides
- Worry about active metabolites that depend on the kidney for elimination
What 4 criteria make for the ideal marker?
- Unrestricted (100%) diffusion across the glomerulus
- No additional or little tubular secretion or loss by reabsorption
- No additional metabolism by renal tubular cells
- Doesn’t alter renal function
Which marker is used mostly in clinical trials?
Inulin
Which 2 markers are used more in practice?
Serum creatinine and creatinine clearance
What is the most common clinical test for assessment of renal function to assess GFR?
Creatinine clearance (can be measured or estimated
What is creatinine?
Product of creatine metabolism from muscle (directly dependent on muscle mass)
What is the normal range of serum creatinine?
0.5-1.5
If creatinine clearance decreases, what does serum creatinine do?
Rise
What % of serum creatinine is filtered and secreted?
90% filtered and 10% secreted (minimal reabsorption)