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Pharmacology 2: Renal Dosing Flashcards

1
Q

What is the importance of dosing medications based on renal function?

A
  1. Avoid accumulation of drug and/or active metabolites
  2. Optimize pharmacologic effort
  3. Provide cost-effective therapy (reduced dose with equivalent efficacy
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2
Q

What are some examples of non-renal elimination?

A

Liver, feces, sweat

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3
Q

What are 3 factors in renal elimination?

A
  1. Glomerular filtration
  2. Tubular secretion
  3. Tubular reabsorption
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4
Q

What does the GFR represent?

A

The functional status of the kindeys (as renal mass decreases secondary to aging or disease) there is a progressive decrease in GFR

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5
Q

What is a normal GFR?

A

120 ml/min

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6
Q

For medications that require adjustments in kidney disease, what is the GFR when you would do this?

A

Below 50-60 (this is where the drug will begin to accumulate)

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7
Q

What is the GFR in stage 1 kidney disease?

A

Greater or equal to 90

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8
Q

What is the GFR in stage 2 kidney disease?

A

60-89

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9
Q

What is the GFR in stage 3 kidney disease?

A

30-59

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10
Q

What is the GFR in stage 4 kidney disease?

A

15-29

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11
Q

What is the GFR in stage 5 kidney disease?

A

Under 15 or dialysis

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12
Q

What are the drug characteristics that are predictive of a need to modify dosing in patients with renal disease?

A
  1. Potential change in volume of distribution
  2. % renal clearance
  3. Poor removal by dialysis
  4. Potential for adverse response
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13
Q

What are 3 situations where there might be a potential change in the volume of distribution?

A
  1. Acidic drugs (increase BUN and excrete N leading to uremia which will displace acidic drugs from their binding sites)
  2. Highly protein bound drugs (over 90%)
  3. Small volume of distribution
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14
Q

What are 2 examples of acidic drugs?

A

Phenytoin and warfarin

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15
Q

If a drug is bound to protein is it pharmacologically active?

A

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

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16
Q

What is the % cutoff of amount of a dose eliminate unchanged in urine where you worry about renal dosing?

A

30%

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17
Q

What are 2 features of a drug what can result in poor removal by dialysis?

A
  1. Highly protein bound (because it can’t cross the dialysis membrane)
  2. Large volume of distribution
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18
Q

What 2 drugs specifically do we worry about with potential for adverse response related to issues with renal clearance?

A
  1. Digoxin
  2. Aminoglycosides
    - Worry about active metabolites that depend on the kidney for elimination
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19
Q

What 4 criteria make for the ideal marker?

A
  1. Unrestricted (100%) diffusion across the glomerulus
  2. No additional or little tubular secretion or loss by reabsorption
  3. No additional metabolism by renal tubular cells
  4. Doesn’t alter renal function
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20
Q

Which marker is used mostly in clinical trials?

A

Inulin

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21
Q

Which 2 markers are used more in practice?

A

Serum creatinine and creatinine clearance

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22
Q

What is the most common clinical test for assessment of renal function to assess GFR?

A

Creatinine clearance (can be measured or estimated

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23
Q

What is creatinine?

A

Product of creatine metabolism from muscle (directly dependent on muscle mass)

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24
Q

What is the normal range of serum creatinine?

A

0.5-1.5

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25
If creatinine clearance decreases, what does serum creatinine do?
Rise
26
What % of serum creatinine is filtered and secreted?
90% filtered and 10% secreted (minimal reabsorption)
27
If serum creatinine doubles, what % loss of GFR does this correlate to?
50%
28
Is creatinine clearance better for long term or short term evaluation?
Long term (over time)
29
What are 5 factors that can increase serum creatinine?
1. Kidney disease (also muscle trauma) 2. Ingestion of cooked meat 3. Trimethoprim, cimetidine 4. Flucytosine, some cephalosporins 5. Ketoacidosis
30
What can decrease serum creatinine?
Malnutrition
31
Do you know the equation for creatinine clearance?
(Urine concentration * Urine flow rate)/Plasma concentration
32
What are disadvantages to 24 hour urine collection to measure creatinine clearance?
It's inconvenient, takes time to get results, and isn't reliable due to compliance
33
What is the most common formula used to estimate creatinine clearance?
Cockcroft-Gault
34
What 2 formulas are used for creatinine clearance that are easier to use because they don't require weight?
MDRD and CKD-EPI
35
Which equation is the most frequent value provided by laboratories to estimate GFR and stage kidney disease?
MDRD
36
Which equation was developed to more accurately assess GFR over 60ml/Min (compared to MDRD)?
CKD-EPI
37
What are the 3 benefits of MDRD and CKD-EPI equations?
1. Simplified (computer can do it) 2. Validates in various subgroups 3. Don't require weight for calculation
38
Limitations of MDRD and CKD-EPI equations?
1. Not validated in children 18 2. Limited data in elderly (over 70) --> Low serum creatinine concentrations may overestimate GFR 3. Not routinely used in studies to determine medication dosing
39
What are 3 fratures of the Cockgroft-Gault equation (used most frequently for adults)?
1. It is useful for estimating GFR in stable renal function (chronic renal failure) 2. It is not useful in estimating rapidly changing renal function (acute renal failure) 3. Low serum concentrations may alter results (overestimates true GFR)
40
4 Considerations in drug dosing in renally impaired patients?
1. Degree of renal elimination 2. Degree of renal insufficiency 3. Therapeutic window 4. Treatment indication/severity of illness
41
What are 2 options for dosing adjustments?
1. Change the dose | 2. Change the dosing interval
42
Did you look at the list he gave us of drugs requiring major dosing reduction?
GO DO IT
43
Consequence of aminoglycoside accumulation?
Ototoxicity and nephrotoxicity
44
Consequence of vancomycin accumulation?
Nephrotoxicity
45
Consequence of imipenem accumulation?
Seizures
46
Consequence of gabapentin accumulation?
Ataxia, dizziness, nystagumus, and somnolence
47
Consequence of valacyclovir accumulation?
CNS and renal failure
48
Consequence of famotidine accumulation?
Confusion
49
Consequence of lithium accumulation?
Sedation, confusion, seizures
50
Consequence of enoxaparin accumulation?
Bleeding
51
What are drug dependent factors in medication dosing in dialysis?
1. Molecular weight 2. Protein binding 3. Volume of distribution 4. Water solubility 5. Plasma clearance
52
What are dialysis dependent factors in medication dosing in dialysis?
1. Dialysis membrane | 2. Blood and dialysate flow rate
53
What size molecules pass easier through a dialysis membrane?
SMALL ONES
54
Does Chronic ambulatory peritoneal dialysis or hemodialysis have larger pores?
CAPD
55
Are medications that are bound to protein likely to pass through a hemodialysis filter?
NO
56
Does a larger or smaller volume of distribution correlated to a lower likelihood of being removed through dialysis?
Larger (disperse widely to tissues)
57
What types of drugs have a larger volume of distribution?
High degree of lipid solubility
58
If nonrenal clearance is large compared to renal clearance, is dialysis likely to contribute to drug removal?
NOPE
59
What is clearance equal too?
Renal and non-renal clearance
60
What % must dialysis increase renal clearance by to be considered clinically significant?
30%
61
If the blood flow rate is higher, what does this mean with amount of drug delivered?
More drug is delivered
62
If the dialysate flow rate is high, is the likelihood to drug rmeoval higher or lower?
Lower
63
If a drug is not removed by hemodialysis, is it likely to be removed by CAPD?
NO
64
What is supplemental dosing of a drug based on?
What % of the drug was removed during dialysis (if more than 30% of clearance was by dialysis)
65
What is continuous renal replacement therapy (CRRT)?
A technique that allows for continuous hemodialysis, hemofiltration, or hemdiafiltration using pump- assisted blood circulation that is continued for 24 hours (make sure to give supplemental doses to maintian adequate replacement of medications removed via dialysis)
66
What are the 2 features relating to the economic impact of renal dosing?
1. Direct cost savings (patient taking less drug) | 2. Indirect cost savings (decreased risk of adverse affect

Renal 2 (10 decks)

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