Drug Dosing In Ckd

Front 1

What drug dispositions does CKD affect? (4)

Back 1

absorption, distribution, elimination, and metabolism

Front 2

T/F:
Changes in protein binding induced by renal failure can alter the relationship between total drug concentration and response

Back 2

True

Front 3

T/F:
There are only expected changes in renal drug elimination in those pt w CKD

Back 3

False,
Can change hepatic drug metabolism also in CKD

Front 4

Individualization of a drug dosage regimen in a pt with CKD is based on the _____ of the drug and the pts level of _____

Back 4

Individualization of a drug dosage regimen in a pt with CKD is based on the _pharmacokinetics_ of the drug and the pts level of _renal fxn_

Front 5

The effect pf hemodialysis or chronic renal replacement tx on drug elimination is dependent on the characteristics of the ___ and the ___ conditions

Back 5

The effect pf hemodialysis or chronic renal replacement tx on drug elimination is dependent on the characteristics of the _drug_ and the _dialysis_ conditions

Front 6

What percentage of pts w CKD do NOT receive dose adjustments that are necessary?

Back 6

41.1%

Front 7

What does drug tx individualization involve?

Back 7

one or many dose adjustments depending on the drug and fractional reduction in CrCl

Front 8

What type of drugs require a more complex adjustments? (4)

Back 8

Extensively metabolized
Extensively transported
Highly protein bound
Have altered pharmacodynamics

Front 9

How can drug bioavailablity be altered? (4)

Back 9

Changes in GI transit time and pH
GI tract edema
Vomitting and diarrhea
Anatacids

Front 10

What are the clinical consequences of the increase of absolute bioavail. in CKD?

Back 10

Excessive or unexpected ADR

Front 11

What in the gut wall pumps drugs back into the lumen to prevent absorption?

Back 11

P-glycoproteins

Front 12

The Vd can be increased or decreased in pts w CKD due to what 3 things?

Back 12

Increased/decreased protein binding
altered tissue binding
alteration in body composition

Front 13

What are the general affects of acidic drugs on ppb in those w CKD (have decrease albumin lvls)?

Back 13

They decrease binding and increase Vd
(warfarin, phenytoin)

Front 14

What are the general affects of basic drugs on ppb in those w CKD (have increase lvls of alpha acid glycoprotein,aag)?

Back 14

They increase binding and decrease Vd
(quinidine, lidocaine)

Front 15

When fraction unbound is increased, what happens to free concentration?

Back 15

Stays the same, due to the new equilibrium that is established as a result of increased drug elimination/distribution

Front 16

What happens to total concentration as fraction unboune increases?

Back 16

Reduced, due to increase in drug clearance and distribution

Front 17

Net effect is the alteration in the relationship of ____ drug concentration and effect

Back 17

Net effect is the alteration in the relationship of _TOTAL_ drug concentration and effect

Front 18

Why is it important to measure FREE [...] when drug dosing in those pts w CKD?

Back 18

Pts w CKD have hypoalbuminemia and the TOTAL [...] doesnt change while the FREE [...] is increasing which leads to toxicity

Front 19

What other elimination pathways can CKD effect?

Back 19

CYP450 in the liver and intestines reducing nonrenal clearance

Front 20

Where are CYP enzymes most abundant?

Back 20

Liver and intestine (uptake and efflux transporters)

Front 21

By what mechanism does CKD affect drug metabolism and/or transport? (2)

Back 21

When you have CKD there is:
An accumulation of endogenous inhibitors (interfere w metabolism)
Chronic inflammatory state
(cytokines and oxidative stress cause and decrease in CYP enzymes, decreasing transporters thus decreasing metabolism)

Front 22

In CKD, how might a pt be exposed to a new chemical entity?

Back 22

By the impairment of metabolite elimination leading to prolonged exposure to enterohepatic pathway

Front 23

What equation describes net renal Cl?

Back 23

Clr= (GFR*fu)+ Clsecretion - Clreabsorption

Front 24

T/F:
For drugs that are extensively excreted (glucaronide conj), the loss of filtration Cl will have less of an impact than those drugs primarily dependent on GFR

Back 24

True

Front 25

What are the overall effects for ADME in CKD?

Back 25

Availability- increased in drugs
Distribution- increased Vd-acidic; decreased Vd-basic
Metabolism-decreased in CYP2C9; no change in CYP2E1,CYP2C19,CYP3A
Elimination- decreased

Front 26

What is the goal of drug dosing in CKD?

Back 26

Acheive steady state concentrations by adjusting dose or adjusting frequency of the dose

Front 27

What drug characteristics are relevant in drug dosing adjustment strategies?

Back 27

Extent of absorbed drug excreted unchanged in the urine (fe)
ADME
Therapeutic index/target

Front 28

T/F:
A package insert is reliable for initial dosing recommendations

Back 28

True, FDA requires testing w all drugs renally and hepatically

Front 29

What are the 3 predominant modes of renal replacement therapy?

Back 29

Hemodialysis, continuous RRT, peritoneal dialysis

Front 30

How is hemodialysis given?

Back 30

Intermittent: 2-4 hrs 2-3 times a week
Daily: 8-12 hrs every night

Front 31

By increasing the SA of a filter youre ________ the dialysis effectiveness

Back 31

By increasing the SA of a filter youre _increasing_ the dialysis effectiveness

Front 32

What are the 2 processes that affect fluid and drug removal?

Back 32

Diffusion and ultrafiltration/convection (pressure applied across a membrane)

Front 33

What factors influence diffusion? (4)

Back 33

membrane pore size, SA, MW of drug, and time on dialysis

Front 34

What factors influence ultrafiltration/convection? (2)

Back 34

Transmembrane pressure (TMP)
Ultrafiltrate coeff of dialyzer (how leaky the dialyzer is)

Front 35

What drug characteristics are going to effect hemodialysis? (3)

Back 35

MW, protein binding, Vd

Front 36

Please list the conditions found on a hemodialysis Rx (5)

Back 36

Blood flow rate
Dialysate flow rate
Dialysis membrane (Conventional vs high flux)
Time on dialysis
Dialysis reuse

Front 37

T/F:
Vancomycin has to be dosed higher because of the increase in Cl during high flux dialysis

Back 37

True

Front 38

What is the seiving coeff (SC) useful for in continuous RRT?

Back 38

To predict the likelihood that a drug withh cross the hemofilter membrane

Front 39

What are the 3 primary continuous RRT categories?

Back 39

Hemofiltration
Hemodialysis
Hemodiafiltration

Front 40

What is the ratio of drug concentration in the ultrafiltrate to the prefilter plasma concentration?

Back 40

Seiving coefficient (SC)

Front 41

What does it mean when the SC is close to 1.0?

Back 41

That the drug has relatively free passage across the filter

Front 42

What is commonly used to estimate the SC?

Back 42

Fraction unbound (fu) in plasma
*bolded, probably will be asked

Front 43

What factors influence drug removal by peritoneal dialysis? (4)

Back 43

Peritoneal blood flow
Dialysate instillation volume and dwell time (pt specific)
Osmotic ultrafiltration
Membrane resistance (infection)

Front 44

T/F:
In general peritoneal dialysis is more effective in removing drug substances than hemodialysis

Back 44

False
Hemodialysis is more effective in removing drug substance than peritoneal GENERALLY

Front 45

T/F:
If a drug is NOT removed by hemodialysis it is NOT likely to be removed by peritoneal dialysis

Back 45

True
*bolded!