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45 Cards in this Set

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What drug dispositions does CKD affect? (4)
absorption, distribution, elimination, and metabolism
T/F:
Changes in protein binding induced by renal failure can alter the relationship between total drug concentration and response
True
T/F:
There are only expected changes in renal drug elimination in those pt w CKD
False,
Can change hepatic drug metabolism also in CKD
Individualization of a drug dosage regimen in a pt with CKD is based on the _____ of the drug and the pts level of _____
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_
The effect pf hemodialysis or chronic renal replacement tx on drug elimination is dependent on the characteristics of the ___ and the ___ conditions
The effect pf hemodialysis or chronic renal replacement tx on drug elimination is dependent on the characteristics of the _drug_ and the _dialysis_ conditions
What percentage of pts w CKD do NOT receive dose adjustments that are necessary?
41.1%
What does drug tx individualization involve?
one or many dose adjustments depending on the drug and fractional reduction in CrCl
What type of drugs require a more complex adjustments? (4)
Extensively metabolized
Extensively transported
Highly protein bound
Have altered pharmacodynamics
How can drug bioavailablity be altered? (4)
Changes in GI transit time and pH
GI tract edema
Vomitting and diarrhea
Anatacids
What are the clinical consequences of the increase of absolute bioavail. in CKD?
Excessive or unexpected ADR
What in the gut wall pumps drugs back into the lumen to prevent absorption?
P-glycoproteins
The Vd can be increased or decreased in pts w CKD due to what 3 things?
Increased/decreased protein binding
altered tissue binding
alteration in body composition
What are the general affects of acidic drugs on ppb in those w CKD (have decrease albumin lvls)?
They decrease binding and increase Vd
(warfarin, phenytoin)
What are the general affects of basic drugs on ppb in those w CKD (have increase lvls of alpha acid glycoprotein,aag)?
They increase binding and decrease Vd
(quinidine, lidocaine)
When fraction unbound is increased, what happens to free concentration?
Stays the same, due to the new equilibrium that is established as a result of increased drug elimination/distribution
What happens to total concentration as fraction unboune increases?
Reduced, due to increase in drug clearance and distribution
Net effect is the alteration in the relationship of ____ drug concentration and effect
Net effect is the alteration in the relationship of _TOTAL_ drug concentration and effect
Why is it important to measure FREE [...] when drug dosing in those pts w CKD?
Pts w CKD have hypoalbuminemia and the TOTAL [...] doesnt change while the FREE [...] is increasing which leads to toxicity
What other elimination pathways can CKD effect?
CYP450 in the liver and intestines reducing nonrenal clearance
Where are CYP enzymes most abundant?
Liver and intestine (uptake and efflux transporters)
By what mechanism does CKD affect drug metabolism and/or transport? (2)
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)
In CKD, how might a pt be exposed to a new chemical entity?
By the impairment of metabolite elimination leading to prolonged exposure to enterohepatic pathway
What equation describes net renal Cl?
Clr= (GFR*fu)+ Clsecretion - Clreabsorption
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
True
What are the overall effects for ADME in CKD?
Availability- increased in drugs
Distribution- increased Vd-acidic; decreased Vd-basic
Metabolism-decreased in CYP2C9; no change in CYP2E1,CYP2C19,CYP3A
Elimination- decreased
What is the goal of drug dosing in CKD?
Acheive steady state concentrations by adjusting dose or adjusting frequency of the dose
What drug characteristics are relevant in drug dosing adjustment strategies?
Extent of absorbed drug excreted unchanged in the urine (fe)
ADME
Therapeutic index/target
T/F:
A package insert is reliable for initial dosing recommendations
True, FDA requires testing w all drugs renally and hepatically
What are the 3 predominant modes of renal replacement therapy?
Hemodialysis, continuous RRT, peritoneal dialysis
How is hemodialysis given?
Intermittent: 2-4 hrs 2-3 times a week
Daily: 8-12 hrs every night
By increasing the SA of a filter youre ________ the dialysis effectiveness
By increasing the SA of a filter youre _increasing_ the dialysis effectiveness
What are the 2 processes that affect fluid and drug removal?
Diffusion and ultrafiltration/convection (pressure applied across a membrane)
What factors influence diffusion? (4)
membrane pore size, SA, MW of drug, and time on dialysis
What factors influence ultrafiltration/convection? (2)
Transmembrane pressure (TMP)
Ultrafiltrate coeff of dialyzer (how leaky the dialyzer is)
What drug characteristics are going to effect hemodialysis? (3)
MW, protein binding, Vd
Please list the conditions found on a hemodialysis Rx (5)
Blood flow rate
Dialysate flow rate
Dialysis membrane (Conventional vs high flux)
Time on dialysis
Dialysis reuse
T/F:
Vancomycin has to be dosed higher because of the increase in Cl during high flux dialysis
True
What is the seiving coeff (SC) useful for in continuous RRT?
To predict the likelihood that a drug withh cross the hemofilter membrane
What are the 3 primary continuous RRT categories?
Hemofiltration
Hemodialysis
Hemodiafiltration
What is the ratio of drug concentration in the ultrafiltrate to the prefilter plasma concentration?
Seiving coefficient (SC)
What does it mean when the SC is close to 1.0?
That the drug has relatively free passage across the filter
What is commonly used to estimate the SC?
Fraction unbound (fu) in plasma
*bolded, probably will be asked
What factors influence drug removal by peritoneal dialysis? (4)
Peritoneal blood flow
Dialysate instillation volume and dwell time (pt specific)
Osmotic ultrafiltration
Membrane resistance (infection)
T/F:
In general peritoneal dialysis is more effective in removing drug substances than hemodialysis
False
Hemodialysis is more effective in removing drug substance than peritoneal GENERALLY
T/F:
If a drug is NOT removed by hemodialysis it is NOT likely to be removed by peritoneal dialysis
True
*bolded!