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