dialysis and renal dosing

brady, renal

renal drug excretion is the major route for which types of drugs

polar drugs

water soluble drugs

drugs with low molecular weight

drugs that are biotransformed slowly

drugs are excreted though the kidney into the urine by…

glomerular filtration

active tubular secretion

tubular reabsorption

glomerular filtration is a ___ process

passive

glomerular filtration depends on ___ and ____

GFR(CL_GFR) and the fraction of the drug not bound to plasma proteins

f_u stands for

fraction of drug not bound to plasma protein

equation for glomerular filtration

CL_GFR=GFR x f_u

active tubular secretion is carrier mediated that requires ___

energy

how many tubular secretion pathways are there in the kidneys

2

examples of weak acids that go through active tubular secretion pathways

probenecid

penicillin excretion

examples of weak bases that go through active tubular secretion pathways

cimetidine and creatinine

tubular reabsorption is a ___ process

passive

tubular reabsorption depends on

degree of lipophilicity

degree of ionization (pka and pH)

urine flow rate

increased urine flow rate due to diuretics will lead to an ____ in the time for drug reabsorption

decrease

what are the indexes of renal function

glomerular filtration rate (GFR)

creatinine clearance (CrCl)

drugs are usually filtered though the glomerulus in a nonselective process if they are in _____ form

free, non-protein bound

units of renal function are expressed in

volume per time

what is the best overall index of renal function in health and disease

glomerular filtration rate

glomerular filtration can be directly measured but…

collection is often unreliable

GFR is estimated based on…

substances that are filtered in the glomerulus

GFR can be estimated based on the substances that are filtered in the glomerulus but they must be ____ and must have ____

freeely filtered

minimal secretion/reabsorption in the renal tubules

what is most commonly used to estimate GFR

creatinine clearance

what is the basis for most renal dosing recs on package inserts

creatinine clearance

creatinine is a metabolic product of ____

muscle

the rate of creatinine formation determined by ____

muscle mass or lean body weight

creatinine is distributed in ____

total body water

creatinine is not bound to ____

plasma proteins

creatinine is freely filtered at the ____

glomerulus

how is creatinine measured

24 hour urine collection, the serum creatinine sample is taken at midpoint of the urine collection period

what is this equation used for? (note this equation is given on the test, need to know how and why to use)

used to estimate of renal function from timed urine collection

what are the equation options for estimating renal function at steady state SCr concentrations

crockcroft gault equation

MDRD equation

CKDEPI

crockcroft gault estimates ___ and is the most commonly used for medication adjustments

creatinine clearance

MDRD equation can estimate ___

GFR

CKD-EPI equation estimates ___ and is more accurate than ___ equation

GFR;

MDRD

which equation should be used for estimation of renal function in pts with non steady state SCr concentrations

jelliffe equation

which equation should be used to estimate renal function in pts who are obese

salazar and corcoran equation

male IBW formula (not given)

female IBW formula (not given)

when to use the actual body weight

ABW<IBW

when to use adjusted body weight

when ABW is > 120% of IBW

adjusted body weight formula (not given)

if you were to use the jelliffe equation you would first need to estimate…

creatinine production

after estimating the creatinine production using the jelliffe equation, you then need to…

correct Cr production for renal function and adjust the estimated CrCl value based on if the function is getting better or worse

what are the 3 approaches to dose modification for pts with renal insufficiency

Decrease the drug dose and retain the usual dosage interval

Retain the usual dose and increase the dosage interval

Simultaneously decrease the dosage and prolong the dosage interval

dose modification for pts with renal insuff depends on…

route of administration, the dosage forms available, and the pharmacodynamic response to the drug

factors to consider when adjusting doses for renal insuff pts

crcl is a starting point

toxicities

clinical conditions

which meds commonly need renal adjustments

most antibiotics

some diabetes meds

lovenox (enoxaparin)

crestor (rosuvastatin)

brand name of enoxparin

lovenox

brand name of rosuvastatin

crestor

meperidines metabolite (normeperidine) is____ and can lead to ____

neurotoxic; seizures

NSAIDs ___ diuretic response and ____ risk of hyperkalemia if taken with K+ sparing diuretics, ACEis, or ARBs

decrease; increase

chlorpropamide has an _____ half life when taken by pts with renal insuff

increased

metformin renal dosing is based on ____

GFR

pts with renal insuff have ____ clearance of exogenously admin insulin

decreased

AMGs and vanco need renal adjustments bc…

they tend to accumulate and can lead to nephrotoxicity

cimetidine, triamterene, and trimethoprim all ____ of Cr so they lead to a rise in SCr

inhibit tubular secretion

cimetidine, triamterene, and trimethoprim all inhibit tubular secretion of Cr so they lead to…

a rise in SCr

HD depends on

Membrane composition and surface area

Blood and dialysate flow rate

Duration of dialysis treatment

Number of times dialyzer has been use

flow of blood through the dialyzer (QD) varies from ____

100-400 mL/min

increased blood flow rates occurring in HD will lead to

deliver greater amounts of drug to the dialysis membrane

what 4 things determine the dialyzability of a drug

Molecular weight

Water/lipid solubility

Plasma protein binding

Volume of distribution

which sized molecules are more easily removed

small ones (<500 Da)

to be dialyzied a drug has to be ____ in the dialysate solution

soluble

Water ____molecules will tend to remain in the blood compartment rather than diffusing into the dialysate

insoluble

what is the most important determinant of a drug’s dialysance

plasma protein binding

Only _____ (bound or unbound) drug molecules can pass through the pores in the semipermeable dialysis membrane

unbound

Small volumes of distribution (< 1 L/kg) usually demonstrate _____ dialysis clearance rates

high

examples of drugs with small volumes of distribution

AMGs and theophylline

Large volumes of distribution (> 2 L/kg) are generally, _____ for removal by dialysis

NOT available

examples of drugs with large volumes of distribution

digoxin and tricyclic antidepressants

fick principle

arterial-venous difference

dialysance directly measures the efficiency of…

extraction

what is ultrafiltration

Net loss of blood as it passes through the unit

if ultrafiltration leads to the venous blood sample being…

concentrated, artificially elevated

if ultrafiltration occurs it leads to the dialysance being

underestimated

measurements of dialysance can be wrong up to

30% off of what it should be

which parameter is used to predict the time required to remove a given fraction of drug from the body

half life

T or F: Whatever affects half-life of a drug during a dialysis period will influence how effectively dialysis removes a given fraction of drug from the body

T

T or F: Shortest half-life gives largest fraction removed

T

what determines half life

clearance, Volume of distrib