Chapter 7 - Drug Clearance Flashcards
“clearance” is a theoretical concept that describes eliminating drug from the body without doing what???
WITHOUT IDENTIFYING THE SPECIFIC MECHANISM OF THE PROCESS – only care about how much is removed
TOTAL BODY CLEARANCE is a combination of what 2 things
renal clearance and non-renal clearance (but the non-renal clearance is usually negligible!!
name 4 factors that affect the clearance of a drug
age
sex
kidney disease
cardiac disease
how does age affect drug clearance
after the age of 70, clearance decreases
**how does sec affect drug clearance
clearance is 10% lower in females than in males
if a drug undergoes glomerular filtration ONLY, what will the clearance be
130mL/min
true or false
renal clearance changes depending on the drug
FALSE - same for every drug, just different depending on each patient’s renal function
2 methods of measuring renal clearance
-from the elimination rate constant on the plasma profile
-from the urinary excretion rate
true or false
renal clearance is NOT AFFECTED by drugs and their concentration
TRUE
renal clearance of kidney function of a subject is a CONSTANT VALUE and is not affected by varying drugs
true or false
just by looking at the clearance, it’s not possible to tell what the mechanism of excretion is
true
a drug ONLY undergoes glomerular filtration and some of it is reabsorbed
what is the range that the clearance can be
0-129mL/min
a drug undergoes both passive and active secretion. no reabsorption
what can the clearance range be
130-650mL/min
the clearance of a drug is CONSTANT over time
can we assume it is cleared through passive mechanism (glomerular filtration) only
yes
true or false
the graph of pure glomerular filtration is linear
TRUE
rate depends on plasma concentration - 1st order kinetics
the clearance value is LESS THAN the glomerular filtration rate (130mL/min)
what can be assumed?
the drug is reabsorbed
what is the normal value for TOTAL CLEARANCE
650mL/min
formula for half life of drugs solely eliminated through the kidneys
t1/2 = (0.693)(Vd)/Cl
true or false
as the Vd increases, the t1/2 decreases
FALSE
t1/2 increases as the Vd increases
true or false
if the volume of distribution is large, we may need to decrease the dose
false - increase. to keep the plasma concentration high
if clearance is high, half life can be expected to be….
short
true or false
as K decreases, Cl increases
FALSE - ANYTHING CAN HAPPEN TO Cl – we dont know
K does not affect Cl or V — Cl and V affect K
true or false
as K decreases, V increases
FALSE - ANYTHING CAN HAPPEN TO V – we dont know
K does not affect Cl or X
Cl and V affect K
define creatinine clearance
the rate of excretion of creatinine by the kidneys
how does calculating the creatinine clearance save time
dont have to inject the patient with mannitol and do the whole experiment
by what mechanism is creatinine excreted
mostly through glomerular filtration
however, a VERY SMALL amount is actively secreted - therefore the GFR values tend to be a tiny bit higher than if we had measured through inulin clearance
serum creatinine concentration of 2 represents a ____% kidney function
what about a serum creatinine concentration of 4?
50%
4 SCr - 25% renal function
name 3 methods of finding the creatinine clearance from the serum creatinine concentration
jelliffe method
cockcroft gault method
siersback-nielsen method
which method of finding creatinine clearance is NOT FOR PATIENTS UNDER 20 YEARS OLD
jelliffe method
true or false
the siersback-nelsen method is used to calculate creatinine clearance in MATURE ADULTS ONLY
FALSE - this is the jelliffe method
jelliffe method is usually only applicable up to what age
80 years old
3 factors for determining CrCl through the jelliffe method
age
serum creatinine conc
gender (2 diff eqns)
how does the cockcroft gault mehtod differ from the jelliffe method
accounts for age, serum creatinine, and gender, BUT ALSO INCLUDES WEIGHT AS A FACTOR
The siersback-nelsen method is similar to the ____ method of finding creatinine clearance
how?
cockcroft gault
because it accounts for the same 4 factors - age, weight, gender, and serum creatinine - but in nomogram form
95 year old patient has a CrCl of 42.75mL/min and SCr of 0/8mg/dl
the amount of drug in urine was 10.32mL
what do you have to say about her kidney function
just decreased efficacy due to aging. the serum creatinine is normal
only 10.32mL of drug was in the urine probably due to reabsorption - NOT KIDNEY FAILURE
true or false
according to the cockcroft gault equation, women are expected to have 90% the kidney function of men naturally
FALSE - 85%
jelliffe method estimates 90%
75 year old patient has a CrCl of 60.75mL/min and an SCr of 0.8mg/dl
there was found to be 60.75mL of drug in urine
what do you have to say
this is not kidney failure - just deterioration due to age
also this amount of drug in the urine indicates there was little-no reabsorption
patient has a creatinine clearance of 48mL/min
in what scenario would their clearance be exaclty 48mL/min
if the drug is ONLY REMOVED BY FILTRATION and no active secretion
how many scales are there in the siersback-nielsen method of finding CrCl
5
true or false
infants have an estimated eGFR of 130mL/min
FALSE - THIS CONCEPT DOESNT APPLY TO NEWBORNS!!!!!
there’s is like 3mL/min
what does “inulin clearance” refer to
the eGFR ONLY
what does “PAH clearance” refer to
the total excretion - not only filtration!
compare the water content of newborn vs adult
newborns have a higher water content
the half life of PAH and inulin tends to be ______ in a newborn than in an adult
longer half life in a newborn
2 methods of determining the creatinine clearance in PEDIATRICS
what are the parameters used?
-Schwartz and associate
-Traub and Johnson (another nomogram)
both only use height and serum creatinine!!
does NOT account for age or weight
drugs taken orally get to the liver through the hepatic vein or artery
hepatic portal vein and hepatic artery
leaves through vein
2 methods of finding the hepatic clearance
-from total clearance-renal clearance
-from hepatic extraction ratio
drugs with a MW of _____ are destroyed by the liver and cannot be removed by the kidney
500 or more
what is a very important factor that determines the extent of hepatic clearance
hepatic blood flow!
what does an HER of 0.25 mean
25% of the drug was removed from the plasma by the liver
the HER can range from ___ to ___. what do each of these values mean
0-1
if zero - NO drug was removed by the liver
if 1 - ALL of the drug was removed by the liver
