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Science
Medicine
pharmacokinetics
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Flashcards
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Terms in this set (90)
pharmacokinetics =
what the BODY does to the drug
Pharmacokinetics  4 things that occur after administration
distribution
absorption
metabolism
elimination
volume of distribution is the volume that is necessary to cotain the drug ________ at the concentration found in the blood, plasma, water, or all combined
homogeneously
Vd is calculated at time ____ which is the _____ volume of fluid that the drug would occupy if the entire dose were distributed instantly throughout that volume
0
apparent
we know that in real life the drug does not distribute instantly throughout their volume
it takes time for the drug to come to equilibrium with different _____
drug may be lipophilic so need to fill _______ to have enough for _____
compartments
compartment
plasma
remember we are measuring the drug conc in the plasma both ____ and _____ _____
free
albumin bound
a drug that is heavily bound to tissue (protein) or stored in fat will have a low or high Vd
high
drug that has a Vd > TBW is assumed to be ________ and will require a _____ dose to acheive a given plasma conc
goes into cells instead of staying in the ______
lipophilic = unionized
higher
ECF (plasma + ISF)
the higher the Vd = the _____ the loading dose
higher
a drug that has a Vd < TBW is assumed to be _______ and will require a ____ dose to acheive a given plasma conc
stays in the _____ rather than going into cells
hydrophilic  ionized
lower
ECF (plasma + ISF)
Vd is affected by drug characteristics (3)
Vd is affected by patient characteristics (2)
drug
molecular size
ionization
protein binding
patient
burns
pregnancy
be able to calculate Vd with graph given
...
Vd can be given as an apparent volume in L or in units of L/Kg of patients weight = always check
units
**inverse or linear relationship between Vd and rate of elimination
meaning the larger the Vd = the ______ the rate of elimination
if a drug is in a large volumevery little is able to interact with the ______ mechanism like GFR (fixed)
inverse
slower
elimination
breakdown TBW
TBW =
intracellular =
extracellular =
plasma =
RBCs =
total blood =
interstitial =
TBW = 4042L
intracellular = 2/3
extracellular = 1/3 1214L
plasma = 3L
RBCs = 2L
blood = 5L
interstitial = 10L
volume of distribution formula
Vd = dose / [D0]
clearance = the body's ability to
eliminate the drug
2 major sites of elimination
liver
kidneys
2 other elimination methods
hoffman elimination (cisatricurium/nimbex)(no kidneys or liver)
pulmonary elimination
clearance often involves more than one route of
elimination
kidneys + liver
liver clearance
difficult to measure directly unlike the kidneys (GFR) so it is often estimated as
systemic minus all others
3 forms of kinetics
first order
zero order
mixed order
homogeneous drug solution means what
drug is distributed evenly
most common form of elimination?
first order kinetics
first order kinetics:
elimination is directly proportional to
concentration
first order kinetics:
can be estimated by area
under the curve (AUC)
*firstorder kinetics:
clearance in this case is calculated by
dose / AUC
first order kinetics:
curved line graph
yaxis: units are ____ to xaxis (time)
can see how much drug is left at a place in
equal
time
first order kinetics:
straight line graph
yaxis: units are not equal =
logrithmic
first order kinetics:
t1/2 is the duration for
half of the remaining drug to be _____
OR
half of the remaining drug to be _____
half of the process to be complete
absorbed
eliminated
after we complete 1 half life  how much of the drug is remaining?
after another half life is completed how much remains?
50%
50% of what was left aka the remaining
does t1/2 tell you about clinical duration of a drug?
propofol t1/2 is 6hrs
propofol clinical effects off after 5 min
means that the concentration of propofol needed to exert clinical effect is _____ the threashold but sill ____ in blood
no
below
remains
t1/2 is a function of ___ in
rate = [D]k
k
t1/2 = 0.693/k
...
2 constants
ka = constant governing ___
ke = constant governing ___
in first order kinetics talking about which one?
absorption
elimination
elimination
first order kinetics:
if ke = 0.1/hr this means _____ of the remaining drug is eliminated per hour
t1/2 = 0.693/k
t1/2 = 0.693/0.1
t1/2 =
at the end of the t1/2 how much drug will be left?
10%
6.93 hours
half
first order kinetics:
the rate of elimination changes as a function _____ of a drug
more drug = ___ elimination
as time passes less drug = ____ elimination
[D] is always declining so rate is always getting ___
[D] concentration
more
less
slower
first order kinetics:
in contrast to rate of elimination, ___ and ___ do not change with [D]
they are ____
how fast those processes are occuring are the ______ no matter the [D]
k
t1/2
constants
same
first order kinetics:
t1/2 assumes the body is a ______ compartment and there is a _____ time course for each drug
same
predicable
first order kinetics:
another way to think about t1/2 is the
________ / _______
t1/2 = 0.7 x Vd/CL
where 0.7 is the natrual log of 2
volume of distribution
clearance (how fast getting cleared)
first order kinetics:
when is this first order process complete?
never
*first order kinetics:
what do we consider complete first order kinetics
4 5 t1/2 lives
first order kinetics:
% remaining and complete
4 half lives
5 half lives
93.75 complete
96.875 complete
zero order kinetics:
rate =
this means the rate is
_____ of the drug is irrelavant
classic example
k
constant
concentration
alcohol
zero order kinetics:
natural graph is a
straight line
zero order kinetics:
compared to first order in which a lot of the drug is eliminated in the first 2 hours  in zero order the rate is the
same
zero order kinetics:
is half life useful?
no
mixed kinetics/masslaw/capacitylimited:
also known as
mixed order
mixed order kinetics:
dose dependent on how ____ the drug is _____
quickly
metabolized
mixed order kinetics:
at high doses _____ order
at low doses _____ order
zero
first
mixed order kinetics:
do we know exactly when the order switches?
could be dependent on a biologic process
process could be affected by another drug
ginko biloba
no
mixed order kinetics:
potential serious ______
initial dose is ____ order
drug eleminiation does/does not increase with [D]?
gives you info for _____ interval
toxicity
zero
dose not
redosing interval
drug accumulation:
caused by
repeate dosing
drug accumulation:
inversely proportional to _______ of the dose lost in each dosing interval
(drug accumulation is inversely proportional to how much went away)
(how many t1/2s have gone by)
(zero or first order?)
fraction lost = 1  fraction remaining just before _____
fraction remaining is estimated from ______ and ______
drug given 1x every t1/2
accumulation factor =
fraction
next dose
dosing interval
half life
1/0.5 = 2
bioavailability:
how much of the drug is available to do what
what it is being asked to do
bioavailability:
fraction of unchanged drug able to reach ______ _____ following administration
systemic circulation
bioavailability:
factors impacting bioavailability (2)


extent of absorption
first pass elimination
bioavailability:
IV?
IM
SL
SC
PO first pass
rectal
Inhalation
TD
bioavailability:
what else effects this that effects preop patients and their home meds
fasting vs unfasting
First pass elimination:
applies to ______ administered drugs
orally
*First pass elimination:
_______ blood flow delivers drug to _____ prior to entry into the systemic circulation
portal
liver
First pass elimination:
drug can be metabolized directly by the ___ ___ or ____ ____ itself
gut wall
portal blood
First pass elimination:
most commonly, _____ metabolism or excretion into ____ is the major source of decreased bioavailability
liver
bile
First pass elimination:
can be used on purpose in
prodrugs
First pass elimination:
effect of first pass elimination can be calculated by the
extraction ration
First pass elimination:
extraction ratio formula
CL is given
Q is hepatic blood flow and normally
ER = CL(liver)/Q
90l/h
rate of absorption:
different from ____ of absorption
how much different than how fast
100% may be absorbed into the adipose tissue but 0% bioavailabe
2 drugs may 100% absorb into adipose
one in 5 min
one in 5 hours
extent is the same
rate is different
extent
rate of absorption:
determined by (2)


site of administration
drug formation
Immediate effects:
effects are related to ____ ______
need to get to some sort of plasma concentration, above which i will see _____
but also keep below concentration that will cause
plasma concentration
effects
toxicity
Immediate effects:
related to C50 aka the =
concentration associated with 50% maximum effect
Immediate effects:
linear relationship?
at some point /concentration you dont get anymore _____
no
effect
Immediate effects:
in clinical setting you can overshoot C50 and half lives dont matter for awhile
when you get close to C50 you need to know timing to keep above via
half lives
delayed effects:
changes in drug effects in relation to
plasma concentration
delayed effects:
delay is see because time required for drug to get from _____ to _______
plasma
site of action
delayed effects:
most exaggerated delay are related to ______ of substances involved in _______ of a drug
example = warfarin and vit k epoxide reductase
turnover
expression
delayed effects:
does every drug have one?
yes
maintenance dose:
rate out =
rate in
maintenance dose:
attempting to acheive a
steady state of drug
maintenance dose:
amount given = replacement of
drug eliminated
maintenance dose:
______ is the most important parameter here
clearance
maintenance dose:
rate in = rate out mathematically is
Css =
dose rate =
Css = dose rate / CL
dose rate = Css x CL
maintenance dose: plateau principle
assumptions (2)
1if we have constant input (gtt or intervals) referred to as _____


2first order elimination
maintenance dose
constant dose
constant dosing interval
first order elimination
maintenance dose: plateau principle
why does plateau occur?
____ order elimination
1at first
rate in _____ rate out = drug conc ____
2if you stop here
rate out ____ rate in = drug conc ____
3if you keep maintenance dose
and first order
constant rate in _____ first order rate out = ______ in conc
first
greater than
rises
greater than
drops
equals
no change
maintenance dose: plateau principle
once the plateau is acheived, if medication is stopped, how long does it take for the drug to be completely eliminated?
45 half lives
maintenance dose: plateau principle
calculate dosing rate from given C50 (TC) and CL
dosing rate =
F=1 is 100% bio
F=.5 is 50%
dosing rate = CL x TC
once you've given the dose to get to C50 now you want to switch to a maintenance dose:
goal is to achieve Css also called
steady state concentration
once you've given the dose to get to C50 now you want to switch to a maintenance dose:
if doses are intermittent
maintenance dose = dosing rate/F x dosing interval
where dosing rate = CL x TC
...
loading dose:
calculate loading dose
you know what plasma conc needs to be attained [D]
if you know approximate Vd
a loading dose can be calculated from rearranging this equasion
Vd = dose/[D]0
loading dose = Vd x [D]0 = how much drug you need to give to get a loading dose in
know how much volume the drug has to be dissolved in Vd
know conc of drug you are trying to acheive
solve for how much you need to put into the system to get there = loading dose
...
clinical pharmacokinetics:
predicting the plateau conc aka conc at _____
need
bioavailability =
volume of distribution =
CL = Vd / ke
mainteneance dose
steady state
F
Vd
Css = (dose rate)(t1/2) / (0.693)(Vd)
if maintenance dose changes by 25% Css changes in direct proportion by
if elimination is impaired by 50% = half life will be ____ as long = Css is ____ as high
25%
twice
twice
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