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pharmacokinetics

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 volume-very 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 = 40-42L
intracellular = 2/3
extracellular = 1/3 12-14L
--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)
*first-order kinetics:
-clearance in this case is calculated by
dose / AUC
first order kinetics:
curved line graph
-y-axis: units are ____ to x-axis (time)
-can see how much drug is left at a place in
-equal
-time
first order kinetics:
straight line graph
-y-axis: 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/mass-law/capacity-limited:
-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 pre-op 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
pro-drugs
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)
1-if we have constant input (gtt or intervals) referred to as _____
--
--
2-first order elimination
-maintenance dose
--constant dose
--constant dosing interval
-first order elimination
maintenance dose: plateau principle
why does plateau occur?
-____ order elimination
1-at first
--rate in _____ rate out = drug conc ____
2-if you stop here
--rate out ____ rate in = drug conc ____
3-if 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?
4-5 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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