Pharmacokinetics Flashcards
what is the thoeretical volume necessary to account for the total amount of drug in the body if it were present throughout the body in the same concentration as in the plasma
volume of distribution (Vd)
can you measure Vd?
no its theoretical
what is the shortened definition for Vd
theoretical volume measuring the amount of drug concentration you gave in the plasma
what is the theoreical volume of plasma that is completly cleared (100% cleared) of drug in a given period of time, the units are in mL/min. Also can be defined as the bodies ability to eliminate a drug
Clearance (Cl)
what is the time it take for the plasma concentration of a drug to fall by one-half
Elimination half time (T 1/2 Beta)
what is the time it takes for the TOTAL AMOUNT OF THE DRUG in the body to decrease by one-half?
elinination half-life
volume of Distribution: (Vd)
how do you calculate Vd?
by dividing the amount of drug injected by the plasma concentration
Vd = Q/C
volume of Distribution: (Vd)
what is the Vd? do the math
Q=12
C= 2
Vd = Q/C
Vd = 12 / 2
Vd = 6 mL
volume of Distribution: (Vd)
what is the voume of distribution
Q = 12
C = 1
Vd = Q / C
Vd = 12/1
Vd = 12 mL
volume of Distribution: (Vd)
what is the Volume of distribution
Vd = Q /C
Vd = 12 / 3
Vd = 4mL
volume of Distribution: (Vd)
which one has a LOW VD?
what type of drugs are these?
C
water loving drugs
Muscle relaxants (polar)
volume of Distribution: (Vd)
which one has a large VD?
What drugs are these?
B
Induction agents (non-polar)
what is Pharmacokinetics?
what the BODY does to the DRUG
Body compartments:
The human body is schematically represented in the following figure. shown are the plasma volume (PV), interstitial Volume (ISV), intracellular volume (ICV), and fat adipose tissue.
Body compartments:
what makes up the extra-cellular volume (ECV)
ISV and PV
ECV = ISV + PV
Body compartments:
outline the ECV
Body compartments: Distribution of drugs:
drugs with different properies have different volumes of distribution. MR, which are ionized are restricted to where?
extracellular space
Body compartments: Distribution of drugs:
describe drugs that are confined to the ECV
ECV = ISV + PV
Muscle relaxants
Small Vd
Water Soluble
Ionized (polar-charged)
(bc they are water loving they are charged, charged molecules do not cross the lipid bylayers thus stay in the ECV and does not get into adipose tissue and have Small Vd)
\Body compartments: Distribution of drugs:
what is the numerical value for SMALL Vd
0.3-0.5 L/kg
Body compartments: Distribution of drugs:
what type of Vd does this picture depict
Large Vd
b/c the drug has moved into the ICV and adipose tissue
Body compartments: Distribution of drugs:
describe drugs that have cause this
Induction agents
large Vd
Lipid Soluble
fat loving non-polar -uncharged
Body compartments: Distribution of drugs:
what is the numerical value for a large Vd
2.0-2.5 L/kg
Body compartments: Distribution of drugs:
comparison b/t ped and adult
on a weight basis the noenate/infant have an expanded ECV. see picture
why do noenated need more SCh on a mg/kg basis? give 2 reasons
- greater Vd
- immature NMJ
- the NMJ is immature b/c they have inadequate number of nicotinic receptors, or the receptors may not be responsive to ACh.
- THE ECV of a neonate/infant is twice that of an adult.
if neonate/infants need more SCh why do they need the same amount of NDMR as the adult on a weight base mg/kg basis?
- more NDMR is needed bc the ECV of the neonate is larger.
- Less drug is needed however b/c the NMJ is immature
- so less drug is needed to block the channels
- thus the cancel themselfs out and equal the same dose as an adult
Kinetics:
what type is when a constant amount of the drug is eliminated per unit of time? ex 2 mp/min
Zero order kinetics
Kinetics:
what does the graoh look like with zero order kinetics?
the concentration of the drug in the plasma falls linerally with time
Kinetics:
what are the ONLY 3 drugs that are eliminated by zero order kinetics
ETOH
Phenytoin
ASA
Kinetics:
is zero order an amount per unit of time or a fraction per unit time
an amount per unit time
Kinetics:
Most drugs are eliminated how?
1st order kinetics
Kinetics:
define 1st order kinetics
a constant fraction of a drug is eliminated per unit of time
Kinetics:
drugs that are eliminated by 1st order behave in one of which 2 ways?
1 compartment
or
2 compartments
Kinetics:
how can you always tell 1st order graph
it will have a log (ln) on the Y axis
Kinetics:
what does the graph with 1st order 1 compartment model look like
like zero order but with a Log on the Y axis
Kinetics:
what is the only drug that is eliminaed by 1st order kinetics 1 compartment model?
Albumin
Kinetics:
what does the graph look like for 1st order 2 compartment elimination
a fast curvilinear line
Kinetics:
name the drugs that are eliminated by 1st order 2 compartment model
all other drugs besides the zero order (ASA, ETOH, and Phenytoin) and the 1st order 1 compartment drug (albumin)
Kinetics: 1st order 2 compartment
when in the graph is the Alpha phase and what does it represent?
distibution phase
Kinetics: 1st order 2 compartment
where is the beta phase and what dose it represent?
elimination phase
Kinetics: 1st order 2 compartment
where is the point of equilibrium?
Kinetics: problem
what kind of plot is this? and how do you know?
1st order, 2 compartment
- it’s curved
- its a log (Y axis goes from 10 - 1,000)
side note
when doing Vd i said the formula was
Vd= Q/C
flip to see real formula
Vd = Q / Cp (t=0)
you never have to worry obout the t=0 b/c we always assume it is just that 0 so i shortened it
Kinetics: problem
label the distribution part and the elimiantaion part
as well as the alpha and beta
Kinetics: problem
find the concentration of the drug at t = 0 if the drug is distributed instantaneously into its volume of distribution (and describe how you found it)
find the equilibrium point and follow angle of the beta slope
100 mg/L
Kinetics: problem
2500 mg of a drug was administered and plotted on the graph. what is the Vd if this drug
Vd = Q / Cp (t=0)
Q= 2500 mg
Cp (t=o) = 100 mg/L
Vd = 2500 / 100
Vd = 25 L
Kinetics: problem
what is the T 1/2(beta) of this drug?
or the half-time elimination
find the concentration at equilibrium time 0. (100)
then find 1/2 that (50)
see where it meets the graph on the beta axis
answer 4 hrs
Kinetics: problem
2 mg of a drug is given what is the Vd?
watch the trick plasma concentration is in mcg and the drug is in mg- convert one to the other
Cp(t=o) = 100mcg/L
Q = 2mg or 2000mcg
2000/100 = 20 L
Vd = 20 L
half life problems:
a drug is eliminated by 1st order kinetics and has a 1/2 life of 6 hours how much drug remains after 18 hours if 10 mg is administered
1.25 mg
half life problems:
160 mg of a drug is administed and 20 mg remain 30 hours later. how much of the is lost in the next 20 hours, if the drug is eliminated by first ordr kinetics
15 mg more will be lost
half life:
how may 1/2 lives (1/2 times) are required to eliminate 98% of a drug
6
Pharmacokinetics: Hepatic metabolism
how many phases of reactions are there?>
3
Pharmacokinetics: Hepatic metabolism
what phase is when the reactions involving chemical biotransformation of a molecule, usually to more water soluble and often inactive metabolites
Phase I
Pharmacokinetics: Hepatic metabolism
what are the 4 types of phase I reactions
oxidation
reduction
methylation
hydrolysis
Pharmacokinetics: Hepatic metabolism
what enzyme is responsible for many of the phase I reactions (oxidation, reduction, methylation, hydrolysis).
cytochrome P-450 system
Pharmacokinetics: Hepatic metabolism
what phase reaction invlove conjugation of a drug or its metabolite w/ endogenous molecules; conjugation reactions make drugs water soluble for excretion by the kidneys or billary system.
Phase II
Pharmacokinetics: Hepatic metabolism
what are types of Phase II reactions
glucuronidation, gluthathione conjugation, sulfation and ACETYLATION
Pharmacokinetics: Hepatic metabolism
what phase reaction are eliminatin reactions that involve ATP-binding cassette (ABC) transport proteins?
Phase III
Pharmacokinetics: Hepatic metabolism
Quickly describe each Phase reaction
- Phase I- oxidation, reduction, methylation, hydrolysis
- Phase II- Acetylation
- Phase III- ATP-binding cassette (ABC)
Pharmacokinetics: protein binding
most drugs bind to what?
plasma proteins
Pharmacokinetics: protein binding
what is the most abundant plasma protein
Albumin
Pharmacokinetics: protein binding
do protein bound drugs leave circulation
no- only free unbound drugs do
Pharmacokinetics: protein binding
patients who have ______ are more sensitive to injected drugs b/c protein binding is reduced. thus more of the drug is free or unbound
Hypoproteinuria (hypoalbuminemia)
Pharmacokinetics: protein binding
when protein binding is decreased what happens to Vd?
it is increased
