Exam 1 Pharmacokinetics Flashcards
Who writes drug prescribing information
drug companies
who approves drug prescribing information?
FDA
What is pharmacokinetics?
the way the drug moves in and through the body
What is LADME?
Liberation Absorption Distribution Metabolism Elimination
You can’t get absorption until you have ____.
Liberation
drug movement through compartments
distribution
drug removal from body
elimination
transformation of parent compound
metabolism
drug enters circulation
absorption
drug release- from whatever dosage form it is
liberation
Tpk
time to peak concentration
F means
fraction of drug that is bioavailable
PPB means
protein binding
Vd means
volume of distribution
T1/2
Half life
How can liberation be modified?
by making drug buffered,
enteric coated, delayed/controlled/extended,
sustained release,
and abuse resistant
what is the purpose of enteric coated medicine?
it won’t dissolve until it gets into intestine
traditional liberation
a tablet dissolving/breaking apart in liquid
buffered medicine changes liberation how?
medicine needs to be in basic environment to disassociate.
example of buffered medicine
aspirin
4 different types of movement across membranes that is involved in absorption
Passive diffusion
Active transport
Facilitated diffusion
Endocytosis
most common absorption movement
passive diffusion
movement of molecules is gradient driven (concentration dependent.
passive diffusion
in passive transport, Rate of transport is dependent on ____.
concentration gradient
diffusion through pumps, it uses energy and can go against concentration gradient
Active transport
type of diffusion through channels, it requires energy. it is the same as active transport
Facilitated diffusion
fastest absorption route
IV
slow absorption routes
otic and ocular
fast absorption routes
Sublingual/Buccal
Inhalation
IV
Variable absorption routes
IM
SubQ
Topical
Rectal
example of slow IM absorption
DEPO shot for contraception
Absorption Factors (8)
- Physical state
- Area of absorbing surface
- concentration
- solubility and binding
- membrane permeability
- vascularity and blood flow
- GI motility and emptying
- Vehicle
Absorption Factors
For physical state, what effects rate for absorption drug when it is a liquid versus a solid
liquid is absorbed faster
Absorption Factors
Why are liquids absorbed faster than solids?
it doesn’t have to go through liberation phase like solid does. It is closer to particle size that it needs to be to get absorbed.
Absorption Factors
how does the area of absorbing surface effect absorption?
larger surface = more absorbed
Absorption Factors
how does concentration affect absorption?
higher concentration of drug gets absorbed more rapidly
Absorption Factors
membrane permeability can be affected by ____.
disease
example of disease that affects BBB
meningitis
Absorption Factors
What is the vehicle of the drug?
how drug is carried- example is cream vs ointment
What is absorption?
when drug moves from site of administration to site of “measurement” in body
movement of one area to area of “measurement”
in absorption, what is the step slowing things down?
rate limiting step: crossing membranes
drug must be in a dissolved state in order to _______-.
penetrate membranes
Oral dosage form issues for absorption
- Emesis
- pH
- Food
- Other drugs
- GI motility
- Surface area
- dosage form
- H20 Solubility
- drug at absorption site
Example of other drugs affecting absorption
taking antacids with Iron, Iron needs acidic environment to dissolve and get into system
What is delayed release?
when you take drug in a solid form, wait a period of time, and then the drug gets released
IR release is ________.
immediate release
SR release is_______.
sustained release
XR release is_______.
extended release
SR,CR, and XR release drugs cause what to happen to absorption time?
absorption time gets stretched out instead of all of it being absorbed at once
CR release is_______.
controlled release
what is immediate release?
taking a standard tablet, as soon as you take it it gets into your system
Drug formulation, ionization, size, and solubility affect ____.
absorption
how can a patient affect absorption?
pH food,liquid other meds gi motility surgery
do intravenous medication skip the absorption phase?
yes
how does IV drug administration skip absorption phase?
it gets automatically inserted into central compartment (blood), it does not need to cross membranes
reversible transfer of drug to and from a body compartment/ tissue space
distribution
is a bound drug considered a free or active drug?
no
cardiac output, regional blood flow to tissue, tissue volume, and tissue selective binding are things that can affect _____.
distribution
what is function of efflux pumps?
to get something out/ get rid of it
p-glycoprotein is an example of an _____.
efflux pump
function of p-glycoprotein
to pump drugs out of cells that aren’t supposed to be there
tumor cells produce a lot of this
p-glycoprotein
problem with p-glycoprotein concerning drugs
can be difficult to get drug to pass these to get into cells, a reason why cancer cells are so hard to treat.
this allows tissue penetration without crossing the lipid bilayer
paracellular transport via capillary membrane
what is paracellular transport dependent on?
blood flow
this is key to protecting and maintaining homeostasis environment in brain
blood brain barrier (BBB)
a drug leaving brain capillaries has to traverse through _____ and ______.
the capillary wall
and
astrocyte membrane
these are tightly joined and covered by fatty barrier called the glial sheath (astrocytes)
brain capillaries
what type of drugs penetrate the BBB poorly?
highly ionized
what type of drugs penetrate the BBB more rapidly?
fat-soluble drugs
drugs that penetrate the central nervous system need to be ________ to penetrate the brain and reach their target site
lipid soluble
What is metabolism?
Changing one chemical to another chemical
Why does metabolism occur?
Trying to metabolize thing so we can get them out of the body
are all drugs metabolized?
no, Not all drugs are metabolized, some drugs are eliminated unchanged
Where does metabolism occur?
Most occurs in liver
Phase I metabolism phase
function to convert lipophilic molecules into more polar molecules
Introduces or unmasks a polar functional group in which metabolism phase?
Phase I
Phase II metabolism phase
conjugation reaction to increase polarity
__________ is most common of Phase II reactions – adds a glucose-like molecule
Glucuronidation
Cytochrome P450 enzymes are mostly located in the _____.
liver
six Cytochrome P450 enzymes that metabolize over 90% of drugs
CYP3A4 – 60% CYP2C9 – 15% CYP2C19 – 15% CYP2E1 – 2% CYP1A2 – 2%
60% drugs metabolized through this pathway
CYP3A4
A drug may be a ______ for more than one isozyme
substrate
the drug/molecule that gets metabolized
substrate
drug/molecule that increases synthesis of one or more CYP isozymes
Inducer
reduces activity of or competes for isozyme
inhibitor
drug increases synthesis of isozyme for which it is a substrate
Autoinducer
metabolism is what kind of rxn?
chemical
this facilitates the chemical conversion of a substrate (drug) to a metabolite product
enzyme
this results in increased serum metabolite concentration (or decreased drug concentration)
CYP 450 Enzyme Induction
When an enzyme ______ is present, the activity of the enzyme is increased which pushes the reaction to the right
inducer
This results in increased serum drug concentration
CYP 450 Enzyme Inhibition
When an enzyme _______ is present, the activity of the enzyme is decreased which pushes the reaction to the left
inhibitor
Drug “A” is substrate of CYP3A4
Drug “B” is an inducer of 3A4
If drug “B” is added to the drug regimen, what would happen to the serum concentration of drug “A”?
there would be more metabolite of A
Routes of removal of drug from the body:
KIDNEY, liver, bile, intestine, lung, milk, dialysis,
“artificial kidney” where we remove toxic things synthetically from body
Dialysis
renal elimination type where there is passive diffusion of free drug, drug can’t be bound to protein. move from capillary to glomerular space
Glomerular filtration
renal elimination type where there is Active transport, from capillary to PCT, drugs can compete for active transport (e.g. probenecid)
Proximal tubular secretion
renal elimination type where drug concentration increases as filtrate moves distally, drug may diffuse back into systemic circulation
Distal tubular reabsorption
What lab tests might help determine renal function?
Creatinine, BUN
Usually drug interaction are ______ issues
metabolism
in pediatrics, why should IM be given in lateral thigh vs. buttocks or arm
↓ muscle mass in those areas
In neonates, why is IV preferable to IM?
erratic absorption
pediatric metabolism depends on what variables?
Drugs mother was on during pregnancy
Age of patient
During first few weeks/months why would baby need lower doses
metabolic rate is lower
During toddler and early childhood, metabolic rate is higher than even at adult so dose would have to be ______.
higher
A full term newborn has what percent of glomerular filtration rate (GFR) and tubular excretion capacity of an adult
33%
when does GFR reach adult values
6-12 months
what is steady state?
Concentration when the amount in = the amount out.
can you get steady state concentration with just one dose?
no
What determines how long to steady state?
half life
what is half life
time required to change the amount of drug in the body by one-half during elimination (or during a constant infusion)
