L8, L9 Pharmacokinetics Flashcards
What makes up pharmacokinetics?
drug absorption
drug distribution
drug metabolism
drug excretion
drug in circulation will be at ______ with tissue reservoirs?
equilbrium
only a fraction of drug that binds to specific receptors will have a ____
pharmacological effect
how does the drug get to the site of action?
- crosses membrane
- gets into systemic circulation or lymph system
- needs to workout how best to get the drug into circulation
what is the first barrier to oral administration of drugs?
GI epithelium
what is membrane diffusion favored by?
concentration gradient - high
+ change on drug (inside of cell is -)
what does the pKa represent?
pH value when 1/2 of the drug in protonated and half deprotonated
what is pH trapping
for weakly acidic drugs, the protonated, electrically neutral drug is predom. in the highly acidic environment of the stomach. the uncharged drug can pass through lipid bilayers of GI mucosa. the weakly acidic drug is then trapped as it is deprotonated to its electrically charged form in the more basic environment of the plasma.
what is the version of Henderson Hasselablch equation that I will use?
Pka - pH = log [HA]/[A-]
HA protonated form
A- deprotonated form
a weakly acidic drug in an acidic enviromment will ne ?
protonated - neutral
a weakly acidic drug in an basic or neutral environment will be?
deprotonated - charged
what is pKa
acid dissociation constant
if the pH < pKa -
protonated form favored (HA, BH+)
if pH > pKa -
unprotonated form favored ( A-, B)
define absorption
getting drug into circulation
bioavailability
what is bioavilability
drug reaching circulation / drug administered
what are routes of administration?
enteral - oral, by mouth
parenteral - directly to circulation, CSF etc. using SC, IM, IV, IA, IT (intrathecal)
mucous membrane - sublingual, nasal, rectal etc.
transdermal - nicotine patch, androgel etc.
what are the advantages of enteral drug administration?
simple
cheap
self-administer
low infection rate
what are the disadvantages of the enteral administration drug route?
passes through GIT
first pass metabolism
relatively slow delivery
which drugs pass through the cell membrane more efficiently?
hydrophobic and neutral drugs
what is first pass metabolism?
after drugs pass GI epithelium they are carried by the portal system to the liver before entering systemic circulation. With this process, liver enzymes may inactivate a fraction of the ingested drug
what are the advantages of parenteral drug administration?
rapid onset
high bioavailability
what are the disadvantages of parenteral drug administration?
infection
need skilled personal for delivery
hurts
irreversible effect
what is the fastest way to get a drug to target organ?
IV, IA or intrathecal
for drugs that are soluble in oil-based solutions what parenteral route should I use?
IM
what are advantages of mucous membrane drug administration?
DIRECT ACTION rapid absorption low infection incidence convenient no harsh GI environment + first pass metabolism
mucous membranes are highly vascular and drugs enter ____ into the systemic circulation
directly
what is atropine?
from Atropa belladonna - Deadly nightshade
counters “rest and digest” form PNS
competitive antagonist of muscarinic receptor
it dilates pupil, increase heart rate, reduces salivation
in order for a drug to pass transdermally, what should the drug be?
highly lipophilic - nicotine or estrogen patches
what is transdermal administration ideal for?
drugs that must be slowly and continuously administered over extended periods of time
what are the benefits of transdermal drug administration?
- no infection risk
- simple
- convenient
what is the rate of absorption affected by?
local, regional and systemic factors
what has the greatest effect on absorption?
regional blood flow
the rate of absorption affects what?
- local concentration of the drug
- duration of action
what primarily achieves drug distribution? what plays a minor role in drug distribution?
circulatory system
lymphatic system
once the drug hits systemic circulation, it is able to go where?
to any target organ - except brain and testes…
what is used to define and monitor therapeutic drug levels?
concentration of drug in plasma
what is the volume of distribution?
extent to which the drug partitions between the plasma and the tissue compartments
its the fluid volume that would be required to contain the total amount of absorbed drug in the body at a concentration equivalent
to that in the plasma at steady state
what is the equation for volume of distribution?
Vd = Dose / [Drug]plasma
when are Vd low?
drugs that are retained within vascular compartment
when are Vd high?
drugs that are highly distributed into muscle, adipose and nonvascular compartments
a drug that is highly distributed, gives a ____ plasma concentration for a set dose
lower
what is the most abundant plasma protein?
albumin
drugs with high affinity for plasma proteins keep Vd ____ and free drug ___
low
low
what happens to the drug concentration in the distribution phase?
results in sharp decrease
in the plasma drug concentration shortly after
intravenous administration of a drug bolus - because
of the drug elimination from the body
what happens to the drug concentration during the elimination phase?
the plasma drug concentration decreases more
slowly during the elimination phase due to the “
reservoir” of drug in tissues that can diffuse
back into blood to replace the drug that
has been eliminated
*The half time for drug________ is longer than the
half time for drug _____
elimination
distribution
what is the first extracellular compartment where drug concentration increases?
vessel rich group
which groups have a higher capacity for taking up drug than vessel rich?
muscle rich and adipose rich
what group accumulates the greatest amount of drug at the slowest rate?
adipose rich group
what drug character can enter liver cells?
hydrophobic drugs
what can the liver do to drugs?
- may make them more active
- usually become inactive and ready for excretion (biotransformation - red/ox conj/hyd)
where are most drugs broken down?
liver
where are most drugs excreted?
by the kidney
some in bile
some oral drugs not fully absorbed - feces
what determines the kinetics of drug elimination by the kidney?
balance of filtration, secretion, and reabsorption
what factors influence renal excretion?
increased urine flow
pH trapping
how do drugs get from liver to intestines?
ABC transporters (ATP binding cassette)
define clearance?
the amount of active drug cleared relative to the amount in plasma
what is the equation for clearance?
clearance = metabolism + excretion / [drug in plasma]
clearance = clearance (by kidney + liver + anywhere else)
what happens to the rate of drug elimination when plasma drug concentration is increased?
increases
*amount of drug excreted is proportional to the concentration in the plasma
E = (Vmax X C) / (Km + C)
what happens if you saturate the mechanisms involved in clearance?
you no longer see first order kinetics
what is half life?
the amount of time over which the drug concentration in the plasma decreases to one-half of its original value
follows first order kinetics - what I will be dealing with
what factors increase half life?
decreasing clearance
- liver, kidney, cardiac failure
- inhibition of CY P450
increasing Vd (plasma concentration LOW)
- major = drug properties - solubility, binding to plasma proteins, binding within compartments
- minor = obesity, edema/ascities
what is the therapeutic range?
steady state when what goes in = whats going out
where do we want the steady state concentration to lie?
within the therapeutic range
what is the loading dose?
allows you to get to therapeutic range quicker
takes Vd into account
huge dose one time
what is maintenance dose?
dose required to maintain the drug concentration within the therapeutic range
how many half-lifes does it take to reach a steady state concentration in the plasma?
4 half lives
what happens when drug delivery beats the rate of breakdown?
saturation leads to zero order elimination
