pharmacokinetics?
Quantitative analysis of drug movement into, throughout, and out of the body (Absorption, distribution, metabolism, excretion) ADME
what is ion trapping?
an effect of ionization where a weak acid depolarizes after being absorbed so it gets trapped
graph of IV bolus injection?
log plot
Enteral?
oral, rectal, sublingual (GI)
Parenteral?
not enteral, IV, IM, SC, topical, inhalation
which is more absorptive? stomach or sm. intestine?
small intestine (can do weak acid and weak bases)
chelation does what?
binding to metals make it hard to absorb
how can you help acid sensitive drugs?
use coating so it can at least pass the stomach
what is first pass metabolism?
drugs can get metabolized in intestine and liver before it even gets into bloodstream
using SC or IM, is lipid or water soluble faster?
water soluble
bioavailability is mathematically:
AUCoral/AUCiv=Fsmaller F means it is likely means given IV and not PO
distribution:
REVERSIBLE transfer of drug from general circulation to other parts of the body
Vd (volume of distribution)-
Dose(t0)/Plasma drug concentration
High plasma drug concentration means…
low Vd
Low plasma drug concentration means…
high Vd
over 40 Vd means
drug is in tissue
order of drug distribution between tissue?
VRG/blood, muscle, tissue
albumin can do what to drugs?
keep them in the blood and not be eliminated
metabolism?
drug goes from active to inactive
excretion?
drug leaves body unchanged
how to measure normal renal function? (filtration)
serum creatinine levels in blood (from muscle breakdown) of 1.0mg/dl
secretion in kidney?
more efficient than filtration. active transporters for weak acids and weak basis.
how is secretion related to drug elimination?
drugs can compete for transport so one drug can stay and the other may leave
reabsorption in kidney?
urine to blood. opposite movement
biotransformation meaning?
metabolism
xenobiotic?
foreign substance that is introduced to body
Phase I metabolism
small tweak. create or unmask chemically reactive functional group
phase II metabolsim
adding more substrates or what not, bigger tweak
metabolism can make drugs…
active, more active, inactivated, or toxic
cytochrome p450 system
divergent family of mixed function oxidases, found largely in liver, also kidney, lung, intestine, and others(CYP3A4/5, CYP2C8/9, CYP2D6)
how does CYP3A4 act on drugs?
substrate, inhibitor or inducer
clearance is measured as…
volume / time
elimination is measured as…
mass / time
half life is measured as…
time
first order elimination concept
process where elimination rate is directly proportional to the amount of drug in the body at any point in time. a CONSTANT FRACTION is eliminated at any given time
high clearance relation to half life
inversely, high clearance means smaller half life
Vd relation to half life?
directly, high Vd means longer half life
two fundamental biological parameters
Vd and clearance
when drugs are not first order>
still treat as first order
pharmacokinetic compartment
volume of body fluids/tissues within which a drug is in rapid equilibrium
central compartment 1
systemic circulation plus all fluids/tissues in RAPID equilibrium with the systemic circulation
peripheral or tissue compartments
SLOW equilibrium with the systemic equilibrium
every compartmental model has
compartment 1, and Ke (elimination), and drug input EXCEPT for IV bolus
only compartment model that has no absorption process or input kinetics
IV BOLUS infusion
what does IV bolus injection look like on a semi-log plot graph? and why?
negative linear slope (due to excretion)
[Drug] equals
Dose/Vd
Half life, t(1/2), equals…
(Vd/Cl)*0.693
Bioavailability (F) =
AUCoral/AUCiv
What does it mean when Bioavailability is 1?
all of the drug was absorbed
why does the IV continuous infusion graph plateau?
the input rate is equal to the elimination rate (it finally caught up)
Css (concentration at steady state) =
R0/Cl