lecture 2 Flashcards
What are the 4 major processes involved in drug pharmokinetics, and what are their “sites”
- absoprtion- small intestine
- distribution- cardiovascular system
- metabolism - liver
- elimination- kidney
when comparing a concentration- time profile between an orally and IV administered drug, what will be the difference
IV drug will not have an absorption phase
what is Cmax
the highest concentration achieved by the drug in the plasma
what is Tmax
time it takes for the drug to reach highest measured concentration
duration of drug action is _________ when the dose is doubled
extended by 1 half life
what does the dose interval need to be in order for the drug to be completely cleared between each dose
greater than 5 half lives
define steady state
drug concentration is no longer changing, the rate of elimination = dosing rate
what is dosing rate versus dosing interval?
dosing rate is the dose of drug per unit time, dosing interval is just time interval
total body clearance=
hepatic clearance + renal+ other clearance
what is the point of a loading dose
to reach therapeutic levels quicker with drugs that have longer half lives
in general withdrawal times approximate how many half lives for 99.9% clearance. what about 95% clearance of the drug
10, 5
which class of drugs are more readily absorbed? why?
lipophilic drugs- the ADME of PK require all drugs to go through cell membranes- the lipid bilayer
why would SQ and IM have a lower Cmax than IV given at the same dose?
due to absorption time- ADME processes are happening all at once so even though full dose isn’t absorb D+M+E are already underway
a large difference between oral and IV dose suggest
the drug has poor bioavailability (the % of dose that reaches systemic circulation)
describe the first pass effect
the loss of drug due to metabolism in the GI and or liver before it enters systemic circulation
what is one way to by pass the first pass effect
rectal administration- 50% of circulation from rectal area bypasses the liver
why is absorption of acidic drugs better in an acidic environment, and the same concerning basic drugs
acids are ionized in basic environments, ionized molecules have a harder time passing through lipid bilayer
higher volume of distribution means
more drug in tissues from blood
what does vd tell you
predicts cmax after a single dose (dose/vd) - a low vd means that drug is mostly in ECF, high means its going to the cells
each unit of pKa away from pH results in a _________ in the concentration of the drug in that compartment
10 fold change
what is ion trapping
since molecules are in the ionized form when their pKa is far away from the environmental pH, they can get stuck in areas that put them in their ionized state. the rumen is a prime location for this and can lead to drugs getting degraded before they enter the circ.
why can only free non bound drugs distribute into tissues
they are too large to pass through the membrane
drugs that are protein bound may be desirable because
they have longer acting time since there is a slow release as they become unbound from the proteins
metabolism of drugs usually leads them being
more polar/ able to dissolve in water
what are the two phases of drug metabolism
phase 1 : redox
phase2: enzymatic
what is important to consider concerning drug metabolism
age, species and health
what is cytochrome p450?
the main enzyme involved in phase one metabolism, it catalyzes oxidation reaction RH+O2+NADPH+H–> R-OH +H2O+ NADP+
phase 2 of drug metabolism leads to
increasing water solubility by conjugating the drug to exogenous substrates and deactivates active metabolites
what are the 3 most important types of conjugation reactions involved in drug metabolism
- glucuronidation
- sulfate conjugation
- acetylation
what is p-glycoprotein, what does it do?
the most important of transport proteins- and efflux transporter- moves substrates out of the cells
where are large drug molecules typically excreted? small?
bile, urine
rate of renal excretion = ?
filtration + secretion - reabsorption
what is enterohepatic recirculation?
molecules eliminated in the bile get reabsorbed when they go back into the SI
what drug reaction typically under goes enterohepatic recirculation
glucuronidation
