AD (ME) gelatin Flashcards
define bioavailability
the measure of extent of absorption of unchanged administered product, that reaches the systemic circulation
define distribution
reversible transfer of substance between the site of measurement and other sites within the body
define metabolism
irreversible loss of unchanged substance by chemical conversion
define excretion
irreversible loss of unchanged substance
define elimination
irreversible loss of unchanged substance from site of measurement
define absorption
all processes from site of admin to site of measurement
what affects pharmacokinetics?
the physiochemical and structural properties of the drug
the dosage form
the route of admin
physiology of the body
other factors e.g. age, gender, size, smoke?
give examples of drugs with a very narrow therapeutic window, medium window and large window
digoxin - very narrow
cyclosporine - medium
valproic acid - large
what is the sequence of events an oral drug takes before entering the systemic circulation?
take drug –> dissolves in GI lumen –> absorption occurs across the gut wall –> liver –> systemic circulation
what is the difference between absolute F and relative F?
absolute is with reference to an IV dose whereas relative is between 2 formulations either by the same of different RoA
to be bioequivalent, on a graph, 2 drugs must…
- same AUC
- same Tmax
- same Cmax
same or similar tbh
why is the SI the organ for absorption?
- good blood flow
- large SA
- good permeability
what factors affect GE?
co admin of drugs
food
age
what aspect of absorption does GE affect?
the rate NOT the extent
how does GE differ between fed and fasted state?
fasted - quick GE so fast delivery to the SI and there is no major difference between the particle size
fed - delayed GE affecting the rate of absorption (slower) and there IS a difference in particle size
so food affects absorption through stomach to SI, but how does food affect absorption in the SI itself?
it doesn’t because food isn’t absorbed in the SI so has no effect on transit time
what kind of drugs have to be given on a fasted stomach?
EC drugs and usually those with high solubility are said to be given when fasted because don’t need the assistance of food to increase absorption
- poorly soluble drugs however are taken with food e.g. griseofulvin (anti-fungal)
transcellular movement is best for drugs that are…
LIPOPHILIC/POLAR and NONIONISED and SMALL
a drug that is a polar and hydrophilic (charged), although rare, crosses the membrane how?
paracellular transport e.g. metformin
why should poorly permeable drugs not be given as MR formulations?
because they will end up being absorbed in the parts of the SI that aren’t as good at absorption! so further along the SI, the absorption rate declines
it’s best in the duodenum –> jejunum –> ileum –> LI
in which part of the SI are most metabolic enzymes found?
in the jejunum
why can you not have grapefruit juice with statins?
which statin is it okay with though?
the furanocumarins in the grapefruit juice are irreversible inhibitors of CYP3A4 so statin can’t be metabolised so plasma conc of statins increases loads
- okay with rosuvasatin because not metabolised by CYP3A4
give an example of a drug with low F due to extensive first pass metabolism:
sildenafil, simvastatin
what does rate of distribution depend on?
- perfusion (the more perfused the quicker the dd)
- permeability (the more perm the quicker the dd)
- properties of drug (lipophilic and unionised, quicker dd)
- binding of drug to plasma proteins
- binding to acidic phospholipids in tissue membranes
when is distribution perfusion rate limited? blood flow is bad
when the permeability of the drug is good i.e. for small lipophilic molecules (permeable drugs)
when is distribution permeability rate limited? membrane barrier is bad
when drugs are large, ionised and polar (impermeable drugs)
why do we need to know Vd?
to determine loading dose
do acidic drugs have a high or low Vd?
low because they have strong affinity for plasma proteins so they’re ionised and stay in the blood
do basic drugs have a high or low Vd?
high because they have high affinity for acidic phospholipids (a1 glycoprotein) in the tissues
what do steroids bind to?
globulins (in the blood) so low Vd
define Kp
the tissue to plasma partition coefficient so the higher the Kp, the more drug is partitioned in the tissue so the larger the Vd
determined using tissue homogenate or in silicon using predictive equations
give approximate volume of plasma and volume of tissue water
Vp = 3L Vtw = 39L
give an example of a poorly soluble drug?
elotinib
