AD (ME) gelatin

Question 1

define bioavailability

Answer 1

the measure of extent of absorption of unchanged administered product, that reaches the systemic circulation

Question 2

define distribution

Answer 2

reversible transfer of substance between the site of measurement and other sites within the body

Question 3

define metabolism

Answer 3

irreversible loss of unchanged substance by chemical conversion

Question 4

define excretion

Answer 4

irreversible loss of unchanged substance

Question 5

define elimination

Answer 5

irreversible loss of unchanged substance from site of measurement

Question 6

define absorption

Answer 6

all processes from site of admin to site of measurement

Question 7

what affects pharmacokinetics?

Answer 7

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?

Question 8

give examples of drugs with a very narrow therapeutic window, medium window and large window

Answer 8

digoxin - very narrow
cyclosporine - medium
valproic acid - large

Question 9

what is the sequence of events an oral drug takes before entering the systemic circulation?

Answer 9

take drug –> dissolves in GI lumen –> absorption occurs across the gut wall –> liver –> systemic circulation

Question 10

what is the difference between absolute F and relative F?

Answer 10

absolute is with reference to an IV dose whereas relative is between 2 formulations either by the same of different RoA

Question 11

to be bioequivalent, on a graph, 2 drugs must…

Answer 11

• same AUC
• same Tmax
• same Cmax
  same or similar tbh

Question 12

why is the SI the organ for absorption?

Answer 12

• good blood flow
• large SA
• good permeability

Question 13

what factors affect GE?

Answer 13

co admin of drugs
food
age

Question 14

what aspect of absorption does GE affect?

Answer 14

the rate NOT the extent

Question 15

how does GE differ between fed and fasted state?

Answer 15

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

Question 16

so food affects absorption through stomach to SI, but how does food affect absorption in the SI itself?

Answer 16

it doesn’t because food isn’t absorbed in the SI so has no effect on transit time

Question 17

what kind of drugs have to be given on a fasted stomach?

Answer 17

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)

Question 18

transcellular movement is best for drugs that are…

Answer 18

LIPOPHILIC/POLAR and NONIONISED and SMALL

Question 19

a drug that is a polar and hydrophilic (charged), although rare, crosses the membrane how?

Answer 19

paracellular transport e.g. metformin

Question 20

why should poorly permeable drugs not be given as MR formulations?

Answer 20

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

Question 21

in which part of the SI are most metabolic enzymes found?

Answer 21

in the jejunum

Question 22

why can you not have grapefruit juice with statins?

which statin is it okay with though?

Answer 22

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

Question 23

give an example of a drug with low F due to extensive first pass metabolism:

Answer 23

sildenafil, simvastatin

Question 24

what does rate of distribution depend on?

Answer 24

• 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

Question 25

when is distribution perfusion rate limited? blood flow is bad

Answer 25

when the permeability of the drug is good i.e. for small lipophilic molecules (permeable drugs)

Question 26

when is distribution permeability rate limited? membrane barrier is bad

Answer 26

when drugs are large, ionised and polar (impermeable drugs)

Question 27

why do we need to know Vd?

Answer 27

to determine loading dose

Question 28

do acidic drugs have a high or low Vd?

Answer 28

low because they have strong affinity for plasma proteins so they’re ionised and stay in the blood

Question 29

do basic drugs have a high or low Vd?

Answer 29

high because they have high affinity for acidic phospholipids (a1 glycoprotein) in the tissues

Question 30

what do steroids bind to?

Answer 30

globulins (in the blood) so low Vd

Question 31

define Kp

Answer 31

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

Question 32

give approximate volume of plasma and volume of tissue water

Answer 32

Vp = 3L
Vtw = 39L

Question 33

give an example of a poorly soluble drug?

Answer 33

elotinib