Metabolism & Clearance

Question 1

glucuronidation

Answer 1

UDP-glucuronosyltransferase
UGT

Question 2

sulfation

Answer 2

sulfotransferases
SULT

Question 3

acetylation

Answer 3

N-acetyltransferases
NAT

Question 4

Amino acid conjugation

Answer 4

ex. glycine
low activity in newborns, fatal benzyl acid toxicity

Question 5

glutathione conjugation

Answer 5

glutathione-S-transferase

Question 6

methylation

Answer 6

catechol O-methyl transferase or thiopurine methyl transferase
COMT or TPMT

Question 7

CYP2D6 activity & polymorphism

Answer 7

absent or ultrarapid
no activity or buildup of codeine

Question 8

CYP2C19 activity & polymorphism

Answer 8

defective (race dependent)
metabolizes prodrug for clopidogrel

Question 9

TPMT activity & polymorphism

Answer 9

Caucasians have diminished or deficient activity
severe myelosuppression with azathiopurine

Question 10

solute carriers (SLCs)

Answer 10

OAT, OCT, OATPs, & MATE

Question 11

transporters responsible for bioavailability

Answer 11

OATP2B1
P-gp (ABCB1, MDR1)
MCT
PEPT1

Question 12

OATP2B1 location & activity

Answer 12

uptake in gut, liver, and systemic circulation
large MW organic anions
P1B3 and P1B1 are liver specific

Question 13

P-gp location & activity

Answer 13

kidney, liver, & BBB
protects and eliminates compounds from cells

Question 14

MCT location & activity

Answer 14

intestine
transports low MW organic anions
can improve oral absorption

Question 15

PEPT1 location & activity

Answer 15

intestine
transports peptides
can improve oral absorption

Question 16

transporters responsible for liver activity

Answer 16

OATPs
BCRP (ABCG2)
P-gp

Question 17

BCRP location & activity

Answer 17

intestine, liver, BBB, and some cancers
protects and eliminates compounds from cells

Question 18

transporters responsible for renal activity

Answer 18

OAT
OCT
MATE

Question 19

OAT location & activity

Answer 19

renal secretion (uptake)
organic anion transporter

Question 20

OCT location & activity

Answer 20

renal secretion (uptake)

Question 21

MATE location & activity

Answer 21

apical membrane of kidney
recognize cations for efflux

Question 22

transporters with activity in the BBB

Answer 22

BCRP & P-gp

Question 23

Equilibriative nucleoside transporters (ENTs)

Answer 23

transport nucleosides, regulate uptake of purines and pyrimidines

Question 24

where does renal secretion occur

Answer 24

proximal tubules

Question 25

where does renal reabsorption occur

Answer 25

along the nephron

Question 26

when CLr > CLrf (excretion exceeds filtration)

Answer 26

secretion occurs

Question 27

when CLr < CLrf (filtration exceeds excretion)

Answer 27

reabsorption occurs

Question 28

what induces CYP1A2

Answer 28

smoking

Question 29

what induces CYP2C19

Answer 29

rifampin, secobarbital

Question 30

what induces CYP2E1

Answer 30

ethanol, isoniazid

Question 31

what induces CYP3A4

Answer 31

carbamazepine, phenobarbital, rifampicin, phenytoin, SJW, troglitazone

Question 32

what does carbamazepine do acutely and chronically

Answer 32

acute- inhibit 3A4 chronic- induce 3A4

Question 33

SJW induces 3A4 & P-gp (ABCB1) which

Answer 33

increases clearance of indinavir reduces bioavailability of talinolol

Question 34

fluoxetine (prozac) inhibits CYP2C9

Answer 34

warfarin metabolism is lost, conc increases

Question 34

itraconazole inhibits CYP3A4

Answer 34

increases CYP3A4 substrates

Question 34

fluvoxamine (luvox) inhibits CYP1A2

Answer 34

increases CYP1A2 substrates

Question 35

cyclosporine inhibits OATP1B1

Answer 35

prevents CL and leads to accumulation of rosuvastatin

Question 35

talinolol is a P-gp inhibitor

Answer 35

leads to accumulation of digoxin

Question 36

probenecid is a OAT1 inhibitor

Answer 36

reduces renal secretion, given with cidofovir (vistide) to reduce accumulation

Question 37

clarithromycin inactivates CYP3A4

Answer 37

midazolam concentrations rise

Question 38

furanocoumarins in GFJ inhibit CYP3A4 intestinal metabolism

Answer 38

increased bioavailability and systemic concentrations of CYP3A4 substrates felodipine

Question 39

naringin in GFJ is an OATP inhibitor

Answer 39

reduces bioavailability of fexofenadine