exam 3

Question 1

cyps account for 70% of metabolism . whtat cyps are involved most inmeyabolism

Answer 1

VYP3A4/5, CYP 2D6, 2C19. 2B6

Question 2

what organ plays the most role in metabolism

Answer 2

liver

Question 3

0examples of prodrugs:

Answer 3

probenecid

codeine: ctyp 2d6 removes methyl group and yields morphine

Question 4

contributer to unexpected metabolism

Answer 4

DDI/ food interactions
induces expression
natural variability

Question 5

cyps that have genetic variation:

Answer 5

cyp2c9: decreased functional genee varient exists
cyp2c19: defective gene varient in 3-16% of individuals
cyp2d6: highly polymorphic

Question 6

phase !! metabolism enzyme examples

Answer 6

NAT
COMT
TPMT

Question 7

when should you watch for metabolism variability

Answer 7

regulates a majorroute of elimination
yields pharmacologically active metabolites
the drup has a narrow TI

Question 8

role of membrane transporters:

Answer 8

move nutrients or metabolites/ toxins across membranes

Question 9

three sides of membrane

Answer 9

basolateral membrane: access to organs, often facing blood
intracellular membrane:
apical membrane

Question 10

influx

Answer 10

movement of ions into cells

Question 11

efflux:

Answer 11

movement of ions out of cell

Question 12

OASTPs

Answer 12

OATP1. mediates hepatic uptake of drugs

Question 13

influx transporters examples

Answer 13

OATP
PEPT1
ASBT
MCT1
oct2

Question 14

efflux transporters examples

Answer 14

BCRP

PGP

Question 15

OATP1 and OATP2 function

Answer 15

mediate uptake into gut

Question 16

clearance

Answer 16

total elimination of drug from body

Question 17

liver can metabolize/eliminate significant portion of absorbed drug through what effect

Answer 17

first pASs effect

Question 18

clearance is determinant on two major parameters

Answer 18

blood flow

difference between incoming concentration (arterial blood) and outgooing concentraion (venous blood)

Question 19

ER= fraction of drug removed from body by organ

Answer 19

fraction of drug removed from body by organ

Question 20

what does a high extraction ratio mean

Answer 20

since ER is the amount of drug removed by the liver, a high ER would mean that majority of the drug is removed by first pass metabolism

Question 21

intrinsic clearance

Answer 21

measure of intrinsic hepatic eliminating ability (google definition: ability of the liver to remove drug in the absense of flow limitations or protein binding)

Question 22

factors increases blood flow

Answer 22

supine position and exercise
transiently increases after eating
transiently increases after dug exposure

Question 23

factors that decrease bloodflow

Answer 23

thermal stress
disease states, CHF, cirrhosis
drug exposure

Question 24

factors that mediate protein binding

Answer 24

saturation at high conc
changes in protein conc
displacement of protein binding sites

Question 25

albumin binds to which kind of drugs

Answer 25

acidic and neutral drugs | most abundant found protein in humans

Question 26

most important protein for binding of basic drugs

Answer 26

AAG

Question 27

ke

Answer 27

rate of elimination via renal clearance

Question 28

U

Answer 28

amount in urine

Question 29

factors affecting renal clearance

Answer 29

GFR tubular secretion tubular reabsorption urinary elimination

Question 30

CLrf

Answer 30

renal clearance by filtration

Question 31

if CLr is > than CLrf.

Answer 31

tubular secretion must occur

Question 32

if CLrf > CLr

Answer 32

reabsorption must occure

Question 33

what size compounds tend to be eliminated by biliary excretrion

Answer 33

high MW compounds

Question 34

enteroheparic recyclinng

Answer 34

occurs when excreted drug in bile is reabsorbed back into the liver

Question 35

hepatocyte hopping

Answer 35

metabolized drug hops between hepatocytes until it reaches efflux transpporter prevents saturation of biliary excretion

Question 36

ABCC3 responsible for

Answer 36

hepatocyte hopping

Question 37

most drug interaction involve which phase enzymes

Answer 37

phase 1

Question 38

CYP2E1 inducers

Answer 38

ethanol, isoniazid

Question 39

CYP3a4

Answer 39

rifampin, phenytoin, st johns wort,

Question 40

DDIs that arent always bad

Answer 40

poinavir/ ritonavir AIDS. ritinovir increases oral bioavailability of lopinavir, reducing its daily dose LDOPA/carbidopa

Question 41

grape fruit juice

Answer 41

increaes bioavailability / systemic conc of 3A4 substrates inhibits OATP