EXAM II

Question 1

What is a strong inhibitor?

Answer 1

fivefold increase in AUC

Question 2

What is a moderate inhibitor?

Answer 2

two- to fivefold increase in AUC

Question 3

What is a weak inhibitor?

Answer 3

1.25 to twofold increase in AUC

Question 4

What is fm?

Answer 4

fraction of drug being metabolized by an enzyme of interest

Question 5

What is Cui?

Answer 5

unbound concentration of inhibitor/perpetrator

Question 6

What is Ki?

Answer 6

potency of perpetrator

Question 7

What is the time course of maximum concentration equal to in a DDI?

Answer 7

five inhibitor half-lives plus five victim drug half-lives

Question 8

The extent of drug inhibition decreases with a(n) _____ in the natural rate of enzyme degradation (kdeg)

Answer 8

increase

Question 9

The extent of drug inhibition increases with a(n) _____ in the enzyme inactivation rate by the drug (kint)

Answer 9

increase

Question 10

What does the onset and offset of enzyme induction depend on? (3)

Answer 10

half-life of inducer, time to make new CYP proteins, and rate of their degradation

Question 11

Addition of an inducer affects what type of metabolizer more?

Answer 11

extensive metabolizers

Question 12

Inhibition of pgp or BCRP can cause?

Answer 12

increased substrate bioavailability

Question 13

Inhibition of liver uptake can cause?

Answer 13

increased plasma exposure of substrate

Question 14

What type of drugs are at risk for renal transport DDIs?

Answer 14

drugs with high tubular secretion

Question 15

What may prevent nephrotoxicity?

Answer 15

uptake inhibition

Question 16

What is the mechanism of the drug interaction between St John’s Wort and digoxin?

Answer 16

induction of pgp

Question 17

What is the mechanism of the drug interaction between grapefruit juice and fexofenadine?

Answer 17

inhibition of uptake by OATP1A2

Question 18

Atorvastatin and its metabolites are substrates of what transporter?

Answer 18

OATP1B1

Question 19

What does the free hormone hypothesis state?

Answer 19

drug concentrations in tissues are directly related to the unbound concentration of drug in blood

Question 20

PK-based optimization is only useful in what situations? (3)

Answer 20

low variability in pharmacodynamics, low intra-patient and high inter-patient variability PK

Question 21

V = 0.25L/kg x TBW

Answer 21

no 3rd space fluid and TBW not >1.2 x IBW

Question 22

V = 0.25L/kg x IBW + 0.1L/kg[TBW-IBW]

Answer 22

no 3rd space fluid and TBW >1.2 x IBW

Question 23

V = 0.25L/kg x TBW* + 1L/kg x 3rd space weight

Answer 23

3rd space fluid and TBW* not >1.2 x IBW

Question 24

V = 0.25L/kg x IBW + 0.1L/kg[TBW*-IBW] + 1L/kg x 3rd space weight

Answer 24

3rd space fluid and TBW* >1.2 x IBW

Question 25

What is the CL for functionally anephric patients?

Answer 25

0.0043 L/kg/hr

Question 26

What is the CL for surgically anephric patients?

Answer 26

0.0021 L/kg/hr

Question 27

What are peak and trough concentrations defined as (aminoglycosides)?

Answer 27

0.5hr following infusion and 0.5hr prior to next dose

Question 28

What are the divisible values for tobramycin, gentamicin, and amikacin?

Answer 28

20, 20, and 50mg

Question 29

When should you round up and down?

Answer 29

Loading doses = up, maintenance = down