PK & Genomics

Question 1

Bioavailability definition

Answer 1

percent of drug absorbed from extravascular administration relative to IV admin

IV drugs all have a bioavailability of 1

Question 2

Absolute bioavailability (F) equation

Answer 2

Question 3

Characteristics of highly distributed drugs

Answer 3

Lipophilic
Low MW
Uncharged
Low protein binding

Question 4

Serum level correction is needed for highly ________ drugs when the _____ is low

Answer 4

highly protein bound(> 90%)
serum albumin (< 3.5 g/dL)

Question 5

Corrected calcium formula

Answer 5

Question 6

Corrected phenytoin formula

Answer 6

Question 7

Volume of distribution formula

Answer 7

Question 8

Clearance formula using rate of elimination (Re)

Answer 8

Question 9

Clearance formula using AUC

Answer 9

Question 10

First order clearance rate changes per unit of time

Answer 10

constant percentage per unit of time

Question 11

Zero order clearance rate with changing concentrations

Answer 11

constant amount of drug removed per unit of time

Question 12

Michaelis-Menten Kinetics

Answer 12

Saturable
Non-linear
Increases in dose when saturated can lead to disproportionate increases in concentration

Question 13

Drugs that follow non-linear kinetics

Answer 13

Phenytoin
Theophylline
Voriconazole

Question 14

Michaelis-Menten constant

Answer 14

Km = concentration at 1/2 Vmax

Question 15

Vmax

Answer 15

max rate of metabolism

Question 16

Elimination rate constant formula

Answer 16

Question 17

Half life formula

Answer 17

Question 18

> 95% of a drug is eliminated after ___ half lives

Answer 18

5 half lives

Question 19

95% of steady state is reached after ____ half lives

Answer 19

5 half lives

Question 20

Loading dose formula

Answer 20

Question 21

Genetic testing:
Abacavir (Ziagen)
+ combo products (Trumeq)

Answer 21

HLAB*5701
+ patients are at greater risk for hypersensitivity
do not use

Question 22

Genetic testing:
Azathioprine

Answer 22

TPMT
Low activity -> increased risk of life-threatening myelosuppression

Question 23

Carbamazepine (Tegretol) Genetic Testing

Answer 23

HLAB*1502
positive patients at greater risk of hypersensitivity

more prevalent in patients of Asian descent

Question 24

Genetic testing:
Cetuximab (Erbitux)
Panitumumab (Vectibix)

Answer 24

KRAS
+ patients -> drug will not be effective

Question 25

Genetic testing:
Trastuzumab (Herceptin)
Ado-trastuzumab emtansine (Kadcyla)
Lapatinib (Tykerb)
Pertuzumab (Perjeta)

Answer 25

HER2
negative patients -> drug will not be effective

Question 26

Genetic testing:
Clopidogrel (Plavix)

Answer 26

CYP2C19
- *1 allele = normal metabolizer
- *2 or *3 allele = poor metabolizer

Plavix is less effective in poor metabolizers since it is a prodrug. Consider alternative treatment

Question 27

Genetic testing:
Codeine

Answer 27

CYP2D6
- ultra rapid metabolizers at higher risk of overdose

codeine -> 2D6 -> morphine