MODULE 1

Question 1

Paracelsus

Answer 1

dose define the poision

Question 2

toxicokinetics

Answer 2

what the body does to the xenobiotic

Question 3

toxicodynamics

Answer 3

what the xenobiotic does to the body

Question 4

summation

Answer 4

2+2=4

Question 5

synergism

Answer 5

2+2=10

Question 6

potentiation

Answer 6

0+2+10

Question 7

antagonism

Answer 7

2+2=0

Question 8

clearance

Answer 8

overall efficiency of xenobiotic removal from body

Question 9

bioaccumulation

Answer 9

the net accumulation of xenobiotic in an organism from all exposure routes

Question 10

bioconcentration

Answer 10

net accumulation of a xenobiotic in on organism is from water only

Question 11

biomagnification

Answer 11

occurs when xenobiotic concentrations increase through at least three trophic levels

Question 12

weak acid

Answer 12

more non-ionized
diffused into tissue

Question 13

weak base

Answer 13

more ionized
become trapped

Question 14

most important property

Answer 14

lipophilicity

Question 15

most common absorption pathway

Answer 15

passive diffusion

Question 16

active transport

Answer 16

ATP-binding cassette

Question 17

facilitated diffusion

Answer 17

OAT family

Question 18

relative lipid solubility

Answer 18

octanol-water partition coefficient

Question 19

only form that can passively diffuse

Answer 19

nonionized form

Question 20

most abundant plasma protein binding protein

Answer 20

albumin

Question 21

detoxification

Answer 21

biotransformation results in a less toxic metabolite

Question 22

bioactivation

Answer 22

biotransformation results in more toxic metabolite

Question 23

High and very low metabolism in organs

Answer 23

High- liver
very low- brain

Question 24

Phase 1

Answer 24

Cytochrome P450-dependent monooxygenases
cytochrome P450 reductase
Cofactor: NADPH

Question 25

Glucuronidation

Answer 25

enzyme: UDP-glucuronsoyl transferase cofactor: UDP-glucuronic acid

Question 26

Sulfation

Answer 26

enzyme: sulfotransferase cofactor:PAPS

Question 27

Acetylation

Answer 27

Enzyme: N-acetyltransferase Cofactor: acetyl coenzyme A

Question 28

Glutathione

Answer 28

Enzyme: glutathione S-transferase Cofactor: glutathione

Question 29

methyl mercury

Answer 29

neurotoxic environmental toxicant

Question 30

CYP3A4

Answer 30

human liver

Question 31

paracellular

Answer 31

small molecules can cross cellular membranes

Question 32

Excretion

Answer 32

glomerular filtration, tubular reabsorption, tubular secretion

Question 33

tubular secretion

Answer 33

movement of xenobiotics into kidney filtrate

Question 34

enterohepatic cycling

Answer 34

Xenobiotics excreted in the bile into intestine can be reabsorbed and distributed back to the liver (increase half-life)

Question 35

most important excretion route

Answer 35

renal excretion

Question 36

acid-base equation

Answer 36

What would be more preferentially absorbed from the stomach (pH=2): a weak acid with pKa=3 or a weak acid with a pKa=4? Log [HA]/[A-] = 3-2 = 1 Take antilog: [HA]/[A-] = 10 Log [HA]/[A-] = 4-2 = 2 Take antilog: [HA]/[A-] = 100

Question 37

bioavailability

Answer 37

the fraction of an orally administered drug that reaches the systemic circulation in an unchanged form

Question 38

bioavailability short answer

Answer 38

The humans had a pH that resulted in the drug being less non-ionized and readily absorbed The humans had higher amount of plasma binding proteins decreasing the half-life of the xenobiotic The human subject had a polymorphism that resulted in being a poor metabolizer The human subject had a disease that increased the half-life of the xenobiotic

Question 39

rats vs mice

Answer 39

One species is a poorer glucoronidators, meaning that some xenobiotics would stay in the body longer resulting in more toxic effects One species was younger or older than the other species who have lower enzyme activities One species was feed a diet that resulting in inhibition of CYP enzymes (decrease biotransformation of xenobiotics The mice went through bioactivation resulting in a more toxic metabolite The mice had a different pH of the stomach than rats The mice had less albumin present resulting in freer xenobiotic in their system than plasma bound xenobiotics The mice underwent enterohepatic cycling of the xenobiotic, increasing the half-life of the xenobiotic