MODULE 1 Flashcards

1
Q

Paracelsus

A

dose define the poision

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2
Q

toxicokinetics

A

what the body does to the xenobiotic

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3
Q

toxicodynamics

A

what the xenobiotic does to the body

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4
Q

summation

A

2+2=4

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5
Q

synergism

A

2+2=10

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6
Q

potentiation

A

0+2+10

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7
Q

antagonism

A

2+2=0

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8
Q

clearance

A

overall efficiency of xenobiotic removal from body

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9
Q

bioaccumulation

A

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

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10
Q

bioconcentration

A

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

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11
Q

biomagnification

A

occurs when xenobiotic concentrations increase through at least three trophic levels

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12
Q

weak acid

A

more non-ionized
diffused into tissue

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13
Q

weak base

A

more ionized
become trapped

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14
Q

most important property

A

lipophilicity

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15
Q

most common absorption pathway

A

passive diffusion

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16
Q

active transport

A

ATP-binding cassette

17
Q

facilitated diffusion

A

OAT family

18
Q

relative lipid solubility

A

octanol-water partition coefficient

19
Q

only form that can passively diffuse

A

nonionized form

20
Q

most abundant plasma protein binding protein

A

albumin

21
Q

detoxification

A

biotransformation results in a less toxic metabolite

22
Q

bioactivation

A

biotransformation results in more toxic metabolite

23
Q

High and very low metabolism in organs

A

High- liver
very low- brain

24
Q

Phase 1

A

Cytochrome P450-dependent monooxygenases
cytochrome P450 reductase
Cofactor: NADPH

25
Q

Glucuronidation

A

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

26
Q

Sulfation

A

enzyme: sulfotransferase
cofactor:PAPS

27
Q

Acetylation

A

Enzyme: N-acetyltransferase
Cofactor: acetyl coenzyme A

28
Q

Glutathione

A

Enzyme: glutathione S-transferase
Cofactor: glutathione

29
Q

methyl mercury

A

neurotoxic environmental toxicant

30
Q

CYP3A4

A

human liver

31
Q

paracellular

A

small molecules can cross cellular membranes

32
Q

Excretion

A

glomerular filtration, tubular reabsorption, tubular secretion

33
Q

tubular secretion

A

movement of xenobiotics into kidney filtrate

34
Q

enterohepatic cycling

A

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

35
Q

most important excretion route

A

renal excretion

36
Q

acid-base equation

A

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

37
Q

bioavailability

A

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

38
Q

bioavailability short answer

A

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

39
Q

rats vs mice

A

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