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Principles of Toxicology > Toxicokinetics > Flashcards

Toxicokinetics Flashcards

1
Q

Toxicokinetics

A

Study of the movement of an exogenous chemical from entry into body, distribution to organs/tissues via blood, final disposition by by biotransformation and excretion (physical properties)

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2
Q

Toxicodynamics

A

Describes interactions of a toxicant with a biological target and its effects (mechanism/mode of action)

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3
Q

Mechanism of Toxicity Deliver - Most to least effective

A

Intravenous, Inhalation, Subcutaneous, Oral, Dermal

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4
Q

Hapten

A

Haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein

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5
Q

Cytokine

A

any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells

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6
Q

Antigen

A

a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies

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7
Q

Antibody

A

a blood protein produced in response to and counteracting a specific antigen. Antibodies combine chemically with substances which the body recognizes as alien, such as bacteria, viruses, and foreign substances in the blood

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8
Q

Site of most toxic chemical biotransformation

A

Liver

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9
Q

Potentiation

A

This effect results when one substance that does not normally have a toxic effect is added to another chemical, making the second chemical much more toxic; for example: 0 + 2 > 2, not just 2

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10
Q

Synergistic effect

A

2 + 2 = more than 4

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11
Q

Quantal dose-response relationship

A

Allow the analysis of a populations response to varying dosage

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12
Q

Therapeutic index

A

A ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective. The larger the therapeutic index (TI), the safer the drug is.

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13
Q

Selective toxicity

A

the agent acts in some way that inhibits or kills bacterial pathogens but has little or no toxic effect on the patient.

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14
Q

Types of toxic reactions

A

Noncovalent Binding for apolar interactions to form hydrogen and ionic bonds, Covalent Binding (irreversible and permanently changes), Hydrogen Abstraction to form radicals, Electron Transfer ( Fe2+ to Fe3+ ), Enzymatic Reactions

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15
Q

Endogenous ROS Terminators

A

Glutathione (GSH), Cysteine, Catalase, Super oxide dismutase

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16
Q

Exogenous ROS Terminators

A

Vitamin C, vitamin E

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17
Q

Protein that functions to prevent progression of cell cycle

A

IkB

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18
Q

Necrosis

A

Induced by multiple mechanisms•Loss of ER and mitochondrial function•Almost always involve loss of ATP and increases in intracellular Ca2+(mM)

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19
Q

What phase of drug metabolism involves hydrolosis, oxidation, and reduction?

A

Phase I

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20
Q

What phase of drug metabolism involves conjugation reactions?

A

Phase II

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21
Q

What enzyme or process plays the largest role in oxidative xenobiotic metabolism

A

Cytochromes P450

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22
Q

Enzymes involved in the oxidation of ethanol to acetaldehyde

A

Catalase, alcohol dehydrogenase, Cytochrome P450 2E1 (CYP2E1)

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23
Q

What is the name of the enzyme that converts acetylaldehyde to acetic acid?

A

Aldehyde dehydrogenase (ALDH)

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24
Q

What organelle are cytochromes P450 found?

A

Smooth ER

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25
Q

What enzyme is found in high concentrations in the cytosol and specifically converts alcohol to acetylaldehyde?

A

Alcohol dehydrogenase (ADH)

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26
Q

What enzyme is found in peroxisomes and converts alcohol to acetylaldehyde?

A

Catalase

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27
Q

List the two cholinesterases

A

Acetylcholinesterase and butyrylcholinesterase

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28
Q

It is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it is made in the liver, found mainly in blood plasma, and encoded by the BCHE gene.

A

pseudocholinesterase or butyrylcholinesterase

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29
Q

Organophosphates modify which residue of cholinesterases

A

serine

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30
Q

Any of a class of proteins that have carbohydrate groups attached to the polypeptide chain

A

glycoprotein

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31
Q

What are the cofactors of paraoxonases

A

H2O and Ca2+

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32
Q

Enzyme responsible for the synthesis of acetylcholine

A

choline acetyltransferase

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33
Q

Four categories of xenobiotic biotransformation

A

Hydrolosis, reduction, oxidation, conjugation

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34
Q

Hydrolytic enzymes all use this a a cofactor

A

H2O

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35
Q

Three types of enzymes that can undergo both reductive and oxidative metabolism

A 
alcohol dehydrogenase
 \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
 cytochromes P540 (anaerobic)
Fill in the missing term.
aldehyde oxidase (anaerobic)
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36
Q

Cytochromes P450 must be kept under _________ to reduce molecules.

A

Anaerobic

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37
Q

What condition is required to ensure that aldehyde oxidase is reductive?

A

anaerobic conditions

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38
Q

Under anaerobic conditions, aldehyde oxidase (AO) is known to reduce hydroxylamines and what else ?

A

N-oxides

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39
Q

Under anaerobic conditions, cytochromes P450 are known to reduce quinones and what else can it do?

A

halogen removal

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40
Q

Organophosphates irreversibly inhibits what enzyme

A

acetylcholine esterase

41
Q

The organic product of the aldehyde dehydrogenase is

A

carboxylic acid

42
Q

What enzyme is primarily responsible for reducing [acetaldehyde] during alcohol consumption?

A

Aldehyde dehydrogenase (ALDH)

43
Q

A class of proteins found within cells that are responsible for sensing xenobiotics. That induce and inhibit target xenobiotic genes.

A

nuclear receptors

44
Q

The action of acetylcholine esterase to metabolize acetylcholine ___________ synaptic transmission by metabolizing acetylcholine.

A

terminates

45
Q

The action of acetylcholine esterase to metabolize acetylcholine ___________ muscles

A

relaxes

46
Q

in general, esterases metabolize esters into

A

carboxylic acid and alcohol

47
Q

The hemes in catalase are ligated by what type of amino acid?

A

Tyrosine

48
Q

The cytochrome P450 heme is ligated by what type of amino acid?

A

Cysteine

49
Q

A small organelle that is present in the cytoplasm of many cells and that contains the reducing enzyme catalase and some oxidases.

A

Peroxisome

50
Q

What is a bad function of drug metabolism?

A

reduced efficacy

51
Q

What is not part of the ADME acronym?

A

Elimination (ADME = absorption, distribution, metabolism, excretion)

52
Q

Drug metabolizing enzymes are primarily found in which organs?

A

liver, intestines, and kidneys

53
Q

Drug metabolizing enzymes are highest in which organ

A

liver

54
Q

Which metabolizing enzyme dominates all of drug metabolism?

A

Cytochrome P450s (CYPs)

55
Q

Which metabolizing enzyme dominates phase I drug metabolism?

A

Cytochromes P450 (CYPs)

56
Q

Which metabolizing enzyme dominates Phase II drug metabolism?

A

GSTs (glutathione S transferases)

57
Q

Which drug metabolizing enzyme is the most abundant in the cytosol?

A

Alcohol dehydrogenase

58
Q

Which drug metabolizing enzyme is the most abundant membrane-bound enzyme?

A

Cytochromes P450

59
Q

What organelle are cytochromes P450 generally found?

A

Smooth ER

60
Q

Good function of drug metabolism include: Drug clearance, _____, homeostasis, activation of a prodrug

A

toxin removal

61
Q

The bad functions of drug metabolism

A

reduced efficacy, increased toxicity

62
Q

The ability of an enzyme to metabolize a wide range of substrates

A

promiscuity

63
Q

The contributions of cytochromes P450 in drug disposition is similar to their expression levels. (T/F)

A

False

64
Q

Which cytochrome P450 isoform plays the largest role in drug metabolism and can metabolize a majority of clinically relevant drugs?

A

CYP 3A4

65
Q

Which cytochrome P450 binds to small molecules and can metabolize ethanol like alcohol dehydrogenase?

A

CYP2E1

66
Q

What toxic metabolite is produced from metabolism of acetaminophen by cytochromes P450 (CYP)?

A

NAPQI NAPQI (N-acetyl-p-benzoquinone imine)

67
Q

The cytochrome P450 catalytic cycle involves the following protein cofactors (Select all that apply)?

A

B, C

Cytochrome b5 and NADPH reductase is also known as NADPH Cytochrome P450 reductase

68
Q

The product(s) of acetylcholinesterase is/are ? (Select all that apply)

A

Alcohol, Carboxylic acid

69
Q

The product(s) of paraoxonase is/are ? (Select all that apply)

A

Alcohol, carboxylic acid

70
Q

The product(s) of alkaline phosphatase is/are ? (Select all that apply)

A

Alcohol, phosphate

71
Q

A defect in epoxide hydroxylase leads to _______ syndrome by reactive metabolite formation and subsequent immunological reactions. (Abbreviations are OK)

A

DRESS or Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms

72
Q

Aldehyde dehydrogenases increase blood levels of acetaldehyde during alcohol consumption. (T/F)

A

False, reduce these levels and convert to acetic acid

73
Q

What is the non-organic substrate of catalase

A

Hydrogen peroxide

74
Q

The product(s) of amidases is/are ? (Select all that apply)

A

Carboxylic acid and amine

75
Q

The product(s) of epoxide hydrolases is/are ? (Select all that apply)

A

Alcohol (diol)

76
Q

The product(s) of alcohol dehydrogenase (ADH) with alcohol is/are ? (Select all that apply)

A

Aldehyde

77
Q

The product(s) of aldehyde dehydrogenase is/are ? (Select all that apply)

A

Carboxylic acid

78
Q

Thioesterases metabolize thioesters into? (Select all that apply)

A

Thiol, carboxylic acid

79
Q

What products are produced from metabolism of H2O2 with Glutathione Peroxidase? (Check all that apply)

A

GSSG (glutathione disulfide), Water

80
Q

Gray baby syndrome is caused by what drug?

A

Chloramphenicol

81
Q

UDP-glucuronosyltransferases (UGTs) have which of the following cofactor(s)?

A

UDP-glucuronic acid (UDP-GA)

82
Q

Sulfotransferases (SULTs or STs) have which of the following cofactor(s)?

A

3’-phosphoadenosine 5’-phosphosulfate (PAPS)

83
Q

Glutathione-S-tranferases (GSTs) have which of the following cofactor(s)?

A

Glutathione

84
Q

N-acetyl Tranferases (NATs) have which of the following cofactor(s)?

A

Acetyl-CoA

85
Q

Catechol-O-methyltransferases (COMTs) have which of the following cofactor(s)?

A

S-adenosyl methionine (SAM)

86
Q

Histamine methyltransferases (HMTs) have which of the following cofactor(s)?

A

S-adenosyl methionine (SAM)

87
Q

Aldose reductase (AR) metabolizes b-D-glucose into ___________

A

sorbitol

88
Q

Aldose reductase functions in catecholamine breakdown and the ______________ pathway.

A

Polyol

89
Q

CYP2A6 and CYB2B6 metabolize

A

nicotine and coumarins

90
Q

Cytochrome 2C9 metabolizes

A

Warfarin

91
Q

Cytochrome 3A4 metabolizes

A

A majority of clinically relevant drugs

92
Q 
Of the functional groups that are shown, flavin-containing monooxygenases (FMO) oxidize what types of groups?
Methyls
Thiones
Primary amines
Tertiary amines
aldehydes
A

Thiones, Tertiary amines

93
Q

What organelle are monoamine oxidases (MAO) found in?

A

Mitochondria

94
Q

The purpose of monoamine oxidases (MAOs) is to _________________.

A

Inactivate neurotansmiters

95
Q

Xanthine Dehydrogenase (XDH) results in superoxide production. (T/F)

A

False, Xanthine oxidase does

96
Q

Aldehyde oxidase (AO) metabolizes aldehydes. What else does it metabolize?

A

heterocyclic aromatics

That characteristic makes it of interest to the pharmaceutical industry, since many drugs have this group.

97
Q

Your friend has an extremely low tolerance to alcohol. This could be do to relatively low concentrations of what enzyme?

A

Aldehyde dehydrogenase

98
Q

What is it called, when the phase II metabolic pathway is blocked forcing metabolism down the Phase I pathway?

A

Metabolic switching

Principles of Toxicology (2 decks)

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