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Principles of Toxicology > Toxicokinetics > Flashcards

Toxicokinetics Flashcards

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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
What enzyme is found in high concentrations in the cytosol and specifically converts alcohol to acetylaldehyde?
Alcohol dehydrogenase (ADH)
26
What enzyme is found in peroxisomes and converts alcohol to acetylaldehyde?
Catalase
27
List the two cholinesterases
Acetylcholinesterase and butyrylcholinesterase
28
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.
pseudocholinesterase or butyrylcholinesterase
29
Organophosphates modify which residue of cholinesterases
serine
30
Any of a class of proteins that have carbohydrate groups attached to the polypeptide chain
glycoprotein
31
What are the cofactors of paraoxonases
H2O and Ca2+
32
Enzyme responsible for the synthesis of acetylcholine
choline acetyltransferase
33
Four categories of xenobiotic biotransformation
Hydrolosis, reduction, oxidation, conjugation
34
Hydrolytic enzymes all use this a a cofactor
H2O
35
Three types of enzymes that can undergo both reductive and oxidative metabolism
``` alcohol dehydrogenase ____________________ cytochromes P540 (anaerobic) Fill in the missing term. aldehyde oxidase (anaerobic) ```
36
Cytochromes P450 must be kept under _________ to reduce molecules.
Anaerobic
37
What condition is required to ensure that aldehyde oxidase is reductive?
anaerobic conditions
38
Under anaerobic conditions, aldehyde oxidase (AO) is known to reduce hydroxylamines and what else ?
N-oxides
39
Under anaerobic conditions, cytochromes P450 are known to reduce quinones and what else can it do?
halogen removal
40
Organophosphates irreversibly inhibits what enzyme
acetylcholine esterase
41
The organic product of the aldehyde dehydrogenase is
carboxylic acid
42
What enzyme is primarily responsible for reducing [acetaldehyde] during alcohol consumption?
Aldehyde dehydrogenase (ALDH)
43
A class of proteins found within cells that are responsible for sensing xenobiotics. That induce and inhibit target xenobiotic genes.
nuclear receptors
44
The action of acetylcholine esterase to metabolize acetylcholine ___________ synaptic transmission by metabolizing acetylcholine.
terminates
45
The action of acetylcholine esterase to metabolize acetylcholine ___________ muscles
relaxes
46
in general, esterases metabolize esters into
carboxylic acid and alcohol
47
The hemes in catalase are ligated by what type of amino acid?
Tyrosine
48
The cytochrome P450 heme is ligated by what type of amino acid?
Cysteine
49
A small organelle that is present in the cytoplasm of many cells and that contains the reducing enzyme catalase and some oxidases.
Peroxisome
50
What is a bad function of drug metabolism?
reduced efficacy
51
What is not part of the ADME acronym?
Elimination (ADME = absorption, distribution, metabolism, excretion)
52
Drug metabolizing enzymes are primarily found in which organs?
liver, intestines, and kidneys
53
Drug metabolizing enzymes are highest in which organ
liver
54
Which metabolizing enzyme dominates all of drug metabolism?
Cytochrome P450s (CYPs)
55
Which metabolizing enzyme dominates phase I drug metabolism?
Cytochromes P450 (CYPs)
56
Which metabolizing enzyme dominates Phase II drug metabolism?
GSTs (glutathione S transferases)
57
Which drug metabolizing enzyme is the most abundant in the cytosol?
Alcohol dehydrogenase
58
Which drug metabolizing enzyme is the most abundant membrane-bound enzyme?
Cytochromes P450
59
What organelle are cytochromes P450 generally found?
Smooth ER
60
Good function of drug metabolism include: Drug clearance, _____, homeostasis, activation of a prodrug
toxin removal
61
The bad functions of drug metabolism
reduced efficacy, increased toxicity
62
The ability of an enzyme to metabolize a wide range of substrates
promiscuity
63
The contributions of cytochromes P450 in drug disposition is similar to their expression levels. (T/F)
False
64
Which cytochrome P450 isoform plays the largest role in drug metabolism and can metabolize a majority of clinically relevant drugs?
CYP 3A4
65
Which cytochrome P450 binds to small molecules and can metabolize ethanol like alcohol dehydrogenase?
CYP2E1
66
What toxic metabolite is produced from metabolism of acetaminophen by cytochromes P450 (CYP)?
NAPQI NAPQI (N-acetyl-p-benzoquinone imine)
67
The cytochrome P450 catalytic cycle involves the following protein cofactors (Select all that apply)?
B, C | Cytochrome b5 and NADPH reductase is also known as NADPH Cytochrome P450 reductase
68
The product(s) of acetylcholinesterase is/are ? (Select all that apply)
Alcohol, Carboxylic acid
69
The product(s) of paraoxonase is/are ? (Select all that apply)
Alcohol, carboxylic acid
70
The product(s) of alkaline phosphatase is/are ? (Select all that apply)
Alcohol, phosphate
71
A defect in epoxide hydroxylase leads to _______ syndrome by reactive metabolite formation and subsequent immunological reactions. (Abbreviations are OK)
DRESS or Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms
72
Aldehyde dehydrogenases increase blood levels of acetaldehyde during alcohol consumption. (T/F)
False, reduce these levels and convert to acetic acid
73
What is the non-organic substrate of catalase
Hydrogen peroxide
74
The product(s) of amidases is/are ? (Select all that apply)
Carboxylic acid and amine
75
The product(s) of epoxide hydrolases is/are ? (Select all that apply)
Alcohol (diol)
76
The product(s) of alcohol dehydrogenase (ADH) with alcohol is/are ? (Select all that apply)
Aldehyde
77
The product(s) of aldehyde dehydrogenase is/are ? (Select all that apply)
Carboxylic acid
78
Thioesterases metabolize thioesters into? (Select all that apply)
Thiol, carboxylic acid
79
What products are produced from metabolism of H2O2 with Glutathione Peroxidase? (Check all that apply)
GSSG (glutathione disulfide), Water
80
Gray baby syndrome is caused by what drug?
Chloramphenicol
81
UDP-glucuronosyltransferases (UGTs) have which of the following cofactor(s)?
UDP-glucuronic acid (UDP-GA)
82
Sulfotransferases (SULTs or STs) have which of the following cofactor(s)?
3’-phosphoadenosine 5’-phosphosulfate (PAPS)
83
Glutathione-S-tranferases (GSTs) have which of the following cofactor(s)?
Glutathione
84
N-acetyl Tranferases (NATs) have which of the following cofactor(s)?
Acetyl-CoA
85
Catechol-O-methyltransferases (COMTs) have which of the following cofactor(s)?
S-adenosyl methionine (SAM)
86
Histamine methyltransferases (HMTs) have which of the following cofactor(s)?
S-adenosyl methionine (SAM)
87
Aldose reductase (AR) metabolizes b-D-glucose into ___________
sorbitol
88
Aldose reductase functions in catecholamine breakdown and the ______________ pathway.
Polyol
89
CYP2A6 and CYB2B6 metabolize
nicotine and coumarins
90
Cytochrome 2C9 metabolizes
Warfarin
91
Cytochrome 3A4 metabolizes
A majority of clinically relevant drugs
92
``` Of the functional groups that are shown, flavin-containing monooxygenases (FMO) oxidize what types of groups? Methyls Thiones Primary amines Tertiary amines aldehydes ```
Thiones, Tertiary amines
93
What organelle are monoamine oxidases (MAO) found in?
Mitochondria
94
The purpose of monoamine oxidases (MAOs) is to _________________.
Inactivate neurotansmiters
95
Xanthine Dehydrogenase (XDH) results in superoxide production. (T/F)
False, Xanthine oxidase does
96
Aldehyde oxidase (AO) metabolizes aldehydes. What else does it metabolize?
heterocyclic aromatics | That characteristic makes it of interest to the pharmaceutical industry, since many drugs have this group.
97
Your friend has an extremely low tolerance to alcohol. This could be do to relatively low concentrations of what enzyme?
Aldehyde dehydrogenase
98
What is it called, when the phase II metabolic pathway is blocked forcing metabolism down the Phase I pathway?
Metabolic switching

Principles of Toxicology (2 decks)

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