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Toxicology > Exam 1 > Flashcards

Exam 1 Flashcards

1
Q

study of the adverse effects of chemical, physical or biological agents on people, animals, and the environment

A

toxicology

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2
Q

who said, “the dose makes the poison”

A

Percelsus

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3
Q

Hazard x Exposure=

A

Risk

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4
Q

a substance that is foreign to the body or to an ecological system, usually a synthetic chemical

A

xenobiotic

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5
Q

any toxic substance usually used to denote substances made by humans

A

toxicant

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6
Q

toxic substances that are produced naturally by a living organisms such as plants, animals, fungi, or bacteria

A

toxins

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7
Q

Dose that gives 1/2 the maximal response

A

ED50 (effective dose)

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8
Q

Dose required to get 50% of the population to report a specific toxic effect

A

TD50 (toxic dose)

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9
Q

dose required to kill 50% of a population

A

LD50 (lethal dose)

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10
Q

Ratio of the dose required to produce a toxic effect to the dose need to elicit the desired therapeutic response

A

TI (therapeutic index)

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11
Q

TD1/ED99=

A

MOS: Margin of safety

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12
Q

<24 hrs of exposure (often only a single dose)

A

acute

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13
Q

repeated exposure for 1 month or less

A

subacute

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14
Q

repeated exposure for 1 to 3 months

A

subchronic

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15
Q

repeated exposure for >3 months

A

chronic

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16
Q

the amount or concentration of drug responsible for a given level of response

A

potency

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17
Q

the level of response a drug can elicit

A

efficacy

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18
Q

what does ADME stand for?

A

Absorption, distribution, metabolism and elimination

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19
Q

Which in ADME: the transfer of a xenobiotic from the site of exposure into the systemic circulation

A

Absorption

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20
Q

Which in ADME: Xenobiotic reaching their site or sites of action

A

Distribution

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21
Q

Which in ADME: Xenobiotics are biotransformed thus increasing or decreasing toxicity

A

Metabolism

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22
Q

Which in ADME: Removal of xenobiotics from blood and their return to the extern environment

A

elimination

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23
Q

when repair is exceeded by dysfunction or when repair malfunctions toxicity can occur

A

toxicity

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24
Q

Transfer from site of exposure to systemic circulation; when lipid solubility increases this also increases

A

absorption

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25
Q

during first pass elimination, what is it they pass to gain enterance?

A

GI cells, liver and lungs

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26
Q

During first pass elimination, cells metabolize toxicants (incr./decre) their concentration at sites where toxicity can occur

A

Decrease

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27
Q

What are the major excretory organs?

A

liver and kidney

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28
Q

Diffusion back into the systemic circulation at sites of excretion as opposed to removal

A

reabsorption

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29
Q

Give electron status and philicity of lewis acids and bases

A

Lewis acid: accepts electrons, electrophiles
Lewis base: donates electrons, nucleophiles

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30
Q

A molecule or molecular fragment that contains one or more unpaired electrons in its outer orbital.

A

free radical

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31
Q

What happens in a Fenton Reaction?

A

Ferric turns to ferris
Free radical is always looking for unpaired electron and will take from other entity, causing damage

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32
Q

LEO the lion says GER

A

Losing Electrons is Oxidation
Gaining electrons is reduction

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33
Q

Imbalance of cellular oxidants and antioxidants in favor of oxidants

A

oxidative stress

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34
Q

Reversibility of noncovalent and covalent bonding

A

Noncovalent: reversible
Covalent: irreversible

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35
Q

Destroys cell membrane and/or subcellular organelles

A

Direct toxicities

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36
Q

Alter structure and function of proteins or DNA

A

Indirect Toxicities

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37
Q

Two types of cell deaths

A

Necrosis: sudden death
Apoptosis: self-removal

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38
Q

self-digestion of cell’s own components through lysosome-mediated mechanism

A

autophagy

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39
Q

Which part of the cell determines the form of cell death?

A

mitochondria

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40
Q

Three types of repair from toxicity

A

molecular, cellular, and tissue

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41
Q

Inflammation major events

A

Recruit inflammatory cells (macrophages and leukocytes) to undergo respiratory burst.
Phagocytosis of cell components for degradation by macrophages

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42
Q

What does Vd tell you about affinity?

A

Small Vd: toxicants have high affinity for plasma proteins
Large Vd: toxicants have high affinity for tissue proteins

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43
Q

In a Steady State Concentration (Css) model, the drug concentrations fluctuate within the upper and lower boundaries as a result of rate in being ______ rate out

A

equal to

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44
Q

How to solve for k

A

ln(y1)-ln(y2)/x2-x1

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45
Q

how to solve for T1/2

A

0.693/k

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46
Q

how to solve for Vd (volume distribution)

A

Vs=Dose/k*AUC

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47
Q

How to solve for CL (clearance)

A

Cl=0.636(Vd)/T1/2

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48
Q

How to solve for absolute F

A

F= (AUC/Dose)test/(AUC/Dose)IV

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49
Q

Non-saturated fatty acids provide ___, ____ and target for ______

A

Provide shape, fluidity and target for free radicals

50
Q

Passive diffusion is not ___, not ______ to substance, and not requiring ____

A

not saturable, not selective to substance, and not requiring energy

51
Q

Higher lipophilicity (TDD) means (higher/lower) Log P

A

higher

52
Q

Active transport moves xenobiotics (against/not against) concentration gradients and (does/does not) require energy

A

against, does

53
Q

Facilitated diffusion moves xenobiotics (against/not against) concentration gradients and (does/does not) require energy

A

not against, does not

54
Q

Active and facilitated transport are (saturable/non-saturable) while active transport is (saturable/non-saturable)

A

saturable, non-saturable

55
Q

Cmax depends on the ____ and _____ of absorption

A

rate and intensity

56
Q

Tmax is inversely related to the ___ of absorption

A

rate

57
Q

AUC is directly proportional to the ____ of absorption

A

intensity

58
Q

Which ionization species is more easy to pass across the cell membrane?

A

non-ionized

59
Q

For pulmonary absorption, particle ____ determines toxicity

A

size

60
Q

Distribution occurs (slower/quicker) than elimination

A

quicker

61
Q

What are the parameters to describe a distribution process?

A

Volume of distribution (Vd) and ratio of tissue to blood concentration (T/B)

62
Q

Equation for Volume

A

Volume= amount/concentration

63
Q

What is the relationship between volume and concentration

A

Inverse

64
Q

What are the small, medium and large volumes of distributions?

A

Vd<0.5: small
0.52: large

65
Q

What ratio provides information on tissue binding of a drug or toxicant?

A

Tissue/blood (T/B)

66
Q

On a plasma/time curve for decrease renal blood flow, What is the relationship between Cmax and CLs? Tmax and AUC? T1/2 and F

A

Cmax/CLs: inverse
Tmax/AUC: inverse
T1/2/F= Bioavailability stays the same

67
Q

On a plasma/time curve for increased hepatic enzyme activity, What is the relationship between Cmax and CLs? Tmax and AUC? T1/2 and F

A

Cmax/CLs: inverse
Tmax/AUC: direct
T1/2/F= direct

68
Q

On a plasma/time curve for increased displacement, What is the relationship between Cmax and CLs? Tmax and AUC? T1/2 and F

A

Cmax/CLs: inverse
Tmax/AUC: t/max stays constant
T1/2/F= t1/2 stays constant

69
Q

Which processes affect ADME?

A

Absorption: Cmax, Tmax, F, Ka
Distribution: (Vd, Css)
Metabolism: (Km,CLs)
Elimination: (K, t1/2, CLs)

70
Q

A series of enzyme-catalyzed processes that alter the physiochemical properties of foreign chemicals from those that favor absorption across biological membranes to those favoring elimination in urine or bile

A

xenobiotic metabolism

71
Q

Which principle #: xenobiotic metabolism is the process of converting insoluble compounds which are readily absorbed into soluble chemicals which can readily be excreted

A

P1

72
Q

Which principle #: Biotransformation is catalyzed by various enzyme systems that can be divided into 4 categories based on the reaction they catalyze

A

P2

73
Q

Which principle #: In general, individual xenobiotic-biotransformation enzymes are located on a single organelle

A

P3

74
Q

Which principle #: In general, xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities

A

P4

75
Q

Which principle #: several xenobiotic-biotransforming enzymes are inducible, meaning their expression can be increased

A

P5

76
Q

Which principle #: There can be species and gender differences in xenobiotic metabolism that must be taken into account during research studies

A

P6

77
Q

Which principle #: Genetic variation in xenobiotic-biotransformation enzyme results in inter-individual variations in toxic responses

A

P7

78
Q

Which principle #: Environmental factors can also induce variation in drug metabolism

A

P8

79
Q

Which principle #: Mass spectrometry is widely used to characterize the structure of metabolites

A

P9

80
Q

Three phase I reactions

A

Hydrolysis, Oxidation, Reduction

81
Q

Phase II reaction

A

Conjugation

82
Q

Phase II reactions add endogenous _____ to the functional groups

A

moieties

83
Q

Grapefruit uses ____ of (this enzyme) to (incres/decres) the effects of a variety of drugs by increasing their _______

A

inhibition of CYP3A4, increases, bioavailability

84
Q

The primary functional unit of the kidney

A

nephron

85
Q

What does the glomera filtrate?

A

Size and charge filter

86
Q

(more/less) positive charge means more likely to gain access to the kidney

A

more

87
Q

Which segment of the proximal tubule metabolizes glutathione (GSH)

A

S3

88
Q

Why is the kidney susceptible to toxicants?

A

A lot of blood flow in comparison to size, sensitive to system vasoconstriction (BP)

89
Q

What inorganic element binds to the S3 segment of the proximal tubul?

A

Inorganic mercury

90
Q

Cadmium nephrotoxicity chart

A

Cd binds to GSH or MT.
If MT, goes to urine or kidney.
In kidney leads to cytotoxicity
If GSH, turns to bile and no nephrotoxicity occurs.

91
Q

TCM chart to liver and kidney

A

To liver: processes with cP450
To kidney: combines with GSH then processed in proximal tubule. Beta-Lyase then converts to reactive thiol which causes nephrotoxicity

92
Q

What happens to A2M in rats? Where is A2M present?

A

Cancer warning on gasoline, but A2M only affects male rats
Kidney uptake in S2 segment of proximal tubule where lysosome inefficiently breaks down A2M. This causes lysosomal overload leading to necrosis. Cell proliferation leads to neoplastic (carcinogenesis) in kidney

93
Q

Ethylene glycol toxicity and intervention

A

Ethylene glycol turns to glycolaldehyde, turning to glyco-acids, turns to oxalate connecting to calcium. Calcium oxalate crystals accumulate in kidney leading to cell death and kidney failure.
Intervention: ethanol and fomepizole. Avoids crystallization process
or dialysis

94
Q

The basic anatomic unit of the liver

A

lobule

95
Q

What are the 5 functions of the liver?

A

nutrient homeostasis, synthesis, secretion, excretion and defense organ

96
Q

Identify the livers zone: closest to portal vein and arterioles (peri-portal region). Youngest cells, highest glucose storage, high oxygen, high nutrients

A

zone 1

97
Q

Identify the livers zone: most active regenerative activity

A

Zone 2 (mid-zone)

98
Q

Identify the livers zone: centrilobular; high in p450 enzymes, relatively hypoxic

A

Zone 3

99
Q

Excessive accumulation of fat or lipid materials; damage initially reversible

A

steatosis

100
Q

Extensive damage in hepatocytes reversible in the early stages; becomes irreversible to coagulative

A

necrosis

101
Q

slow or ceased bile flow; requires BSP test

A

cholestasis

102
Q

disruption in hepatic architecture due to necrosis and deposition of collagen fibers

A

cirrhosis

103
Q

formation of carcinoma

A

neoplasia

104
Q

Determine the condition given the AST:ALT Ratio
AST:ALT > 1
2:1
AST:ALT=1
AST:ALT<1

A

AST:ALT > 1 (cirrhosis)
2:1 (alcoholic liver disease)
AST:ALT=1 (ischemia)
AST:ALT<1 (hepatocellular damage)

105
Q

A _____ liver is pre-neoplastic

A

cirrhotic

106
Q

What type of reaction phase in the liver is APAP

A

Phase II reaction

107
Q

What is the treatment method for APAP?

A

activated charcoal

108
Q

What is the ethanol metabolism?

A

Ethanol is treated with ADH, Catalase, or CYP2E1 to form acetaldehyde which is treated with ALDH to form acetic acid

109
Q

Which compound promotes fatty acid steatosis in the liver?

A

acetic acid

110
Q

CYP2EI is an ____ cP450 enzyme

A

inducible

111
Q

Which liver zone does allyl alcohol target?

A

Liver zone 1

112
Q

What metabolizes allyl alcohol? Which zone does this toxicity occur?

A

ADH metabolizes to acrolein, with toxicity occurring in zone 1 due to oxygen dependency

113
Q

What is the mechanism of cell death for CCl4?

A

CCl4 causes lipid peroxidation. This increases plasma membrane permeability and Calcium, causing cell death

114
Q

What is the penetration level of alpha, beta, gamma and x-rays for concrete, lead, plastic and paper?

A

Alpha- stopped by paper
Beta- stopped by plastic
Gamma and x-ray- stopped by lead

115
Q

How is radiation measured?

A

By Bq (Baquro) and Ci (Curie)

116
Q

What is the name for two and three centromeres chromosomes?

A

2: dicentrics
3: tricentric

117
Q

Which phase of the cell cycle is low radio-sensitive? high?

A

S phase- low
M phase- high

118
Q

Stage of ARS that lasts from a few minutes to days characterized by nausea, vomiting, diarrhea, lethargy, etc.

A

Prodromal Stage

119
Q

Individual appears healthy, duration varies with dose

A

latent stage

120
Q

What is the survival rate in increasing to decreasing order:
GI syndrome, Hematopoietic Syndrome and Cerebrovascular syndrome

A

Hematopoietic>GI>Cerebrovascular

Toxicology (2 decks)

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