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House Pharmacology > Toxicokinetics > Flashcards

Toxicokinetics Flashcards

1
Q

Toxicity is the (intrinsic or extrinsic?) quality of a chemical to __________

A

Intrinsic

produce an adverse effect

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2
Q

Toxicity is the Capacity to induce ______,_______, and ___________ effects

A

teratogenic, mutagenic and carcinogenic

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3
Q

Anything can be a poison
T/F

A

T

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4
Q

The _____ makes the poison

A

Dose

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5
Q

Absorption
The process by which toxicants ————————

A

cross body membranes and enter the bloodstream

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6
Q

Many environmental toxicants enter the food chain and are absorbed together with food.

T/F

A

T

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7
Q

_________ is the most common route of unintentional exposure to a toxicant (especially for children)

While

intentional overdoses most frequently occur via the ______

A

accidental ingestion

oral route.

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8
Q

Poisons in the GI tract usually produce systemic injury to an individual before they are absorbed

T/F

A

F
They usually do not

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9
Q

Absorption of toxicants can take place along the entire GI tract: from the mouth to the rectum.

T/F

A

T

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10
Q

Organic toxicant (acid or base) are usually absorbed by ________ in the part of the GI tract where it exists in its (ionized or non-ionized?) form

A

simple diffusion

non-ionized

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11
Q

The ______________ can be used to determine the fraction of a toxicant that is in the non- ionized form and estimate the rate of absorption from the stomach or intestine

A

Henderson–Hasselbalch equations

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12
Q

According to the HH equation, weak organic acids are mainly present in the non-ionized (lipid soluble) form in the ________ and ionised form in the ______

A

stomach

intestine

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13
Q

Factors that affect the HH equation include __________ and _________

A

surface area and blood flow rate.

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14
Q

Most toxicants are absorbed by __________ though

A

simple diffusion

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15
Q

After oral ingestion, about ___% of lead,__% of manganese, ___% of cadmium, and __% of chromium salts are absorbed.

A

10

4

1.5

1

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16
Q

Absorption: GIT

Particles and particulate matter can also be absorbed

T/F

A

T

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17
Q

Absorption: GIT
Particles and particulate matter can also be absorbed
In this case, ______ determines absorption and is _______ related to absorption

A

particle size

inversely

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18
Q

_______ arsenic significantly more toxic than its _______ form due to increased ________

A

powdered

coarse granular

surface area

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19
Q

Absorption: GIT

In general, absorption through the GIT is influenced by:

Characteristics of the toxicant

○ Must have sufficient _______ partition

○ Be relatively (ionizer or non-ionized?) in most parts (lipid- soluble)

○ If a particle, must be of relatively ___ size

A

aqueous - lipid

non-ionized

low

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20
Q

Absorption: GIT

Affected by Other xenobiotics/toxicants:

○Cd decreases the absorption of _______

Ca decreases ____ absorption

Mg decreases absorption of ______
—

A

Zn and Cu

Cd

Fluoride

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21
Q

Absorption: GIT
ž
—
Affected by GI ________/______ within various segments of the GI tract

  • could be as an effect of _____/______
A

Motility/residency time

Laxatives/Anti-diarrheas

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22
Q

Absorption: GIT

Affected by Age

  • Well water with a (low or high?) nitrate content produces _______ more frequently in (infants or adults ?) than in (infants or adults?)

*(Lower or Higher?) pH of the neonatal GI tract is permissive for the growth of bacteria

*Bacteria in the GI tract convert ____ to _____, increasing the risk of methemoglobinemia
ž
—
— —

A

High; methemoglobinemia

Infants
Adults

Higher

nitrate to nitrite

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23
Q

Absorption: GIT

Snake venoms are much (more or less?) toxic by the oral route relative to intravenous exposure

Why?

A

Less

because they are broken down by digestive enzymes

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24
Q

Absorption : GIT

nitroaromatic compounds are reduced by intestinal microflora to potentially ______ and ________ amines.

—
—

A

toxic and carcinogenic aromatic

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25
Q

Absorption: Lungs

Absorption or deposition of airborne poisons in the lungs can result in

Death from poisoning— __________
Occupational disease— _________

A

carbon monoxide

silicosis

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26
Q

Absorption: Lungs

Gases (e.g., _______,_______ ,_______ )

Vapors of volatile or volatilizable liquids (e.g., _______ and __________)

Aerosols

A

carbon monoxide, nitrogen dioxide, and sulfur dioxide

benzene and carbon tetrachloride

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27
Q

Absorption: Lungs

Depends on Gas molecules partition between two media:

_______ and ______ during the absorptive phase

______ and ———- during the distributive phase

A

Air and blood

blood and other tissues

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28
Q

Absorption: Lungs

Factors such as _______ and ______ of molecules are less important

more important is the _________________

A

dissociation and lipid solubility

blood-to-gas partition coefficient.

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29
Q

Chloroform has a relatively (low or high?) blood to gas partition coefficient (approximately ___), whereas ethylene has a (low or high?) coefficient (____)

A

High

20

Low

0.14

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30
Q

Absorption: Lungs

The site of deposition of aerosols and particulates depends largely on the __________

A

size of the particles

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31
Q

Absorption: Lungs

The __________ the particle, the further into the respiratory tree the particle will deposit
As particle size ____eases, the number of particles in a unit of space increases along with the total surface area of the particles

A

smaller (finer)

decr

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32
Q

Absorption: Skin

Exposure is usually limited by its __________ nature.

A

relatively impermeable

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33
Q

Absorption: Skin

Fatal exposures to insecticides (and even gases e.g. sarin – nerve gas) have occurred in _______ after absorption through intact skin

A

agricultural workers

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34
Q

Absorption: Skin

Passage through the ________ is the rate-determining step.

A

stratum corneum

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35
Q

Absorption: Skin

All toxicants move across the stratum corneum by ________

A

passive diffusion

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36
Q

____philic compounds are absorbed more readily across the stratum corneum , ____ proportional to their lipid solubility and _____ related to molecular weight

A

Lipo

directly

inversely

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37
Q

Absorption: Skin

Hydrophilic compounds are more likely to penetrate the skin through appendages such as _______

A

hair follicles

38
Q

The permeability of hydrophilic molecules doesn’t depend on diffusivity and thickness of the stratum corneum

T/F

A

F

also depends on it

39
Q

Absorption: SKIN

Arrange in terms of decreasing absorption rate

Forehead skin, scrotal skin, palm skin

A

Scrotal skin > forehead skin > palm

40
Q

Absorption: Skin

Several factors influence the absorption of toxicants through the skin:

*The ______ of the stratum corneum: caustic agents/Diseases

*The _____ state of the stratum corneum e.g. occlusive application

*_______: occupational exposure e.g. agricultural workers

*______ as carriers - dimethyl sulfoxide (DMSO)

*____________

A

integrity

hydration

Temperature

Solvents

Molecular size (again nanoparticles)

41
Q

Nanoparticles are relevant in absorption in which of the following routes

Skin
GIT
lungs

A

All 3 bby!

42
Q

In studying effects of toxicants, other routes of administration may also be used.

Intravenous – ____% absorption Intraperitoneal – _______
Subcutaneous – influenced by _____/____
Intramuscular - influenced by _____/_____

A

100

Hepatic first pass

blood flow/formulation

blood flow/formulation

43
Q

Distribution is a (slow or rapid ?) process.

A

Rapid

44
Q

The rate of distribution to organs or tissues is determined primarily by
________ and ________

A

blood flow

rate of diffusion

45
Q

Distribution

Some toxicants selectively accumulate in certain parts of the body as a result of

_____ binding
high solubility in ____

Lungs e.g. ______ accumulates in the lungs
Bone e.g. ____

A

protein

fat; paraquat

Lead

46
Q

The target organ for toxicity may be the site of accumulation

T/F

A

T

47
Q

The target organ for toxicity may be the site of accumulation and this is always the case

T/F

A

F

this is not always the case

48
Q

Distribution

Binding to plasma proteins is the major site of protein binding

Several different plasma proteins

Albumin
α1- ___ glycoprotein
Transferrin-a ______- transports ___
Ceruloplasmin, which carries _____

A

Acid

beta globulin; Fe

copper

49
Q

Distribution

Because of their high _______, plasma proteins and the toxicants bound to them (can or cannot?) cross capillary walls.

A

molecular weight

Cannot

50
Q

Consequently, the fraction of a toxicant bound to plasma proteins is not immediately available for distribution into the extravascular space but available for filtration by the kidneys

T/F

A

F

Not available for both

51
Q

a toxicant in a storage depot (including fat deposits) is not in equilibrium with the free fraction of the toxicant in plasma

T/F

A

F

It is

52
Q

Distribution

The binding of chemicals to plasma proteins is important for two reasons:

1) Toxicity is typically manifested by the amount that is (bound or unbound?) .

2) Risk of adverse effects resulting from ________________ – ______ displacement

A

unbound

interactions with other highly bound compounds

protein binding

53
Q

Distribution

The potential for these compounds to produce carcinogenic, developmental, and endocrine effects is related to their ______________

A

accumulation/storage in body fat

54
Q

toxicants with a (low or high?) lipid/water partition coefficient may be stored in body fat
concern is the possibility of increase in the concentration of toxicant in blood/target organ of toxicity may occur if ______________ occurs

A

High

rapid mobilization from fat

55
Q

Distribution
Compounds such as _____,_____, and _____ may be incorporated and stored in the bone matrix.

A

fluoride, lead, and strontium

56
Q

___%of the lead in the body is eventually found in the _______.

A

90

skeleton

57
Q

Toxicants can be released from the bone by ________ at the ____ surface and _____ of bone crystal through _______ activity.

A

ionic exchange

crystal

dissolution

osteoclastic

58
Q

Toxicants are also distributed into the brain

T/F

A

T

59
Q

Only the free fraction of a toxicant equilibrates rapidly with the brain.

T/F

A

T

60
Q

Distribution

Most toxic chemicals pass the placenta by _________
Exceptions → antimetabolites (_____ transport): structurally similar to ____________________

A

simple diffusion

Active transport

endogenous purines and pyrimidines

61
Q

Under steady-state conditions, the concentrations of a toxic compound in the plasma of the mother and fetus are usually different

T/F

A

F

They are usually the same

62
Q

Metabolism

Rationale for metabolism:

Eventual _______________.

Unacceptably _____________

— —

A

accumulation to toxic levels

long duration of action.

63
Q

Metabolism
It can make the xenobiotic less toxic ( _______ ), but in some cases it can make it more toxic (________).

E.g. the oxidation of ethanol (alcohol) to _______ ( _______ ), and the subsequent oxidation of that to _____ is an example of _________.

A

detoxication; activation

Acetaldehyde; activation

acetic acid; detoxication

64
Q

Metabolism
So, the biotransformation of drugs can result in:

a loss of activity e.g., acetaminophen to _______________; morphine to _____________)

no change in activity e.g., the conversion of fluoxetine to its N-demethylated metabolite ___________

an increase in activity (e.g. codeine to _________; morphine to ________
—

A

acetaminophen glucuronide

morphine 3-glucuronide

norfluoxetine

morphine

morphine 6-glucuronide.
ž

65
Q

Inhibitors/Inducers can not inhibit or induce their own metabolism

T/F

A

F

They can

66
Q

Inhibition/Induction are (reversible or irreversible?) , adaptive responses

A

reversible

67
Q

Metabolism

Four discernable phenotypes:

List them

A

Poor metabolizers (PMs)
Intermediate metabolizers (IMs) Extensive metabolizers (EMs)
Ultra-rapid metabolizers (UM)

68
Q

organophosphate toxicity is more in male or female???

A

Female

69
Q

( male or female?) rats sleep longer than (male or female?) on hexobarbital

A

Female sleep longer than male

70
Q

The _______ is perhaps the most important organ for the excretion of xenobiotics

A

kidney

71
Q

Toxicants with (low or high?) lipid/water partition coefficient are reabsorbed from the tubules of the nephron more efficiently
ž ž
ž

A

High

72
Q

Elimination
In this case, urinary excretion (i.e., not reabsorbed) of the (ionized or non-ionized?) moiety is favored

A

ionized

73
Q

bases are excreted to a greater extent at (lower or higher?) pH whereas excretion of acids predominates at (lower or higher?) urinary pH

A

Lower

Higher

74
Q

Elimination

A practical application of this knowledge is illustrated by the treatment of phenobarbital poisoning with ___________

In a similar manner, urinary ______ can be used to increase the excretion of a weak _____ like phencyclidine (PCP) in drug abusers.

A

sodium bicarbonate.

acidification

base

75
Q

there is competition for renal secretion

T/F

With reason

A

T

It’s by active transport

76
Q

Penicillin is actively secreted by the organic acid systems (OATs) of the kidney; competes with ______ and thus lengthen its half-life and duration of action

A

probenecid

77
Q

many functions of the kidney are incompletely developed at birth

T/F

A

T

78
Q

some xenobiotics are eliminated more (slowly or rapidly?) in newborns than in adults, and therefore may be (more or less?) toxic to newborns.

A

Slowly

More

79
Q

the clearance of penicillin by premature infants is only about ____% of that observed in older children.
ž
ž

A

20

80
Q

Elimination
The non-absorbed portion contributes to the _________ of most chemicals to some extent.

One other factor contributing to that is __________, which likely occurs by ______ out of enterocytes or via ______ of intestinal cells during the normal turnover of this epithelium.

A

fecal excretion

intestinal secretion

passive diffusion

exfoliation

81
Q

First Pass Effect and direct excretion into the bile is also a source of elimination.

T/F

A

T

82
Q

Protein bound compounds are not available for active biliary excretion

T/F

A

F

They are fully available

83
Q

_______ and ________ conjugates have a high predilection for excretion into bile

A

Glutathione and glucuronide

84
Q

_____ excretion of toxicants and/or their metabolites is most often the major source of fecal excretion

A

Biliary

85
Q

The secretion of toxic compounds into milk is extremely important

T/F

With reasons

A

T

1)a toxic material may be passed with milk from the mother to the nursing offspring

2)compounds can be passed along the food chain via dairy products

86
Q

Toxic agents are excreted into milk by _______

A

simple diffusion

87
Q

Compounds that can accumulate in fat such as pesticides, PCBs, PBBs and furans have been found in human breast milk, and milk can be a major route of their excretion

T/F

A

T

88
Q

Metals chemically similar to Ca, such as Pb, and chelating agents that form complexes with calcium also are also excreted into milk to considerable extents
ž
ž
T/F

A

T

89
Q

Quantitatively, the excretion of toxic agents in sweat and saliva is of major importance.

T/F

A

F

Minor

90
Q

Toxic compounds excreted into sweat may produce ________.

Substances excreted in saliva enter the ____, where they are usually ____ to become available for ______

A

dermatitis

mouth

swallowed

GI absorption.

House Pharmacology (50 decks)

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