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Toxicology Lec > Mechanism of Toxicity and ADME > Flashcards

Mechanism of Toxicity and ADME Flashcards

1
Q

MECHANISM OF TOXICITY

involves toxicant delivery to its target or targets and interactions with endogenous target molecules

A

toxicity

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2
Q

MECHANISM OF TOXICITY

toxicity starts from/begins with _______________, until the site(s) are reached

A

delivery

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3
Q

MECHANISM OF TOXICITY

biotransformation of agents to a more harmful product

A

toxication

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4
Q

MECHANISM OF TOXICITY

other term for toxication or biotransformation of agents to a more harmful product

A

metabolic activation

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5
Q

MECHANISM OF TOXICITY

biotransformation of the toxicant to
prevent or to eliminate damage

A

detoxification

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6
Q

MECHANISM OF TOXICITY

what is the main difference between biotransformation and metabolism?

A

biotransformation - chemical way to metabolize
metabolism - natural way

both occur at the liver

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7
Q

MECHANISM OF TOXICITY

Controlled, organized process whereby individual cells break into small fragments that are phagocytosed by adjacent cells or macrophages

A

apoptosis or programmed cell death

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8
Q

MECHANISM OF TOXICITY

cellular injury progresses to _______________ if molecular repair mechanism fails or the damage is ____________

A

cell necrosis; irreversible

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9
Q

MECHANISM OF TOXICITY

What are the common causes of carcinogenesis?

A
  1. failure of DNA repair
  2. failure of apoptosis
  3. failure to terminate cell proliferation
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10
Q

Steps involved in Mechanism of Toxicity

A
  1. delivery
    2a. interaction w/target molecule
    2b. alteration of biological environment
  2. cellular dysfunction
  3. inappropriate repair and adaptation
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11
Q

T/F: toxic action of drug is always an exaggeration of its therapeutic action

A

F - not necessarily an exaggeration

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12
Q

Nature of Toxic Action

one toxicant may exert ____________________ of toxic action

A

several mechanisms

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13
Q

Nature of Toxic Action

intensity of toxic effect depends primarily on the _______________________ of the ultimate toxicant and its site of action

A

concentration and persistence

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14
Q

List down the 5 evidences of Poisoning

A
  1. circumstantial
  2. post-mortem
  3. experimental
  4. chemical
  5. symptomatic
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15
Q

poisoning evidence from various evidence; not very reliable

A

circumstantial

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16
Q

evidence acquired after autopsy or after death

A

post-mortem

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17
Q

What time of samples are used in post-mortem?

A

tissue, organs, or body fluids

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18
Q

evidence acquired after administering suspected substance to living being and noting its effect or symptoms

A

experimental

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19
Q

chemical evidence of poisoning pertains to the detection of suspected substance via ______________ of sample of __________________ collected

A

analysis; body fluids

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20
Q

evidence of poisoning wherein signs and symptoms are observed

A

symptomatic

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21
Q

What are the 5 Spectrum of Undesirable Effects?

A

AIIRS
1. allergic rxns
2. idiosyncratic rxns
3. immediate vs delayed toxicity
4. reversible vs irreversible toxicity
5. systemic or local

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22
Q

immunologically mediated adverse reaction to a chemical

A

chemical allergy

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23
Q

genetically determined abnormal reactivity to
a chemical

A

chemical idiosyncrasy

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24
Q

oversensitivity to the smallest dose or no effect at high doses

A

idiosyncratic rxns

25
Q

toxicity within 24 hrs

A

immediate

26
Q

example of immediate toxicity

A

anaphylactic shock (e.g., corrosive H2SO4)

27
Q

effect observed after a long period of time

A

delayed toxicity

28
Q

examples of delayed toxicity

A

carcinogens, teratogens, mutagens

29
Q

Differentiate: carcinogen, teratogen, & mutagen

A
  1. carcinogen: cause cancer
  2. teratogen: birth defects
  3. mutagen: gene mutations
30
Q

affected organ undergoes repair

A

reversible

31
Q

T/F: paracetamol affects the liver but the organ has regeneration ability

A

T

32
Q

affected organ does not undergo repair

A

irreversible

33
Q

example of irreversible toxic effects

A

ethanol affects brain cells (brain cells/neurons do not regenerate)

34
Q

occurs at the site of first contact

A

local effect

35
Q

examples of local effect/toxicity

A
  1. acid - coagulative necrosis
  2. bases - liquefactive necrosis
36
Q

fatal since the poison is absorbed and distributed in the body

A

systemic

37
Q

systemic effect requires _________________ and _______________ of a toxicant to entry point

A

absorption and distribution

38
Q

example of systemic effect/toxicity

A

tetraethyl lead w/c can pass the BBB

39
Q

What are the factors affecting the effect of poisons?

A
  1. poison-related
  2. patient-related
40
Q

What are the poison-related factors affecting the effect of poisons?

A
  1. route of admin
  2. concentration
  3. solubility
41
Q

What are the patient-related factors affecting the effect of poisons?

A
  1. age of px
  2. habit
  3. tolerance
  4. idiosyncrasy/unknown cause
42
Q

Transfer of a chemical from the site of
exposure usually an external or internal body surface into the systemic circulation

A

absorption

43
Q

generally reduces the toxic effects of chemicals that reach their target sites by way of the systemic circulation

A

presystemic elimination (FPE)

44
Q

Major excretory organs

A

kidney and liver

45
Q

T/F: highly lipophilic compounds possess short duration due to effective elimination

A

F - very long duration due to inability of effective elimination

46
Q

possible excretion routes

A
  1. mammary gland (breast milk)
  2. bile
  3. intestinal lumen from blood
47
Q

nontoxic parent molecule upon metabolism becomes a toxic metabolite

A

toxication / metabolic activation

48
Q

metabolic activation may lead to the possible production of?

A
  1. electrophiles
  2. free radicals
  3. nucleophiles
  4. redox active reactants
49
Q

What are the 5 different mechanisms of detoxification?

A

detoxification of …
1. toxicants with no func grp
2. nucleophiles
3. electrophiles
4. free radicals
5. protein toxins

50
Q

process(es) and enzyme involved in the detoxification of toxicants w/o func grp

A

processes: hydroxylation/carboxylation, conjugation

enzyme: cyp 450 transferanse

51
Q

process(es) and enzyme involved in the detoxification of nucleophiles

A

process: conjugation
enzyme: transferases

52
Q

process(es) and enzyme involved in the detoxification of electrophiles

A

process: conjugation
enzyme: glutathione S transferase

53
Q

process(es) and enzyme involved in the detoxification of free radicals

A

process: redox
enzyme: superoxide dismutase, glutathione peroxidase, catalase

54
Q

process(es) and enzyme involved in the detoxification of protein toxins

A

process: reduction
enzyme: thioredexin

55
Q

________________________ + ______________________ = toxicity

A

ultimate toxicant + target molecule

56
Q

What are the types of reactions of the ultimate toxicant with the target molecule?

A
  1. covalent binding
  2. noncovalent binding
  3. hydrogen abstraction
  4. electron transfer
  5. enzymatic reaction
57
Q

What are the effects of toxicants on target molecules?

A
  1. dysfunction of target molecules
  2. destruction of target molecules
  3. neoantigen formation
58
Q

T/F: necrosis does not cause inflammation while apoptosis causes inflammation

A

F - necrosis cause inflammation; apoptosis does not

59
Q

apoptosis: _______________
necrosis: cell swelling

A

formation of blebbing

Toxicology Lec (4 decks)

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