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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
toxicity within 24 hrs
immediate
26
example of immediate toxicity
anaphylactic shock (e.g., corrosive H2SO4)
27
effect observed after a long period of time
delayed toxicity
28
examples of delayed toxicity
carcinogens, teratogens, mutagens
29
Differentiate: carcinogen, teratogen, & mutagen
1. carcinogen: cause cancer 2. teratogen: birth defects 3. mutagen: gene mutations
30
affected organ undergoes repair
reversible
31
T/F: paracetamol affects the liver but the organ has regeneration ability
T
32
affected organ does not undergo repair
irreversible
33
example of irreversible toxic effects
ethanol affects brain cells (brain cells/neurons do not regenerate)
34
occurs at the site of first contact
local effect
35
examples of local effect/toxicity
1. acid - coagulative necrosis 2. bases - liquefactive necrosis
36
fatal since the poison is absorbed and distributed in the body
systemic
37
systemic effect requires _________________ and _______________ of a toxicant to entry point
absorption and distribution
38
example of systemic effect/toxicity
tetraethyl lead w/c can pass the BBB
39
What are the factors affecting the effect of poisons?
1. poison-related 2. patient-related
40
What are the poison-related factors affecting the effect of poisons?
1. route of admin 2. concentration 3. solubility
41
What are the patient-related factors affecting the effect of poisons?
1. age of px 2. habit 3. tolerance 4. idiosyncrasy/unknown cause
42
Transfer of a chemical from the site of exposure usually an external or internal body surface into the systemic circulation
absorption
43
generally reduces the toxic effects of chemicals that reach their target sites by way of the systemic circulation
presystemic elimination (FPE)
44
Major excretory organs
kidney and liver
45
T/F: highly lipophilic compounds possess short duration due to effective elimination
F - very long duration due to inability of effective elimination
46
possible excretion routes
1. mammary gland (breast milk) 2. bile 3. intestinal lumen from blood
47
nontoxic parent molecule upon metabolism becomes a toxic metabolite
toxication / metabolic activation
48
metabolic activation may lead to the possible production of?
1. electrophiles 2. free radicals 3. nucleophiles 4. redox active reactants
49
What are the 5 different mechanisms of detoxification?
detoxification of … 1. toxicants with no func grp 2. nucleophiles 3. electrophiles 4. free radicals 5. protein toxins
50
process(es) and enzyme involved in the detoxification of toxicants w/o func grp
processes: hydroxylation/carboxylation, conjugation enzyme: cyp 450 transferanse
51
process(es) and enzyme involved in the detoxification of nucleophiles
process: conjugation enzyme: transferases
52
process(es) and enzyme involved in the detoxification of electrophiles
process: conjugation enzyme: glutathione S transferase
53
process(es) and enzyme involved in the detoxification of free radicals
process: redox enzyme: superoxide dismutase, glutathione peroxidase, catalase
54
process(es) and enzyme involved in the detoxification of protein toxins
process: reduction enzyme: thioredexin
55
________________________ + ______________________ = toxicity
ultimate toxicant + target molecule
56
What are the types of reactions of the ultimate toxicant with the target molecule?
1. covalent binding 2. noncovalent binding 3. hydrogen abstraction 4. electron transfer 5. enzymatic reaction
57
What are the effects of toxicants on target molecules?
1. dysfunction of target molecules 2. destruction of target molecules 3. neoantigen formation
58
T/F: necrosis does not cause inflammation while apoptosis causes inflammation
F - necrosis cause inflammation; apoptosis does not
59
apoptosis: _______________ necrosis: cell swelling
formation of blebbing

Toxicology Lec (4 decks)

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