Basic Mechanisms of Toxicants I (3)

Question 1

What are the types of exposures? What are their timing?

Answer 1

• acute: a single exposure lasting less than 24 hours
• chronic: exposures are essentially for the lifetime of the species
• subchronic: repeated exposures of less than a lifetime (like 3 months)

Question 2

What are the types of effects?

Answer 2

local
systemic
cumulative

Question 3

What is a local effect? Give examples

Answer 3

the site of action takes place at the point of contact

like skin, mucous membrane of the eyes, nose, mouth, and throat - anywhere along the respiratory or GI system

Question 4

What are systemic effects?

Answer 4

the toxic substance has been absorbed and distributed throughout the body

Question 5

What are cumulative effects?

Answer 5

over a period of time, the material is only partially excreted and the remaining quantities are gradually collected

• the retained toxic compound accumulates and becomes great enough to cause a pathological response

Question 6

What are factors affecting toxicity?

Answer 6

Question 7

List the routes of entry for a toxin

Answer 7

• percutaneous
• inhalation
• oral
• ocular

Question 8

Is there a breed disposition to toxic effects?

Answer 8

not really proven

Question 9

What are the 3 most common toxicity types in canine?

Answer 9

chocolate
rodenticides
pharmaceuticals

Question 10

What are the 4 mechanisms of toxicity?

Answer 10

1. delivery: site of exposure to the target
2. reaction of the ultimate toxicant with the target molecule
3. cellular dysfunction and resultant toxicity
4. repair or disrepair

Question 11

What is delivery - mechanism of toxicity?

Answer 11

exposure site to skin, GI tract, respiratory tract, etc via absorption, reabsorption, toxication to the ultimate toxicant delivered to the target molecule (macromolecules) at the target site

Question 12

What is reaction of the ultimate toxicant with the target molecule - mechanism of toxicity?

Answer 12

delivery —> interaction with target molecule and alteration of biological environment (interfere with cellular function)

Question 13

What are the last 2 steps - mechanism of toxicity?

Answer 13

altering the biological environment and interaction with the target molecule causes cellular dysfunction and injury —> inappropriate repair and adaptation

these two steps lead to toxicity

Question 14

Regarding mechanisms of toxicity, what are attributes of the target?

Answer 14

has to react to toxicant (not only bind)

accessibility

critical function

Question 15

Regarding mechanisms of toxicity, what are reaction types?

Answer 15

• non-covalent binding
• covalent binding
• hydrogen abstraction
• electron transfer
• enzymatic reaction

Question 16

Regarding mechanisms of toxicity, what are outcomes?

Answer 16

• dysfunction
• destruction
• neoantigen formation: (non harmful converted to harmful and particularly from treatments like chemotherapy or radiation, which induce DNA damage. It can create mutations in normal tissues, leading to the expression of new, abnormal peptides—neoantigens)

(necrosis, apoptosis)

Question 17

What are categories and classification of agents?

Answer 17

think of organ systems
then environmental to get a broad understanding

Question 18

Give an example of a molecular mechanism of toxicity

Answer 18

chemicals that specifically interact with protein target

toxin goes in —> binds to target —> affects target —> creates toxicity

Question 19

Regarding chemicals that specifically interact with the protein target, what can these chemicals then do?

Answer 19

activate or inactivate ION channels - can cause widespread cellular dysfunction and cause cell death

Question 20

Which molecules are extremely important in neurotransmission, muscle contraction, and nearly every cellular function?

Answer 20

Na+
Ca2+
K+

Question 21

Regarding chemicals that activate or inactivate ion channels. what are some examples regarding animal venoms and toxins?

Answer 21

• puffer fish “Fugu”
• kraits (elapid snakes)

Question 22

How do banded kraits toxins interfere with ion channels?

Answer 22

Question 23

How do puffer fish toxins interfere with ion channels?

Answer 23

tetrodotoxin

no Na+ channels to open = ATP

Question 24

How do black mamba and green mamba toxins interfere with ion channels?

Answer 24

block K+

Question 25

How do certain spiders toxin interfere with ion channels?

Answer 25

blocks Ca2+ = decreased muscle contraction

Question 26

How do poison dart frogs interfere with ion channels?

Answer 26

poison secreted through skin are from insects they ingest - alkaloids

Question 27

What is another mechanism regarding chemicals that specifically interact with protein targets? Give an examplw

Answer 27

chemicals that inhibit enzymatic processes of bioactive metabolites that alter ion channels and metabolism

sarin inhibits acetylcholinesterase and elevates acetylcholine levels to active signaling pathways & ion channels

Question 28

How do organophosphates and carbamates affect acetylcholinesterase?

Answer 28

they bind to the serine residue in the active site, preventing it from binding to acetylcholine to degrade

covalent bonding so basically irreversible - body has to synthesize more acetylcholinesterase if it wants to degrade Ach

Question 29

What are strong nucleophiles that reactivate ACh-esterase?

Answer 29

2PAM

Question 30

What does 2PAM do?

Answer 30

binds to the phosphorus and keeps it from binding into acetylcholinesterase

Question 31

What are the first lines of defense against biological nerve gases?

Answer 31

atropine

pralidoxime (2PAM)

Question 32

What does atropine do?

Answer 32

mAChR blocker - central respiratory depression

Question 33

What does pralidoxime do?

Answer 33

reactivation of acetylcholinesterase