3. Basic Mechanisms of Toxicants 1

acute

exposure over a few hours is considered a ____ exposure

subacute

exposure over days-weeks is considered a ____ exposure

subchronic

exposure over months is considered a ____ exposure

chronic

exposure over years is considered a ___ exposure

local

a ____ effect occurs at the point of contact

systemic

a ___ effect occurs after a toxic substance has been absorbed and distributed throughout the body

cumulative

a ____ effect occurs over a period of time as a toxic compound bioaccumulates

cumulative

highly fat soluble toxicants with low excretion rates and toxicants that are incorporated into bone are associated with what type of effect

1. delivery from site of exposure to target site

2. reaction of ultimate toxicant (final stage before interaction) with the target molecule

3. cellular dysfunction and resultant toxicity

4. repair or dysrepair

what are the mechanisms of toxicity

1. reactivity

2. accessibility

3. critical function

what are the attributes of the target that affect the toxicity mechanism

1. noncovalent binding

2. covalent binding

3. hydrogen abstraction

4. electron transfer

5. enzymatic reaction

what are some of the reaction types that can alter the mechanism of toxicity

1. dysfunction

2. destruction

3. neoantigen formation

what are some of the various outcomes that can result from different mechanisms of toxicity

cause cellular dysfunction and cell death due to alterations in Na+, Ca2+, and K+ levels which are important for basically everything in the cell

what is the result of chemicals that interact with protein targets to activate or inactivate ion channels

a-bungarotoxin from Kraits/elapid snakes

which ion channel mediated animal venom works to block the postsynaptic neurotransmitter nicotinic acetylcholine receptor nAChR

block K+ channels

what is the mechanism of action of ion channel mediated dendrotoxins from green and black mamba snakes

Ca2+ channel blockage

what are the effects of the ion channel mediated w-agatoxin from Funnel web spiders, w-conotoxin from coneshells, and SNX-482 from the tarantula spider

tetrodotoxin from puffer fish

which ion channel mediated animal toxin works to block Na+ channels

lidocaine, bupivacaine, novacaine, etc....

what other Na+ channel blockers do we use clinically

alkaloids

which ion channel mediated toxin is produced by poison dart frogs (dendrobates) to act as both a Na+ channel inhibition as well as nicotinic antagonist

alter ion channels and metabolism

what is the effect of chemicals interacting with protein targets to inhibit enzymatic processes of bioactive metabolites

a-amanitin

which enzyme mediated substance from plants inhibits RNA polymerase

Na+/K+ ATPase inhibitor

what is the mechanism of action of the enzyme mediated digoxin/digitoxin from plants

physostigmine

which enzyme mediated plant based substance acts as anticholinesterase

block muscarinic AChR

what is the mechanism of action from enzyme mediated atropine from the atropine belladonna plant

botulinum toxin

which enzyme mediated substance has a bacterial origin and works to inhibit synaptic proteins

activates Ga2 proteins

what is the mechanism of action for the enzyme mediated cholera toxin

inhibits Ga i/oi proteins

what is the mechanism of action of enzyme mediated pertussis toxins

acts as an irreversible anticholinesterase by preventing acetylcholinesterase from binding to break down acetylcholine this elevating acetylcholine and activating signaling pathways and ion channels

what is the result of the binding of the enzyme mediated sarin binding

binds and to sarin to reactivate acetylcholinesterase to prevent permanent damage

what is the result of oximes binding to sarin

1. atropine-mAChR blocker to offset ACh excess and preventing binding for smooth and cardiac mm. overload

2. pralidoxime-reactivates acetylcholinesterase to get rid of accumulating ACh levels

what are considered to be the first like of defense against "nerve gases" as they