Toxicity Flashcards

1
Q

What is cytotoxicity vs genotoxicity

A

cytotoxicity- cellular destruction

Genotoxicity- Changes in genetic material that is passed along

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2
Q

What is an example of cytotoxicity and genotoxicity

A

Cytotoxicity- lipid peroxidation

Genotoxicity- Covalent binding

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3
Q

What is receptor mediated toxicicity and how long does it last

A

toxicity is caused by binding of the parent compound to receptor/enzyme/ion channel (very targeted)
-adverse rxn is usually disapates when drug administeration is discontinued or further expose terminated

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4
Q

What is naloxone and what receptor does it work on

A

Naloxone for emergency tx for opiod addiction tx

-antagonist at mu receptor site for opiote (has short half life so needs to be repeatdly admined)

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5
Q

How does acetaminophen work and what does it target

A

Works on cyclooxgenase enyme to inhibit protaglandin systhesis

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6
Q

Where does acetaminophen work better

A

Works better on cyclooxgenase in CNS compared to the peripherry

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7
Q

What will happen when too much acetaminophen is injested

A

Will go thru phase II using p450 and create reactive intermediate which can leads to covalent binding to sulfhydryl groups of hepatic pros

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8
Q

How can the reactive intermediate in acetaminophen phase II be delt with

A

Glutathione (GSH) will protect + convert it to a non reactive product

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9
Q

What is used to produce more GSH for aceaminophen overdoses

A

N-acytl-cystein

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10
Q

What is the mathew rumack nomogram used for

A

To determine if one has acetaminophen poisining or if there is a potential for it

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11
Q

What does a depletion of GSH in phase II cause

A

Cause an increase of intracellular calcium (damaging)

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12
Q

How can acetaminophen be used as a marker for liver damage

A

If half life of acetaminophen increases from 4 to 8 hours

-it indicates that biotransformation of acetaminophen is taking a hit aka liver damage

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13
Q

What is the typical route of biotransformation of isoniazid

A

will be transformed to acetylisoniazid then to either isonicotinic acid or diacetylyhrazine which are both non tox

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14
Q

Why does isoniazid go thru phase I rxn

A

Slow acetylators are more suseptible as there is a greater degree of intermediate Acetylhdrazine that will instead go thru phase I then to the non toxic substance

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15
Q

What is the phase I rxn of isoniazid

A

Intermediate (acetylhydrazine) will go through phase I rxn and generate free radicals that can lead to covelent binding (causing liver necrosis)

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16
Q

What happens in iproniazid biotransformation in slow acetalators

A

intermediate (isopropyl hydrazine) will go thru phase I pathway in slow acetylators and be biotransformed in to free rads that cause damage

17
Q

What happens in normal ox dissociation curve

A

as PO2 goes down more o2 will be released

18
Q

what occurs in the presence of CO for the oxygen dissociation curve

A

In presense of CO; it will bind to hemoglobin and shift curve to right and reduce carrying capacity

-Need more of a reduction of PO2 to release O2

19
Q

At 50% COHb what percentage decrease do you need in PO2 to release 1 o2 at tissues

A

90% reduction in PO2

20
Q

What is the mechanism of action for cyanide posioning

A

reversible binding to cytochrome oxidase in the mitochondria blocking electron transport

21
Q

How is cynanide delt with in the body

A

Enzymes rhodanese and thiosulfate ion (50% of cyanide in 1 hour)

22
Q

What can be formed to clean up cyanide and how is it made

A

Methemoglobin

-can be produced with sodium nitrite

23
Q

What is the mechanism of toxicity for organophosphate pesticides

A
  • toxicity is caused by inhibition of cholinesterase (responsible for hydrolysis of acetylcholine)
  • blocks active site (pseudosubstrate)
24
Q

What is the tx for organophosphate pesticides

A

Tx involves pralidozime and atrophine- bind out inhibitor

25
How do free rads cause cell injury
Free radicals can initiate chain rxns by taking an electron from a stable molecule which then becomes an unstable free radical itself
26
What is the defense mechanism against free radicals and what does it form
GSH -will donate proton (H) to deal with substrate (free rad) then form GSGS
27
What are the 3 ways nucleophilic thiol group (GSH) helps deal with free rads
1. Conjugation catalyzed by glutathione transferase 2. Donation of a proton to reactive metabolites or free radicals 3. Chemical rxn with rective metabolite to form a conjugate
28
How is GSH remade after it is made to GSGS
Must be transfered back through the use of NADPH and GSSG reductase
29
Where does the NADPH come from that is needed for the formation of GSH
NADPH comes from NADP using G6P dehydrogenase
30
What does a deficiency in the conc of GSH in the rbcs cause
Leads to hemolysis
31
What are the most significant reactive oxygen species (3)
Superoxide anion Hydroxyl radical hydrogen peroxide
32
What is redox cycling and example of it
Production of reactive oxygen species ex- quinone is reduced to produce unstable semiquinone which is oxidized again (process keeps repeating)
33
What doe reactive oxygen species do in the body
Damage DNA Oxidise fatty acids in lipids Oxidation of amino acids in pro Oxidation of enzyme cofactors
34
What systems deal with reactive oxygen species (3)
Superoxide dismutase Glutathion peroxidase catalase
35
What vits are natural scavengers of ROS
Vit C + E
36
What are the steps to deal with superoxide (2)
1. Superoxide--> Hydrogen peroxide by Superoxide dimutase | 2. Hydrogen peroxide-->water by Catalase/ Glutathione peroxidase
37
How are hydroxyl radicals delt with and what enzyme is utalized
Glutathione peroxidase is used with GSH
38
Which are the major pathways that a cell can go thru that has no point of return (cytotoxic events) (5)
1. Lipid peroxidation (#1 for cell damage) 2. Covalent binding to macromolecules 3. Changes in Thiol status 4. Enzyme inhibition 5. Ischemia
39
How does lipid peroxidation develop and what is responsible for it
A hydroxyl radical removes a hydrogen atom from the unstaurated fatty acid of the membrane phospholipid and produces a free radical -Lipid radical reacts w molecular oxygen and produces a lipid peroxide radical (and continues again and again)