Toxicology Flashcards

1
Q

What is LD50

A

Dose of xenobiotic which causes death in 50%

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2
Q

What is acute toxicology

A

Short lived
Rapid development when chemical still in body
From ST exposure

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3
Q

Can acute toxicology be helped by antidotes

A

Yes

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4
Q

What is chronic toxicology

A

Delayed toxicity after chemical left body

From LT or ST exposure

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5
Q

How does xenobiotic get distributed and why highly in liver

A

To tissues which are perfused

80% of blood goes to liver so xenobiotic in high conc

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6
Q

How do toxins get detoxified in metabolism

A

Phase II conjugation eg glutathione

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7
Q

Why is elimination through bile good for xenobiotic

A

Stops exposure of other organs

It is pre systemic elimination

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8
Q

What is an issue with elimination in bile

A

De conjugation can occur which makes them lipophillic for enterohepatic recirculation

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9
Q

Where does de conjugation occur other than bile

A

Bladder

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10
Q

Name some high risk organs

A

Lungs (high perfusion)

Kidney (high conc in filtrate)

Brain (high perfusion)

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11
Q

What are the 2 toxins produced by oxidative stress

A

Cytotoxicity

Genotoxicity

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12
Q

What makes ROS in oxidative stress in mitochondria

A

Oxidation and reduction of xenobiotics and reactive metals

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13
Q

Which ROS is produced by mitochondria

A

H2O2 hydrogen peroxide

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14
Q

Other than hydrogen peroxide h2o2 what other 3 ROS are there

A

O2- (superoxide)

O• (free radical)

OH• (hydroxyl radical)

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15
Q

How can O2- superoxide production get made safe

A

Conversion to H2o2 hydrogen peroxide

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16
Q

Which reaction via reactive metals can convert h2o2 into unsafe OH• hydroxyl radical

A

Fenton reaction

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17
Q

Other than conversion to h2o2 what else can O2- superoxide be converted to

A

RNS via reaction with NO to form peroxynitrate

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18
Q

How can generation of ROS in oxidative stress damage dna

A

It can oxidise dna bases causing mutations

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19
Q

What gets oxidised by ROS in proteins causing misfolding

A

SH disulfide

20
Q

How can lipid peroxidation via ROS cause dna damage as well as membrane damage

A

Forms malondialdehyde which damages dna

21
Q

Why does oxidative stress cause less ROS removal

A

Depletes glutathione

22
Q

What can increased calcium via ROS cause issues

A

Damage to ca ATPase and cell death (apoptosis)

23
Q

How does Paraquat get into cells but can’t be removed

A

Via polyamine transporters

Ionised so can’t leave and no efflux channels

24
Q

What happens to paraquat to form a radical superoxide O-

A

Addition of an electron

25
Q

If glutathione is at high levels what happens to the paraquat superoxide radical

A

Converted to H2o2 then into water

Reforms paraquat

26
Q

If reduced glutathione becomes depleted from converting h202 into water via paraquat recycling what happens

A

Undergoes Fenton reaction and causes things like lipid peroxidation and death

27
Q

What are dna binding toxins called

A

Genotoxins or procarcinogens

28
Q

What does pro carcinogens need for activation

A

Metabolic enzymes

29
Q

Give an example of a pro carcinogen activation by metabolic enzymes

A

Benzoapyrene converts to diol epoxide which binds to guanine

Benzoapyrene is converted via CYP1A1

30
Q

How does aromatic amines cause dna binding / pro carcinogens

A

Their n acetylation and n oxidation in phase II produces nitrenium ion which binds to dna

31
Q

Which toxins target acH esterase

A

Organophosphorus insecticides OPs

32
Q

Which AA do organophosphorus insecticides bind to on ach esterase

A

Serine Active site

33
Q

How does OP form a covalent bond with serine

A

Hydrolysis

34
Q

How can position of hydrolysis determine if covalent bond with serine is irreversible blocking ach esterase forever

A

If hydrolysis occurs near serine the bond can be reversed by antidotes which promote this

If hydrolysis occurs elsewhere then bond is irreversible (aging)

35
Q

Which 3 cyps promote napqi production from paracetamol

A

2e1
1a2
3a4

36
Q

Why does overdose on paracetamol cause liver damage

A

No glutathione transferase to detoxify it

Napqi covalently binds to proteins and damages function causing necrosis

37
Q

What treatment is given for paracetamol overdose

A

N acetyl cysteine (precursor for glutathione)

38
Q

Where is salicylate from hydrolysis of aspirin in plasma absorbed highly

A

Stomach and intestines

39
Q

What is salicylate metabolised into

A

Glycine, glucoronide, oxidised

40
Q

What happens to 13% of salicylate without metabolism in liver

A

Excreted in kidney

41
Q

What does overdose on aspirin cause

A

Long half life of salicylate (absorbed easy as unionised)

Slow elimination

Can’t be conjugated

42
Q

How does salicylate overdose cause respiratory alkalosis

A

Causes hyperventilation by uncoupling OP with the tca cycle. This stops proton gradient generating ATP = hyperventilating for oxygen

43
Q

How can metabolic acidosis occur via salicylate build up

A

More lactate due to lack of aerobic resp

44
Q

The plasma ph decreases when hyperventilating which causes salicylate to unionise even more. What cns effects does it have

A

Neurotoxic effect

Glucose can’t be used by neurones in brain

45
Q

How can salicylate overdose be treated/ stop absorption

A

Activated charcoal

Alkalanise urine to ionise salicylate