Toxicology

Question 1

What is LD50

Answer 1

Dose of xenobiotic which causes death in 50%

Question 2

What is acute toxicology

Answer 2

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

Question 3

Can acute toxicology be helped by antidotes

Answer 3

Yes

Question 4

What is chronic toxicology

Answer 4

Delayed toxicity after chemical left body

From LT or ST exposure

Question 5

How does xenobiotic get distributed and why highly in liver

Answer 5

To tissues which are perfused

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

Question 6

How do toxins get detoxified in metabolism

Answer 6

Phase II conjugation eg glutathione

Question 7

Why is elimination through bile good for xenobiotic

Answer 7

Stops exposure of other organs

It is pre systemic elimination

Question 8

What is an issue with elimination in bile

Answer 8

De conjugation can occur which makes them lipophillic for enterohepatic recirculation

Question 9

Where does de conjugation occur other than bile

Answer 9

Bladder

Question 10

Name some high risk organs

Answer 10

Lungs (high perfusion)

Kidney (high conc in filtrate)

Brain (high perfusion)

Question 11

What are the 2 toxins produced by oxidative stress

Answer 11

Cytotoxicity

Genotoxicity

Question 12

What makes ROS in oxidative stress in mitochondria

Answer 12

Oxidation and reduction of xenobiotics and reactive metals

Question 13

Which ROS is produced by mitochondria

Answer 13

H2O2 hydrogen peroxide

Question 14

Other than hydrogen peroxide h2o2 what other 3 ROS are there

Answer 14

O2- (superoxide)

O• (free radical)

OH• (hydroxyl radical)

Question 15

How can O2- superoxide production get made safe

Answer 15

Conversion to H2o2 hydrogen peroxide

Question 16

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

Answer 16

Fenton reaction

Question 17

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

Answer 17

RNS via reaction with NO to form peroxynitrate

Question 18

How can generation of ROS in oxidative stress damage dna

Answer 18

It can oxidise dna bases causing mutations

Question 19

What gets oxidised by ROS in proteins causing misfolding

Answer 19

SH disulfide

Question 20

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

Answer 20

Forms malondialdehyde which damages dna

Question 21

Why does oxidative stress cause less ROS removal

Answer 21

Depletes glutathione

Question 22

What can increased calcium via ROS cause issues

Answer 22

Damage to ca ATPase and cell death (apoptosis)

Question 23

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

Answer 23

Via polyamine transporters

Ionised so can’t leave and no efflux channels

Question 24

What happens to paraquat to form a radical superoxide O-

Answer 24

Addition of an electron

Question 25

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

Answer 25

Converted to H2o2 then into water Reforms paraquat

Question 26

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

Answer 26

Undergoes Fenton reaction and causes things like lipid peroxidation and death

Question 27

What are dna binding toxins called

Answer 27

Genotoxins or procarcinogens

Question 28

What does pro carcinogens need for activation

Answer 28

Metabolic enzymes

Question 29

Give an example of a pro carcinogen activation by metabolic enzymes

Answer 29

Benzoapyrene converts to diol epoxide which binds to guanine Benzoapyrene is converted via CYP1A1

Question 30

How does aromatic amines cause dna binding / pro carcinogens

Answer 30

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

Question 31

Which toxins target acH esterase

Answer 31

Organophosphorus insecticides OPs

Question 32

Which AA do organophosphorus insecticides bind to on ach esterase

Answer 32

Serine Active site

Question 33

How does OP form a covalent bond with serine

Answer 33

Hydrolysis

Question 34

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

Answer 34

If hydrolysis occurs near serine the bond can be reversed by antidotes which promote this If hydrolysis occurs elsewhere then bond is irreversible (aging)

Question 35

Which 3 cyps promote napqi production from paracetamol

Answer 35

2e1 1a2 3a4

Question 36

Why does overdose on paracetamol cause liver damage

Answer 36

No glutathione transferase to detoxify it Napqi covalently binds to proteins and damages function causing necrosis

Question 37

What treatment is given for paracetamol overdose

Answer 37

N acetyl cysteine (precursor for glutathione)

Question 38

Where is salicylate from hydrolysis of aspirin in plasma absorbed highly

Answer 38

Stomach and intestines

Question 39

What is salicylate metabolised into

Answer 39

Glycine, glucoronide, oxidised

Question 40

What happens to 13% of salicylate without metabolism in liver

Answer 40

Excreted in kidney

Question 41

What does overdose on aspirin cause

Answer 41

Long half life of salicylate (absorbed easy as unionised) Slow elimination Can’t be conjugated

Question 42

How does salicylate overdose cause respiratory alkalosis

Answer 42

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

Question 43

How can metabolic acidosis occur via salicylate build up

Answer 43

More lactate due to lack of aerobic resp

Question 44

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

Answer 44

Neurotoxic effect Glucose can’t be used by neurones in brain

Question 45

How can salicylate overdose be treated/ stop absorption

Answer 45

Activated charcoal Alkalanise urine to ionise salicylate