L19 intro to toxicology

Question 1

list the three principles of toxicology

Answer 1

1. effects of toxicants are (usually) proportional to dose
2. there can be variability in sensitivity to toxicants between species and within species
3. acute&chronic toxic effects may be different/mediated by different mechanisms

Question 2

Define LD 50

Answer 2

(lethal dose 50) amount of substance estimated to kill 50% of population in one single acute dose

Question 3

how can LD50 vary within species

Answer 3

due to route of administration e.g if snake venom is injected it will be more lethal than if it is swallowed

Question 4

define therapeutic index

Answer 4

measurement of safety of a drug

LD50/ ED50 or TD50/ED50

Question 5

is a smaller or larger TI more safe?

Answer 5

larger TI means greater margin of safety

Question 6

effects of acute alcohol toxicity

Answer 6

CNS depression
visual impairment
muscular inco-ordination
slowed reactions

Question 7

effects of chronic alcohol toxicity

Answer 7

liver cirrhosis
brain damage
cancer

Question 8

benefits of alcohol?

Answer 8

very low levels have cardiovascular benefits

Question 9

Where is botulinum toxin produced, what are its effects?

Answer 9

clostritium botulinum bacterium

botulism (blurred vision difficulty speaking/swallowing)

Question 10

botulinum toxin mechanism of action

Answer 10

blocks ACh release inhibiting neuromuscular transmission

Question 11

therapeutic uses of botulinum toxin

Answer 11

treatment for: 
overactive muscles
spasms and dystonia 
excessive blinking/squint 
excessive sweating

Question 12

how is paracetamol metabolised

Answer 12

major - conjugation with sulfate and glucuronic acid

minor - oxidation then conjugation with gluthione (limited supply)

Question 13

how does paracetamol become toxic

Answer 13

1. overdose leads to an increase in the minor metabolism pathway which depletes the limited supply of gluthione, making the pathway toxic
2. the toxic metabolite reacts with liver proteins causing hepatic necrosis and then death

Question 14

antidote for paracetamol overdose and how it works

Answer 14

N-acetylcysteine regenerates gluthione making the pathway no longer toxic

Question 15

affects of alcohol on paracetamol toxicity?

Answer 15

alcohol can increase the liver damage caused by paracetamol overdose

Question 16

how does aspirin become toxic

Answer 16

1. it is metabolised to salicylic acid then conjugated with glucaronic acid/glycine (limited supply)
2. salicylate (metabolite) interferes with ETC

Question 17

how does the toxic metabolite of aspirin cause damage

Answer 17

it interferes with the ETC leading to :

1. decrease in atp production
2. increase in oxygen usage
3. increase in CO2 production

this leads to
hyperventilation and increase in blood pH (alkalosis)

Question 18

what can severe overdose of aspirin lead to

Answer 18

acidosis

lack of ATP to brain may be fatal

Question 19

aspirin overdose antidote

Answer 19

infusion of HCO3 to lower pH (with glucose)

Question 20

how was thalidomide toxic

Answer 20

one enantiomer of thalidomide was embryotoxic and interfered with expression of genes involved in formation of blood vessels

Question 21

thalidomide uses now

Answer 21

treats:
leprosy
aids
some cancers

Question 22

how is grapefruit juice toxic

Answer 22

contains furanocoumarins which inhibit cytochrome P450 3A4 which inhibits the metabolism of many drugs

Question 23

name drugs grapefruit juice toxin inhibits the metabolism of

Answer 23

antihistamines
statins
antiarrhythmics
ca channel antagonists 
hormones
sedatives
antidepressants
Erectile Dysfunction drugs
immunosuppressants

Question 24

name the 7 branches of toxicology

Answer 24

clinical
forensic
industrial/occupational
environmental
ecotoxicology
regulatory
genetic

Question 25

explain clinical toxicology

Answer 25

diagnosis treatment and prevention of poisoning
drug overdoses
adverse drug reactions
drug - drug interactions

Question 26

example of organ specific toxicity

Answer 26

paracetamol metabolism damage to liver

Question 27

example of systemic toxicity

Answer 27

aspirin alters pH and can effect entire body and can effect metabolism in entire body

Question 28

example of clinical toxicology

Answer 28

paracetamol, aspirin

Question 29

explain forensic toxicology

Answer 29

crimes involving toxins

Question 30

forensic toxicology examples

Answer 30

poisonings using chemicals such as arsenic, mercury, atropine, cyanide

Question 31

explain industrial/ occupational toxicology

Answer 31

industrial diseases &toxins and causes

Question 32

example of industrial/occupational toxicology

Answer 32

mining - asbestos, uranium, coal (lung disease)
construction - asbestos (lung cancer)
rubber&dye industries - aromatic amines(bladder disease
plastic manufacturing - vinyl chloride (liver disease)

Question 33

examples of environmental toxicology

Answer 33

tobacco smoking
lead in petrol
air pollution (ozone, NO)
industrial pollution
pesticides

Question 34

what is ecotoxicology

Answer 34

focusses on damage to non human life - impact of pollutants on ecosystems

Question 35

examples of ecotoxicology

Answer 35

pesticides
oil spills in ocean
effects on food chains
endocrine disruptions

Question 36

explain asian vulture crisis (example of ecotoxicology)

Answer 36

3 species of vulture are now critically endangered due to toxin diclofenac

diclofenac was used on cattle, dead cattle would be eaten by vultures and the diclofenac ingested.
diclofenac caused severe kidney failure in vultures

less vultures = more feral dogs = more diseases passed to humans (e.g rabies)

Question 37

what is genetic toxicology

Answer 37

study of mutagens and carcinogens

Question 38

what can mutagens cause

what can carcinogens cause

Answer 38

mutagens- point gene mutation , chromosome abnormalities (numerical and structural)

Question 39

define regulatory toxicity and what it involves

Answer 39

testing the safety of chemicals by:

1. observation (epidemiology)
2. in vitro
3. in vivo

acute tests
sub chronic tests (up to 90 days)
chronic tests (up to 2 years)