L19 intro to toxicology Flashcards
list the three principles of toxicology
- effects of toxicants are (usually) proportional to dose
- there can be variability in sensitivity to toxicants between species and within species
- acute&chronic toxic effects may be different/mediated by different mechanisms
Define LD 50
(lethal dose 50) amount of substance estimated to kill 50% of population in one single acute dose
how can LD50 vary within species
due to route of administration e.g if snake venom is injected it will be more lethal than if it is swallowed
define therapeutic index
measurement of safety of a drug
LD50/ ED50 or TD50/ED50
is a smaller or larger TI more safe?
larger TI means greater margin of safety
effects of acute alcohol toxicity
CNS depression
visual impairment
muscular inco-ordination
slowed reactions
effects of chronic alcohol toxicity
liver cirrhosis
brain damage
cancer
benefits of alcohol?
very low levels have cardiovascular benefits
Where is botulinum toxin produced, what are its effects?
clostritium botulinum bacterium
botulism (blurred vision difficulty speaking/swallowing)
botulinum toxin mechanism of action
blocks ACh release inhibiting neuromuscular transmission
therapeutic uses of botulinum toxin
treatment for: overactive muscles spasms and dystonia excessive blinking/squint excessive sweating
how is paracetamol metabolised
major - conjugation with sulfate and glucuronic acid
minor - oxidation then conjugation with gluthione (limited supply)
how does paracetamol become toxic
- overdose leads to an increase in the minor metabolism pathway which depletes the limited supply of gluthione, making the pathway toxic
- the toxic metabolite reacts with liver proteins causing hepatic necrosis and then death
antidote for paracetamol overdose and how it works
N-acetylcysteine regenerates gluthione making the pathway no longer toxic
affects of alcohol on paracetamol toxicity?
alcohol can increase the liver damage caused by paracetamol overdose
how does aspirin become toxic
- it is metabolised to salicylic acid then conjugated with glucaronic acid/glycine (limited supply)
- salicylate (metabolite) interferes with ETC
how does the toxic metabolite of aspirin cause damage
it interferes with the ETC leading to :
- decrease in atp production
- increase in oxygen usage
- increase in CO2 production
this leads to
hyperventilation and increase in blood pH (alkalosis)
what can severe overdose of aspirin lead to
acidosis
lack of ATP to brain may be fatal
aspirin overdose antidote
infusion of HCO3 to lower pH (with glucose)
how was thalidomide toxic
one enantiomer of thalidomide was embryotoxic and interfered with expression of genes involved in formation of blood vessels
thalidomide uses now
treats:
leprosy
aids
some cancers
how is grapefruit juice toxic
contains furanocoumarins which inhibit cytochrome P450 3A4 which inhibits the metabolism of many drugs
name drugs grapefruit juice toxin inhibits the metabolism of
antihistamines statins antiarrhythmics ca channel antagonists hormones sedatives antidepressants Erectile Dysfunction drugs immunosuppressants
name the 7 branches of toxicology
clinical forensic industrial/occupational environmental ecotoxicology regulatory genetic
explain clinical toxicology
diagnosis treatment and prevention of poisoning
drug overdoses
adverse drug reactions
drug - drug interactions
example of organ specific toxicity
paracetamol metabolism damage to liver
example of systemic toxicity
aspirin alters pH and can effect entire body and can effect metabolism in entire body
example of clinical toxicology
paracetamol, aspirin
explain forensic toxicology
crimes involving toxins
forensic toxicology examples
poisonings using chemicals such as arsenic, mercury, atropine, cyanide
explain industrial/ occupational toxicology
industrial diseases &toxins and causes
example of industrial/occupational toxicology
mining - asbestos, uranium, coal (lung disease)
construction - asbestos (lung cancer)
rubber&dye industries - aromatic amines(bladder disease
plastic manufacturing - vinyl chloride (liver disease)
examples of environmental toxicology
tobacco smoking lead in petrol air pollution (ozone, NO) industrial pollution pesticides
what is ecotoxicology
focusses on damage to non human life - impact of pollutants on ecosystems
examples of ecotoxicology
pesticides
oil spills in ocean
effects on food chains
endocrine disruptions
explain asian vulture crisis (example of ecotoxicology)
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)
what is genetic toxicology
study of mutagens and carcinogens
what can mutagens cause
what can carcinogens cause
mutagens- point gene mutation , chromosome abnormalities (numerical and structural)
define regulatory toxicity and what it involves
testing the safety of chemicals by:
- observation (epidemiology)
- in vitro
- in vivo
acute tests
sub chronic tests (up to 90 days)
chronic tests (up to 2 years)
