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Toxicology Flashcards

1
Q

What are toxins?

A

Toxicants produced by living organisms

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2
Q

Define toxicodynamics

A

Interactions between toxicants and biological systems and the mechanisms of their toxic effects

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3
Q

Define toxicokinetics

A

The routes of toxicants through the body

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4
Q

Which route of absorption of toxicants is most important?

A

GI tract

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5
Q

Why is the GI tract the most important site of absorption for toxicants?

A
  • Large Surface area
  • Range of pH values
  • Rich in active transport mechansims
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6
Q

What property must a toxicant have in order to be absorbed by the skin?

A

Highly lipophilic

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7
Q

What kind of toxicant are the kidneys the main route of excretion for?

A

Small water soluble toxicants

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8
Q

What kind of toxicants is the liver important in excreting?

A

Large polar substances

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9
Q

Give an example of a toxicant which causes significant bioaccumulation

A

DDT

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10
Q

What is bioaccumulation?

A

The concentration and biomagnification of toxicants through a food chain, this usually affects the largets predator most

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11
Q

What is acute toxicity?

A

The response to short term exposure of high levels of a toxic substance, producing a sudden onset of symptoms

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12
Q

What is chronic toxicity?

A

The response to longer term exposure of low levels of a toxic substance, typically delayed symptoms which are hard to trace

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13
Q

What are the types of toxicity?

A
  • Biochemical lesion
  • Disruption of homeostasis
  • Tissue lesions
  • Genetic toxicity
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14
Q

What is a biochemical lesion?

A

Any disruption to the body’s usual biochemical processes

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15
Q

What is teratology?

A

The disruption of development of embryos//foetuses

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16
Q

Why are not all organs equally affected by exposure to a toxin?

A
  • Some are exposed to a higher concentration of a toxicant
  • Some are inherently more susceptible to a toxicant
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17
Q

What factors affect an individual’s toxic response?

A
  • Age
  • Species
  • Genetics
  • Drug interactions
  • Environmental factors
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18
Q

What is the LD50?

A

The concentration of substance required to kill 50% of the test population (usually mice)

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19
Q

What is the NOAEL (no observed adverse effect level)?

A

The dose which has not caused any adverse effects during tests

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20
Q

What is the unit of ADI?

A

mg per kg per day

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21
Q

How is the ADI (acceptable daily intake) calculated?

A

NOAEL/ a safety factor

The safety factor is usally 100 depends on how the NOAEL was calculated

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22
Q

What is the ADI?

A

The daily intake of a chemical which during an active life time appears to be without appreciable risk on the basis of all known facts at the time

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23
Q

What is TD50?

A

The dose which will induce toxic effects in 50% of the population

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24
Q

What is MTD?

A

Maximum tolerated dose/minimum toxic dose

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25
What is MED?
Minimum effective dose
26
How is the therapeutic index calculated?
LD50/ED50
27
What is the ED50?
The dose of a drug which produces an effect in 50% of a population
28
What does the therapeutic index represent?
Indicates the realtive safety of a drug
29
How is the therapeutic ratio calculated?
MTD/MED
30
What does the therapeutic ratio?
Represents a therapeutic window
31
How are standard safety margins calculated?
LD1/ED99
32
What is LD1?
The dose required to kill 1% of the test population
33
What is E99?
The dose at which it is therapeutucally effective in 99% of a test population
34
How is the chronicity index calculated?
90 day LD50/acute LD50
35
When should vomiting be induced?
If the patient is concious and the toxicant has been ingested
36
What treatments are given for 'internal' exposure to a toxicant?
* Induction of vomiting * Gastric lavage * Activated charcoal
37
How can elimination be enhanced?
* diuretics administered * decrease reabsorption by polarising acidic/basic poisons
38
What is the treatment for methanol posioning?
* NaH2CO3 * Administration of large amounts of ethanol * Supported by haemodialysis
39
What is the main source of ricin?
Seeds of Castor oil plant
40
What is the chemistry of ricin?
* glycosylated protein * A/B toxin with 2 domains * B ensures the uptake of the protein into cells * A has the enzymatic activity
41
How does ricin cause posioning?
* Inactivates ribosomes
42
What are the symptoms of ricin poisoning?
* Fever * Nausea * Vomiting * Seizures
43
What is the treatment for ricin posioning?
* Early decontamination * Supportive treatment
44
What is the main source of atropine?
Members of the nightshade family e.g. the berries of deadly nighshade
45
What is the chemistry of atropine?
Plant alkaloid
46
What is the mechanism of atropine poisoning?
Blocks muscarinic acetylcholine receptors
47
What are the symptoms of atropine poisoning?
* Increased heart rate * Suppression of digestion and sweating * High blood pressure * Dilated pupils
48
What is the treatment for atropine poisoning?
* Early decomtamination * Antidote: anticholinesterase * Supportive treatment
49
What is the main source of α-amanitin?
Death cap mushroom
50
What is the chemistry of α-amanitin?
Cyclic peptide formed from 8 amino acids
51
What is the mechanism of α-amanitin?
Inhibits RNA polymerase II
52
What are the symptoms of α-amanitin poisoning?
* Renal and liver failure * Diarrheoa and cramps * Symptoms appear many hours/days after poisoning
53
What is the treatment for α-amanitin poisoning?
* Supportive treatment * Liver transplant
54
What is the source of botulinum toxin A?
Anaerobic bacteria
55
What is the chemistry of botulinum toxin A?
Protein made from a heavy and light chain. The heavy chain mediates specific uptake into cholinergic nerve terminals
56
What are the symptoms of botulinum toxin A poisoning?
* Muscle weakness * Paralysis * Dry mouth * Wide pupils
57
What is the main source of tetrodotoxin?
Found in animals (such as the pufferfish) but produced by bacteria
58
What is the treatment for botulinum toxin A?
* Decontamination * Life support * Anti-toxin
59
Give a medical use of botulinum toxin A
Local injection can be used to control unwanted muscle contraction
60
What is the chemistry of tetrodotoxin?
Animal alkaloid
61
What is the mechanism of poisoning by tetrodotoxin?
Blocks voltage gated Na+ channels and therefore action potentials
62
What are the symptoms of tetrodotoxin poisoning?
* Paresthesia * Muscle weakness * Paralysis * Respiratory problems
63
What is the treatment for tetrodotoxin poisoning?
* Decontamination * Antiarrhythmics
64
What is the main source of conotoxins?
Coneshell snails
65
What is the chemistry of conotoxins?
Mixture of small peptides, the exact mixture varies
66
What is the mechanism of poisoning for conotoxins?
Neurotoxicity at a range of specific targets (each peptide blocks different ion channels)
67
What are the symptoms of conotoxin poisoning?
* Burning * Pain * Paralysis * Death
68
What is the effect of ω conotoxin? How might this be useful as a medicine?
Very specifically irreversibly binds to N-type Ca2+ channels which are involved in pain signal transmission so may provide a non-addictive analgesic
69
What is the main source of fasciculin?
Venom of black mamba
70
What is the chemistry of fasciculin?
3 finger peptide with disulfide bonds
71
What is the mechanism of fasciculin poisoning?
Blocks acetylcholinesterase and enhances neuromusiclar transmission
72
What are the symptoms of fasciculin poisoning?
* Paralysis * Unconsciousness * Death within 20 mins
73
What is the treatment for fasciculin poisoning?
* Artificial ventilation * Injection of antivenom
74
What are the disadvantages of using natural toxins for therapeutic use?
* most are small proteins so there are problems with pharmacokinetics * toxin levels
75
What are the advantages of using natural toxins for therapeutic use?
* Large source of compounds * Some highly selective

Mechanisms of Drug Action (8 decks)

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