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Mechanisms of Drug Action > Toxicology > Flashcards

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
Q

What is MED?

A

Minimum effective dose

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26
Q

How is the therapeutic index calculated?

A

LD50/ED50

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27
Q

What is the ED50?

A

The dose of a drug which produces an effect in 50% of a population

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28
Q

What does the therapeutic index represent?

A

Indicates the realtive safety of a drug

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29
Q

How is the therapeutic ratio calculated?

A

MTD/MED

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30
Q

What does the therapeutic ratio?

A

Represents a therapeutic window

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31
Q

How are standard safety margins calculated?

A

LD1/ED99

32
Q

What is LD1?

A

The dose required to kill 1% of the test population

33
Q

What is E99?

A

The dose at which it is therapeutucally effective in 99% of a test population

34
Q

How is the chronicity index calculated?

A

90 day LD50/acute LD50

35
Q

When should vomiting be induced?

A

If the patient is concious and the toxicant has been ingested

36
Q

What treatments are given for ‘internal’ exposure to a toxicant?

A
  • Induction of vomiting
  • Gastric lavage
  • Activated charcoal
37
Q

How can elimination be enhanced?

A
  • diuretics administered
  • decrease reabsorption by polarising acidic/basic poisons
38
Q

What is the treatment for methanol posioning?

A
  • NaH2CO3
  • Administration of large amounts of ethanol
  • Supported by haemodialysis
39
Q

What is the main source of ricin?

A

Seeds of Castor oil plant

40
Q

What is the chemistry of ricin?

A
  • glycosylated protein
  • A/B toxin with 2 domains
  • B ensures the uptake of the protein into cells
  • A has the enzymatic activity
41
Q

How does ricin cause posioning?

A
  • Inactivates ribosomes
42
Q

What are the symptoms of ricin poisoning?

A
  • Fever
  • Nausea
  • Vomiting
  • Seizures
43
Q

What is the treatment for ricin posioning?

A
  • Early decontamination
  • Supportive treatment
44
Q

What is the main source of atropine?

A

Members of the nightshade family e.g. the berries of deadly nighshade

45
Q

What is the chemistry of atropine?

A

Plant alkaloid

46
Q

What is the mechanism of atropine poisoning?

A

Blocks muscarinic acetylcholine receptors

47
Q

What are the symptoms of atropine poisoning?

A
  • Increased heart rate
  • Suppression of digestion and sweating
  • High blood pressure
  • Dilated pupils
48
Q

What is the treatment for atropine poisoning?

A
  • Early decomtamination
  • Antidote: anticholinesterase
  • Supportive treatment
49
Q

What is the main source of α-amanitin?

A

Death cap mushroom

50
Q

What is the chemistry of α-amanitin?

A

Cyclic peptide formed from 8 amino acids

51
Q

What is the mechanism of α-amanitin?

A

Inhibits RNA polymerase II

52
Q

What are the symptoms of α-amanitin poisoning?

A
  • Renal and liver failure
  • Diarrheoa and cramps
  • Symptoms appear many hours/days after poisoning
53
Q

What is the treatment for α-amanitin poisoning?

A
  • Supportive treatment
  • Liver transplant
54
Q

What is the source of botulinum toxin A?

A

Anaerobic bacteria

55
Q

What is the chemistry of botulinum toxin A?

A

Protein made from a heavy and light chain. The heavy chain mediates specific uptake into cholinergic nerve terminals

56
Q

What are the symptoms of botulinum toxin A poisoning?

A
  • Muscle weakness
  • Paralysis
  • Dry mouth
  • Wide pupils
57
Q

What is the main source of tetrodotoxin?

A

Found in animals (such as the pufferfish) but produced by bacteria

58
Q

What is the treatment for botulinum toxin A?

A
  • Decontamination
  • Life support
  • Anti-toxin
59
Q

Give a medical use of botulinum toxin A

A

Local injection can be used to control unwanted muscle contraction

60
Q

What is the chemistry of tetrodotoxin?

A

Animal alkaloid

61
Q

What is the mechanism of poisoning by tetrodotoxin?

A

Blocks voltage gated Na+ channels and therefore action potentials

62
Q

What are the symptoms of tetrodotoxin poisoning?

A
  • Paresthesia
  • Muscle weakness
  • Paralysis
  • Respiratory problems
63
Q

What is the treatment for tetrodotoxin poisoning?

A
  • Decontamination
  • Antiarrhythmics
64
Q

What is the main source of conotoxins?

A

Coneshell snails

65
Q

What is the chemistry of conotoxins?

A

Mixture of small peptides, the exact mixture varies

66
Q

What is the mechanism of poisoning for conotoxins?

A

Neurotoxicity at a range of specific targets (each peptide blocks different ion channels)

67
Q

What are the symptoms of conotoxin poisoning?

A
  • Burning
  • Pain
  • Paralysis
  • Death
68
Q

What is the effect of ω conotoxin?

How might this be useful as a medicine?

A

Very specifically irreversibly binds to N-type Ca2+ channels which are involved in pain signal transmission so may provide a non-addictive analgesic

69
Q

What is the main source of fasciculin?

A

Venom of black mamba

70
Q

What is the chemistry of fasciculin?

A

3 finger peptide with disulfide bonds

71
Q

What is the mechanism of fasciculin poisoning?

A

Blocks acetylcholinesterase and enhances neuromusiclar transmission

72
Q

What are the symptoms of fasciculin poisoning?

A
  • Paralysis
  • Unconsciousness
  • Death within 20 mins
73
Q

What is the treatment for fasciculin poisoning?

A
  • Artificial ventilation
  • Injection of antivenom
74
Q

What are the disadvantages of using natural toxins for therapeutic use?

A
  • most are small proteins so there are problems with pharmacokinetics
  • toxin levels
75
Q

What are the advantages of using natural toxins for therapeutic use?

A
  • Large source of compounds
  • Some highly selective

Mechanisms of Drug Action (8 decks)

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