Module 9 Unit 1

Question 1

The range of toxicity mechanisms

Answer 1

–  Immune system related 
–  Receptor-mediated 
–  Enzyme related 
–  Direct physical damage 
–  DNA-related
–  Reproduction and development

Question 2

What are Immune system related toxic

Answer 2

•   Inflammation
•   Hypersensitivity
•   Immune suppression

Question 3

Receptor-mediated

Answer 3

agonist or antagonist (substance which interferes with or inhibits the physiological action of another.)

Question 4

Enzyme related

Answer 4

•  inhibition

Question 5

Direct physical damage

Answer 5

•  eg. to cell membranes

Question 6

DNA-related

Answer 6

•   altered gene expression leading to neoplasia

*   altered gene repair leading to neoplasia

Question 7

Reproduction and development

Answer 7

conception or foetal development

Question 8

Example of inflammatory reaction

Answer 8

•   exposure to lime (CaCO3) on building sites

*   Direct skin contact leads to skin damage and local inflammatory reaction

Question 9

What Strychnine (rodent bait) have an effect of animals

Answer 9

•   Strychnine bindsto receptorsinCentralNervous system
•   Competitivelyinhibits binding ofglycineto the receptor
• Glycine is an inhibitory neurotransmitter
• inhibition of glycine leads to increase activity in CNS
• Excitment and convulsions, tetanus of skeletal muscles

Question 10

What does Organophosphates affect

Answer 10

enzyme inhibitors
inhibit an enzyme Acetylcholinesterase (responsible for termination activity of the neurotransmitter Acetyl Choline at nerve terminals )

Question 11

What does OP insecticides cause

Answer 11

irreversible phosphorylation of AChE active site
•  Acetyl Choline’s actions are enhanced/prolonged
•  There are ACh receptors in the central nervous system and a range of organs
•  phosphate group can migrate in enzyme active site = “ageing”

Question 12

Signs of OP toxicity

Answer 12

– In the autonomic (involuntary) nervous system • Salivation, Lacrimation, Urination, Defaecation 
– In skeletal muscles  
• twitching 
• tremors 
• Paralysis 
– In central nervous system  
• Seizures and unconsciousness

Question 13

How to treat OP toxicity

Answer 13

– Limit absorption
•  Gastric lavage
•  adsorption (activated charcoal)
– Block access of Ach to receptor
•  Atropine a receptor blocker at some autonomic receptors – Reactivate phosphorylated AChE
•  Pralidoxime
•  needs to be given before AChE “ages” and the anticholineterase is irreversibly inactivated

Question 14

Other mechanisms of OP action

Answer 14

•   Chronic low dose exposure leads to receptor desensitisation to Ach -> ? cognitive deficits and behavioural change
•   OP induced delayed neuropathy (OPIDN)- permanent damage to peripheral nerves

Question 15

What toxic is an example of direct physical damage

Answer 15

Paraquet : contact herbicide

Toxicokinetics: Limited absorption; localisation in the lungs, slow absorption from GIT, excreted in urine

Question 16

What is the mechanism of action of paraquat

Answer 16

transfers an electron to oxygen, free radicals form lipid hydroperoxide ⇒ Membrane damage, cellular degeneration and necrosis

Question 17

What happens when paraquat is absorbed

Answer 17

– lung is major target organ for toxicity 
• tachypnoea, progressive dyspnoea 
• haemorrhage 
• oedema 
• damage to alveolar epithelial cells 
• fibrosis 
•  a delayed response (days to weeks)

Question 18

Why is paraquat lung selective

Answer 18

– taken up selectively by alveolar epithelial cells
• concentration of paraquat in lungs
– abundance of O2 in lungs
• good environment for production of oxygen free radicals

Question 19

What initates a free radical (has unpaired electron) casacade

Answer 19

Paraquat

Question 20

What effect does hydroxyl radical have

Answer 20

•  HO•
–  highly reactive
–  initiates free radical chain reaction in lipid
•  lipid peroxidation
•  cell membrane damage
•  loss of cell function
•  cell death
•  Death of alveolar lining cells in lung
•  Development of scarring in alveoli
•  Fibrous scarring impairs gas exchange
•  Scarring is irreversible

Question 21

How to treat paraquat poisoning

Answer 21

– administer adsorbant 
• remove paraquat from gut 
• clay, Fuller’s earth, ground-up kitty litter 
– reduce inspired oxygen levels 
• reduce free radical production

Question 22

Why are cats highly susceptible to toxicity (>40mg/kg)

Answer 22

Because cats lack glucuronidation, paracetamol need less to have the same effect. More will be metabolise in phase 1, forming nucleophilic cell macromolecules with paracetamol with N-acetyl-β-benzoquinone imine (highly reactive) which is toxic

Question 23

What does nucleophilic cell macromolecules with paracetamol cause

Answer 23

Liver and red blood cell damage

Question 24

Paracetamol toxicity – treatment

Answer 24

– need to replenish/maintain glutathione pool
– cannot administer
• glutathione
• cysteine (cannot be absorbed)
– give N-acetyl cysteine
• will be synthesised into glutathione
• can directly mop up reactive intermediate

Question 25

What does selective toxicity mean

Answer 25

toxic effect vary between individuals and between species