From Poisons to Surgery Part 2

Question 1

What enzyme breaks down acetylcholine into acetyl and choline

Answer 1

Acetylcholineesterase (AChE)

Question 2

How does acetylcholinesterase break down acetylcholine into Acetyl and choline

Answer 2

1. enzyme has amino acid near binding site with negative charge
2. -ve part of enzyme interacts with +ve N on acetylcholine, holding it in place
3. Serine part of enzyme interacts with double bonded oxygen part of acetylcholine
4. Hydrolysis of water occurs, causing a release of choline and acetate unbound from the enzyme

Question 3

How fast does Neostigmine react with acetylcholinesterase and why does that inhibit acetylcholine break down

Answer 3

it reacts slowly and is slowly reversible, inhibiting ACh as when Neostigmine is bound to AChE, ACh cannot bind

Question 4

Why is Sarin an irreversible acetylcholinesterase inhibitor and thus acetylcholine can never be broken down?

Answer 4

the structure of Sarin is sufficiently similar to ACh that is can bind to AChE, however different enough that it cannot unbind

Question 5

What type of drugs are Sarin, Soman nerve gases, Novichok and organophosphate insecticides?

Answer 5

poisons

Question 6

What is an example of organophosphate insecticides

Answer 6

malathion for head lice

Question 7

Why can Sarin gas/Novichok Kill?

Answer 7

1. Ach levels are increased due to never being broken down as Sarin gas in irreversibly bound to AChE
2. nicotinic receptors are overstimulated and thus a depolarizing block is caused
3. Person will not be able to breathe due to the voluntary breathing muscles always contracting

Question 8

Name 2 AChE inhibitor drugs that are antidotes for curare poisoning

Answer 8

• Pyridostigmine
• Neostigmine

Question 9

How can Pyridostigmine/ neostigmine be antidotes for curare poisoning

Answer 9

1. curare binding to nACh receptors means they have less availability for ACh
2. if you give pyridostigmine, it inhibits ACh reuptake, so ACh levels increase.
3. this means there is more chance of ACh binding to receptors over curare, thus negating Curare’s effects

Question 10

Name a disease in which AChE inhibitor drugs pyridostigmine/neostigmine have therapeutic action

Answer 10

myasthenia gravis

Question 11

What is myasthenia gravis

Answer 11

• an autoimmune condition where antibodies target nicotinic receptors
• the Antibodies inactivate the nAChR receptors, reducing muscle control

Question 12

What are symptoms of Myasthenia gravis

Answer 12

Weakness of muscles of the eyes, eyelids and face

Question 13

Name 4 AChE inhibitor drugs that can treat Alzheimer’s

Answer 13

• donepezil
• tacrine
• galantamine
• rivastigmine

Question 14

where is galantamine found

Answer 14

In snow drop plants

Question 15

Why must you be careful if you give too much of any AChE inhibitor drug

Answer 15

if you give too much AChE inhibitor drug, you will raise the levels of ACh too much, causing a depolarizing block, similar to Sarin gas poisoning