Week 4: From nerve gas to dementia

Question 1

in the periphery, the
cholinergic system innervates …

Answer 1

muscles and provides muscle contractions through nicotinic receptors

and there is innervation of
the lungs,
the heart and
glands within the body.

Question 2

Within the brain [separate from the periphery], the cholinergic system relates to processes like…

Answer 2

activation, wakefulness, and sleep and also attention.

Question 3

Within attention, there’s a role for acetylcholine in ……

Answer 3

memory

Question 4

the cholinergic system in the brain
originates within the

Answer 4

basal forebrain

Question 5

Brain Cholinergic system: most cells in the______ and _________receive innervation, have synapses with cholinergic
neurons.

Answer 5

cortex
hippocampus

Question 6

the number of cholinergic cells in the brain is ________

Answer 6

small

Question 7

anything that acts on the cholinergic system, which can - penetrate the blood brain barrier - which is hard - will have an effect on the

Answer 7

CNS

Question 8

the cholinergic system is based on a group of cells which have the ability to make
_________

Answer 8

acetylcholine

Question 9

To make acetylcholine, you use __________ which comes from metabolism.

Answer 9

acetyl-CoA,

Question 10

choline is a dietary substance, which you’ll find in ______, but also in _________

Answer 10

fats
cholinergic neurons.

Question 11

these two chemicals, ________ and __________are combined by the action of an enzyme called choline acetyltransferase, which makes acetylcholine.

Answer 11

choline
and
acetyl-CoA

Question 12

an enzyme called ________ makes acetylcholine.

Answer 12

choline acetyltransferase,

Question 13

Acetylcholine is released from _______ into the synaptic cleft, where it diffuses and interacts with _______ or
__________ receptors.

Answer 13

vesicles
muscarinic
nicotinic

Question 14

There’s a very active system for breaking down acetylcholine back to acetate and choline, which is __________ (which is an enzyme),

Answer 14

acetylcholinesterase

Question 15

Myasthenia gravis is a _________ where, essentially, there’s an autoimmune disease attacking the_________ on muscles for acetylcholine, and one of things you can do to test whether somebody has this is to give a very short-acting _____________to see what
effect that has on _____________.

Answer 15

muscle disorder
receptors
acetylcholinesterase inhibitor
muscle contraction

Question 16

Acetylcholinesterase Inhibitors: AChE

Function: _____________
Effect: ________________

Answer 16

Inhibit the Break down acetylcholine.
Increasing both the level and duration of the NT action

Question 17

Acetylcholinesterase Inhibitors and Glaucoma:

Prevent breakdown of ____________.
Result: Maintains ___________concentration in the synapse.
Application: Used in the treatment of glaucoma, an _______ disease.

Answer 17

acetylcholine
higher acetylcholine
eye

Question 18

Alzheimer’s Disease: Characterized by a loss of __________

Answer 18

Cholinergic neurons that produce acetylcholine

Question 19

Alzheimer’s Disease:

Potential Treatment: Inhibiting ________ breakdown leading to………

Answer 19

acetylcholine
Increased communication between nerve cells which in turn may temporarily improve or stabilize the symptoms of dementia

Question 20

Drugs used in glaucoma or myasthenia gravis typically do not __________.

Answer 20

cross the blood-brain barrier

Question 21

Nerve agents are extremely potent and rapid ____________

Answer 21

enzyme inhibitors.

Question 22

Nerve Agents

Nerve agents are extremely potent and rapid enzyme inhibitors.
Potential: They can ___________ the enzyme discussed.

Answer 22

irreversibly inhibit

Question 23

All nerve agents exert predominant effect by inhibiting _____________ at the nerve junction,

Answer 23

acetylcholinesterase

Question 24

Prolonged overactivation of acetylcholine in the body can lead to several potential consequences:

Answer 24

Muscle Weakness:
Paralysis
Respiratory Distress:
Cognitive Effects:
Autonomic Dysfunction:
Seizures:
Gastrointestinal Effects:

Question 25

Competitive Inhibition: Some drugs, like _____________, work by binding to the active site of the enzyme, competing with ___________ for binding. This prevents ____________ from being broken down, leading to its ____________ in the synaptic cleft.

Answer 25

acetylcholinesterase inhibitors
acetylcholine
acetylcholine
accumulation

Question 26

Irreversible Inhibition: Nerve agents, as mentioned earlier, can _________ inhibit the enzyme. They form ___________with the enzyme, rendering it permanently inactive.

Answer 26

irreversibly
strong covalent bonds

Question 27

ACh / nerve agents: Certain drugs or agents can interfere with the production of the __________ in the first place. This reduces the availability of the _______ to break down __________.

Answer 27

acetylcholine-degrading enzyme
enzyme
acetylcholine

Question 28

Muscle Contraction and Acetylcholinesterase Inhibitors:

Normal Muscle Contraction:
Nerves signal the muscle to contract.
___________ is released.
___________ receptors activate, causing muscle contraction.

Answer 28

Acetylcholine
Nicotinic

Question 29

Muscle Contraction and Acetylcholinesterase Inhibitors:

Acetylcholinesterase Inhibitors:
Prevent the breakdown of acetylcholine.
Acetylcholine builds up at the _
_______.
Result: Muscle ___________ until acetylcholine naturally diffuses away, then it _________.

Answer 29

receptor
remains contracted
relaxes

Question 30

What are the two different mechanisms of enzyme inhibition we discussed?

Answer 30

Reversible and irreversible, or competitive and non-competitive inhibitors.

Question 31

Describe the interaction between neostigmine and ACh…

Answer 31

Neostigmine inhibits the hydrolosis of ACh by competing with ACt for attachment to acetylcholinesterase at sites of cholinergic transmission

Question 32

What happens to acetate and choline after acetylcholine is hydrolyzed?

Answer 32

They are released and typically taken up and reused.

Question 33

What are the characteristics of neostigmine and similar inhibitors?

Answer 33

Neostigmine and similar inhibitors inhibit acetylcholinesterase which is responsible for the degradation of ACh. So with acetylcholinesterase inhibited, more ACh is present,…..thus it indirectly stimulates both nicotinic and muscarinic receptors

Question 34

What happens when an irreversible inhibitor targets one of the binding sites within the active site of acetylcholinesterase?

Answer 34

An irreversible inhibitor binds to one of the binding sites, preventing acetylcholine docking and hydrolysis. This leads to the loss of the enzyme’s function.

Question 35

How do nerve agents like VX and sarin kill individuals exposed to them?

Answer 35

Nerve agents cause death by asphyxiation due to muscle contractions, including those in the lungs and airways. They also lead to peripheral jerks, changes in heart rate, perspiration, and pupil constriction. In severe cases, they affect the central nervous system

Question 36

Why are neostigmine and similar inhibitors considered relatively weak in their interactions?

Answer 36

These inhibitors are considered weak because they can either self-hydrolyze or diffuse away from the active site.

Question 37

What is the role of butyrylcholinesterase in military applications?

Answer 37

Butyrylcholinesterase can mop up active toxic agents and has been used in the military for protection.

Question 38

How do liquid nerve agents like VX and sarin differ from gases like mustard gas?

Answer 38

Liquid nerve agents have a more limited area of exposure and can be used more selectively.

Question 39

What is the significance of binary agents in chemical warfare?

Answer 39

Binary agents are two chemicals that, when combined in an explosion, form a highly toxic chemical agent.

Question 40

How did the development of nerve agents like soman and sarin differ from earlier chemical warfare agents?

Answer 40

Soman and sarin were developed as liquids, which allowed for more precise delivery compared to gases.

Question 41

What are the advantages of using chemicals like VX and sarin over mustard gas in warfare?

Answer 41

Liquid nerve agents like VX and sarin can be more selectively targeted and have a catastrophic effect in small quantities.

Question 42

What is the primary protective measure against chemical warfare agents in the Gulf War?

Answer 42

The primary protection included wearing nuclear biological protection gear and gas masks.

Question 43

What is the main function of atropine in protecting against chemical warfare agents?

Answer 43

Atropine can block the effects of acetylcholine, helping to counteract the increased acetylcholine levels.

Question 44

How does organophosphate exposure affect farmers who use sheep dip containing these compounds?

Answer 44

Farmers exposed to organophosphates in sheep dip can experience adverse health effects, including potential cognitive impairment.

Question 45

Why were organophosphate-based insecticides historically used in agriculture?

Answer 45

Organophosphate-based insecticides were used because they could kill insects without harming humans due to differences in metabolism.

Question 46

What was the outcome of studies conducted on farmers exposed to organophosphates in sheep dip?

Answer 46

Studies examined potential organophosphate poisoning in farmers and raised concerns about their health effects.

Question 47

How did the development of acetylcholinesterase inhibitors lead to potential treatments for Alzheimer’s disease?

Answer 47

Acetylcholinesterase inhibitors were explored as treatments for Alzheimer’s disease due to their ability to boost the cholinergic system, which is linked to attention and memory.

Question 48

What were some challenges associated with early acetylcholinesterase inhibitors used in Alzheimer’s disease treatment?

Answer 48

Early inhibitors had short durations of action and poor penetration of the central nervous system.

Question 49

What mechanisms underlie the cognitive improvement observed in Alzheimer’s patients treated with acetylcholinesterase inhibitors?

Answer 49

Acetylcholinesterase inhibitors improve cognitive function by boosting the cholinergic system, which is linked to attention, arousal, and memory.