Week 4: From nerve gas to dementia Flashcards

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1
Q

in the periphery, the
cholinergic system innervates …

A

muscles and provides muscle contractions through nicotinic receptors

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

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2
Q

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

A

activation, wakefulness, and sleep and also attention.

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3
Q

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

A

memory

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4
Q

the cholinergic system in the brain
originates within the

A

basal forebrain

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5
Q

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

A

cortex
hippocampus

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6
Q

the number of cholinergic cells in the brain is ________

A

small

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7
Q

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

A

CNS

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8
Q

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

A

acetylcholine

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9
Q

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

A

acetyl-CoA,

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10
Q

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

A

fats
cholinergic neurons.

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11
Q

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

A

choline
and
acetyl-CoA

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12
Q

an enzyme called ________ makes acetylcholine.

A

choline acetyltransferase,

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13
Q

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

A

vesicles
muscarinic
nicotinic

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14
Q

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

A

acetylcholinesterase

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15
Q

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 _____________.

A

muscle disorder
receptors
acetylcholinesterase inhibitor
muscle contraction

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16
Q

Acetylcholinesterase Inhibitors: AChE

Function: _____________
Effect: ________________

A

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

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17
Q

Acetylcholinesterase Inhibitors and Glaucoma:

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

A

acetylcholine
higher acetylcholine
eye

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18
Q

Alzheimer’s Disease: Characterized by a loss of __________

A

Cholinergic neurons that produce acetylcholine

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19
Q

Alzheimer’s Disease:

Potential Treatment: Inhibiting ________ breakdown leading to………

A

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

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20
Q

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

A

cross the blood-brain barrier

21
Q

Nerve agents are extremely potent and rapid ____________

A

enzyme inhibitors.

22
Q

Nerve Agents

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

A

irreversibly inhibit

23
Q

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

A

acetylcholinesterase

24
Q

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

A

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

25
Q

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.

A

acetylcholinesterase inhibitors
acetylcholine
acetylcholine
accumulation

26
Q

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

A

irreversibly
strong covalent bonds

27
Q

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 __________.

A

acetylcholine-degrading enzyme
enzyme
acetylcholine

28
Q

Muscle Contraction and Acetylcholinesterase Inhibitors:

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

A

Acetylcholine
Nicotinic

29
Q

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 _________.

A

receptor
remains contracted
relaxes

30
Q

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

A

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

31
Q

Describe the interaction between neostigmine and ACh…

A

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

32
Q

What happens to acetate and choline after acetylcholine is hydrolyzed?

A

They are released and typically taken up and reused.

33
Q

What are the characteristics of neostigmine and similar inhibitors?

A

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

34
Q

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

A

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.

35
Q

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

A

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

36
Q

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

A

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

37
Q

What is the role of butyrylcholinesterase in military applications?

A

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

38
Q

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

A

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

39
Q

What is the significance of binary agents in chemical warfare?

A

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

40
Q

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

A

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

41
Q

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

A

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

42
Q

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

A

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

43
Q

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

A

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

44
Q

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

A

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

45
Q

Why were organophosphate-based insecticides historically used in agriculture?

A

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

46
Q

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

A

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

47
Q

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

A

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.

48
Q

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

A

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

49
Q

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

A

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