Cholinergic system

Question 1

what are the harmful effects of cholinergic?

Answer 1

1. insecticides - organophosphate - target the cholinergic signalling -> increase Ach
2. bioweapons - sarin - a nerve agent
3. disease: AD, myasthenia gravies, sympathetic and parasympathetic modulation

Question 2

where do you find these Ach receptors in the brain?

1. muscarinic
2. nicotinic
3. muscarinic + nicotinic

Answer 2

1. muscarinic - midbrain, medulla, pons
2. nicotinic - substantia nigra, locus corelrulus, septum
3. muscarinic + nicotinic - cerebral cortex, corpus striatum, thalamus, hypothalamus, hippocampus, cerebellum

Question 3

where does the Ach acts in the somatic and autonomic nervous system?

Answer 3

somatic - skeletal muscle

autonomic - sympathetic + parasympathetic - smooth muscle (blood vessel), glands, cardiac muscle

Question 4

what is the main function of sympathetic and parasympathetic?

Answer 4

• sympathetic: fight, flight and fright (freeze)

- parasympathetic- feed and breed, rest and digest

Question 5

what is the difference between nicotinic and muscarinic receptors?

1. agonist
2. antagonist
3. receptor type
4. ion channel feature
5. targets
6. signal type
7. mode of action at synapse

Answer 5

1. agonist -
N - nicotine 
M - muscarine 
2. antagonist 
N - competitive - curare
M - inverse - atropine
3. receptor type 
N - inotropic 
M - metabotropic 
4. ion channel feature
N - fast, brief, ms
M - slow prolonged, s
5. targets 
N - NMJ, autonomic ganglia, some CNS
M - myocardial and some smooth muscle (inhibitory), CNS
6. signal type 
N - excitation 
M - excitation + inhibition 
7. mode of action at synapse 
N - post-synaptic but now pre-synaptic in CNS
M - pre and post-synaptic

Question 6

why is the function of Ach in skeletal muscle?

Answer 6

• somatic MN release ACh at NMJ

- net entry of Na+ through ACh receptors channel initiates a muscle AP

Question 7

what is Ach synthesised from and what degrades them?

Answer 7

synthesised from - choline acetyl transferase enzyme (ChAT)

degraded by - choline esterase (AchE) at the synapse

Question 8

what is myasthenia gravis and what causes it?

Answer 8

• autoimmune disorder
• increased muscle weakness upon activity
• auto antibodies against Ach at the post synapse of nAchR

Question 9

what is common b/w organophosphates, novichok and AD?

Answer 9

• AchE activity blocked

- therefore, acculumuation of Ach at synapse -> chronic depolarisation

Question 10

name an antidote and how is its mode of action different for nerve agents and in ageing

Answer 10

pralidoxime,
nerve agents - couples with it and displaces the nerve agent from the binding site
ageing - permanent binding

Question 11

What symptoms would be expected from AchE inhibitors?

Answer 11

SLUDGEM
salivation, lacrimation, urination, defecation, gastrointestinal upset, emesis (vomiting), miosis (excess constriction of pupil)
MUDDLES
miosis, urination, diarrhea, diaphoresis (unusual excess sweating as symptom or drug side effect), lacrimation, excitation, and salivation

Question 12

what are the drugs used for OP poisoning?

Answer 12

1. atropine
2. diazepam - reduces Ach release from synapse, anticonvulsant drug
3. pralidoxime

Question 13

how is AchE inhibitor used in MG?

Answer 13

Use to prolong Ach in NMJ to improve neuromuscular transmission

Question 14

how is AchE inhibitor used in AD?

Answer 14

• Cholinergic deficit in forebrain in AD.
• AchE inhibitors potentiate Ach synapse levels, thus potentiate cholinergic action.
• Donepezil (Aricept®), rivastigmine (Exelon®), and
  galantamine (Razadyne®).
• Reversible and selective inhibitors of AchE.
• Show temporary benefit 12-24 months.
• Do not alter the course of the disease