Cholinergic Mechanisms

Question 1

Cholinergic neurotransmission

Answer 1

1. reuptake of choline
2. transport of ACh into vesicles
3. exocytosis of ACh
4. interactions between ACh and receptors
5. termination of ACh effects by acetylcholinesterase

Question 2

Drugs target on the cholinergic transmission

Answer 2

1. inhibition of reuptake - hemicholinium
2. blockage of vasicular ACh transport (VAT) - vesamicol
3. inhibition of exocytosis of ACh containing vesciles - botulinum toxin and clacium channel blockers
4. receptor agonists/antagonists
5. acetylcholinesterase inhibitors

Question 3

Drugs that promote cholinergic transmission

Answer 3

Act by stimulating or mimicking ACh
- Muscarinic receptor agonists
- pilocarpine (treating glaucoma, topical application)
- bethanechol (postoperative urinary retention)
- nicotinic receptor agonists
- nicotine (an aid for the relief of nicotine withdrawal
symptoms)
- Acetylcholinesterase inhibitors
- physostigmine (glaucoma)
- neostigmine, pyridostigmine (myasthenia gravis)

Question 4

Drugs that inhibit cholinergic transmission

Answer 4

Serve to reduce the effects mediated by ACh

• antimuscarinic agents (widely used) - atropine
• botulinium toxin: blocks exocytosis of ACh
• neuromuscular blocking drugs: depolarising and non-depolarising agents
• ganglionic blockers: hexamethonium

Question 5

Muscarinic vs nicotinic

Answer 5

Type
Muscarinic: G-protein coupled receptors, 5 subtypes (M1-M5), respond to ACh via second messengers IP3 and cAMP
Nicotinic: Ligand-gated ion channels, 3 classes (muscle, ganglionic and CNS types), repond to ACh by increased cation permeability, mediate fast excitatory synaptic transmission

Location
Muscarinic: peripheral tissues, including the heart, smooth muscles, sweat glands, nerve terminals. Also in CNS,
Nicotinic: ANS ganglia, neuromuscular junctions of the somatic nervous system, CNS

Question 6

Cholinergic drugs

Answer 6

1. Muscarinic receptor agonists
2. Muscarinic receptor antagonists
3. Nicotinic receptor agonists
4. Ganglionic blockers
5. Neuromuscular blocking agents
6. Exocytosis blocking agents
7. Acetycholinesterase inhibitors

Question 7

Muscarinic receptor agonists

Answer 7

Carbachol (open angle glaucoma, miosis during cateract surgery),
bethanechol (urinary retention - difficulty in urinating, dry mouth),
pilocarpine (chronic open-angle glaucoma, acute angle-closure glaucoma, dry moth, diagnosis test of cystic fibrosis)

Muscurinic receptor agonists are mainly used in glaucoma

Question 8

Clinical uses of antimuscarinics / muscarinic antagonists

Answer 8

Atropine - resuscitation - injection is used in the treatment of bradycardia in cardiac arrest after myocardial infarction. premedication in anaethesis, ant-spasmodic and anti-diarrhoea

Other clinical

• overactive bladder (tolterodine, oxybutynin, darifenacin - all three block the M3 receptor)
• motion sickness
• parkinson’s
• asthma
• peptic ulcer