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Discuss the types and distribution of cholinergic receptors
- Nicotinic:
- N1 – skeletal muscle
- N2 – ganglionic
- Muscurinic G-protein linked:
- M1 – parietal cell, CNS
- M2 – Cardiac muscle (inhibitory)
- M3 – Visceral SM (contraction) and Vascular smooth muscle (Relaxation)
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Describe muscurinic Ach receptors
- M1 and M3: Gq linked
- M2 – Gi linked
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Describe synthesis of Acetylcholine (Ach)
- Made from acetyl CoA and choline in nerve terminals
- Catalized by choline acetyltransferase
- Packaged in synaptic vesciles
- Uptake of choline is rate limiting step
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Describe Ach termination
- By enzyme acetylcholinesterase
- Splits into Acetate and choline
- Choline taken up by nerve terminal
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Discuss lstructure of Acetylcholinesterase active site
- Active site has 2 regions
- - 1. Anionic site binds choline
- - 2. Esteric site transferes Acetyl group to OH group
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Discuss drugs which affect Ach synthesis
- Hemicholinium: competitively inhibits choline uptake
- Vesamicol: inhibits packaging of Ach in vesicles
- Triethycholine: inhibits choline uptake, taken up itself, converted to acetyltriethylcholine, stored as false NT
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Discuss drugs which affect Ach release
- Botulinum toxin:
- - breaks down SNARE proteins
- - prevents release of vesicles
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Discuss why muscurinic agonists channot be administered. Discuss two exceptions
- Poor absorption from GI tract
- Many Side effects
- Exceptions: Pilocarpine and Carbachol (Bethanachol)
- Pilocarpine: lowers intra occular pressure, treats glaucoma
- Carbachol (Bethanacol): Increase GI motility / bladder emptying
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Discuss Atropine and its effects on the following body parts:
- Competetive Ach antagonist
- Eye: Mydriasis, Cyclopledgia, increase intro occular pressure
- GI: reduce motility, treats enuresis
- CV:
- -- low dose: slows heart rate
- -- higher dose: speeds heart rate
- -- Toxic dose: dilates cutaneous blood vessels
- Secretions: blocks secretions- salivary, sweat glands, lacrimal glands, airways
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Discuss the mechanism of actions of anti-cholinesterases
- Edrophonium: short term
- Neostigmine: medium duration
- Isoflurophate: irreversible
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Discuss D-tubocurarine
- Competetive NAchR receptor antagonist at NMJ
- Relaxes skeletal muscle
- Motor paralysis
- Lowers blood pressure
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Discuss Succinylcholine
- Depolarizes membrane
- Maintains depolarization above threshold
- Muscle reverts to flaccid state
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