Pharma 3 Flashcards
Where are preganglionic and postganglionic neurons found?
Preganglionic: Brain stem or lateral horn of spinal cord and synapse
Postganglionic : autonomic ganglion that lies outside of the CNS
What do parasympathetic postganglionic neurons release?
AcetylCholine
What do all sympathetic postganglionic neurons release?
Noradrenaline
Except sweat gland-ACh
What do all preganglionic neurons release?
ACh
In GPCRs, what do different G proteins do?
Gs- binds to alpha- activates adenylate cyclase
Gi- binds to alpha- inhibits adenylate cyclase
Gq- binds to alpha- activates phospholipase C-beta
What are the two types of cholinceptor in the CNS?
Nicotinic: Tabacco alkaloid nicotine Ligand gated ion channels, pentamers, an ACh binding site on each alpha subunit Muscarinic Fungal alkaloid muscarine GPCRs
What are the two types of adrenoceptor in the autonomic nervous system?
alpha adrenoceptors
beta adrenoceptors
Both are GPCRs
What are the actions of the parasympathetic nervous system?
Constricts pupils, stimulates tears Stimulates salivation Constricts bronchi, stimulates secretion Slows heart rate Increases gut motility, secretion and relaxes sphincters Erects penis
What are the actions of the sympathetic nervous system?
Dilates pupil Constricts blood vessels Dilates bronchi Increases heart rate and contractility Slows gut motility, stops secretion, shuts sphincters Contracts vas deferens in ejaculation
How is acetylcholine produced?
The enzymes ChAT produces it from holine and acetyl CoA from the mitochondria
Name four toxins involved in the release of neurotransmitter:
Vesamicol-blocks uptake and storage of ACh in synaptic vesicles
Tetrodoxin- blocks voltage gated sodium channels (no release)
Botulinum toxin- cleaves SNARE proteins to block vesicle function (no release)
Nerve gases, neostigmine-inhibit AChE, increasing concentration and effects of ACh
What does alpha-lactrotoxin do?
Massive ACh release Muscle spasms Later: Depletion of vesicle pool Desensitisation of NMJ Inhibition of endocytosis All leading to paralysis
Name a competitive and an irreversible non-depolarising blocker:
Tubocurarine-stopped by anticholinesterases
Alpha-bungarotoxin
How do depolarising blockers work?
Phase 1 block
1. Persistant activation of endplate nicotinic receptors by suxamethonium
2.Prolonged depolarisation of endplate
3.Inactivation of voltage-gated sodium channels
Phase 2 block:
4. Desensitisation of endplate nicotinic receptors
5. Repolarisation of endplate
6.Receptor densensitisation maintains blockade
What does suxamethonium do?
It's a depolarisng blocker- agonist Used clinically Rapid onset of paralysis Short duration Side effects include decreased heart rate (m2 mAChR activation in heart)
