Drugs acting on the parasympathetic nervous system (L10) Flashcards
what is the parasympathetic system?
rest and digest
part of the autonomic nervous system
what is the autonomic nervous system?
- controls the smooth muscle and glands
- outside the influence of voluntary control
- divided into the sympathetic and the parasympathetic
what happens in ‘rest and digest’?
- pupils contract
- lens of eye readjusts for closer vision
- airways in lungs contract
- breathing rate decreases
- HR decreases
- blood vessels to limb muscles constrict
- blood vessels to visceral organs dilated
- salivary secretions normalise
- brain activity normalises
organisation of the parasympathetic system relative to neurotransmitters
long preganglionic fibre
short postganglioic fibre
both neurones contain ACh as their neurotransmitter
organisation of the sympathetic system relative to neurotransmitters
short preganglionic fibre
long postganglionic fibre
preganglionic = ACh postganglioic = NA
organisation of the somatic system relative to neurotransmitters
contains ACh on its own and has no autonomic ganglion
sympathetic system exceptions
sweat glands
• sympathetic but both neurones have ACh
adrenal glands
• adrenaline release from the adrenal glands
• no autonomic ganglion
• ACh action on the adrenal medulla causes release of adrenaline
PNS ACh pharmacology
- precursor is choline
- ACh is synthesised from choline and acetylCoA by cholineacetyl transferase (CAT)
- vesicles protect it from enzymatic breakdown
- ACh released into synaptic cleft
- ACh receptors can be nicotinic or muscarinic
- response cannot continue so ACh is broken down by acetylcholinesterase to choline and acetate
what are the 2 different classes of ACh receptors?
muscarinic - called this as they have an affinity for an extract from the mushroom Amanita muscarina
nicotinic - have an affinity for an extract from tobacco - nicotiana
what are the 3 main muscarinic (mACh) receptor subtypes?
M1,2,3
a family of receptors - GPCR
slow response - seconds
located at postganglionic parasympathetic synapses meaning they don’t mediate the effect go ACh in the ganglia, they mediate the effect of ACh in the target organ
what are the 2 main nicotinic (nACh) receptor subtypes?
neuronal type - brain and autonomic ganglia (excitatory)
muscle type - NMJ (excitatory)
ligand gated ion channels
fast response - milliseconds
what are muscarinic agonists known as?
parasympathomimetics
effects of muscarinic agonists are similar to the the parasympathetic activation
what are muscarinic antagonists known as?
parasympatholytics
effects of muscarinic antagonists are against the parasympathetic activation
what are some muscarinic receptor agonists?
pilocarpine - used to treat glaucoma and xerostomia
what are some muscarinic receptor antagonists?
atropine and tropicamide - used to treat bradycardia, to decrease secretions and pupil dilation in eye surgery
ipratropium - asthma
hyoscine - to decrease gastric motility and motion sickness
where are neuronal type nACh receptors found?
located on both sympathetic and parasympathetic ganglia
neuronal type nACh receptor agonists
activate both systems
the effect is autonomic confusion and therefore neuronal nicotinic agonists are not clinically used
neuronal type nACh receptor antagonists
loss of sympathetic and parasympathetic reflexes
not of great therapeutic value
where are muscle type nACh receptors found?
located at the NMJ
stimulation by ACh causes depolarisation and contraction of the skeletal muscle fibre
muscle type nACh receptor agonists
initial depolarisation and muscle fibre contraction
as the synthetic agonist is not metabolised rapidly by ACh, the fibre is persistently depolarised resulting in loss of further electrical excitability - known as depolarising block
paralysis/muscle relaxation - for surgery
muscle type nACh receptor antagonists
hyperpolarisation - inhibition of EPPs
muscle fibre relaxation
paralysis - for surgery
non-depolarising blocker
drugs affecting ACh synthesis
rate limiting process in precursor (choline) uptake
hemicholinium blocks the choline uptake
drugs affecting ACh release
ACh release is inhibited by botulinum toxin and bungarotoxin
causes parasympathetic and motor paralysis if ingested
injected locally to treat muscle spasms and for BOTOX
drugs affecting ACh metabolism
acetylcholine can be inhibited by anticholinsterases
this increases ACh transmission
effects on the autonomic nervous system:
• reflect increased transmission at parasympathetic postganglionic synapses
effects on the NMJ:
• increases muscle tension and twitching
• at large does can cause a depolarising block
