Drugs acting on the parasympathetic nervous system (L10)

Question 1

what is the parasympathetic system?

Answer 1

rest and digest

part of the autonomic nervous system

Question 2

what is the autonomic nervous system?

Answer 2

• controls the smooth muscle and glands
• outside the influence of voluntary control
• divided into the sympathetic and the parasympathetic

Question 3

what happens in ‘rest and digest’?

Answer 3

• 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

Question 4

organisation of the parasympathetic system relative to neurotransmitters

Answer 4

long preganglionic fibre
short postganglioic fibre

both neurones contain ACh as their neurotransmitter

Question 5

organisation of the sympathetic system relative to neurotransmitters

Answer 5

short preganglionic fibre
long postganglionic fibre

preganglionic = ACh 
postganglioic = NA

Question 6

organisation of the somatic system relative to neurotransmitters

Answer 6

contains ACh on its own and has no autonomic ganglion

Question 7

sympathetic system exceptions

Answer 7

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

Question 8

PNS ACh pharmacology

Answer 8

• 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

Question 9

what are the 2 different classes of ACh receptors?

Answer 9

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

Question 10

what are the 3 main muscarinic (mACh) receptor subtypes?

Answer 10

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

Question 11

what are the 2 main nicotinic (nACh) receptor subtypes?

Answer 11

neuronal type - brain and autonomic ganglia (excitatory)

muscle type - NMJ (excitatory)

ligand gated ion channels
fast response - milliseconds

Question 12

what are muscarinic agonists known as?

Answer 12

parasympathomimetics

effects of muscarinic agonists are similar to the the parasympathetic activation

Question 13

what are muscarinic antagonists known as?

Answer 13

parasympatholytics

effects of muscarinic antagonists are against the parasympathetic activation

Question 14

what are some muscarinic receptor agonists?

Answer 14

pilocarpine - used to treat glaucoma and xerostomia

Question 15

what are some muscarinic receptor antagonists?

Answer 15

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

Question 16

where are neuronal type nACh receptors found?

Answer 16

located on both sympathetic and parasympathetic ganglia

Question 17

neuronal type nACh receptor agonists

Answer 17

activate both systems

the effect is autonomic confusion and therefore neuronal nicotinic agonists are not clinically used

Question 18

neuronal type nACh receptor antagonists

Answer 18

loss of sympathetic and parasympathetic reflexes

not of great therapeutic value

Question 19

where are muscle type nACh receptors found?

Answer 19

located at the NMJ

stimulation by ACh causes depolarisation and contraction of the skeletal muscle fibre

Question 20

muscle type nACh receptor agonists

Answer 20

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

Question 21

muscle type nACh receptor antagonists

Answer 21

hyperpolarisation - inhibition of EPPs

muscle fibre relaxation

paralysis - for surgery

non-depolarising blocker

Question 22

drugs affecting ACh synthesis

Answer 22

rate limiting process in precursor (choline) uptake

hemicholinium blocks the choline uptake

Question 23

drugs affecting ACh release

Answer 23

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

Question 24

drugs affecting ACh metabolism

Answer 24

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