disorder of PNS Flashcards
what does the PNS represent ?
The PNS represents the output of the CNS and (usually) acts independently to regulate the body’s internal environment.
what does the PNS consists of?
- Autonomic nervous system (ANS)
largely outside of voluntary control - Somatic (motor) nervous system (SNS)
under conscious control
Efferent nerves control movement by innervating skeletal muscle.
Afferent nerves respond
what does the autonomic consist of?
- Parasympathetic nervous system
Cranial-sacral output, synapse at ganglia close to innervated tissue. - Sympathetic nervous system
Thoracic-lumbar output, synapse at ganglia either side of vertebral column (sympathetic chain).
Ganglia distal to innervated tissue. - Enteric nervous system
Neurones with cell bodies in the wall of the intestine which innervates GI tract, pancreas and gall bladder.
ANS is characterised by 2 neurones outside cns what are they?
and what are released from them
The ANS is characterised by having 2 neurones outside the CNS
preganglionic fibres arising from the CNS synapse onto
postganglionic nerve in a ganglia.
Postganglionic neurones terminate at the effector.
Acetylcholine (ACh) is released from
all preganglionic neurones of both parasympathetic and sympathetic nerves
all postganglionic parasympathetic neurones
= cholinergic transmission
Noradrenaline (NA) is released from
most postganglionic sympathetic neurones
= adrenergic (noradrenergic) transmission
what are the neurotransmitters in the ANS?
- Cholinergic transmission
all postganglionic parasympathetic nerves release ACh to act on muscarinic acetylcholine receptors (mAChRs)
all motor nerves release ACh which act on nicotinic acetylcholine receptors (nAChRs)
m1 -m5
location
function
g-protein
response
agonist
antagonist
check one note
Q. Why is knowledge of receptor subtypes important?
- selectivity
Allows drug discovery to create better drugs
(more efficacious, safer)
what are the Actions of mAChR agonists = parasympathetic effects
Bradycardia/reduced cardiac output
Vasodilation
Increases secretion (salivation, lacrimation, sweating)
Bronchoconstriction and bronchial secretion
Increased gut motility
Reduction of intraocular pressure (due to pupillary constriction)
Therapeutic uses of mAChR agonists
- Glaucoma
Glaucoma is due increased intraocular pressure which can damage the eye’s optic nerve and lead to blindness.
Pilocarpine (miotic) used as eye drops to reduce intraocular pressure. Pilocarpine is a tertiary amine which is well absorbed into the conjunctival sac and thus action lasts ~ 1 day - Urinary retention and constipation
Bethanechol has been used to
relieve urinary retention (usually due to failure of normal reflex pathway)
increase gut motility
what is SLUDGE?
Salivation: stimulation of the salivary glands
Lacrimation: stimulation of the lacrimal glands
Urination: relaxation of the internal sphincter muscle of urethra, and contraction of the detrusor muscles
Defecation: relaxation of the internal anal sphincter
Gastrointestinal upset: smooth muscle tone changes causing gastrointestinal problems, including diarrhea
Emesis: vomiting
SLUDGE is caused by mAChR agonists- this is why therapeutics using these agents is limited
Actions of mAChR antagonists
Block secretion -salivation, lacrimation, sweating, bronchial secretion are reduced (can cause dry mouth)
Tachycardia (increased heart rate) - modest effect
Pupillary dilation (mydriasis) and ciliary muscle paralysis (cycloplegia); can lead to increase in intraocular pressure and blurred vision
Inhibits gut motility (can cause constipation)
Paralysis of bladder (can cause urinary retention)
Smooth muscle (except gut) relaxation
CNS effects: excitatory (can cause disorientation, mood swings
Therapeutic uses of mAChR antagonists
These anticholinergic drugs all act as competitive antagonists, but are largely unselective and can cause dry mouth/blurred vision/constipation
Ophthalmic
Tropicamide used clinically to dilate pupils (mydriasis) to aid eye examinations; atropine or cyclopentolate paralyse eye (cycloplegia) to treat inflammation
- Bronchodilation
Orally inhaled (aerosol), short-acting drugs such as ipratropium (t1/2 ~ 2-4 hours) used in acute asthma episodes and longer-lasting, M3/M2-selective tiotropium (t1/2 ~ 10 hours) used in chronic obstructive pulmonary disease (COPD) - Reduce intestinal motility
Atropine or dicycloverine act as smooth muscle relaxants (anti-spasmodic agents) to manage irritable bowel syndrome (IBS) and diverticular disease - Urinary incontinence
Parasympathetic system controls bladder contraction, so antimuscarinics are used to prevent incontinence (‘overactive bladder’ OAB).
Tolterodine and oxybutynin (10 x selectivity for M1 and M3 > M2 receptors) in extended release formulation can be taken once/day. Desirable drugs are selective M3 antagonist eg. darifenacin, solifenacin
- Cardiovascular
Atropine used to treat bradycardia after myocardial infarction- Nausea and vomiting (CNS)
Hyoscine (BAN British Approved Name or RINN Recommended International Nonproprietary Name) (scopolamine, USAN) (e.g. Kwells®) given as transdermal patch or orally to treat motion sickness (acts on the ‘vomiting centre’ in the hind brain medulla) - Parkinson’s Disease (CNS)
In drug-induced PD, dopamine deficiency can cause excessive cholinergic activity eg. trihexyphenidyl hydrochloride - Anaesthesia
Pre-medication to inhibit salivation and bronchial secretion and to cause drowsiness eg. atropine or hyoscine. During surgery to prevent vagal inhibition of the heart eg. atropine or glycopyrronium
- Nausea and vomiting (CNS)
Nicotinic ACh receptor subtypes
muscle
ganglion
cns
molecular form
location
function
agonist
antagonist
check one note
subtypes pf nACH receptors
Peripheral nAChRs are present at (i) autonomic ganglia and (ii) neuromuscular junctions (NMJs) are molecularly distinct.
However, drugs affecting ANS ganglia do not discriminate between sympathetic and parasympathetic nerves
(i) nAChRs at autonomic ganglia
Due to lack of discrimination between sympathetic and parasympathetic ganglia most nACh ligands are therapeutically undesirable; however, nicotine (NiQuitin, Nicorette, Nicotinelle) is used to assist smoking cessation.
Ganglion-blocking drugs (trimetaphan, hexamethonium)
1. Cardiovascular
Effects largely due to block of sympathetic system: vasodilation causes fall
in blood pressure. Trimetaphan was used to produce hypotension in surgery
- GastrointestinaI tract
Effects largely due to block of parasympathetic system: inhibition of motility - Genito-urinary system
Effects largely due to block of parasympathetic system: impairment of micturition
