Introduction to the ANS Flashcards
What is meant by pharmacodynamics
What drugs do to the body- their effects
What is meant by pharmacokinetics
How the body responds to the drugs (metabolism, excretion)
Describe the basic function of the ANS
Peripheral functions- not conscious
What are the 3 outputs (branches) of the CNS
§ There are 3 branches to the CNS; the ANS, the somatic nervous system and the neuroendocrine syste
What does the ANS act on
exocrine glands smooth muscle cardiac muscle metabolism host defence
What does the somatic nervous system act on
skeletal muscle,
including the diaphragm and respiratory muscle
What does the neuroendocrine system act on
growth, metabolism, reproduction, development,
salt & water balance,
host defence
List some examples of the ANS in action
§ Some targets of the ANS include:
o Pupillary constriction – constriction mediated by the PNS via the oculomotor nerve (CNIII).
o Cephalic and gastric phases of digestion – vagal nerve PNS mediation.
o Basal heart rate – PNS is dominant at rest (as the intrinsic rate is 100-110bpm which isn’t normal at rest) however as baroreceptors stretch less as BP drops, less inhibition of SNS leading to increased heart rate.
Describe the effect of reduced baroreceptor firing
Loss of fluid (e.g excessive sweating)- BP decreases- decreased rate of firing of arterial baroreceptors- therefore less inhibition of sympathetic neurones- the sympathetic neurone (split into two branches) can then act to increase heart rate, increase BP (vasodilation) and increased force of contraction of the heart
Do all targets have PNS and SNS innervation
Note that most targets in the body receive BOTH PNS and SNS innervation BUT some targets only receive one type branch of the ANS – examples include the blood vessels (only the SNS innervates).
2 opposing effects in blood vessels - NA constricts, histamine dilates
Lungs only receive PNS- dilation is by adrenaline in fight or flight response
Effects of ANS on the eye
Dilatation (Pupil) - symp
Constriction (Pupil)- para
Contraction (Ciliary Muscle)- para
Effects of ANS on trachea and bronchioles
Dilates (Ad)
Constriction- para
Effects of ANS on liver
Glycogenolysis
Gluconeogenesis
Both symp
Effects of ANS on adipose
Lipolysis- symp
Effects of ANS on kidney
Increased renin secretion- symp
Effects of ANS on bladder and ureters
Relaxes detrusor; constriction of trigone and sphincter (symp)
Contraction of detrusor; relaxation of trigone and sphincter (para)
Effects of ANS on salivary glands
Thick, viscious secretion- sympathetic
Copious, watery secretion - para
Effects of ANS on skin
Piloerection - symp Increased sweating (C)- symp (cholinergic)
Effect of ANS on heart
Increased rate and contractility- symp
Decreased rate and contractility- para
Effect of ANS on G.I system
decreased motility and tone, sphincter contraction- symp
increased motility and tone, increased secretions- para
Effect of ANS on blood vessels
to skeletal muscle- dilatation- symp
to skin, mucous membranes and splanchnic area)- constrition- symp
Summarise the characteristics of the PNS
o Has LONG pre-ganglionic fibres and SHORT post.
o ALL transmitters are ACh.
o Is DISCRETE – 1:1 pre- vs. post-.
Summarise the characteristics of the SNS
o Has SHORT pre-ganglionic fibres and LONG post.
o Releases mainly A and NA.
o Is DIVERGENT (mass discharge) – 1:20 pre- vs. post
Describe the exemptions of the SNS
ADRENAL GLAND- beaves like post-ganglionic fibre- only peripheral tissue to function like an autonomic nerve- 80% A and 20% NA
Sweat gland- Post ganglionic fibre releases Ach
Explain the exemption of the sweat gland
PSNS is involved in secretions- sweat is a secretion- but sweat needs to be SNS- so Ach was retained in evolution- despite being a SNS response
Why is it important that many pre ganglionic sympathetic fibres can have an effect on many post ganglionic fibres
SNS is involved in stress response- 1 pre ganglionic : many post ganglionic- multiple effects required
increase sweat with increased HR, BP and blood flow, whilst decreasing gut secretions
Summarise the enteric nervous system
network of neurones responding to the gut environment- can communicate and determine response- local signals- no need for brain - but ANS can influence ENS
Describe the enteric sensory neurones in action
Sensory neurone connected to mucosal chemoreceptors and stretch receptors detect chemical substances in the gut lumen or tension in the gut wall caused by food.
Information relayed to submucosal and myenteric plexus via interneurons.
Describe the enteric motor neurones in action
Motor neurones release acetylcholine or substance P to contract smooth muscle or vasoactive intestinal peptide or nitric oxide to relax smooth muscle.
Summarise the somatic nervous system
§ Very simple – just long neurones with eventual ACh release.
What are the Ach receptors
membrane bound- muscarinic or nicotinic
Summarise nicotinic receptors
At all autonomic ganglia
Stimulated by nicotine/acetylcholine
c) Type 1 - Ionotropic
Why is it important that nicotinic receptors are type 1- ionotropic
Swift signal- impoartant fasted method
ganglia linking pre to post
ligand binds (Ach leading to Ca2+ or Na+ influx in post ganglionic fibre)
Summarise the muscarinic receptor
At all effector organs innervated by
post ganglionic parasympathetic fibres and cholinergic sympathetic (sweat glands)
b) Stimulated by muscarine/acetylcholine
c) Type 2 – G-protein coupled
Summarise GPCRs
7-TM receptor
associated G-protein activated- starting I.C machinery (second messenger)- activation of cell signalling
Which of the following effects would be observed after blockade
of nicotinic acetylcholine receptors in an individual at rest?
Constipation- due to blockage of PNS- can’t act on effectors
What effect would blockade of nicotinic acetylcholine
receptors have on heart rate;
At rest
During exercise
At rest- PNS is dominant- so HR will increase if PNS is blocked
During exercise- SNS is dominant during exercise- less of an increase (nicotinc receptor at pre-ganglionic sympathetic neurone blocked)
List the su-types of muscarinic cholioceptors
M1 – Neural (Forebrain – learning & memory)
M2 – Cardiac (Brain – inhibitory autoreceptors)
M3 – Exocrine & smooth muscle (Hypothalamus – food intake)
M4 – Periphery: prejunctional nerve endings (inhibitory)
M5 – Striatal dopamine release
Summarise adrenoreceptors
§ Found at all effector organs innervated by post-ganglionic SNS fibres (not sweat glands).
§ Stimulated by noradrenaline/adrenaline.
§ Type 2 – G-protein coupled.
Describe the location of the different adrenoreceptors
alpha 1- smooth muscle in blood vessels and bronchi, dilator pupillae- contraction
alpha 2- smooth muscle in blood vessels, presynaptically on adrenergic synapses- reduced NT release
beta 1- heart muscle, presynaptically on adrenergic symapses- increased HR and force of contraction, increased NT release
beta 2- smooth muscle in blood vessels and bronchi- relaxation
What do we need to consider for all drugs
What is the drug target?
e.g M3 muscarinic receptors
- Where is the drug target?
e. g gastric S.M, Paneth cells, endocrine cels - What is the end result
of the interaction?
contraction, increased acid production, increased gastrin secretions
What happens when the NT binds to its receptor
it activates it and then it unbinds
Why do we have mechanisms to remove the NT
Don’t want permanent activation
Want effect to be short lived
rapid activation with quick deactivation
Describe the biosynthesis of Ach
Acetyl coA (from mitochondria) + choline — Ach + CoA ( Choline acetyltransferase)
Ach is packaged into vesicles – action potential leads to Ca2+ influx- binds to vesicles- transported to pre-synaptic membrane- Ach released
Describe the metabolism of Ach
Ach can bind to post-synaptic receptor or to acetylcholinesterase (lots of this enzyme- eventually they will all bind to it) Ach converted to choline and acetate
choline taken back up by the nerve terminal- to make more Ach
Describe the biosynthesis of NA
Tyrosine is the precursor (delivered to nerve terminal by blood)
converted to DOPA ( Tyrosine hydroxylase)
DOPA — Dopamine ( DOPA decarboxylase)
Dopamine is packaged into a vesicles
Dopamine — NA (Dopamine B hydroxylase)
Release as normal
Describe the metabolism of NA
No enzyme in the synapse of sympathetic neurones- longer lasting effect
Uptake 1 protein- takes NA back into the pre-synaptic neurone- where it is then metabolised
converted to metabolites in the mitochondria by Monoamine oxidase A- MAO-A
Uptake 2- NA taken into the post synaptic neuron- degraded by COMT (Catechol-O-methyltransferase)
Consequence of blocking enzymes that metabolise NA
Increase NA in pre and post-synaptic neurone (reducing conc gradient)- more NA in synapse- less moves back in by transporter
