A pharmacological perspective of the autonomic nervous system

what are the 2 ways a body can respond in terms of the rapid nervous system response

voluntary: the somsatic nervous system acting on skeletal muscle
involunatary: autonomic nervous system acting on cardiovascular system and other organs

how does the body respond slowly with the nervous system to environemntal changes

with hormones, neurotransmitter, growth factors, all changing gene expression leading to long term adaption

what is the tree diagram with the oranisation of the nervous system

what does the autonomic nervous system act on

 heart
- visceral organs and blood vessels (organs containing smooth muscle)
- glands

what is the autonomic nervous system 

- a group of peripheral neurons and fibre connections that control the activty of heart,organs,bloodvessels, glands

- split into sympathetic, parasympathetic, enteric nervous systems

what is the role of autonminc nervous system

• maintain homeostasis by facilitating the response in organ systems to chnaging inertnal or external environement

what is a peripheral effernt neurone

a neurone that carries signals away from the CNS

what is the structure of peripheral effernt neurones

• made up of preganglionic a ganglia ( the cluster of nerve cell bodies outside of the CNS) and post galnglionic neurones

what is the journey of a signal on a peripheral efferent neurone

signal starts at CNS > preganglionic neurone ( releases ACh at th gap which is detected by nictotine ACh receptors at the ganglion ) > post ganglioninc neurone > effector tissues

what is the nervous pathway for the salivary gland

 -found in parasympathetic system

- long preganglionic fibre is releasing ACh onto a nicotinicreceptor on short post ganglionicfibre

- post ganglionic fibre releases ACh onto muscarinic receptor on salivary gland

- this is in example of what a generic parasympathetic neurone is like

what is the nervous pathway for the blood vessel

short preganglionic neuron releases ACh onto nicotinic receptor

- long postganglionic neuron releases noradrenaline (NA) onto adrenergic receptors (alpha and beta)

- exception to the sympathetic nervous system rsponse

what is the nervous pathway for sweat glands

 - short preganglionic neuron releases ACh onto nicotinicreceptors

- long post ganglionic neuron releases ACh onto mucarinicreceptor on sweat gland,

- this hsows a generic sypathetic nervous system 

what is the nervous pathway for adrenal medulla

preganglionic neurone releases ACh onto nicotinic receptor on adrenal medulla

- adrenal medulla releases NA and adrenaline which act on alpha and beta adrenergic receptors

- this shows an exception to sympathetci nervous system

what is the nervous pathway for skeletal muscle

somatic motor neurone releases ACh onto nicotinic receptor on skeletal muscle

what is the function of sympatetic branch of ANS

• ongoing controll of CVS, body temp, bladder relaxation 

• control fight or flight 

• widespread effects as widespread innervation

what is the function of pasympathetic branch of ANS

• digestion 

• excretin 

• helps eyes focus and adjust for near vision

• less widespread innervation and effects

what is the function and locationof enteric branch of ANS 

• found and control the function of Gastrointestinal tract

• its activity is influenced by sympathetic and parasympatehtic nervous system but can also act independently 

• it uses many differnt neurotransmitters

what si the sympathetci nervous system used to respond to 

stress from enviromental factors or viral/bacterial infections where it will coporate with immune systemto make a response

where does the sympathetci nervous system leave the psinal cord

between T1 and L2

where is the symathetic chain ganglia located

on the poserior wall of the ribcage

what does the sympathetic chain ganglia contain and whats its fnction 

• cell bodies of the postganglioninc sympatehtic neurones

• it allows preganlioninc neurones to synapse with many postganglioninc neurones makign a widespread sympathetic actiavtion

do sympathetic post ganglionic fibres exist as seperate nerves, if not how then 

it goes CNS-ganglia-PBS no they are not sperate they form plexuses around carotid arteries ( like a mesh that wraps around the carotid artery )

how do sympathetic fibres ente the skull 

they enter the skull otgtehr with the carotid arteries

how do sympathetci fibres reach the eye,skin,and salivary glands

they reach as plexuses around the arteries that supply the eye,skin and salivary glands

what are the 3 main sympathetic action in the head

mianly pupil dialiation 

blushinng 

reduced salivation

Where does the first neuron in the parasympathetic system arise from?

brainstem or sacral spinal cord, which is why the parasympathetic system can be known as carnio-sacral autonomic outflow

Which nerve provides most of the parasympathetic innervation to the body?

vagus nerve

compare where the ganglion is loacated in the parasympathetic system and the sympathetic system

• parasympathetic: emedded in the target organ 

• sympathetic: its a seperate chain

what type of neruotransmitters do both the preganglionic and postganglionic neurones release in the parasympathetic outflow

cholinergic ( release acetylcholine)

what are the 2 types of cholinergic receptors and whats the order 

• the first receptor used is nicotinic, which is onthe post ganglionic neurones which detects the neurotransmitter from the preganglionic neurone

•  then muscaranic ( g protein linked ) which is on the target tissue detetcting neurotransmitter released from postganglionic neurones

where does the parasympathetci innervation to th ehead travel through

the ceranial nerves III, VII, IX

what are the outcomes ofr the parasymoathetuic system

• ↑ secretion of tears, saliva, and nasal mucus

• Constricts pupil of the eye (miosis)

where are the preganglionic parasympathetic neurones for the head located?

in the cranial nerve nuclei of the brainstem

Where are the postganglionic parasympathetic neurones for the head located?

in many differnt ganglia 

what does sympathetic nervous system regulate, and at what level does it operate

dstribution of blood around the bod
it is tonically active (regulates at low levels) when resting and not stressed

hwo does the sympathetic NS regulate total peripheral resisitance

by continously constricting the arterioles slightly and the level fo contriction is adjusted when needed

what type of axons do the 2 neuones in the sympathetci efferent system have

• preganglionic: small myelinated type b 

• postganglioninc: unmyelinated type c

what are the steps in the signal to controll blood flow in the ysmpathetic neurotransmisiion

• preganglionic neurone(cns) realse ACh to activate postganglioninc neurone 

• postganglioninc neurone release noradrenaline on the arterial of smooth muscle making it contract 

• this is with the action on alpha1 adrenoreceptors 

what are the 2 types of adreno receptors

alpha and beta

what are the subtypes of alpha adrenorecptors

1. alpha 1 

• constricts the vascular smooth muscle 

• relax bladder 

• glycogenolysis 

    2. alpha 2 

• vasconstriction 

• inhibitry feedback on the vasoconstrition doen by alpha receptors 

what are the subtypes of beta receptors

1. beta 1

• work on heart

• help with cardiac contractig

• increase HR, AV node conduction 

• secretion of renin with increases blood pressure 

      2. beta 2 

• work on lungs 

• bronchodialation

• dialation of vasuclar smooth muscles and skeletal muscle arteries 

• relaxing of smooth muscle in the gastointestinal tract 

• inhibit labour in uterous 

• glycgenolysis 

    3. beta 3 

• lipolysis 

• thermogenesis

which type of adrenoreceptors does adrenaline mainly work on

beta receptors

how is dopamine and noradrenaline synethesis in the presynaptic neurone

1. the percursure tyrosine turn into DOPA with the help fo the enzyme tyrosine hydroxylase

2. DOPA chnages into dopamine with DOPA decarboxylase enzyme 

3. dopamine enters the presynaptic vesicle 

4. in the vesicle dopamine adds oh group- beta hydroxylase into nor adrenaline 

explain the release of noradrenaline from the presynaptic neurone

1. an action potential arrives opening the calcium ion chanels 

2. calcium ion enter and fuse with the vesicle 

3. the vesicle is signalled to fuse with the presynaptic membrane and release noradrenaline

4. noradrenaline binds to the androreceptor on the effector cell

what happens to noradrenaline after it binds to the receptor

1. it can go into astrocytes 

2. it can go back into the presunaptic neurone

3.  its metabolised but MOA in just presynaptic neurone and and COT into its metablites in both astrocytes and presynaptic neurone

What are the effects of stimulation of the sympathetic nervous system?

↑ heart rate and cardiac output
- vasoconstriction
- increased renin release from kidney which increases Na+ and water reabsorption
- Bronchodilatation
- ↑ blood glucose and free fatty acids
- pupil dilation
- bladder relaxation
- piloerection
- ↓ in GI motility
- loss of erection in males
- sweating
- ejaculation

What are the effects of stimulation of the parasympathetic nervous system?

- ↓ heart rate
- ↑ gastrointestinal (gastric acid, pancreatic enzymes) and other secretions (salivary glands, lacrimal glands, bronchosecretion)
- ↑ peristalsis (GI contractions which mix and propel GI contents)
- bronchoconstriction
- visual accommodation - focussing
- pupil constriction (meiosis)
- micturition (contraction of detrusor and relaxation of urethra)
-  defaecation
- erection
- regulating production from food and conservation of energy 

what recpetors are used in the postganglionic recpetors of the parasympatejtic nervous system and how many types are there

muscarinic acetylcholine recptors , 5 types M1-M5

what is the fucntion of the M1 muscaranic AChR

•Secretion from salivary glands

•Gastric acid secretion from stomach

•Memory function in brain

what is the function of the M2 muscarinic AChR

•Slows heart, also has CNS effects, eg hypothermia

what is the function of the M3 Muscarinic AChR

Stimulate insulin secretion from pancreatic beta cells

•Bronchoconstriction

•In general, they cause smooth muscle contraction and increased glandular secretions

what is the antagonist ( blocker) for muscaranic AChR and what type of antogonist is it

- atropine
- competitive, reversible, nonspecific ( so can affect any M1-5)

what is the main actions of atropine

Decreases bronchial, GI and other secretions (saliva, tears)

• Causes tachycardia due to block of parasympathetic actions on heart,

• Causes pupil dilation

fill the blanks in comparision 

compare SNS and PNS:

1. Point of origin of connector nerve cells

2. Proximity of autonomic ganglia to target organs

3. Length of postganglionic fibers

4. Extent of activity

5. Type of neurotransmitter used by postganglionic neurons

6. Purpose of activity

1. Point of origin of connector nerve cells

• SNS: lateral horns of spinal cord grey matter (T1-L2)

• PNS: nuclei CN3,7,9,10 and spinal cord grey matter (S2-4)

2. Proximity of autonomic ganglia to target organs

• SNS: distant 

• PNS: close

3. Length of postganglionic fibers

• SNS: long

• PNS: short

4. Extent of activity

• SNS: widespread action on the body  

• PNS: more discrete control 

5. Type of neurotransmitter used by postganglionic neurons

• SNS: noradrenaline

• PNS: acetylcholine

6. Purpose of activity

• SNS: prepares the body for emergencies and severe muscular activity (consumption of energy)

• PNS: conservation and storage of energy

what relex stabilises the blood pressure by cooperation between the SNS and PNS?

barorecptor reflex

how are the barorecptors activated and what do rhey signal too 

stretching of the aorta and carotid arteries actiavtes them 

they signal to the nucleas tractus soslitarious (NTS) in the medulla

explain the baro receptor reflex 

• 
  bara receptor in aorta and cartif artery 

• when BP rises aterteries strech which is detected by baro recptors hwich send signals to NTS in the medulla 

• if BP is too high

• ↑ Parasympathetic which leads to  ↓ heart rate → ↓ cardiac output (CO)

• ↓ Sympathetic which leads to

          - ↓ heart rate and force which  ↓ CO
          - ↓ arterial constriction which ↓ total peripheral resistance

(TPR)
          - ↓ venous constriction which ↓ venous return & CO

• Since BP = CO x TPR, BP decreases back to normal 

• if BP was too lwo the opposite would happen, sympathetic increases parasympathetic decreases

what branch of the autonmic nervous system is a physiological regulator of salivation 

parasympathetic NS

describe the parasympathetic pathway controlling salivation including: 

• what stimulates it 

• where it orginates 

• the pathway 

• the effect 

1. salivation is triggered by taste, touch, sight, and smell of food.

2. the preganglionc fibres start in the salivary nuclei of the brain stem

3. tehy travel in the cranial nerve VII in submandinular ganglion and cranial nerve IX in otic ganglia 

4. they signal leaves the ganglia and innervates the salibary glands

5. the neurtransmitter releases ACH which acts on M3 muscarinic receptors 

6. this leads to secretion of saliva for digestion and lubrication 

which type of drug reduces salivation causing dry mouth and how 

• drugs that ahve anticholinergic action which blocks the muscarininc recpetors

• e.g 

• Muscarinic blockers: oxybutynin, tolterodine

• α-blockers: terazosin, tamsulosin

• Tricyclic antidepressants: imipramine

• Antipsychotics: olanzapine (but clozapine ↑ saliva)

• Antihistamines

where is the Enteric Nervous System located 

from the mouth to anus 

what neuroens are found at the enteric plexuses

• sensory afferent neurones

• interneurones 

• secretomotor neurones 

• motor nerones

what autonmic nerves influence the enteric nervous system and what do they do 

sympathetic and parasmpathetic effernt nerves, they ste the tone which is the level of activity 

what are the 2 main plexus in the enteric nervous system and what do they control 

1. myenteric plexus: smooth muscle contraction and peristalis( contraction to move food) 

2. submucous plexus control secretion in Gastrintestinal tract

what are NANC

non andrenergic non cholinergic neurotransmitters used in NAS

what is co transmission in the ANS

when neurones release extra neurotransmitters along with ACh and NA

Give an example of sympathetic NANC transmission.

Postganglionic sympathetic fibres release NA + ATP + neuropeptide Y → causes vasoconstriction.

Give an example of parasympathetic Non Androgenic Non cholinergic transmission.

Postganglionic parasympathetic fibres release nitric oxide (NO) + vasoactive intestinal peptide (VIP) → causes smooth muscle relaxation.