NEURO- physiology and pharmacology of the autonomic nervous system

Question 1

outline the effect of the fear / flight / fight response on the body

Answer 1

sympathetic nervous system

acts on heart, blood vessels, kidney, metabolism, lungs, eye, sweat glands, GI

increase HR and contractility

increase constriction of blood vessels

diverts blood flow to skeletal muscle

increased air into the lungs

dilation of pupils

increased fuel in muscles

increased sweating

decreased non-essential functions

Question 2

outline the effect of the sympathetic nervous system on the heart

Answer 2

noradrenaline released by sympathetic nerves / adrenaline in circulation act on beta-1 adrenoreceptors

receptors are found in the SA node (increase frequency of pacemaker potential), conduction system (increase rate of impulses through atria into ventricles) and muscle cells (increase force of contraction)

increases CO

Question 3

outline the effect of the sympathetic nervous system on the blood vessels

Answer 3

noradrenaline / adrenaline acts at alpha 1 adrenoreceptors

receptors found in arteries (constriction - increase TPR and diverts blood to needed areas)

veins - constriction of veins - increases return of blood to the heart (starlings law)

stimulation of beta 2 receptors on skeletal muscle arteries and coronary arteries causes vessels to dilate - increases blood flow to heart and skeletal muscle

Question 4

outline the effect of the sympathetic nervous system on the kidney

Answer 4

noradrenaline acts at beta-1- receptors found on the kidney which releasees renin

renin leads to the production of angiotensin II which causes increased BP and CO via:

constriction of arterioles
release of aldosterone from adrenal cortex which stimulates the increase of Na absorption which in turn increase water retention increasing blood volume

Question 5

outline the effect of the sympathetic nervous system on the metabolism - liver and skeletal

Answer 5

need increased ATP for fear / flight / fight response

liver and skeletal muscle

stimulation of alpha / beta receptors breaks down glycogen into glucose (glycogenolysis)

promotes glucose synthesis (gluconeogeneisis)

Question 6

outline the effect of the sympathetic nervous system on the pancreas

Answer 6

stimulation of alpha / beta receptors

decrease insulin hormone from beta cells decreases glucose uptake

prevents insulin form inhibiting glycogenolysis, gluconeogenesis and lipolysis
leads to increase in glucagon hormone from alpha-cells
leads to increase on conversion of glycogen to glucose

Question 7

outline the effect of the sympathetic nervous system on the adipose tissues

Answer 7

stimulation of beta adrenoreceptors

increase lipolysis - turns triglycerides into free fatty acids and glycerol

free fatty acids - beta- oxygenation into acetyl CoA which enters the Krebs cycle

glycerol - recycled back into glycolysis pathway

both increase ATP yields

Question 8

outline the effect of the sympathetic nervous system on the GI tract

Answer 8

stimulation of alpha / beta adrenoreceptors induces inhibition of GI motility

activation of alpha 1- adrenoreceptors evokes contraction of bladder sphincter - holds in urine

beta -2- adrenoreceptors induces relaxation of smooth muscle allowing filling - hold more urine

bowel / bladder function is non-essential during fear / flight / fight

Question 9

outline the effect of the sympathetic nervous system on the eye

Answer 9

stimualtion of alpha adrenorecptors on dilator pupils cause dialtion of the pupil

leads to more light on the retina

leads to more accurate sight

Question 10

outline the effect of the sympathetic nervous system on the lungs

Answer 10

do not receive sympathetic innervation - only parasympathetic

bronchioles have beta 2 adrenoreceptors which are activated by circulating adrenaline - produces bronchodilation - leads to facilitation of breathing

Question 11

outline the effect of the sympathetic nervous system on the sweat glands

Answer 11

release of ach acting at muscarinic receptors induces sweating

leads to temperature control during fear / flight / fight

Question 12

describe noradrenaline release and termination

Answer 12

NA synthesised into vesicles

vesicles fuse with synaptic membrane and release NA into the synaptic cleft - diffuses down concentration gradient to post synaptic membrane

acts on alpha 1 / beta 1 / 2 receptors - stimulates biological response

NA can either be taken back into presynaptic terminal by uptake transporter - either recycled into vesicle or broken down by monoaminoxidase

Question 13

what is the negative feedback mechanism of NA

Answer 13

too much NA - acts on alpha -2- receptors on presynaptic membrane stimulates the switching off of the neurotransmitter release from presynaptic terminal

Question 14

outline how the NA release, termination, and storage is affected directly

Answer 14

storage - modulate storage on NA - prevent storage in vesicles

reserpine prevents the storage of NA in vesicles = more NA in the cytoplasm = more breakdown by MAO = less NA release = less biological response

facilitation of release - amphetamines / ephedrine -works by reversing the NA uptake transporter = more NA in cleft = more biological response

inhibition of release - guanethidine / clonidine / alpha methyl dopa:
guanethidine - competes with NA for inclusion into the vesicles = less NA release = reduced biological effect
clonidine /amd - stimulates alpha-2- receptors on pre-synaptic membrane - cause less NA release by stimulating negative feedback = less release

termination - cocaine / moclobemide / imipramine -
cocaine / imipramine - inhibit uptake transporter - less NA taken up = more stimulation
moclobemide - block MAO - NA not broken down = more NA in vesicles = more stimulation

Question 15

outline the alpha-1- associated intracellular pathway

Answer 15

g protein coupled receptor

gq

increase activity of phospholipase C - intracellular messengers IP3 and DAG- increase Ca uptake - increased PKC activity - contraction of smooth muscle

Question 16

outline the alpha-2- associated intracellular pathway

Answer 16

gi

decreases AC - reduces cAMP - reduces - leads to inhibition of sympathetic nervous system via reducing NA release

Question 17

outline the beta-1,2,3- associated intracellular pathway

Answer 17

gs

increase AC - increase cAMP - increase PKA - leads to increased:
heart / renal (b1)

inhibition:
smooth muscle (b2) - airways / bv
bladder / fat (b3)

Question 18

outline the rest and digest response on the body

Answer 18

slower heart rate
accommodation of the eye
micturition - time for a pee
GI tract motility / secretions - time for eating / digestion
bronchoconstriction - less oxygen intake required

all effects are caused by the contraction of smooth muscle cells

Question 19

describe the effects of stimulating the PNS on the heart

Answer 19

stimulation of the vagus nerve releases ACH which acts at M2 receptors causing

decrease in HR
decrease in pacemaker potential at SA node
decrease in electrical conduction through atria-ventricular node

as the parasympathetic nerves do not act on the ventricles / blood vessels they do not affect contractility / TPR - EXCEPTION - male genitalia - NO causes dilation of vessels to cause erection

Question 20

describe the effects of stimulating the PNS on the GI tract

Answer 20

stimulation of vagus nerve acts at M3 receptors

causes contraction of circular and longitudinal smooth muscle in GI tract

increases motility
vagus also contains afferent fibres- peristaltic reflex control

also contains enteric nervous system

Question 21

describe the effects of stimulating the PNS on the eye

Answer 21

PNS - major regulator of pupil diameter, intraocular pressure, accommodation

pupil diameter - stimulation of M2 receptors leads to constriction of circular smooth muscle of iris

intraocular pressure - M3 - opens canal of Schlemm at back of pupil - drains aqueous humour from the eye - reduces pressure

accommodation - M3

long distance vision - ciliary muscle relaxed - suspensory
ligaments taut - long focal length

close vision - ciliary muscles contracted - suspensory ligament relaxed

Question 22

describe the effects of stimulating the PNS on the lungs

Answer 22

M3 receptors contracts bronchial smooth muscle cells causing bronchoconstriction

Ach

Question 23

describe the effects of stimulating the PNS on the secretory glands

Answer 23

salivary glands - VII and IX - stimulate acinar cells - increase amylase / mucins

gastric glands- X - stimulate parietal cells

pancreatic glands - X - stimulate acinar cells + islet cells

pancreas - X - increase insulin secretion from beta cells

Question 24

describe the effects of stimulating the PNS on the male genitalia

Answer 24

stimulation releases NO not Ach
NO is lipophilic, membrane-permeable gas
Causes relaxation of vascular smooth muscle cells composing corpus cavernosum 
fills with blood
produces and maintains erection

Question 25

what is the mechanism of action of sildenafil

Answer 25

erectile-dysfunction - prevents breakdown of the actions of NO - increasing the vasodilator effects

Question 26

outline the bladder control interactions between parasympathetic, sympathetic, motor and sensory nerves

Answer 26

parasympathetic release Ach - M3- contraction

sympathetic release Na- B2- relaxation

sympathetic - release Na - act on A1 - contraction of sphincter

external sphincter = controlled by skeletal muscle

brainstem micturition centre - lumbar region

sensory neurones - detect bladder is full - send info to brainstem - causes switching off of sympathetic response (lumbar) - switching on of parasympathetic response (sacral) - vice versa when empty

Question 27

describe the cholinergic transmission at synpases

Answer 27

synthesis of Ach from choline - Ach packaged into vesicle

docked and released into the synaptic cleft -

acts at NIC /M2/ M3 receptors - causes biological response

M2- decrease in HR
M3- bronchial constriction
NIC- skeletal muscle contraction

Question 28

outline how synthesis, release and termination of Ach is altered by drugs

Answer 28

synthesis - occurs at NMJ, ganglia - via choline acetyltransferase (ChAT)
ChAT inhibitors and also changes in Ch /acetyl- CoA can affect synthesis

release
decrease causes tachycardia, dry mouth, blurred vision, GI tract disturbance, skeletal muscle paralysis
clostridium botulinum - toxin enters terminals and degrades Ach containing vesicles

inhibition - Ach-esterase inhibitor - prevents breakdown and resorption of Ach into presynpatic terminal = more Ach into synpase = increase response

Question 29

outline the types of acetylcholinesterase inhibitors

Answer 29

short acting - diagnostic - briefly increasing Ach levels = improve muscle response

medium acting - reverse neuromuscular block (given during surgery) - increasing Ach will outcompete blockers

long acting - novichok - bind to enzyme and cause a structural change meaning it cannot work anymore - cure = new AchE synthesis

Question 30

outline cholinergic receptor subtypes and their associated intracellular pathways

Answer 30

NIC- ligand gated - Na influx = contraction of skeletal muscle

M2- Gi - decrease in AC - decrease in cAMP/ PKA - inhibits HR

M3- Gq- increase PLC, increase IP3/DAG - calcium influx and increase in PKC - contraction of smooth muscle

Question 31

outline the most clinically relevant drugs at NIC receptors

Answer 31

agonist - poor dissociation - stays at site for a long time - produces EJP sustained depolarisation = Na VGC become inactivated = prevents AP generation = paralysis

completive antagonists - bind to receptor and prevent action of Ach

both used during surgery

Question 32

outline the most clinically relevant drugs at muscarinic receptors

Answer 32

agonists

M3- pilocarpine- glaucoma - contracts ciliary muscles - open aqueous canal - increase aqueous outflow from eye - reduced pressure

M3 - bethanechol- bladder - contracts detrusor muscle - avoids voiding bladder

antagonists

M3 - ipratropium - Asthma - relaxation of smooth muscle

Atropine - increase HR after MI induced bradycardia

hyoscine - M3- reduces intestinal spasm - prevents stimulation of vomiting centre in brainstem

solfenacin (M3) - decrease detrusor muscle activity