NEURO- physiology and pharmacology of the autonomic nervous system Flashcards
outline the effect of the fear / flight / fight response on the body
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
outline the effect of the sympathetic nervous system on the heart
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
outline the effect of the sympathetic nervous system on the blood vessels
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
outline the effect of the sympathetic nervous system on the kidney
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
outline the effect of the sympathetic nervous system on the metabolism - liver and skeletal
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)
outline the effect of the sympathetic nervous system on the pancreas
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
outline the effect of the sympathetic nervous system on the adipose tissues
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
outline the effect of the sympathetic nervous system on the GI tract
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
outline the effect of the sympathetic nervous system on the eye
stimualtion of alpha adrenorecptors on dilator pupils cause dialtion of the pupil
leads to more light on the retina
leads to more accurate sight
outline the effect of the sympathetic nervous system on the lungs
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
outline the effect of the sympathetic nervous system on the sweat glands
release of ach acting at muscarinic receptors induces sweating
leads to temperature control during fear / flight / fight
describe noradrenaline release and termination
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
what is the negative feedback mechanism of NA
too much NA - acts on alpha -2- receptors on presynaptic membrane stimulates the switching off of the neurotransmitter release from presynaptic terminal
outline how the NA release, termination, and storage is affected directly
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
outline the alpha-1- associated intracellular pathway
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
outline the alpha-2- associated intracellular pathway
gi
decreases AC - reduces cAMP - reduces - leads to inhibition of sympathetic nervous system via reducing NA release
outline the beta-1,2,3- associated intracellular pathway
gs
increase AC - increase cAMP - increase PKA - leads to increased:
heart / renal (b1)
inhibition:
smooth muscle (b2) - airways / bv
bladder / fat (b3)
outline the rest and digest response on the body
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
describe the effects of stimulating the PNS on the heart
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
describe the effects of stimulating the PNS on the GI tract
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
describe the effects of stimulating the PNS on the eye
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
describe the effects of stimulating the PNS on the lungs
M3 receptors contracts bronchial smooth muscle cells causing bronchoconstriction
Ach
describe the effects of stimulating the PNS on the secretory glands
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
describe the effects of stimulating the PNS on the male genitalia
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
what is the mechanism of action of sildenafil
erectile-dysfunction - prevents breakdown of the actions of NO - increasing the vasodilator effects
outline the bladder control interactions between parasympathetic, sympathetic, motor and sensory nerves
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
describe the cholinergic transmission at synpases
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
outline how synthesis, release and termination of Ach is altered by drugs
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
outline the types of acetylcholinesterase inhibitors
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
outline cholinergic receptor subtypes and their associated intracellular pathways
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
outline the most clinically relevant drugs at NIC receptors
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
outline the most clinically relevant drugs at muscarinic receptors
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
