Physiology and Pharmacology of the Parasympathetic Nervous System Flashcards
Physiology of Parasympathetic Nervous System
hr? eye? bladder? Gi motility? lungs?
Parasympathetic can be thought of as a ‘worker’, keeping the our body ticking over while we go about our normal daily business
Often described as controlling ‘’Rest and digest’’
e.g.
Slowing heart rate : Rest
Accommodation of the eye : Rest (newspaper reading)
Bladder : micturition : Rest (time for a pee)
GI tract motility/secretions : Time for eating / digestion
Bronchoconstriction : Rest, less O2 intake required
Effects on eye, bladder, GI tract, airways are all caused by contraction of smooth muscle cells
General structure of parasympathetic nervous system
where are nerves? cranial 3 - name and innervate cranial 7 - name and innervate cranial 9 - name and innervate cranial 10 - name and innervate
which sacral nerves and innervates what?
length? neurotransmitters and receptor?
brain stem/crainal nerves + sacral nerves
III oculomotor nerve -> eye
vII facial nerve -> lacrimal, sub-mandibular and sub-lingual glands
IX glossophagneal nerve -> parotid glands, pharynx
X vagus nerve -> airways, heart, stomach, liver and pancreas
S2-S4 -> bladder, genitalia, large intestine
Long pre-ganglionic + short post-ganglionic
Ach to NIc and Ach to Mus
Heart
stimulation of what nerve? release what? acts where?
effect? (2)
what does it not have an effect on?
exception where it release NO and not ach?
Stimulation of vagus nerve releases Ach which acts at M2 receptors
Lower Frequency of pacemaker potential at SA node leading to reduction in heart rate
Lower electrical conduction through atria-ventricular node
to balance reduction in heart rate to contraction
From : CO = HR x SV
Stimulation of vagus nerve (Lower HR) will decrease CO
Parasympathetic nerves do not innervate ventricles and most blood vessels So do not affect heart contractility or total peripheral resistance
Exception : male genitalia, where release of NO (not Ach)
causes dilatation of vessels to cause erection
Eye
what does parasympathetic nerves regulate (3)?
what receptor is stimulated? effect (2) (what is opened up and effect?)
what does sympathetic effect?
Parasympathetic nerves are the major influence in regulating:
Pupil diameter, Intra-ocular pressure, Accommodation (Focusing)
Pupil diameter
Stimulation of M3 receptors lead to constriction of the circular smooth muscle of the iris (constrictor pupillae)
Constrict of the pupil (miosis)
Intra-ocular pressure
Constriction of the pupil (M3) has a secondary action
of opening the canal of Schlemm at the back of the pupil
Drains aqueous humour from eye
Reducing pressure within the eye
parasympathetic contract smooth and sympathetic contract radial
How do parasympathetic nerves control accommodation of the eye?
distant vision - cillary muscle? suspensory ligaments? lens? focal length?
close vision - cillary muscle? suspensory ligaments? lens? focal length?
what do lens do?
what are lens held by? what does cranial nerve 3 control?
Distance vision Ciliary muscle relaxed Suspensory ligaments taut (hence tight/stretch out) Long thin lens Long focal length
Close vision Ciliary muscle contracted Suspensory ligaments relaxed Bulged lens shape Reduced focal length
Lens allow light to pass therefore sharp image on retina
Lens is held by suspensory ligaments linked to cillary body which contain cillary muscle controlled by parasympathetic nerves (occulomotor III)
Bladder
what does bladder voiding involve a series of interactions between?
what controls this in the brain?
where does it send info?
what receptors? what effect do they have?
what happens once bladder is full?
what does this do?
where does info go this time?
what receptor is innervated?
what is external sphincter? hence?
Bladder voiding involves a series of interactions between parasympathetic, sympathetic, motor and sensory (afferent) nerves
From brainstem/micturition centre a nerve will go to the lumbar region of the spinal cord from which a sympathetic nerve will go to the B2 receptors on the smooth muscles of the bladder and make it relax so it can fill and targets the a1 receptors of the internal spincter smooth muscles so stay contracted and closed hence: Sympathetic nerves Detrusor muscle relaxed (Fill) Sphincter contracted (Hold urine) Prevent micturition
Once bladder is full, it will stimulate stretch receptors on which send an impulse to the micturition centre in the brain to activate the micturition reflex hence stimulate the parasympathetic and inhibit the sympathetic nerves.
A nerve impulse will go to the sacral region of the spinal cord where a parasympathetic nerve will innervate the m3 receptors of the smooth wall leading to a contraction. A motor nerve will also innervate the external sphincter which has skeletal muscle hence it is a voluntary action. Innervates the nic receptor so contract will hold urine and relax will void urine,
GI tract
stimulation of what nerve?
release?
act on?
effect?
Stimulation of vagus nerve releases Ach which acts on M3 receptors
Contraction of circular and longitudinal smooth muscle in GI tract
Increased motility
Vagus also contains afferent (sensory) fibres – peristaltic reflex control
GI Tract - secretions
Salivary glands - nerve? stimulate? release?
gastric glands - nerve? stimulate? release?
pancreatic glands - nerve? stimulate? release?
pancreas - nerve? stimulate? release?
Salivary glands - VII (facial) & IX (glossopharyngeal)
- stimulate acinar cells - increase amylase / mucins
Gastric glands - X (vagus)
- stimulate parietal cells - increase gastric acid
Pancreatic glands - X (vagus)
- stimulate acinar + islet cells - increase pancreatic secretions
Pancreas - X (vagus)
- increase insulin secretion from beta-cells
Lungs
stimulate?
effect?
antagonists effect?
example drug? used in?
caution for glaucoma? why?
Stimulation of M3 receptors contracts bronchi smooth muscle cells causing bronchoconstriction
Thus,
Muscarinic antagonists are used as bronchodilators to increase airflow
e.g. Ipratropium
Used in COPD (chronic obstructive pulmonary disease)
Need to increase airway flow
Caution
In patients with bladder outflow problems and glaucoma
Mus antagonist will reduce urine outflow, increase intraocular pressure
Conditions also associated with elderly (as is COPD)
These are potential contraindications
Male genitalia
nerve from where?
release?
effect on what? hence effect?
drug ? how does it work?
Specialised sacral parasympathetic ‘vasodilator’ nerves
innervate erectile tissue
Stimulation of these nerves release nitric oxide (NO) NOT Ach
Remember this is an exception to the normal rule
NO is a lipophilic, membrane-permeable gas
NO causes relaxation of vascular smooth muscle cells
composing the corpus cavernosum
Corpus cavernosum dilates and fills with blood
Produces and maintains erection
Sidenafil (Viagra) - erectile-dysfunction, prevents breakdown of the actions of NO – increasing it vasodilator effects
How do M3 receptors cause contraction of smooth muscle?
what kind of g protein?
what binds to these receptors?
effect on molecules produced? (2)
where is M3 receptors expressed? (3)
Ach will bind to the M3 receptor activating thr Gq pathway hence PIP2 will convert to DAG and IP3 via PLC
DAG will act on NA+ ion channels to increase membrane permeability so there’s more of a NA+ influx which will cause a depolarisation and activate VGCC so there is a Ca2+ influx
IP3 will attach onto a IP3 receptor on SR causing Ca2+ to be released from stores.
Hence there is an increased Ca2+ release via 2 mechanisms which will lead to Ca-calmodulin and myosin light chain kinase (MLCK) and to a contraction via actin/myosin interactions
M3 receptors expressed in GI / eye / broncho smooth muscle cells
Cholinergic synapse
what breaksdown Ach?
synthesis of acetylcholine = chaT
Ach released to the synpatic cleft where it will bind to the NI, M2 or M3 receptors (Nic receptor – skeletal muscle (NMJ), ganglia (ANS), and Mus receptors – e.g. Heart (M2), smooth muscle (e.g. M3 in airways/eye etc))
After the action, ach Esterase breaks down Ach and chlonie is re-upaten to synthesise Ach again.
Biological response
e.g. decrease heart rate, bronchoconstriction, skeletal muscle contraction
Direct and Indirect Regulation of Cholinergic Transmission
ChaT inhibitor?
Mus agonists?
Ach esterase inhibitors?
direct vs indirect?
Synthesis of Acetylcholine
ChAT inhibitor
Indirect cholinergic inhibitor
Mus receptors agonists acting as direct parasympathomimetics
Acetylcholinesterase (AchE) inhibitors acting as indirect
parasympathomimetics
Direct – Drugs that act at cholinergic receptors
Indirect – Drugs that act at altering release/termination of transmission
Synthesis of Acetylcholine
Drugs
occurs where?
equation for ach formation? via what?
where is components made from?
chats inhibitor example? effect?
Occurs in NMJ, ganglia, parasym post-ganglionic fibres, CNS
Choline + Acetyl CoA -> Acetylcholine + CoA
via Choline acetyltransferase (ChAT)
Choline : From diet (liver, fish)
Taken up by choline carrier at pre-synaptic terminal
Acetyl CoA : Produced by cellular respiration
ChaT inhibitors (e.g. fa64a) are potentially v dangerous Biological weapons
Changes in choline levels and acetyl CoA production will both alter Ach levels/cholinergic transmission
Link Ach synthesis to metabolic activity
Cholinergic Transmission - Release
drugs
effect? hence what effects?
example of drug? effect? use of effects (2)
Decrease cholinergic actions
e.g. Produce tachycardia, dry mouth, blurred vision, GI tract disturbance, skeletal muscle paralysis
Clostridium botulinum – causes botulism
Bacteria produces toxin (1kg enough to kill world population)
Toxin enters terminals and degrades Ach-containing vesicles
ANS and motor fibres are inhibited – paralysis Clinical Scenario?
Botox - Very low levels of botulinum toxin used to produce local paralysis (cosmetic, clinical uses)
Also, used to prevent excess sweating (hyperhidrosis)
