autonomic physiology and pharmacology Flashcards
what’s the difference between autonomic and somatic nervous system efferent pathways?
somatic - to skeletal muscle
autonomic
- ganglion split into pre-ganglionic (small myelinated) fibre and post-ganglionic (unmyelinated) fibre
- goes to smooth muscle, cardiac muscle, glands, GI neurones
whats the difference between autonomic and somatic nervous system target connection?
somatic
- specialised neuron muscular junction
- alpha motor neurons release ACh directly onto the nicotinic receptors on the end plate
- ionotropic receptors with integral ion channels, depolarization always excites the skeletal muscle
autonomic
- neurotransmitter released from varicosities
- metabotropic receptors (G-protein coupled), they either depolarize or hyperpolarize
describe the outflow from CNS and location of ganglia of parasympathetic nervous system (rest and digest system):
Cranio-sacral outflow (in the brain and sacrum)
Ganglia lie close to or near the target
(long preganglionic fibres & short postganglionic fibres)
what are 2 autonomic neurotransmitters?
Acetylcholine acts on cholinergic receptors
e.g. Nicotinic receptors (ionotropic) & Muscarinic receptors (metabotropic)
Noradrenaline acts on adrenergic receptors
e.g. alpha receptors & beta receptors
describe the outflow from CNS and location of ganglia of sympathetic nervous system (fight or flight system):
Thoracolumbar outflow (in thoracic and lumbar segments)
(T1-T12 & L1-L2)
Ganglia close to the spinal cord in the sympathetic trunk
(para-vertebral ganglia)
(short preganglionic fibres & long postganglionic fibres)
all preganglionic fibers release acetylcholine, which acts on nicotinic cholinergic receptors.
what do parasympathetic and sympathetic post ganglionic fibers release?
parasympathetic - acetylcholine which acts on cholinergic muscarinic receptors on the target.
Sympathetic postganglionic fibres release noradrenaline, which acts on either alpha or beta-type adrenergic receptors.
What is the one exception to preganglionic fibres that go straight through?
There is one exception of preganglionic fibres that go straight through
sympathetic trunk → celiac ganglia → postganglionic cells on adrenal gland
This releases adrenaline & noradrenaline into the blood.
(mass hormonal activation if this works)
what are 2 exceptions to the rule in sympathetic post-ganglionic fibres?
There are two exceptions to the rule in sympathetic postganglionic fibres:
1- Sympathetic cholinergic fibers that innervate sweat glands
2- Non-adrenergic non-cholinergic (NANC) transmitters e.g. peptides
using the eye as an example, describe what the sympathetic system does:
Noradrenaline activates a1 receptors on the radial muscle of the iris
Radial muscle contracts & makes the pupil larger
- Noradrenaline activates b2 receptors on ciliary muscle around the lens
The ciliary muscle relaxes & eye focuses far away
using the eye as an example, describe what the sympathetic system does:
Acetylcholine activates muscarinic receptors on the sphincter (circular) muscle of the iris
Contracts sphincter muscle & makes pupil smaller
- Acetylcholine activates muscarinic receptors on ciliary muscle around the lens
Ciliary muscle contracts & eye focuses close-up
An example of two different types of antagonistic actions
using the heart as an example, describe what the sympathetic system does:
Noradrenaline activates {{c1::b1 receptors}} on the pacemaker cells
Increases heart rate
- Noadrenaline activates {{c1::b1 receptors}} on the myocytes
Increases strength of contraction
using the heart as an example, describe what the parasympathetic system does:
- Acetylcholine activates muscarinic receptors on pacemaker cells
> Decreases heart rate - Little effect on myocytes
> Little effect on the strength of contraction
Explain the sympathetic and parasympathetic effect on the lungs
Sympathetic system
- Noradrenaline activates b2 receptors on the smooth muscle of airways
> Makes smooth muscle relax & dilates airways
Parasympathetic system
- Acetylcholine activates muscarinic receptors on the smooth muscle of airways
> Makes smooth muscle contract & constricts airways
Why do patients with asthma and heart problems take salbutamol?
Why do patients with hypertension and lung problems take atenolol?
Because salbutamol is a b2 agonist
→ dilates airways, but does not affect the heart.
Because atenolol is a b1 antagonist
→ decreases heart rate, but does not affect airways.
Explain the redirection of blood during exercise
Explain the sympathetic and parasympathetic effects on the blood vessels
Sympathetic System
Tissues that contain b2 receptors e.g. heart and skeletal tissue
→ vasodilation & increase in blood flow during fight or flight
Tissues that contain a1 receptors e.g. kidneys, GI tract …etc.
→ vasoconstriction & decrease in blood flow during fight or flight
Parasympathetic System
Does not affect the majority of blood vessels
Exceptions - salivary glands & genitalia
Explain the sympathetic and parasympathetic effects on the salivary glands:
Sympathetic system
- Noradrenaline activates b receptors
Stimulates thick secretion rich in enzymes
Parasympathetic system
- Acetylcholine activates muscarinic receptors
Stimulates profuse watery secretion
An example of dual innervation with non-antagonistic actions i.e. no relax vs contract
Explain the sympathetic and parasympathetic effect on the blood vessels:
Sympathetic system
- Noradrenaline activates a1 receptors on the smooth muscle of vessels
> Makes smooth muscle contract (vasoconstriction) & blood flow decreases - Noradrenaline activates b2 receptors on the smooth muscle of vessels
> Makes smooth muscle relax (vasodilation) & blood flow increases
Parasympathetic system
Usually no effect, except in genitalia and salivary glands. (EXCEPTIONS)
i.e. the response depends on what receptors each tissue expresses
Single-system (sympathetic) innervation of the blood vessels means that a tone is continually maintained, so you either increase activity or decrease it.
using the bladder as an example explain the sympathetic and parasympathetic effects:
Sympathetic system
- Noradrenaline activates a1 receptors on the smooth muscle of the sphincter
Contracts smooth muscle and stops urination - Noradrenaline activates b2 receptors on the smooth muscle of the bladder wall
Relaxes smooth muscle and reduces pressure
Parasympathetic system
- Acetylcholine activates muscarinic receptors on the smooth muscle of the sphincter
Relaxes smooth muscle and causes urination - Acetylcholine activates muscarinic receptors on the smooth muscle of the bladder wall
Contracts smooth muscle and increases pressure
explain the effects of parasympathetic & sympathetic on the reproductive tract as an example:
Sympathetic system
- Noradrenaline activates a1 receptors on the smooth muscle of the urethra
Contracts smooth muscle and causes ejaculation
Parasympathetic system
- Acetylcholine activates muscarinic receptors on the smooth muscle of the corpus cavernosum
Relaxes smooth muscle & causes erection
An example of dual innervation with complementary effects
what is the baroreceptor reflex?
a type of autonomic reflex that detects blood pressure, and sends info to the integrating centre in the brain, then that centre coordinates sympathetic and parasympathetic outflow to the tissues accordingly..
what does the hypothalamus do?
it’s a portion of the brain responsible for central control, it coordinates autonomic, somatic, and endocrine activity.
Both of them together control the sympathetic and parasympathetic systems
what type of receptors does the neuromuscular junction use?
nicotinic
what are the 8 steps of synaptic transmission?
- Synthesis and packaging of neurotransmitters (usually) in presynaptic terminals
- Na+ action potential invades the terminal
- Activates voltage-gated Ca2+-channels
- Triggers Ca2+-dependent exocytosis of pre-packaged vesicles of transmitter
- Transmitter diffuses across cleft and binds to ionotropic and metabotropic receptors to evoke
a postsynaptic response - Presynaptic autoreceptors inhibit further transmitter release by closing calcium channels
- The transmitter is (usually) inactivated by an enzyme or is uptaken into glia or neurones
- Transmitter is metabolised within cells
what are the 5 ways to inhibit AP transmission, targeting NMJ transmission?
1- inhibit choline transporter
e.g. hemicholinium
2- Block voltage-gated Ca2+ channels
e.g. black widow spider venom
3- Block vesicle fusion
e.g. botulinum
4- Use non-depolarising nicotinic receptor blockers
(competitive antagonists → high affinity & low/zero efficacy)
e.g. d-tubocurarine
5 - Use depolarising nicotinic receptor blockers
(keep muscle depolarised and stop voltage-gated sodium channels from working again)
e.g. succinylcholine
How does an anticholinesterase work?
e.g. eserine
An anticholinesterase blocks acetylcholinesterase
→ stops breakdown of ACh so it hangs around in the synaptic cleft for longer.
when targeting postsynaptic parasympathetic transmission, what do muscarinic receptors do?
Muscarinic receptor agonists - e.g. carbachol, pilocarpine
- mimic the effect of the parasympathetic system
(slow heart rate, contract smooth muscle in airways and bladder, increase gut motility, increase bronchial secretions and salivation, constrict pupil)
Muscarinic receptor antagonists - e.g atropine
- will block effects of the parasympathetic system i.e. mimic the effect of the sympathetic system
(increase heart rate, relax smooth muscle in airways and bladder, reduce gut motility, bronchial secretions and salivation, dilate pupil)
What is Glaucoma and how are muscarinic agonists used to relieve it?
Glaucoma is raised intraocular pressure.
Muscarinic agonists contract the ciliary muscle supporting the lens and the sphincter muscle of the pupil to increase drainage of the aqueous humour through the canal of Schlemm
what are 5 ways to inhibit AP transmission when targeting postganglionic sympathetic transmission?
1- Blocking the enzymes that produce NA
e.g. carbidopa
2- Blocking the transporter that fills the vesicles with NA
e.g. reserpine
3- introducing a “false” transmitter
e.g. methyldopa
- looks like NA but doesn’t bind to receptor
4- Activating inhibitory presynaptic (α2) autoreceptors
- inhibits voltage gate Ca2+ channels, so reduces the release of vesicles.
e.g. methyldopa
5- Blocking α or β postsynaptic receptors
e.g. doxazosin or propranolol
how does the mechanism of removing neurotransmitters differ in NMJ than in postganglionic cleft?
NMJ - usage of an enzyme called acetylcholinesterase to break down acetylcholine and then it’s taken up the presynaptic terminal
Postganglionic cleft - usage of a reuptake molecule to take noradrenaline back into the presynaptic terminal
what are 3 ways to potentiate AP transmission when targeting postganglionic sympathetic transmission?
1- Stimulate NA release
e.g. amphetamine
2- Inhibit uptake into:
Neurones
e.g. cocaine & tricyclic antidepressants
Glia
e.g. phenoxybenzamine
- Allows NA to hang out around the cleft longer
3- Activate postsynaptic receptors
e.g. phenylephrine and salbutamol
All of the above-mentioned drugs are known as sympathomimetics
summary: Mention some clinical applications of alpha and beta agonists:
α1 agonists (contraction of muscle) can be used as decongestants and dilate the pupil (mydriatics)
- α2 agonists can be used in the treatment of hypertension
- β2 agonists (relaxation of muscle) can be used in the treatment of asthma
- β1 antagonists can be used in the treatment of hypertension, angina and cardiac arrhythmias
