The Autonomic Nervous System Flashcards
List the four main functions of the autonomic system
- Gather information from internal physiology and the external environment
- Integrate information for assessment and meaning
- Effect a motor response (behavioural/chemical/neurochemical secretion)
- Regulate body homeostasis for optimal performance
With the aid of a diagram, outline the divisions of the nervous system (CNS and PNS), naming drugs used in the SNS and PsNS
• NERVOUS SYSTEM:
o CNS
Brain and spinal cord
o PNS
Spinal nerves – carry impulses to and from the spinal cord
Cranial nerves – carry impulses to and from the brain
• Somatic nervous system – conscious control
• Autonomic nervous system – subconscious control
o Sympathetic Nervous System – SNS – fight/flight, sympathises with you
Dry mouth
Rapid breathing
Muscles tense
Sweaty palms
Heart races
• Caused by the SNS acting on cardiac muscle, smooth muscle, and exocrine glands
Can prevent urination with agents potentiating the SNS (e.g. imipramine)
o Parasympathetic Nervous System – PsNS – rest & digest – suppresses SNS
Prevent Urination by:
blocking muscarinic receptors with Tolterodine (Detrol; 1-2 mg bid; $103/month) (others include oxybutynin (Ditropan), Trospium (Sanctura), propantheline, hyoscyamine)- Med. Let. 46: 64, 2004
stimulating sympathetic nervous system (imipramine) (Tofranil)
• used to help children with bedwetting problems
• a little dangerous- can cause lethal cardiac arrhythmias, even in children
• bedwetting more commonly treated with antidiuretic hormone currently
In theory, could combine phenylephrine and albuterol but not done in practice
No sympathetic nervous system agents are used to induce urination but 1 receptor blockers are used to ease urination in benign prostatic hyperplasia
Drugs include Terazosin (Hytrin); Doxazosin (cardura); Alfuzosin (uroxatral) and Tamsulosin (Flomax)
o Enteric Nervous System – gut
What will happen to an animal that has no PsNS? What about if it has no SNS?
• If an animal has a denervated parasympathetic nervous system, it will die immediately
o If an animal has a denervated SNS, it will live as long as no stressors are present
• Lecture focusses on SNS and PsNS
How does the ANS communicate to peripheral organs and tissues? Which cells aid this?
• The ANS communicates to peripheral organs and tissues via neurons (typically unipolar), using action potentials to trigger neurotransmitter release o Speed of transmission is aided by glial cells: CNS glia: • Astrocytes • Oligodendrocytes – myelinate neurons • Ependymal cells • Microglia PNS glia: • Schwann cells – myelinate neurons • Satellite cells
Outline the differences between neurons involved with the SNS and PsNS, their synapses, and the neurotransmitters used, as well as target tissues/organs
• SNS:
o Short preganglionic axon, releasing ACh
o Long postganglionic axon releasing noradrenaline/directly signals to effector organ
o Chain of ganglia between the cranial and sacral areas – the thoracolumbar division
Ganglia = collection of neurons OUTSIDE the CNS
o Targets smooth muscle; cardiac muscle; endocrine glands; brown fat
• PsNS:
o Long preganglionic axon, releasing ACh
o Short postganglionic axon, releasing ACh
o Stems from cranial/sacral nerves – the craniosacral division
o Targets smooth muscle; cardiac tissue; exocrine glands; brown fat
What is the main advantage of dual innervation?
• Dual innervation of many organs/effector tissues –> a ‘brake’ and an ‘accelerator’; this allows more control over function and effect
o SNS = accelerator
o PsNS = brake
o Neuromodulation = clutch
Using a diagram to aid you, outline the acetylcholine synthesis and degradation pathways
- Synthesised in the nerve terminal
- Acetyl-coenzyme A (AcCoA) is produced in the mitochondria
- Choline accumulates in the terminals through active uptake from interstitial fluid
- AcCoA + choline acetylcholine
- ACh is degraded/removed by acetylcholinesterase
diagram: https://en.wikipedia.org/wiki/Acetylcholine#Biochemistry - also in lecture notes
Using a diagram to aid you, outline the synthesis of catecoleamines (norepinephrine/epineprhine)
Diagram: https://www.google.com/url?sa=i&url=http%3A%2F%2Fclinchem.aaccjnls.org%2Fcontent%2F49%2F4%2F586&psig=AOvVaw14pMAyJTxAAdUipwgmGIe_&ust=1577281227373000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCND008y0zuYCFQAAAAAdAAAAABAD
After excitosis, what can noradrenaline do? Which drugs can be used to affect this?
after exocytosis of NA, it can:
interact with α1 receptors
be reaccumulated into the nerve via axoplasmic pump
be degraded by monoamine oxidise – occurs outside the nerve
drugs can affect these:
imipramine blocks the axoplasmic pump (so does cocaine)
pargyline blocks monoamine oxidase
potentiate sympathetic effects by:
adding α-receptor antagonist
blocking axoplasmic pump (imipramine + cocaine)
block monoamine oxidase (pargline)
inhibit sympathetic effects by antagonising the α-receptor
Outline the function of the adrenergic receptors
Adrenergic receptors:
Respond to adrenaline
Multiple effects of adrenaline –> multiple receptor subtypes (isoforms)
α-adrenoreceptors:
α1 – expressed on most sympathetic target tissue
Activates phospholipase C –> increased inositol triphosphate (IP3) + diacylglycerol (DAG) –> increase in i[Ca2+]
Agonist: phenylephrine
Antagonist: terazosin
α2 – stimulates smooth muscle, pancreas, platelets, nerve terminals
Inhibits adenalyte cyclase –> reduced cAMP
β-adrenoreceptors:
β1 – heart + salivary glands
Activates adenylyl cyclase –> increased cAMP
β2 – smooth muscle, skeletal muscle, nerve terminals, mast cells
Activates adenylyl cyclase –> increased cAMP
Promotes glycogenolysis
Agonist: albuterol
Proparanolol = nonselective β-antagonist; no selective β2 antagonist for clinical use
β3 – skeletal muscle, adipose tissue
Activates adenylyl cycles –> increased cAMP
Outline the pharmacology of the cholinergic receptor subtypes, providing a brief overview of the cholinergic receptor family and pre/post-synaptic differences
Respond to acetylcholine
Drugs which induce different actions of ACh (nicotine and muscarine) were used to classify receptor isoforms
Nicotinic acetylcholine receptors (NiAChRs):
Muscle
Ganglion
CNS
Preganglionic – PsNS and SNS
Excitatory response to stimulation - ALWAYS
Stimulated by nicotine
Ligand-gated ion channel – transports Na+
Pentameric ionotropic receptors:
Subunits: α2, β,γ, δ,ϵ
Muscarinic-acetylcholine receptors (mAChRs):
M1 – coupled to phospholipase C; stimulatory
M2 – coupled to adenylyl cyclase; inhibitory
M3 – coupled to phospholipase C; stimulatory
M4 – coupled to adenylyl cyclase; inhibitory
M5 – coupled to phospholipase C; stimulatory
Postganglionic
Smooth muscle
Cardiac muscle
Glands of parasympathetic fibres
Effector organs of cholinergic sympathetic fibres
Stimulated by muscarine
GPCRs:
Signal via second-messenger systems to achieve a response by influencing:
Adenylyl cyclase
GIRKs
Phospholipase C
Can be excitatory or inhibitory
Preganglionic fibres release small molecules and peptide neurotransmitters to elicit complex ganglionic neuron responses:
Single/low-frequency stimulation: –> ACh release, activating NiAChRs –> fast EPSP in the postganglionic neuron
High-frequency stimulation: –> more ACh release alongside release of luteinising-hormone-releasing-hormone (LHRH, a peptide). Complex postganglionic response including:
Fast EPSP
Slow IPSP – mediated via mAChR-activation of GIRKs
Delayed EPSP due to LHRH binding peptidergic receptors
Outline the 2 main types of parasympathomimetic drugs, giving at least 2 examples of drugs and their function
- Drugs which directly stimulate cholinergic receptors:
Methacholine
Carbachol
Poiolocarpine
Muscarine
Phyostigmine:
• Generalised drug; blocks all over the body – used locally as eye drops to treat glaucoma - reversible
Neostigmine:
• Was used in the treatment myasthenia gravis due to direct action on motor end plate – reversible
• Augments peristalsis to promote defecation
• Contracts urinary bladder
Sildenafil – preserves cGMP; promotes erection; vasodilatory effects
• Prevent degradation of cGMP by blocking phosphodiesterase 5
• Nitric Oxide (NO) interacts with soluble guanylyl cyclase to produce cGMP
o cGMP interacts with protein kinase G to phosphorylate proteins
o opens potassium channel to hyperpolarize smooth muscle
o net effect is relaxation of smooth muscle
o phosphodiesterase breaks down cGMP (this step blocked by Sildenafil)
Parathion (insecticide), DFP (toxic nerve gas) – irreversible effect
Prevent urination caused by overactive bladder (usually affecting detrusor) – tolterodine is used for this (muscarinic agonist); other drugs include oxybutynin, trospium, propantheline, hyoscyamine - Drugs which inhibit cholinesterase enzyme:
Drugs which preserve the action of ACh by preventing the action of cholinesterase
Outline the 2 main types of parasympatholytic drugs, giving at least 2 examples of drugs and their function
Antagonise the actions of ACh
Nicotine (in large doses)
Atropine –> pupil dilation; spasm relief; prevention of bronchial secretion; tachycardia; urinary retention; constipation; dry mouth
Naturally occurs in mandrake and Atropa belladonna (deadly nightshade)
Competitive inhibitors occupy AChRs and prevent ACh acting
Persistent depolarisers cause prolonged depolarisation of the ACh receptor ∴ preventing excitation of the receptor by released ACh
Name 2 drugs which stimulate and block (respectively) alpha adrenergic receptors, highlighting the receptor subtype they act on where possible
α1 stimulators:
Methoxamine
Phenylepinephrine
α blockers: Phenoxybenzamine Phentolamine Prazocin (α1 blockers) Yohimbine (α2 blockers)
Name 2 drugs which stimulate and block (respectively) beta adrenergic receptors, highlighting the receptor subtype they act on where possible
β-stimulators: Isoproterenol β2-stimulators: Salbutamol Terbutaline
β-blockers: Propranolol Metaprolol β1 blockers: Atenolol β2 blockers: Butoxamine
Which 3 toxins can affect the ANS? How do these work?
Botulinum toxin:
o Produced by C. botulinum
o Inhibits ACh release –> muscle paralysis and death
o In small doses is used as Botox to prevent wrinkle development
Latrotoxin:
o Venom of the black widow spider
o Increased ACh release –> pain, cramps, sweating, fast pulse
Fasciculins:
o Toxic proteins found in mamba venom
o Bind AChE, blocking its activity
o Cause intense muscle fasciculation (contraction), paralysing/killing prey
Name and describe the effects of 2 irreversible acetylcholinesterase inhibitors
Sarin gas:
o Chemical weapon; inhibits AChE
Insecticides (malathion and organophosphates) inhibit ACE
Reactivators of the irreversibly blocked enzyme (pralidoxime) have been developed as snake bite antidotes, and protection against nerve agents
How can you selectively block muscle nicotinic acetylcholine receptors? What is the name and effect of the drug used for this?
Muscle NiAChRs are selectively blocked curare (plant-derived arrow poison)
o Curare is a competitive antagonist of ACh
o When bound to a receptor, curare elicits no response
o Antidote = AChE inhibitor
Outline how parasympathetic ACh release modulates cardiac function
Muscarinic generation of Gβγ directly –> GIRK activation in pacemaker cardiocytes –> slowed depolarisation ∴ slower heart rate
Muscarinic generation of GαI in cardiac muscle –> lower cAMP and PKA levels –> reduced opening of L-type Ca2+ channels –> reduced force of heart contraction
∴ parasympathetic release of ACh reduces cardiac output in 2 ways
Outline how sympathetic norepinephrine release modulates cardiac function
β1-adrenergic generation of Gαs in pacemaker cardiocytes –> increased cAMP + PKA levels ∴ reducing the threshold voltage for AP initiation –> increased rate of heartbeat
β1-adrenergic elevation of cAMP and PKA in cardiac muscle increased L-type Ca2+ channel opening –> increased force of heart contraction
∴ sympathetic NA release increases cardiac output in 2 ways
With reference to the role of the hypothalamus, outline how there is a central autonomic network coordinating autonomic function
- PsNS and SNS share a sensory pathway – their inputs are sent to the hypothalamic paraventricular nucleus; this facilitates central pre-autonomic control
- PVN can signal to the pituitary; directly or indirectly controlling hormone release
Hypothalamus-coordinated outputs:
• Autonomic: action on smooth muscles in central and peripheral vasculature
• Behavioural: conscious thirst, driving search for fluids
• Endocrine: release of vasopressin into blood; promotes water reabsorption by kidneys
• Stress hormones coordinate the release of these
Outline the effect of alcohol on the autonomic nervous system
• Chronic alcohol use can cause demyelination –> chronic neuropathies
o Reduces the rate of saltatory conduction, forcing APs to take the ‘slow route’ through an axon instead of jumping between myelinating cells
• Chronic neuropathies conduction block/slowed conduction/impaired ability to conduct impulses at high frequencies
Outline the effects of nicotine on the autonomic nervous system, and explain the pharmacodynamics of nicotine
Chronic smoking increases the nicotine receptors in the prefrontal cortex; caused by tolerance to nicotine ∴ need more receptors to achieve the same effect
Nicotine pharmacodynamics:
Refers to the effects that nicotine has on the body
Nicotine is a potent agent affecting numerous organ systems: Cardiovascular Endocrine Musculoskeletal Neurologic Post-absorption, nicotine binds to receptors in the brain + other sites in the body --> stimulant and some sedative effects Binds to: CNS Cardiovascular system Exocrine glands Gastrointestinal system Adrenal medulla PNS Neuromuscular junctions Sensory receptors
