Parasympathetic NS Flashcards
What does stimulating the PNS cause?
= Rest + digest.
Eyes = pupillary sphincter contraction = miosis = pinpoint.
Tears.
Salivation.
Bronchoconstriction + Mucus secretion.
Gastric secretion, motility + urination.
Decreased HR and AVN conduction.
What NTs and receptors are used in the PNS?
Acetylcholine.
ACh released at the ganglia, activating nicotinic ACh receptors.
At the target tissue = ACh released to act on MUSCARINIC receptors!!!
How do PNS ganglia differ from sympathetic ganglia?
PNS ganglia are closer to the tissue whilst sympathetic ganglia are arranged close to the spinal cord in the Sympathetic chain.
Both have autonomic ganglia utilise ACh at ganglion-type Nicotinic ACh receptors!!!
BUT Sympathetic releases NA usually at tissue, whilst PNS uses ACh on muscarinic receptors.
What is the structure of autonomic ganglia receptors?
Ganglion-type nicotinic ACh receptor.
Fast EPSP = Na+ in, K+ out.
Pentameric w/ 2 ACh binding site.
2 Alpha3 subunits, 3 Beta subunits.
Usually need simulatenous firing from several pre-ganglionic nerve fibres to generate an AP.
What is Muscarine?
Mushroom derived water soluble toxin that activates muscarinic ACh receptors.
= leading to PNS activation!
= Vomit, diarrhoea, watery eyes, convulsions…
How are the Muscarinic receptors different?
M1, M3, M5 are Gq coupled.
M2 and M4 are Gi/Go coupled.
M1, M3, M5 = activate PLC = IP3 + DAG and Ca2+ = excitation
M2 + M4 = inhibit AC = less cAMP.
Where are M1, M3, and M5 receptors found?
M1 = gastric + savlivary glands.
M3 = Salivary and gastric glands.
GI tract, eye, airway + bladder smooth muscle.
and endothelium of blood vesslel!!!
M5 = salivary glands + Iris and ciliary muscle.
Where are M2 and M4 receptors found?
Cardiac myocytes and pre-synaptically.
M4 = CNS.
How can muscarinic activation cause SM contraction and secretion?
M3 = Gi tract, airway, bladder + eye SM.
M5 = iris and ciliary SM.
= Gq coupled = activate PLC = Increased DAG and IP3 and cause Ca2+ release….
Activate SM contraction and secretion.
How do M2 and M4 muscarinic receptors exert their effects?
M2 and M4 are Gi/Go coupled, inhibiting AC and reducing cAMP.
They also open K+ channels = hyperpolarisation.
M2 = Cardiac inhibition = reduce contractility and rate of contraction!
AND neural inhibition via presynaptic M2.
M4 has central effects like tremor and hypothermia..
What are the symptoms of parasympathetic stimulation?
SLUDGE = salivation, lacrimation (tears), urination, diarrhoea, gastric upset, emesis (vomiting + nausea)…
DuMBBELS = high doses.
Miosis (M3+M5), bradycardia (M2), bronchoconstriction (M3).
What are the descriptors of muscarinic agonists, antagonists and AChE inhibitors?
Muscarinic agonists + AChE inhibitors= parasympathomimetic!
Muscarinic antagonists = ParasympathoLYTIC.
What is Bethanechol and its therapeutic uses?
Bethanechol is a M3 selective agonist, used to treat bladder hypotonia.
= To cause weeing.
as M3 receptors in bladder SM.
How can ACh be modified to provitde muscarinic selectively or protect from AChE hydrolysis?
Methyl addition provides Muscarinic receptor selectivity.
Adding carbamyl group protects from AChE hydrolysis…
What is Pilocarpine?
Pilocarpine is an M3 selective agonist = parasympathomimetic.
M3 agonism activates sphincter pupillae contraction - to put tension on trabecular meshwork to improvde drainage of AH!!!
= Miotic = used for Glaucoma.
Dry mouth from radiotherapy or Sjorgen’s syndrome.
= stimulates salivary gland activation.
Dry eyes = triggers lacrimation/tears.
What is Sjorgen’s syndrome?
Autoimmune condition which attacks mouth salivary glands.
= treated with pilocarpine.
What are the side effects of muscarinic agonists?
Bradycardia, vasodilation (M3), visceral/GI smooth muscle contraction (M3), lacrimation, exocrine secretion = all…
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What are the muscarinic antagonists?
ParasympathoLYTICS.
Atropine, Hyoscine, ipratropium + pirenzepine.
What is atropine?
Non-selective competitive antagonist to muscarinic ACh receptors.
= readily absorbed + penetrates BBB = CNS depression.
= delirium.
What are the clinical uses of atropine?
Used adjunct to anaesthesia in order to dry any secretions + reduce mucus.
Used during anticholinesterase poisoning (neostigmine, galantamine, donepezil)…
To treat bradycardia
GI hypermotility = anti-spasmodic.
What are the main side-effects of atropine?
Urinary retention.
Constipation.
Blurred vision…
Dry mouth.
What is Hyoscine/Scopolamine?
Non-selective competitive antagonist to musarinic ACh receptors.
What are the therapeutic uses of Hyoscine/Scopolamine?
Alongside Neostigmine for treating myasthenia gravis ( to prevent autonomic side effects… salivtaion, GI distrubrance, bradycardia etc..)
Treating motionn sickness - GI relaxant + secretion suppressor….
CNS depression makes Hyoscine a sedative = blocking vomiting.
= blocks transmission from vestibular apparatus to vomiting centre.
Block respiratory secretions in palliative care/ventilation
What are the side effects of Hyoscine?
Atropine-like effects:;
Constipation, blurred vision, dry mouth, urinary retention.
CNS depression, sedating.
