Parasympathetic NS Flashcards

1
Q

What does stimulating the PNS cause?

A

= Rest + digest.

Eyes = pupillary sphincter contraction = miosis = pinpoint.
Tears.

Salivation.

Bronchoconstriction + Mucus secretion.

Gastric secretion, motility + urination.

Decreased HR and AVN conduction.

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2
Q

What NTs and receptors are used in the PNS?

A

Acetylcholine.
ACh released at the ganglia, activating nicotinic ACh receptors.

At the target tissue = ACh released to act on MUSCARINIC receptors!!!

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3
Q

How do PNS ganglia differ from sympathetic ganglia?

A

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.

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4
Q

What is the structure of autonomic ganglia receptors?

A

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.

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5
Q

What is Muscarine?

A

Mushroom derived water soluble toxin that activates muscarinic ACh receptors.
= leading to PNS activation!
= Vomit, diarrhoea, watery eyes, convulsions…

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6
Q

How are the Muscarinic receptors different?

A

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.

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7
Q

Where are M1, M3, and M5 receptors found?

A

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.

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8
Q

Where are M2 and M4 receptors found?

A

Cardiac myocytes and pre-synaptically.

M4 = CNS.

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9
Q

How can muscarinic activation cause SM contraction and secretion?

A

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.

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10
Q

How do M2 and M4 muscarinic receptors exert their effects?

A

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..

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11
Q

What are the symptoms of parasympathetic stimulation?

A

SLUDGE = salivation, lacrimation (tears), urination, diarrhoea, gastric upset, emesis (vomiting + nausea)…

DuMBBELS = high doses.
Miosis (M3+M5), bradycardia (M2), bronchoconstriction (M3).

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12
Q

What are the descriptors of muscarinic agonists, antagonists and AChE inhibitors?

A

Muscarinic agonists + AChE inhibitors= parasympathomimetic!

Muscarinic antagonists = ParasympathoLYTIC.

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13
Q

What is Bethanechol and its therapeutic uses?

A

Bethanechol is a M3 selective agonist, used to treat bladder hypotonia.
= To cause weeing.
as M3 receptors in bladder SM.

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14
Q

How can ACh be modified to provitde muscarinic selectively or protect from AChE hydrolysis?

A

Methyl addition provides Muscarinic receptor selectivity.

Adding carbamyl group protects from AChE hydrolysis…

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15
Q

What is Pilocarpine?

A

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.

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16
Q

What is Sjorgen’s syndrome?

A

Autoimmune condition which attacks mouth salivary glands.
= treated with pilocarpine.

17
Q

What are the side effects of muscarinic agonists?

A

Bradycardia, vasodilation (M3), visceral/GI smooth muscle contraction (M3), lacrimation, exocrine secretion = all…

P

18
Q

What are the muscarinic antagonists?

A

ParasympathoLYTICS.

Atropine, Hyoscine, ipratropium + pirenzepine.

19
Q

What is atropine?

A

Non-selective competitive antagonist to muscarinic ACh receptors.
= readily absorbed + penetrates BBB = CNS depression.
= delirium.

20
Q

What are the clinical uses of atropine?

A

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.

21
Q

What are the main side-effects of atropine?

A

Urinary retention.

Constipation.

Blurred vision…

Dry mouth.

22
Q

What is Hyoscine/Scopolamine?

A

Non-selective competitive antagonist to musarinic ACh receptors.

23
Q

What are the therapeutic uses of Hyoscine/Scopolamine?

A

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

24
Q

What are the side effects of Hyoscine?

A

Atropine-like effects:;

Constipation, blurred vision, dry mouth, urinary retention.

CNS depression, sedating.

25
Q

What is pirenzepine?

A

An M1 selective antagonist.

Use to be used for peptic ulcers but was discontinued.

26
Q

What is darifenacin?

A

M3 selective antagonist.

To inhibit micturition and involuntary bladder contraction.

M3 in bladder SM

Used to treat urinary incontinenace.

27
Q

What are the side effects of Darifenacin?

A

Less severe atropine like effects:
Dry mouth, blurred vision, constipation…

28
Q

How do airway smooth muscle contract?

A

ACh released from parasympathetic nerve induces bronchoconstriction.

M3 ACh receptors in bronchi SM.
BUT also M2 receptors on parasympathetic nerve/presynaptic nerve…

M3 are Gq coupled = PLC = IP3 + DAG = Ca2+ for contraction.

M3 agonism causes bronchoCONSTRICTION!!!!

29
Q

What is ipratropium?

A

Ipratropium is a quarternary ammonium compound like ACh.

an M3 and M2 competitive antagonist.

Used to treat irritant induced bronchospasm, asthma, COPD… to induced bronchorelaxation.

30
Q

What are the side effects of ipratropium?

A

Does not cross the BBB = no CNS effects.

Has no effect on mucociliary clearance.

BUT:
Ipratropium blocks both M2 and M3 = M2 on presynaptic receptor used as an autoreceptor…
= can be outcompeted..

31
Q

Why is ipratropium obsolete?

A

M3 AND M2 blockade…

M2 blockade reduces the negative feedback of M2 activation on ACh release at the synapse.
= leading to enhanced ACh production…

Enhanced ACh production will outcompete ipratropium to induce bronchoconstriction.
= Block partially overcome.

32
Q

What is Tiotropium?

A

An M3 and M2 competitive antagonist.
BUT
Rapidly dissociates from M2… preserving negative feedback loop on ACh release.
= Allowing ACh to exert negative feedback on M2 receptors to reduce ACh release.