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PA20016 > The peripheral nervous system > Flashcards

The peripheral nervous system Flashcards

1
Q

What did Oliver and Schafer discover about the adrenal glands?

A

Extracts increase blood pressure due to adrenaline.

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2
Q

What happens if the vagus nerve is stimulated?

A

There is a release of “vagusstoff” that causes a slowed heartbeat.

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3
Q

What was vagusstoff later identified as?

A

Acetylcholine - causes slowed heart beat.

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4
Q

What experiment did Otto Loewi do with two hearts?

A

Stimulated the vagus nerve of one heart that was linked in fluid to another heart - found that the heart rate of the second heart reduced too, substance must have been released from stimulation.

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5
Q

What does muscarine stimulate?

A

Stimulation of the parasympathetic nervous system - pupils constrict etc.

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6
Q

What type of receptors are muscarinic receptors?

A

G-protein coupled receptors.

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7
Q

What are the names of the muscarinic receptors?

A

M1, M2, M3, M4, M5.

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8
Q

What are the two groups of muscarinic receptors?

A

M1, M3, M5 and M2 M4.

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9
Q

What agonists do muscarinic receptors respond to?

A

Muscarine, ACh.

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10
Q

What agonists do nicotinic receptors respond to?

A

Nicotine, ACh.

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11
Q

How do muscarinic and nicotinic receptors differ?

A

Nicotinic are ionotropic (ion channels) and muscarinic are G protein coupled.

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12
Q

What are M1/M3/M3 receptors coupled to?

A

They activate Gq to trigger the IP3 pathway.

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13
Q

What is the molecular pathway for the Gq coupled receptors?

A

Once activated, phospholipase C is stimulated which cleaves PIP2 in the membrane into DAG and IP3. These are important second messengers - IP3 opens Ca2+ channels on intracellular organelles, and DAG activates protein kinase C that causes protein phosphorylation which can cause muscle contraction and glandular secretion.

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14
Q

Where are M1 receptors found?

A

Glands - gastric and salivary.

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15
Q

Where are M3 receptors found?

A

Exocrine glands (salivary, gastric), smooth muscle (GI tract, airways, eyes, bladder), blood vessels (endothelium).

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16
Q

Where are M5 receptors found?

A

In the periphery (salivary glands, iris, cilliary muscle).

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17
Q

What do muscarinic receptors on glandular cells result in?

A

Secretion.

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18
Q

What do muscarinic receptors on smooth muscle lead to?

A

Contraction.

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19
Q

What effect does ACh have on intact blood vessels and why?

A

Relaxation as the endothelium releases NO that relaxes smooth muscle due t binding of the M3 and M1 receptors.

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20
Q

What effect does ACh have on blood vessels that are rubbed and why?

A

ACh loses dilator activity and there is contraction due to the lack of endothelium, so there are no M3 and M1 receptors to cause release of NO to relax the smooth muscle.

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21
Q

What receptors does ACh act on in blood vessels?

A

M3 and M1 receptors on the endothelium.

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22
Q

What actions do the M2/M4 muscarinic receptors have?

A

They are inhibitory - they are Gi coupled, meaning adenylyl cyclase is inhibited which prevents second messenger cascade of cAMP to PKA, resulting in decreased calcium conductance, increased K+ conductance.

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23
Q

What effect does binding to M2/M4 receptor have?

A

Cardiac inhibiton, neural inhibition and central effects such as tremor and hypothermia.

24
Q

Where does the sympathetic nervous system originate?

A

Thoracic and lumbar regions.

25
Q

Where does the parasympathetic nervous system originate?

A

The medullary and sacral regions.

26
Q

What are some of the effects of parasympathetic nervous system stimulation?

A

Pupillary sphincter constriction, tears, mucus secretion, salivation, bronchoconstriction, mucus secretion, gastric secretions, increases GI motility, urination, penile erection and decreased heart rate and atrioventricular node conduction.

27
Q

What effect does muscarine have?

A

SLUDGE - salivation, lacrimation (crying), urination, diarrhoea, gastric upset and emesis. DUMBBELS - diarrhoea, urination, miosis (pupils), bradycardia, bronchoconstriction, emesis, lacrimation and salivation.

28
Q

What are muscarinic agonists called?

A

Parasympathomimetic

29
Q

What are muscarinic antagonists called?

A

Parasympatholytic.

30
Q

What are drugs that have indirect actions to affect the muscarinic receptor?

A

Inhibitors of ACh breakdown - parasympathomimetic.

31
Q

What are some agonists that act on muscarinic and nicotinic ACh receptors?

A

Acetylcholine, methacholine, carbachol and bethanechol.

32
Q

What can bethanechol be used to treat?

A

Bladder hypotonia.

33
Q

Why does methacholine have extra selectivity for muscarinic receptors over nicotinic receptors?

A

There is an extra methyl group on the choline backbone - this gives the selectivity.

34
Q

What are some other agonists that act on muscarinic and nicotinic receptors?

A

ACh and pilocarpine.

35
Q

What can pilocarpine be used to treat?

A

Can be used in eyedrops for glaucoma due to selectivity for constrictor pupillae, sweat, salivary and lacrimal M receptors (it has minimal effects on the GI tract, smooth muscle and heart). It can also be used for dry mouth or dry eyes.

36
Q

What effects do muscarinic antagonists have?

A

Inhibition of secretions, tachycardia, mydriasis, inhibition of GI motility, smooth muscle relaxation, bronchodilation and CNS excitation.

37
Q

What is mydriasis?

A

Dilation of the pupil.

38
Q

What is a non-selective competitive muscarinic antagonist?

A

Atropine, hyoscine, ipratropium.

39
Q

What can atropine be clinically used for?

A

Used in addition to anaesthesia, treating anticholinesterase poisoning, treating bradycardia and treating GI hypermotility.

40
Q

What are the main side effects of atropine?

A

Urinary retention, dry mouth, blurred vision and constipation.

41
Q

What effect does hyoscine have?

A

GI relaxant, suppresses secretions, CNS depression/excitation,

42
Q

What are some of the clinical uses of hyoscine?

A

In use with anaesthesia, bowel pain, respiratory secretions in pallative care, motion sickness.

43
Q

What is hyoscine sedating?

A

It crosses the blood brain barrier.

44
Q

What is an M1 selective antagonist?

A

Pirenzepine.

45
Q

What is the effect of pirenzepine?

A

It inhibits vagus-induced histamine release by blocking M1 on G cells and blocking M1 enhancement of parasympathetic ganglia signalling - but the mechanism is unclear.

46
Q

What are the effects of pirenzepine on smooth muscle and the CNS?

A

Little effect on either.

47
Q

What are some M3 selective antagonists?

A

Darifenacin, oxybutynin and tolterodine.

48
Q

What effects do M3 selective antagonists have?

A

They inhibit involuntary bladder contraction and inhibit micturition.

49
Q

What can M3 antagonists be used to treat?

A

Urinary incontinence.

50
Q

What are some of the side effects of M3 antagonists?

A

Dry mouth, blurred vision and constipation. Similar to atropine but less severe.

51
Q

How does cholinergic signalling occur in the airways?

A

A parasympathetic nerve releases ACh that acts on the airway smooth muscle and binds to M3 receptors that activate the Gq protein, resulting in the release of Ca2+ and leads to contraction.

52
Q

What is ipratropium?

A

A quaternary ammonium compound that is poorly absorbed and lacks CNS effects. It does not inhibit mucocillary clearance from bronchi.

53
Q

What can ipratropium be used to treat?

A

Irritant induced bronchospasm, asthma, bronchitis, COPD.

54
Q

How is negative feedback involved in ACh?

A

Neuronal ACh release on the parasympathetic nerve is inhibited by M2 receptor feedback - the released ACh acts on M3 receptors on the airway smooth muscle, but ACh remaining in the synapse acts back on the M2 receptors on the parasympathetic nerve.

55
Q

How can competitive antagonists be overcome?

A

Increasing the concentration of ACh.

56
Q

What is a problem with muscarinic antagonists?

A

As there is a negative feedback mechanism, antagonists can block both the presynaptic and postsynaptic receptors, resulting in enhanced ACh production and the muscarinic block can be partially overcome.

57
Q

What is tiotropium?

A

An M3 selective antagonist - it binds all receptors but there is a fast dissociation at M2 so that there is preservation of the negative feedback pathway - M2 receptors on the presynaptic membrane not blocked.

PA20016 (10 decks)

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