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Pharmacology & Physiology 1 > The Autonomic Nervous System > Flashcards

The Autonomic Nervous System Flashcards

1
Q

Which physiological functions are controlled by the Autonomic nervous system?

A
  • Heart rate
  • Blood pressure
  • Airway diameter
  • Eye focusing
  • Secretions (e.g. saliva, sweat, mucus, enzymes)
  • Bladder, Genitalia, alimentary tract action
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2
Q

Name some parasympathomimetric drugs

A
  • Neostigmine
  • Physotigmine
  • Edrophonium
  • Parathion
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3
Q

How do Parasympathetic postganglions produce physiological responses?

A

Ach released on muscarinic receptors on organs

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4
Q

Describe the ganglionic structure of the parasympathetic nervous system

A

Ach receptor –> Ach receptor

Long preganglion , shorter post ganglionic

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5
Q

What are cholinoceptors?

A

Nicotinic Ach Receptors are ligand gated ion channels that allow ions to enter

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6
Q

Which type of Ach receptor is present on post synaptic neuron?

A

Nicotinic Ach receptor

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7
Q

What is the effect of the vagus nerve on secretory cells?

A

Ach from Vagus nerve augments acid production on M1
causing secretions in salivary and sweat glands via M3
–> under sympathetic control (Adrenal gland)

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8
Q

What type of nAchR are there ?

A

Neuronal nicotinic receptors
- work on autonomic ganglion

Muscle nicotinic Receptors
- Act on skeletal muscle

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9
Q

Where in the body does the parasympathetic nerves act upon?

A
  • Salivary gland
  • GI Tract
  • Heart
  • Acid cells
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10
Q

What are the parasympathetic effects on the eye?

A

M3 contraction of circular muscle

Causes narrowing of pupils

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11
Q

What are NANC nerves?

A

Parasympathetic nerves that don’t utilise NA or Ach

Called non adrenergic non cholinergic NANC Nerves

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12
Q

Where in the body does the sympathetic nervous system operate?

A
  • Arteries, heart
  • Sweat glands
  • Adrenal glands
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13
Q

What are the 2 types of cholinoceptors?

A

N₁/Nm - skeletal muscle

N₂/Nn - autonomic ganglia CNS

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14
Q

What is the effect of M3 receptors when activated?

A

M3 releases messengers and NO when activated

Non vascular smooth muscle contracts when M3 activated

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15
Q

Describe the ganglionic structure of the sympathetic nerves

A

Ach –> NA
Short pre ganglion , longer post ganglion

Ach –> Ach
Short pre ganglion , longer post ganglion

Ach lightly myelinated
slightly longer pre ganglion

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16
Q

Which neurotransmitter do most postganglionic parasympathetic neurons release?

A

Acetylcholine

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17
Q

What are the 2 neurones making up the autonomic system?

A

Parasympathetic
Sympathetic

Both have opposing effects on tissue (some tissues only have single nerve supply)

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18
Q

What are the different selective nicotinic antagonists?

A 
Tubocararine
Atropine
Hysocine hexamethonium 
Pirenzipene
Ipratorium paricuronium
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19
Q

What type of receptors are muscarinic receptors?

A

All muscarinic receptors are GPCRs involved in parasympathetic responses

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20
Q

What is the function of the Autonomic Nervous System?

A

Its a connection between the CNS and the peripheral organs

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21
Q

How do nAchR produce effects on their target cells?

A
  1. Ach binding causes a conformational change; opening
    channel pore
  2. Influx of cations
  3. Produces EJP (excitatory junction potential) in target
    cell
  4. Effect terminated by unbinding of Ach
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22
Q

What are some clinical uses of muscarinic blockers?

A
  • Paramedication e.g. hyoscine used before anasthesia to reduce secretions, sedation & prevent vagal effects
  • Heart - block mAchR to increase AV conduction
  • Opthamology - produce pupil dilation (mydriasis) for examination
  • Bronchodilation in COPD
  • Antispasmidic in GI Colic
  • Antiche poisoning treatment
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23
Q

Which neurotransmitter is present in all autonomic ganglia?

A

Acetylcholine

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24
Q

Which parasympathetic nerve effects cardiac heart rate?

A

Vagus nerve

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25
Q

What is Isoprenaline?

A

A synthetic research tool / medications used to treat slow heart rate

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26
Q

What is the effect of M2 and M4 receptors?

A

Coupled to Gₐ receptors
Decrease adenylate cyclase activity
Decreases [cAMP]

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27
Q

What are the muscarinic selective agonists?

A

Muscarine bethanescol

Pilocarpine

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28
Q

Name the various parasympathetic nerves and their location

A
  • Cranial Nerve III (oculamotor) - pupil
  • Cranial Nerve VII (facial) - submaxillary, sublingual,
    lacrimal glands
  • Cranial Nerve IX (glossopharyngeol) - parolid glands
  • Cranial Nerve X (Vagus) - heart, kidney, bronchi, GI tract
    to colon
  • Sacral Nerves - remainder of GI Tract, bladder, &
    Genitalia
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29
Q

Name the selective nicotinic agonists

A

Nicotine muscarine
Bethanecol
Lobeline
Pilocarpine

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30
Q

Where in the body do the 2 systems produce opposite effects?

A

Myocardium (heart rate & force) - PS decreases, S
increases

Intestine smooth muscle motility - PS increases, S decreases

Iris smooth muscle - PS constricted, S dilated

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31
Q

What is the parasympathetic effect of Ɣβ subunits on the heart?

A

βƔ subunits cause basal slowing of the heart
1. βƔ subunits dissociate and interact with K+ channel
GIRK
2. K+ channel permanently open - membrane
hyperpolarises
3. less Ca2+ channels open - less cAMP
4. slows heart rate - less pacemaker activity

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32
Q

How do sympathomimetric drugs work?

A

By directly binding to sympathetic adrenergic receptors

or indirectly by increasing NA levels

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33
Q

What are the 5 types of muscarinic receptors?

A

M1 - CNS, Peripheral neurons, gastric parietal cells
M2 - atria, SAN, AVN
M3 - Visceral smooth muscle, secretory glands,
endothelial cells
M4 - CNS
M5 - CNS

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34
Q

Which neurotransmitter do most postganglionic sympathetic neurons release?

A

Nor Adrenaline

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35
Q

What is the effect of the parasympathetic vagus nerve on heart rate?

A
  • Membrane potential hyperpolarises
  • Decreases action potentials
  • M2 muscarinic receptors negatively coupled to cAMP
  • less Ca2+uptake in SR
  • Pacemaker in SAN less effective
36
Q

What are the 2 types of adrenergic receptors?

A

α adrenergic receptors
- NA -> Adrenaline -> Isoprenaline

β adrenergic receptors
- Isoprenaline -> Adrenaline -> NA

37
Q

What are the clinical uses of nAchR blockers?

A

Muscle relaxants
Direct blockers : tubocurarine pancuronium, vecuronium, atacurilum
Depolarising blockers : suramethonium

38
Q

What are the two sections of sympathetic nerves?

A

Paravertebral chain of ganglia ~25

Prevertebral ganglia near aorta

39
Q

What is the major part of the autonomic sytem, cholinergic neurons work under?

A

Parasympathetic responses

40
Q

What is the use of adrenoceptor blockers?

A

Slow heart rate and improve profusion by increasing NA release
e.g. Atenolol

41
Q

How do parasympathomimetric drugs work?

A

Inhibit Achesterase

boost cholinergic transmission of parasympathetic nerve

42
Q

How do sympathetic postganglions produce physiological responses?

A

Release NA on adrenoceptors on organs

43
Q

Why does the parasympathetic nervous system have no vascular effect ?

A

There are no mucarinic receptors on SAN

M3 expressed on endothelial cells lining blood vessels

44
Q

How do NANC transmitters operate on the postganglionic sympathetic neurone?

A

Use ATP on neuropeptide Y

cause vasoconstriction

45
Q

What is GIRK k+ channel?

A

G-Protein coupled inwardly rectifying potassium channels activated via signal transduction

46
Q

Why do some postganglionic sympathetic neurones release Ach?

A

To stimulate Muscarinic Ach receptors on tissues

47
Q

Give examples of indirectly acting parasympathomimetics

A

Acetylcholinesterase Inhibitors: tacrine, donepzil, rivastigmine

  • used in dementia
  • clinically used in neuromuscular diseases
    e. g. myasthesia gravis, Eaton Lambert syndrome
48
Q

Where do the 2 systems produce similar effects?

A

In some salivary glands they both increase secretions

49
Q

Describe the structure of postganglionic motor / somatic neurons

A

Heavily myelinated to skeletal muscle (not part of ANS)

50
Q

Summarise the sympathetic nervous system

A

Thoracolumbar outflow
Short preganglionic fibres
NA main terminal messenger

51
Q

Which receptor type are adrenoceptors?

A

All adrenoceptors are G Protein Coupled Receptors

52
Q

Name the paraverterbral sympathetic nerves and where they’re located

A
  • Superior Cervical ganglia - pupil, facial glands, head
    circulation
  • Middle & Inferior ganglia - Heart and lungs
  • Remaining paravertebral ganglia - Sweat glands pilomotor (hair), muscles, skin blood vessels, and skeletal muscle
53
Q

What causes cation channels to open in pacemaker regions?

A

Funny channels allow cations into cells (via hyperpolarisation not depolarisation)
causing Voltage gated channels to open

54
Q

Do effector organs receive sympathetic or parasympathetic innervations?

A

Many effector organs receive signals from both parasympathetic and sympathetic
nerves with the effects often being opposite of each other

55
Q

Name the muscarinic selective antagonists

A

Atropine
Hyoscine
Pirenzipene
Ipratorium

56
Q

What is a sympathomimetric drug?

A

A drug that mimics the stimulation of the sympathetic nerves

57
Q

Where does the prevertebral ganglia function?

A

GI tract

58
Q

How does the NANC VIP function?

A

Vasoactive Intestinal Peptide
causes dilation
on salivary glands and bronchial smooth muscle

59
Q

Which tissues receive a single input from parasympathetic nerves only?

A
  • Ciliary eye muscles: accommodates near vision

- Pancreas & Sensory stomach cells - increased secretions

60
Q

Which autonomic nervous system do adrenergic effects work under?

A

The sympathetic nervous system

61
Q

What is the effect of Nitric Oxide NANC ?

A

Nitric oxide works on parasympathetic pelvic nerves

Causing an erection

62
Q

How do Somatic nevres produce physiological responses?

A

Release Ach onto nAchR on motor end plates

63
Q

Explain the effect of M1, M3 and M5 receptors

A

Coupled to G₉₁₁ receptors
Activate phospholipase C enzyme
PIP₂ –> IP₃ + DAG

64
Q

What are the parasympathetic effects on muscarinic receptors?

A
  • reduces heart rate
  • vasodilation
  • increased saliva & gastric acid production
  • increased tear formation
  • visceral smooth muscle contraction
  • pupil constriction
65
Q

What are the different physiological effects of adrenoceptors?

A

α₁ - Vascular smooth muscle contraction
α₂ - Inhibits transmitter release
β₁ - Main cardiac effects
β₂ - Vascular dilation, airway relaxation

66
Q

What is the effect of β₁ adrenoceptor on cardiac action potentials?

A

When stimulated, cardiac contractions are stronger but depolarisation action potentials are briefer

67
Q

Which tissues do sympathetic nerves supply a single input to?

A
  • Blood vessels: mainly constricted

- Sweat glands:increased secretions

68
Q

Summarise the parasympathetic nervous system

A

Saccrocranial outflow
Long preganglionic fibres
Ach main terminal messenger

69
Q

How is the α₁ adrenoceptor activated?

A
  1. Adrenaline or NA binds to α₁ receptor
  2. α₁ subunit on G protein activated
  3. Activates Phospholipase C enzyme
    - -> cleaves PIP₂ –> IP₃ + DAG
  4. IP₃ binds to its recptor on SR
  5. Causes release of Ca2+ from SR
70
Q

How do β adrenoceptors cause their respective effects?

A

β adrenoceptors are coupled to Adenyl Cyclase enzyme via Gₛ α subunit

71
Q

Outline how β₁ adrenoceptors cause stronger contraction force

A
  1. Adenyl Cyclase activated by NA binding to receptor
  2. ATP converted to cAMP
  3. cAMP interacts with pacemaker channel in SAN
  4. cAMP activates PKA
  5. PKA activates Ca2+ channels - influx of Ca2+
  6. Increased Ca2+ uptake in SR = stronger contractions
  7. Briefer = Ca2+ taken up faster
72
Q

How do α₂ adrenoceptors cause the negative feedback of neurotransmitter release?

A
  1. Ca2+ channels activity decreased on sympathetic
    nerve terminal
  2. NA released
  3. Less Ca2+ channels opened - negative feedback
  4. reduces levels of cAMP released
73
Q

What is the effect of adrenoceptors on vascular smooth muscle?

A
  1. K+ channels open –> k+ influx (hyperpolarisation)
  2. Cell ready for contraction again
  3. Cardiac stimulation increased by β₁ adrenoceptors
  4. β₁ & β₂ relax vascular smooth muscle (esp. airways)
74
Q

What is the effect of an activated α₁ adrenoceptor?

A

Contraction of:

  • Vascular smooth muscle
  • Iris muscle (pupil dilation)
  • Pilomotor muscle
75
Q

Which antagonist is a parasympathomimetric drug effecting the eye?

A

Atropine belladonna blocks cholinergic receptors in the eye causing the pupilto open

76
Q

Explain how β₂ adrenoceptors are activated

A
  1. more K+ activity (than in cardiac cells)
  2. less dominant release process
  3. Ca2+ uptake
  4. PKA inhibits smooth muscle contraction as
    tropomyosin not phosphorylated
77
Q

Outline how β adrenoceptors cause renin release in kidney

A

Juxta glomular apparatus (JGA) located between afferent and efferent renal
arteries => increase renin release when:
Angiotensinogen (inactive) –> Angiotensin I (active)

78
Q

Name some directly acting parasympathomimetics and their functions

A

Pilocarpine (mAchr agonist) - treats glucoma & dry mouth, used in sweat tests

Bethanecol (mAchR agonist) - occasionally used to aid bladder/gastric emptying

Succinylcholine (nAchR agonist) - high affinity: used in surgery depolarising paralysis

79
Q

What other processes are β adrenoceptors involved in?

A
  • Carbohydrate metabolism (β₁)
  • Renin release from kidney
  • Lipolysis (β₃)
80
Q

How is Glucoma caused?

A

Stems from poor drainage of fluid though trabecular network

often due to dilated iris

81
Q

What is the sympathetic effects of α₁ receptors on the eye?

A

α₁ contraction of radial muscle
Muscarinic receptors on ciliary muscles
- pull on suspensory ligaments allowing lens to bulge

82
Q

Summarise the effect of adrenoceptors on smooth muscle

A

Increased cAMP –> decreased Ca2+ release / increased K+ channel activity
–> decreased myosin light chain kinase –> decreased contraction

83
Q

Name some uses of adrenoceptor agonists

A

Eye drops - ephedrine, brimonidine
Nasal decongestant - phenylephrine, ephedrine
Prolongation of local anaesthetic - adrenaline
Asthma inhalers - salbutamol (ventolin)
Cardiac stimulants - adrealine, dobutamine
Anti-obesity - BRL37344 in development
Acute anaphylaxis - adrenaline
Premature labour - β agonists
Overactive bladder - β₃ agonist mirabegron

84
Q

What is parathion?

A

Parasympathomimetic: Highly toxic cholinesterase inhibitor

so Ach not broken down

85
Q

What causes the effect of adrenoceptors on cardiac and smooth muscle to be so different?

A

Despite the same receptors and process, the effect is opposite due to the difference in cell type

Pharmacology & Physiology 1 (9 decks)

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