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FPP > Physiology/Pharmacology of the autonomic nervous system > Flashcards

Physiology/Pharmacology of the autonomic nervous system Flashcards

1
Q

What are the 3 sub divisions of the nervous system?

A
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2
Q

What does the autonomic nervous system do?

A

It conveys output of the CNS to the rest of the body except for motor innervation of the skeletal muscle - this is controlled by the somatic nervous system.

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3
Q

branches of ANS

A

Sympathetic NS
Parasympathetic NS
Enteric NS

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4
Q

what is the sympathetic NS

A

flight/fight/fright response
usually excitatory response
adrenergic receptor at target tissue (exception)
noradrenaline main neurotransmitter

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5
Q

what is the parasympathetic NS

A

rest/digest or feed/breed system
usually inhibitory response
muscarinic receptor at target tissue
acetylcholine main neurotransmitter

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6
Q

what is the enteric NS

A

located within and controls gastrointestinal tract
second brain (can act independent of CNS)
controls motor movement and enzymatic secretion in gut
Acetylcholine, dopamine, serotonin

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7
Q

in the sympathetic nervous system where does the pre synaptic neuron start

A

Pre-synaptic neuron starts from the middle of the spinal cord (Thoracic region and Lumbar region).

Short pre-synaptic neuron and long post-synaptic neuron

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8
Q

where does the pre synaptic Neuron start from in the parasympathetic nervous system

A

Pre-synaptic neuron starts from the brainstem and the sacral region of the spinal cord.

Long pre-synaptic neuron and short post-synaptic neuron

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9
Q

where is the ANS located and what it function without

A

located outside CNS but cannot function without it

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10
Q

in the parasympathetic nervous system, where are pre ganglionic cell bodied located?

A

Preganglionic cell bodies located in brainstem and sacral region of SC.

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11
Q

in the sympathetic nervous system, where are pre ganglionic cell bodied located?

A

Preganglionic cell bodies located in the lateral gray of spinal cord

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12
Q

what acts like a modified ganglion?

A

Adrenal gland acts like a modified ganglion and there is no post-synaptic neuron

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13
Q

what happens in the sympathetic nervous system

A
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14
Q

what happens in the para sympathetic nervous system

A
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15
Q

the pre synaptic neuron in SNS and PNS are both

A

cholinergic (Ach neurotransmitter)

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16
Q

what is the post synaptic neuron in the SNS

A

adrenergic

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17
Q

what is the post synaptic neuron in the PNS

A

cholinergic

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18
Q

what is the post synaptic neuron in the somatic NS

A

doesnt have one

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19
Q

what are the 2 receptors in the parasympathetic nervous system

A

nicotinic receptor
muscarinic receptor

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20
Q

what is the structure of nicotinic receptor

A

Pentameric ligand gated ion channel

5 subunits made up of α, β, γ, δ, ε

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21
Q

what subunits is a ganglionic nicotinic receptor made of

A

α2β3 subunits

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22
Q

what subunits is a NMJ (neuromuscular junction) nicotinic receptor made of

A

α2βδε

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23
Q

what is needed for activation in a nicotinic receptor

A

2 Ach molecules need to bind to 2a subunits for activation

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24
Q

where is a nicotinic receptor found

A

found at autonomic ganaglia, NMJ and CNS

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25
Q

are nicotinic receptors excitatory or inhibitory?

A

excitatory signalling, increased cation permeability (mainly Na/ K)

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26
Q

what structure does a muscarinic receptor have

A

g protein coupled receptors (7 transmembrane domain)

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27
Q

how many types of muscarinic receptors are there

A

5 types (m1-m5)

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28
Q

in muscarinic receptors, what increases the intracellilar calcium and activates PKC (excitatory signalling)

A

M1, M3, M5 coupled with GQ activated phospholipase C

increases IP3 and DAG pathway

increases intracellular calcium and activated PKC

29
Q

in muscarinic receptors what dcereases intracellular calcium

A

M2, M4 coupled with Gi inhibits adenyl cyclase

decreases cAMP pathway

decreases intracellular calcium and increases K+ conductance (inhibitory signalling)

30
Q

Describe the M1, M3, M5 cholinergic receptor signalling pathways

A

M1, M3, M5 coupled with Gq activates phospholipase C (PLC) to increase IP3 and DAG pathway that increase intracellular calcium and activate PKC(excitatory signalling)

31
Q

Describe the M2, M4 cholinergic receptor signalling pathways

A

M2, M4 coupled with Gi which inhibits adenyl cyclase and decreases the cAMP pathway and decreases intracellular calcium. It also increases K+ conductance (inhibitory signalling).

32
Q

where are muscarinic receptors found

A

target tissues (heart, glands, smooth muscles)

33
Q

what happens in parasympathetic signalling of the M2 muscarinic recptor in the heart

A
  1. Ach binds to M2 receptor
  2. alpha subunity in g-protein stops adenyl cyclase from making cyclic amp
  3. cyclic amp needed for HCN channel activation (which are found in sino atrial node - which dictates heart rate. activating HCN = increased heart rate, deactivating HCN = decreased heart rate)
  4. therefore Ach activates m2 receptor, adenyl cylase activity decreases, cyclic amp decreases, HCN channel decreases - heart rate decreases
  5. the beta, gamma part of g protein activates K channel, causing hyperpolarisation, cell excitability goes down, heart rate goes down

SUMMARY: Decreased probability of HCN channel in SAN (sinoatrial node) and increased potassium current (hyperpolarization)

34
Q

What is the rate limiting step in the synthesis of Ach

A

Uptake of choline (made by liver or from diet) into the nerve terminal vis sodium dependent choline transporter is the rate limiting step in the synthesis of Ach.

35
Q

how does the acetylation of choline happen

A

Choline acetyltransferase catalyses acetylation of choline using acetyl CoA.

36
Q

what are the 6 ways we can modulate (modify) signal transduction

A
  1. synthesis
  2. storage
  3. release
  4. receptor
  5. reuptake
  6. degradation
37
Q

what medication causes bronchoconstriction in asthma?

A

In asthma, bronchoconstriction happens due to the action of Ach on muscarinic receptors on smooth muscle cells in the airways.

When Ach binds to Ms receptors, it activates a pathway involving Gq proteins, which activates enzyme PLC

PLC activation leads to the production of IP3, which opens calcium (Ca²⁺) channels.

The influx of Ca²⁺ into the muscle cells increases muscle contraction, causing the airways to narrow.

Ipratropium bromide is an anticholinergic medication/ antagonist that blocks the action of Ach at the muscarinic receptors. This prevents the cascade that leads to Ca²⁺ increase and smooth muscle contraction, ultimately reducing bronchoconstriction and helping to open up the airways.

38
Q

how can we stop the symptoms of overactive bladder, what medication does this?

A

In an overactive bladder, acetylcholine (Ach) binds to muscarinic receptors on bladder smooth muscle cells, especially the M3 receptors.

This leads to contraction of the bladder muscle (detrusor muscle), causing frequent urination.

Darifenacin hydrobromide is a selective M3 muscarinic receptor antagonist. By blocking the M3 receptors, it prevents Ach from binding and activating these receptors in the bladder.

Without Ach binding to the M3 receptors, the pathway leading to muscle contraction is not triggered. This helps reduce involuntary bladder contractions and decreases the urgency and frequency of urination associated with overactive bladder.

THE DRUG BETMIGA ALSO DOES THE SAME THING

39
Q

how can we stop the symptoms of IBS/ stomach cramps, what medication does this?

A

In the digestive tract, smooth muscle contraction (which can lead to cramps and pain) is often driven by acetylcholine (Ach) binding to muscarinic receptors on muscle cells, specifically the M3 receptors. This binding increases muscle contractions, leading to the cramps associated with conditions like IBS.

Buscopan is an antimuscarinic medication that acts as an antagonist at muscarinic receptors in the digestive tract, especially at M3 receptors. By blocking these receptors, Buscopan prevents Ach from binding and activating them.

With Ach blocked from reaching these receptors, the signal to contract the smooth muscles in the intestines is reduced. This helps relax the muscles and relieves the spasms, cramps, and discomfort associated with IBS and other stomach cramps.

40
Q

what does bethanechol do?

A

Bethanechol directly stimulates muscarinic receptors in the smooth muscle of organs like the bladder and gastrointestinal (GI) tract. By activating these receptors, it increases muscle contractions, particularly in situations where muscle tone may be too low (such as a weak bladder or GI tract).

Bethanechol STIMULATES muscarinic receptors, it promotes bladder contraction and helps empty the bladder or improves bowel motility.

^ THEREFORE OPPOSITE OF BUSCOPAN WHERE IT STOPS THAT

41
Q

what receptor is found in the sympathetic nervous system

A

adrenergic receptor

( remember PNS was nicotinic and muscarinic)

42
Q

how many types of adrenergic receptors are there and what are they called?

A

Adrenergic receptor (α1, α2, β1, β2, β3)

43
Q

whats the structure of adrenergic receptor

A

G-protein coupled receptors (7 transmembrane domain)

44
Q

where are adrenergic recptors found

A

Found at target tissues (heart, lungs, glands, smooth muscles)

45
Q

in adrenergic signalling what causes an increase in intracellular calcium and activate PKC.

A

α1 coupled of Gq which activates phospholipase C (PLC) to activate IP3 and DAG pathway that increase intracellular calcium and activate PKC.

46
Q

in adrenergic signalling what causes a decrease in intracellular calcium and inhibits PKA.

A

α2 coupled of Gi which inhibits adenyl cyclase and decreases the cAMP pathway to decrease intracellular calcium and inhibit PKA.

47
Q

in adrenergic signalling what causes an increase in intracellular calcium and activates PKA.

A

β1, β2, β3 coupled of Gs which activates adenyl cyclase to increase intracellular calcium and activate PKA.

48
Q

3 main types of g proteins

A

Gq- stimulatory
coupled to PLC

Gs- stimulatory
coupled to adenylyl cyclase

Gi - inhibitory
coupled to adenylyl cyclase

49
Q

what are the 4 adrenergic receptors coupled to?

A

alpha-adrenergic receptors:

A1 - coupled to Gq

A2 - coupled to Gi

Beta-adrenergic receptors:

B2, B2 - coupled to Gs

50
Q

Describe alpha 1 adrenergic receptor signalling pathways

A

α1 coupled of Gq which activates phospholipase C (PLC) to activate IP3 and DAG pathway that increase intracellular calcium and activate PKC.

51
Q

Describe alpha 2 adrenergic receptor signalling pathways

A

α2 coupled of Gi which inhibits adenyl cyclase and decreases the cAMP pathway to decrease intracellular calcium and inhibit PKA.

52
Q

Describe beta 1,2,3 in adrenergic receptor signalling pathways

A

β1, β2, β3 coupled of Gs which activates adenyl cyclase to increase intracellular calcium and activate PKA.

53
Q

what happens in sympahtetic signalling involving β1 adrenoceptors in heart

A
  1. adrenaline binds to B1 receptor (B1 is coupled with Gs)
  2. alpha subunit in g protein activates adeynyl cyclase
  3. this increases cyclic amp production
  4. increased HCN channel = heart rate increase
  5. also activated PKA which phosphorylates L-type calcium ion, increasing calcium levels = increased heart rate

SUMMARY: Increased probability of HCN channel, Increased intracellular calcium entry from L-type calcium channel, causes increased heart rate)

54
Q

what is the main neurotransmitter in sympahtetic neurone

A

noradrenaline

55
Q

in the sympathetic synapse, what happens to the neurotransmitter in the synaptic cleft, is it degraded?

A

no its not degraded like the PNS like Ach, they get taken back up by NET (NOREPINEPHRINE) and packaged into vesicles again

56
Q

what is the sequence of events in a sympathetic neurone

A
57
Q

why is an A2 receptor found on presynaptic terminal

A

its an inhibitory signal, stopping further transmission/ exocytosis - ie a negative feedback system

58
Q

what do antidepressants do

A

stop NAT

59
Q

People on MAO inhibitors must avoid diet containing what

A

People on MAO inhibitors (stops breakdown of NET, norepinephrine) must avoid diet containing high level of tyramine, such as cheese and wine. Tyramine can cause hypertensive crisis.

60
Q

what is Direct sympathomimetics

A

drugs that directly activate adrenoceptors and mimic the physiological effects of these receptors. E.g. phenylephrine

61
Q

what is Indirect sympathomimetics

A

drugs that do not directly activate the adrenoceptors but achieve the same effect by increasing the concentration of noradrenaline in the synaptic cleft (increased neurotransmitter release). E.g. amphetamine (stimulant), tyramine (cheese effect with MAO inhibitors), ephedrine (nasal decongestant)

62
Q

what drug causes the opposite effect of ipratropium bromide

A

salbutamol - b2 agonist

63
Q

what medication causes bronchodilation in asthma?

A

Salbutamol targets beta-2 (B2) receptors on the smooth muscle cells in the airways. It is a B2 agonist, which means it stimulates these receptors.

When salbutamol binds to the B2 receptors, it triggers a pathway that relaxes the smooth muscles around the airways.

This muscle relaxation leads to bronchodilation—the airways widen, making it easier to breathe by reducing tightness and allowing more air to flow in and out of the lungs.

64
Q

whats 2 drugs are used to treat hypertension

A

clonidine = alpha 2 agonist

prazosin = alpha 1 antagonist

65
Q

what drugs restarts the heart, anaphylaxis

A

adrenaline - non selective adrenergic receptor agonist

66
Q

what is an example of when the SNS and PNS work together

A

baroreceptor reflex which stabilizes the blood pressure

micronutrition

67
Q

in SNS bladder filling, what causes relaxation and what causes contraction

A
68
Q

in PNS micronutrition what causes contraction and relaxation

A

FPP (9 decks)

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