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Quick Revision > Autonomic Pharmacology > Flashcards

Autonomic Pharmacology Flashcards

1
Q

What is the rate limiting step of synthesis of ACh?

A

Uptake of choline via transporter (CHT)

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2
Q

What is ACh synthesised from and by which enzyme?

A

Choline and AcCoA by choline acetyl transferase

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3
Q

What happens to ACh once it has been synthesised?

A

Stored in vesicle via a transporter

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4
Q

What happens after depolarisation via an action potential?

A

Ca influx via voltage activated Ca channels

Ca induced release of ACh from vesicles

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5
Q

Once ACh has been released from vesicles via exocytosis what happens?

A

Activation of ACh receptors (nicotinic or muscarinic) causing cellular response

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6
Q

What is responsible for the termination of cholinergic transmission?

A

Degradation of ACh to choline and acetate by AChe

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7
Q

Describe skeletal muscle ACh receptors

A

2 a1
1 y
1 sigma E
1 b1

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8
Q

Describe ganglionic ACh receptors

A

2a3

3B4

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9
Q

What is the primary cause of cholinergic excitatory transmission at ganglia ?

A

Caused by ACh release from preganglionic neurones that activate cation-selective receptors of the postganglionic neurone cell body to elicit excitatory postsypnaptic potential (epsp)

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10
Q

What are most postganglionic neurones innervated by?

A

Most parasympathetic and sympathetic postganglionic neurones are innervated by several presynaptic fibres

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11
Q

Why are ganglion blockers obsolete?

A

Because they have a constellation of effects

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12
Q

How can blockade of cholinergic transmission be achieved?

A
  • Depolarisation block by high concentrations of agonists (e.g. nicotine)
  • Competitive antagonism (e.g. trimetaphan)
  • non-competitive antagonism
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13
Q

Give an example of a drug which blocks cholinergic transmission of ganglia non-competitively

A

Hexamethonium

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14
Q

What are M1, M2 and M3 coupled to?

A

Gq, Gi, Gq

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15
Q

Describe the effect of M1 GPCR at parasympathetic neuroeffector junctions?

A

Gq stimulates phospholipase C and increases acid secretion in the stomach

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16
Q

Describe the effect of M2 GPCR at parasympathetic neuroeffector junctions?

A

Gi inhibits adenylyl cyclase; opening K+ channels this decreases heart rate

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17
Q

Describe the effect of M3 GPCR at parasympathetic neuroeffector junctions?

A

Gq stimulates phospholipase C and increases saliva secretion and contracts visceral smooth muscle

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18
Q

What is the effect of M3 on vascular smooth muscle?

A

Indirectly relaxed by M3 receptor activation via NO

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19
Q

Describe the differences between noradrenergic transmission at sympathetic neuroeffector junctions in comparison to cholinergic transmission at parasympathetic neuroeffector junctions

A

NA not ACh

ACh is degraded into choline and acetate to terminate transmission vs NA is reuptaken by U1 on neurone and U2 on effector cell

NA is metabolised by MAO in the neurone and COMT in the effector cell

NA effector cel is cardiac and smooth muscle vs ACh smooth muscle, gland cell

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20
Q

Which GPCR are involved at sympathetic neuroeffector junctions?

A

B1, B2, a1, a2

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21
Q

Describe the function of B1

A

Coupled to Gs

Stimulates adenylyl cyclase

Increased heart rate and force

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22
Q

Describe the function of B2

A

Coupled to Gs

Stimulates adenylyl cyclase

Relaxes bronchial and vascular smooth muscle

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23
Q

Describe the function of a1

A

Coupled to Gq

Stimulation of phospholipase C

Contraction of vascular smooth muscle

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24
Q

Describe the function of a2

A

Coupled to Gi

Inhibits adenylyl cyclase

Inhibition of NA release

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25
Q

Presynaptic autoreceptors mediate ——– ——– ——— of transmitter release.
——– decrease release, ———- increase release

A

Presynaptic autoreceptors mediate negative feedback inhibition of transmitter release. Agonists decrease release, antagonists increase release

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26
Q

Explain how cocaine works?

A

Blocks U1 on nerve terminal of sympathetic post-ganglionic neurone

Increases the amount of NA in the synaptic cleft, resulting in increased stimulation of adrenoreceptors

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27
Q

Describe the peripheral actions of cocaine

A 
Vasoconstriction (a1)
Cardiac arrhythmias (B1)
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28
Q

Explain how amphetamine works?

A

Substrate for U1 on nerve terminal of sympathetic post-ganglionic neurone and inhibits MAO, enters the synaptic vesicle and displaces NA into the cytoplasm. NA works backwards of U1 and accumulates in cleft causing increased adrenorecptor stimulation

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29
Q

Describe the action of Prazosin

A

Selective, competitive, antagonist of a1. Does not block a2, b1, or b2. Vasodilator used as an anti-hypertensive agent

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30
Q

Describe the action of Atenolol

A

Selective, competitive, antagonist of b1. Does not block b2, a1, or a2. Used as an anti-anginal and anti-hypertensive agent

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31
Q

Describe the action of salbutamol

A

Selective agonist at b2. Does not activate, b1, a1, or a2.

Used as a bronchodilator in asthma

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32
Q

Describe the action of

atropine

A

Competitive antagonist of muscarinic ACh receptors, does not block nicotinic ACh receptors. Blocks all muscarinic ACh receptors with equal affinity (1, 2, 3) – exerts widespread effects by blockade of the parasympathetic division of the ANS

Used to reverse bradycardia following MI and in anticholinesterase poisioning

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33
Q

List the divisions of the ANS

A

Enteric
Sympathetic
Parasympathetic

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34
Q

List the divisions of the PNS and their functions

A

Somatic efferent (i.e. motor fibres to skeletal muscle)

Autonomic (ANS) motor and sensory components

Somatic afferent (i.e sensory fibres from skin and skeletal muscle)

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35
Q

List some ANS reflexes that can be trained?

A

micturition, defecation via voluntary control of skeletal muscle external sphincters of the urethra and anus commanded by somatic efferents)

(focus of the lens, for near vision) can be voluntarily controlled, despite it being an autonomic function

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36
Q

Describe the organisation of the motor ANS

A

Preganglionic neurone, ganglion outside CNS, post ganglionic neurone which terminates at effector cells

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37
Q

What is the transmitter of preganglionic neurones sympathetic/parasympathetic

A

ACh acting via excitatory nicotinic cholinoceptors

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38
Q

What is the classical transmitter for postganglionic neurones

A

NA or ACh

39
Q

Which division of the ANS has a long preganglionic neurone?

A

Parasympathetic division

40
Q

What is the outflow of sympathetic and parasympathetic respectively?

A

Thoracolumbar from spinal cord, craniosacral from brainstem and spinal cord

41
Q

What are the parasympathetic and sympathetic effector cells respectively?

A

Muscarinic cholinoceptors

Adrenoreceptors

42
Q

Where do sympathetic preganglionic neurones synapse with postganglionic neurones?

A

Either in paravertebral ganglia or prevertebral ganglia

43
Q

Sympathetic postganglionic neurones innervate effector cells in organs ———- to the sympathetic ganglia. Their axons (fibres) are generally ———

A

Sympathetic postganglionic neurones innervate effector cells in organs distant to the sympathetic ganglia. Their axons (fibres) are generally long

44
Q

Sympathetic preganglionic fibres —– extensively to synapse with many postganglionic neurones located in one, or several, —- or —–vertebral ganglia. The effect of sympathetic stimulation may sometimes be ——— (as in the ‘fight or flight’ reaction)

A

Sympathetic preganglionic fibres branch extensively to synapse with many postganglionic neurones located in one, or several, pre- or para-vertebral ganglia. The effect of sympathetic stimulation may sometimes be widespread (as in the ‘fight or flight’ reaction)

45
Q

Parasympathetic preganglionic neurones synapse with postganglionic neurones in ——— ganglia that are —— to the CNS and often located in the —– of the target organ. Their axons (fibres) are thus —-. Correspondingly, the fibres of the postganglionic neurones are —–

A

Parasympathetic preganglionic neurones synapse with postganglionic neurones in terminal ganglia that are distant to the CNS and often located in the walls of the target organ. Their axons (fibres) are thus long. Correspondingly, the fibres of the postganglionic neurones are short

46
Q

Typically, preganglionic fibres, both sympathetic and parasympathetic are ——— (see lecture upon the action potential) and are termed —– - —–. They give a —– appearance.

By contrast, postganglionic fibres are largely ———— and appear —- and are termed motor - —–

A

Typically, preganglionic fibres, both sympathetic and parasympathetic are myelinated (see lecture upon the action potential) and are termed motor B-fibres. They give a white appearance. By contrast, postganglionic fibres are largely unmyelinated and appear grey and are termed motor C-fibres

47
Q

List the sympathetic prevertebral ganglion

A

1 coeliac
2 aorticorticorenal,
3 superior mesenteric
4 inferior mesenteric prevertebral ganglia

48
Q

Describe the sympathetic innervation of the adrenal gland

A

the innervation is pre ganglionic and the transmitter is ACh, not NA.
The medulla of the gland releases adrenaline (A) and NA as hormones

49
Q

Where are preganglionic sympathetic fibres locates in the spinal cord?

A

Intermediolateral cell column (lateral horn)

50
Q

How do preganglionic sympathetic fibres exit the spinal cord?

A

ventral (anterior) roots, follow the spinal nerves and white rami communicantes (at levels T1 to L2/3) and then synapse with postganglionic cell bodies

51
Q

Describe the synapsing of preganglionic sympathetic fibres at paravertebral ganglion.

A

paravertebral sympathetic ganglia, from which the postganglionic fibres join the peripheral nerves, via grey rami communicantes, to travel to their target organs in the skin and blood vessels

52
Q

Describe the synapsing of preganglionic sympathetic fibres at prevertebral ganglion.

A

prevertebral sympathetic ganglia of the abdomen via paravertebral ganglia (without synapsing), and onwards in splanchnic nerves to internal organs/vessels

53
Q

Describe the function of chromaffin cells?

A

Chromaffin cells are modified postganglionic neurones that secrete, primarily adrenaline (80%), but also NA (20%) that enter the capillary circulation as hormones

54
Q

Describe the sympathetic innervation of thermoregulatory eccrine sweat glands

A

cholinergic: thus the transmitter is ACh, not NA. Correspondingly, the receptors on the effector cells are muscarinic cholinoceptors, not adrenoceptors. However, the postganglionic fibres innervating the stress (apocrine) sweat glands are adrenergic and activate adrenoceptors

55
Q

What is special about the innervation of pelvic plexus?

A

Preganglionic fibres also innervate neurones in the pelvic plexuses

56
Q

What additional transmitters do postganglionic sympathetic fibres store?

A

adenosine triphosphate (ATP) and neuropeptide Y (NPY)

57
Q

Which cranial nerves are responsible for parasympathetic outflow?

A

III, VII, IX & X

58
Q

Where are parasympathetic usually located?

A

in the target organs (discrete ganglia in head and neck and some plexuses in the pelvis)

59
Q

What level are the sacral spinal nerves?

A

S2-S3

60
Q

What do the pelvic splanchnic nerves innervate?

A

viscera

61
Q

Where are preganglionic parasympathetic fibres located?

A

Brainstem (cranial outflow) comprising midbrain, pons and medulla
OR
Sacral segments (S2-S4)

62
Q

Which nerve originates in the midbrain where is its ganglion and what is its target?

A

CN III
Ciliary
Eye (pupillary constrictor and ciliary body)

63
Q

Which nerve originates in the pons, where is its ganglion and what is its target?

A

CN VII (facial)

Pterygopalatine
Submandibular

Lacrimal glands, glands of nasal cavity
Submandibular and sublingual salivary glands

64
Q

Which nerves originate in the medullar oblongata, where is its ganglion and what is its target?

A

CN IX
CN X

Otic
Widespread

Parotid salivary glands
Bronchial tree, hear, liver, pancreas, upper GI tract

65
Q

Where do preganglionic fibres of the sacral outflow travel?

A

Along the sacral nerves, synapsing upon postganglionic neurones in the walls of the visceral organs in the abdominal and pelvic cavities

66
Q

What additional transmitters do postganglionic parasympathetic fibres release?

A

NO and VIP

67
Q

Describe the process of chemical transmission in the sympathetic ANS

A
  1. Action potential originating in the CNS
  2. travels to presynaptic terminal of preganglionic neurone, triggering Ca2+ entry through voltage-gated, calcium selective, ion channels and the release of ACh by exocytosis
  3. ACh binds to and opens ligand-gated ion channels (nicotinic ACh receptors) in the postganglionic neurone, causing depolarization and the initiation of action potentials that propagate to the presynaptic terminal of the neurone, triggering Ca2+ entry and the release, usually, of noradrenaline
  4. noradrenaline activates G-protein-coupled adrenoceptors in the effector cell membrane to cause a cellular response via ion channels/enzymes
68
Q

Describe the process of chemical transmission in the parasympathetic ANS

A

The process is very similar to that described for the sympathetic division, with the important exceptions that:

  1. ACh is always the classical transmitter used by postganglionic neurones
  2. ACh activates G-protein- coupled muscarinic acetylcholine receptors in the effector cell membrane to cause a cellular response via ion channels/ enzymes
69
Q

What is NANC transmission

A

non-adrenergic, non-cholinergic transmission

70
Q

Describe cotransmission

A

NA or ACh are co-released with a NANC co-transmitter (or modulator), the best studied substances being:

  1. adenosine triphosphate (ATP) and neuropeptide Y (NPY) from sympathetic fibres
  2. nitric oxide (NO) and vasoactive intestinal peptide (VIP) from parasympathetic fibres
71
Q

Give an example of co-transmission in the ANS with regards to electrical stimulation of postganglionic sympathetic fibre to vessel

A
  1. ATP produces a fast contraction of the smooth muscle
  2. Noradrenaline produces a moderately fast response
  3. Neuropeptide Y produces a slow response
72
Q

Give an example of co-transmission in the ANS with regards to electrical stimulation of postganglionic parasympathetic fibre to vessel

A
  1. Acetylcholine and nitric oxide produce a rapid relaxation

2. Vasoactive intestinal peptide can produce a slow, delayed response

73
Q

Which receptors exist as nicotinic ACh receptors in the ganglia

A

LGICs LIGAND GATED ION CHANNELS, selectively activated by the plant alkaloid nicotine

74
Q

Which receptors exist as muscarinic ACh receptors in the ganglia

A

G-protein-coupled receptors (GPCRs), selectively activated by the plant alkaloid, muscarine

Structurally and pharmacologically defined as five subtypes: M1, M2, M3, M4 and M5 that are differentially expressed across tissues/organs, M1-3 being most important in the ANS

75
Q

How are adrenoreceptrs (GPCRs) classified

A

Clinically important subclasses of adrenoceptors, with differing tissue locations, have been characterised structurally and pharmacologically as α1, α2, β1, β2 and β3, all of which are selectively targeted by current therapeutic agents

76
Q

What is the affect of sympathetic stimulation upon the heart?

A

Increases heart rate (β1)

Increases force of contraction in atria and ventricles (β1)

77
Q

What is the affect of parasympathetic stimulation upon the heart?

A

Decreases heart rate (M2) and force (M2) in atria

78
Q

What is the affect of sympathetic stimulation upon the lungs?

A

Relaxes bronchi (β2)
Decreases mucus production (β2)
(decreased airway resistance)

79
Q

What is the affect of parasympathetic stimulation upon the lungs?

A

Constricts bronchi (M3)
Stimulates mucus production (M3)
(increases airway resistance)

80
Q

What is the affect of sympathetic stimulation upon the GI tract?

A 
Reduces intestinal motility (α1, α2, β2)
Constricts sphincters (α1, α2, β2)
81
Q

What is the affect of parasympathetic stimulation upon the GI tract?

A 
Increases intestinal motility and secretions (M3)
Relaxes sphincters (NO, M3)
82
Q

What is the affect of sympathetic stimulation upon the vasculature?

A

Constricts vasculature in most locations (α1), but relaxes in skeletal muscle (β2)

83
Q

What is the affect of parasympathetic stimulation upon the vasculature?

A

Largely no effect, but relaxes vasculature in a few locations (e.g. penis, salivary glands, pancreas (NO, M3)

84
Q

What is the affect of sympathetic stimulation upon the adrenal gland?

A

Release of adrenaline from adrenal medulla (nicotinic AChR)

85
Q

What is the affect of parasympathetic stimulation upon the adrenal gland?

A

None

86
Q

What is the affect of sympathetic stimulation upon the bladder?

A

Relaxes wall (detrusor) of bladder (β2/β3), constricts internal urethral sphincter (α1)

87
Q

What is the affect of parasympathetic stimulation upon the bladder?

A

Contracts wall of bladder (M3), relaxes internal urethral sphincter (NO)

88
Q

What is the affect of sympathetic stimulation upon the male reproductive system?

A

Ejaculation (α1)

89
Q

What is the affect of parasympathetic stimulation upon the male reproductive system?

A

Penile erection (NO, M3)

90
Q

During filling of the bladder ——- activity predominates

A

sympathetic

91
Q

Describe sympathetic activity in filling of the bladder

A

the detrusor is relaxed by the release of NA (NE) that activates β2/β3-adrenoceptors

the internal urethral sphincter is constricted by the release of NA that activates α1-adrenoceptors

92
Q

During voiding of the bladder ——- activity predominates

A

parasympathetic

93
Q

Describe parasympathetic activity in voiding of the bladder

A

the detrusor is contracted by the release of ACh that activates M3-muscarinic ACh receptors

the internal urinary sphincter is relaxed by the release of NO that stimulates the production of cGMP (a relaxant) in smooth muscle cells

94
Q

Describe training of the micturition reflex

A

voluntary control is exerted by somatic efferents that release ACh to contract the skeletal muscle external urethral sphincter surrounding the urethra via nicotinic ACh receptors

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