M&R Session 10 Flashcards
(104 cards)
1
Q
Is the ANS efferent, afferent or both?
A
Entirely efferent
2
Q
What type of input regulates the ANS?
A
Afferent inputs
3
Q
Where do parasympathetic nerves originate from?
A
Lateral horn of medulla and sacral spinal cord
4
Q
Describe parasympathetic pre-ganglionic neurones.
A
Long
Myelinated
5
Q
Describe parasympathetic post-ganglionic neurones.
A
Short
Unmyelinated
6
Q
Where are the ganglia in the parasympathetic division of the ANS?
A
Target tissues
7
Q
Where do sympathetic nerves originate in the sympathetic nervous system?
A
Lateral horn of lumbar and thoracic spinal cord
8
Q
Describe sympathetic preganglionic nerves.
A
Short
Myelinated
9
Q
Describe sympathetic postganglionic nerves.
A
Long
Unmyelinated
10
Q
Where are sympathetic ganglia found?
A
Paravertebral chain
11
Q
Which neurotransmitter is used in all preganglionic neurones?
A
ACh
12
Q
What type of receptors are found on postganglionic neurones in both the sympathetic and parasympathetic nervous systems?
A
Nicotinic AChR
13
Q
Which neurotransmitter and corresponding receptor do postganglionic parasympathetic neurones use?
A
ACh
mAChR
14
Q
Which type of neurotransmitter and corresponding receptor do postganglionic sympathetic neurones utilise?
A
NA
Alpha and beta adrenoceptors
15
Q
How may genes code for adrenoceptors in the human genome?
A
9
16
Q
Are all sympathetic postganglionic neurones noradrenergic?
A
Nope
17
Q
Which sympathetic postganglionic neurones are cholinergic?
A
Sweat glands
Piloerector muscles
18
Q
When can NANC transmitters be released?
A
Coreleased w/NA or ACh
19
Q
Give four examples of NANC transmitters.
A
ATP
Nitric oxide
5-hydroxytryptamine
Neuropeptide
20
Q
How is ATP used as a NANC transmitter?
A
Copackaged into vesicles, especially w/NA
21
Q
What does ATP use as a NANC transmitter regulate?
A
BP
22
Q
Give two examples of neuropeptides used as NANC transmitters.
A
Vasoactive intestinal peptide
Substance P
23
Q
What do sympathetic postganglionic neurones in the adrenal glands differentiate to form?
A
Neurosecretory chromaffin cells
24
Q
What is the function of chromaffin cells?
A
Release adrenaline into blood
25
What type of receptors are found in chromaffin cells?
nAChR
26
Which area/s of the heart does parasympathetic ACh release act on?
Atria - sparse if any input to ventricles
27
What two effects does activation of M2 receptors by ACh have in the heart?
SAN --> bradycardia
| AVN --> decrease cardiac conduction velocity
28
Which receptor subtype is found in the lungs and GI tract and is activated by ACh?
M3
29
What is the affect of ACh release on the lungs and GI tract?
Lungs - bronchial contraction
| GI - increased mobility and secretion
30
What are the effects of ACh release on the GU tract?
Bladder contraction
Sphincter relaxation
Penile erection (increased bloodflow)
31
What is the affect of ACh release on the eye?
Ciliary muscle and iris sphincter contraction
32
What causes the increase in bloodflow which causes penile erection?
Nitric oxide
33
Which receptor type is found in glandular tissue which is activated by ACh release?
M1/3
34
What is the affect of M1/3 activation by ACh in glandular tissue?
Control level and composition of secretion
35
Which component of the lungs, GI tract, GU tract and eye is affected by ACh release?
Smooth muscle
36
What does the ANS exist in parallel but separate to?
Somatic nervous system
37
What effects does NA release have on the heart?
SAN --> +ve chronotropy
| Ventricle --> +ve inotropy
38
Which receptors are activated in the heart by NA?
Beta-1 (mainly)
| Beta-2
39
What does the balance of beta-1 and beta-2 receptors in the heart depend on?
The individual
40
What affect does NA release have on the smooth muscle of the vasculature?
BV contract
| Arteriolar relaxation in some vascular beds
41
What type of receptors constrict visceral BV upon NA release?
Alpha-1
42
What type of receptors dilate BV in exercising tissue?
Beta-2
43
What subtype/s of receptor cause smooth muscle relaxation in the lungs, GI tract and GU tract upon NA release?
Beta-2
| Beta-3
44
What does the activation of receptors (thought to be beta-3) in the GU by NA cause the bladder sphincter to do?
Contract
45
What does alpha-1 activation by NA cause in the eye?
Radial muscle contraction
46
What increases viscous secretion in the salivary glands?
NA release
47
What causes renin release in the kidney?
NA release
48
How is the prostate gland innervated by the ANS?
Parasympathetic on epithelial cells controlling generation of secretion
Sympathetic on smooth muscle contraction --> release of secretory products
49
What additional medication were prostate cancer patients with a better prognosis noted to be taking?
Beta-blockers
50
What is seen in all prostate cancers irrespective of age of patient that affects the rate of development and metastasis?
Neurogenesis
51
What constantly modulates efferent ANS neurone activity?
Afferent/sensory ANS inputs
52
What monitors carbon dioxide, oxygen, arterial pressure, GI tract content and chemical composition?
Sensory neurones
53
What is sensed by the carotid body/ chemoreceptors at carotid artery bifurcation?
Blood oxygen, carbon dioxide and pH
54
How are the inputs to the carotid body/ chemoreceptors at carotid artery bifurcation coordinated?
Glossopharyngeal nerve --> CNS
55
What forms the nucleus tractus solitarius (nTS)?
Primary sensory neurones acting on second order sensory neurones in medulla oblongata
56
What is the function of area postrema?
Detect toxins in blood and CSF
Essential for chemical-induced vomiting
Essential for conditional taste aversion
57
What integrates all visceral afferent information?
Nucleus tractus solitarius
58
What are the 12 basic steps in neurotransmission?
```
Uptake of precursors
Synthesis of transmitter
Vesicular storage of transmitter
Degradation of transmitter
Depolarisation by propagated AP
Depolarisation-dependent influx of calcium ions
Exocytotic release of transmitter
Diffusion to post-synaptic membrane
Interaction w/ post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction w/pre-synaptic receptors
```
59
Which steps of neurotransmission can be targeted by drugs?
```
Degradation of neurotransmitter
Interaction w/post-synaptic receptors
Inactivation of transmitter
Re-uptake of transmitter
Interaction w/pre-synaptic receptors
```
60
Why is degradation of ACh immediate?
Abundance of AChE
61
What can be used to irreversibly inhibit AChE in terrorist attacks?
Sarin
62
How is ACh formed?
Acetyl CoA + choline --> ACh + CoA
| Uses choline acetyltransferase (CAT)
63
Where can cholinergic function be manipulated in the ANS?
Ganglia
| Effector - especially parasympathetic branch
64
What does interfering with the cholinergic function at the ganglia of the ANS effectively do?
Switch off ANS
65
Why can nAChR at autonomic ganglia be targeted and the nAChR at the NMJ be unaffected?
Different receptor structures
66
What is Trimethapan?
Ganglion-blocking drug used in hypertensive emergencies and when hypotension is needed during surgery
67
How many mAChR subtype specific agonists or antagonists are currently available clinically?
Only a few
68
What is Tolterodine?
mAChR antagonist used to treat an overactive bladder w/limited tissue selectivity
69
How can endogenous ACh release be enhanced?
AChE inhibitors
70
Pyridostigmine and Donepezil are AChE inhibitors. What are they used to treat?
Pyridostigmine - myasthenia gravis
| Donepezil - Alzheimer's
71
What often has to be given with a mAChR agonist to prevent unwanted side effects caused by low specificity?
Antagonist
72
How can low specificity mAChR agonists and antagonists be used effectively clinically?
Administer locally not systemically
73
How are mAChR agonists pilocarpine and bethanechol used to treat glaucoma and to stimulate bladder emptying respectively?
Used w/pharmacodynamics to localise drug effects
74
What are mAChR antagonists ipratrapium and tiotropium used to treat?
Asthma
| COPD
75
What are Tolterodine, clarifenacin and oxybutynin?
mAChR antagonists used to treat an overactive bladder
76
What do postganglionic sympathetic neuron axons form to allow for specialised sites of calcium-dependent NA release?
Highly branched atonal network w/numerous varicosities which are regularly arranged
(Beads on a string)
77
What do varicosities allow for?
Coordinated responses on a wide field of the effector organ
78
Give the intermediates of noradrenaline synthesis
Tyrosine --> DOPA --> dopamine --> noradrenaline
79
Which enzymes are needed for NA synthesis?
Tyrosine hydroxylase
DOPA decarboxylase
Dopamine beta-hydroxylase
80
Which stage of NA synthesis takes place in the vesicle?
Conversion of dopamine to NA
81
What type of receptor forms the auto-regulatory feedback system in NA release?
Alpha-2
82
How does alpha-2 activation prevent further NA release?
Beta-gamma subunits inhibit VOCCs
83
How can DOPA be sued to treat Parkinson's disease?
Delivered in pharmacokinetic protected dose
84
How is NA release terminated?
Rapidly by Uptake 1
Rest by Uptake 2
Small amount escapes
85
What is Uptake 1?
High affinity, sodium dependent NA transporter
86
What percentage of released NA is recaptured by Uptake 1?
90-95%
87
What is Uptake 2?
Lower affinity, non-neuronal NA transporter protein
88
Why can NA metabolism only occur after uptake?
Lack of extracellular enzymes
89
What happens to the majority of NA uptaken after release?
~90% is repackaged into vesicles
90
What happens to the NA uptake that is not repackaged into vesicles?
Metabolised by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)
91
What are tyramine, amphetamine and ephedrine examples of?
Indirectly acting sympathiomimetic agents
92
How do indirectly acting sympathiomimetic agents intervene in adrenergic transmission?
Taken up into vesicles --> allow NA leak from vesicles and into synaptic cleft without influx of calcium ions
93
What are tricyclic antidepressants and selective NA re-uptake inhibitors examples of?
Uptake 1 inhibitors
94
Where do Uptake 1 inhibitors exert their major therapeutic action?
CNS
95
What must be minimised by drug choice and dosage when using amitryptyline, imipramine or reboxetine for example?
Peripheral actions e.g. tachycardia and cardiac dysrhythmia
96
What are salbutamol and salmeterol?
Beta-2 selective agonists used to treat asthma
97
What are doxazosin and atenolol, drugs used for CVS disorders incl. hypertension?
Doxazosin - alpha-1 antagonist
| Atenolol - beta-1 antagonist
98
What are the NICE guidelines for treatment of chronic heart failure?
Beta blocker
ACEI
Diuretic
99
What do the NICE guidelines for treatment of chronic heart failure using three classes of drugs cause?
Proven mortality and morbidity benefits
100
Give three examples of proven efficacy drugs which are better than other types of beta-blockers for treatment of chronic heart failure.
Bisoprolol
Metoprolol
Carvedilol
101
Which adrenoceptors do bisoprolol and metoprolol act on in chronic heart failure?
Beta-1
102
Why is Carvedilol which acts on beta-1, beta-2 and alpha-1 receptors very effective?
Causes uniques adaptations to receptors not seen with other drugs
103
How does the paradoxical increase in alpha-adrenoceptor subtypes seen when using Carvedilol to treat chronic heart failure present clinically?
Initially patients become very tired but a week later they are much better
104
What percentage of the population is affected by chronic heart failure, which is classified as a disease of old age?
3%
