Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

MODA > Dr Hiley - PNS > Flashcards

Dr Hiley - PNS Flashcards

0
Q

What is the synaptic vesicle cycle?

A

1) Uptake of transmitter release
2) Synaptic vesicles move to active zone
3) Vesicles dock to the plasma membrane
4) Vesicles undergo ATP-dependent pre-fusion
5) Ca2+ triggers completion of fusion
6) Vesicles retrieved by endocytosis
7) Coated vesicles shed coat and recycle to the interior of nerve terminal
8) Empty vesicles can either refill of pass through an endosomal intermediary sorting station

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What is the synaptic structure of the ANS?

A

Terminal varicose axon branches that form a network in and around the effector cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which vesicular proteins are involved in neurotransmitter release?

A

v-SNAREs and synaptobrevin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which terminal proteins are involved in neurotransmitter release?

A

t-SNAREs, SNAP-25 and syntaxin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Tetanus toxin?

A

Targets synaptobrevin

Stops release of transmitter from inhibitory interneurons
=Motor neuron more excitable = tetani

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the target of botulinum B, D, F and G?

A

Synaptobrevin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which botulinum toxins target synaptobrevin?

A

B, D, F and G

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What do botulinum toxins A and E target?

A

SNAP-25

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which botulinum toxins target SNAP-25?

A

A & E

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does botulinum C1 target?

A

Syntaxin and SNAP-225

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which botulinum toxin targets syntaxin and SNAP-25

A

C1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Botulinum toxin?

A

Attack cholinergic neurons

Heavy chain - C-terminus binds to a glycoside and N-terminus translocates light chain

Light chain - Peptidase which cleaves SNARE

=Muscles weakness and ANS stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the role of synaptotagmin?

A

Ca2+ sensor

Binds syntaxin during membrane fusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are synapsins?

A

Proteins on the surface of the vesicles which links them to the cytoskeleton (regulated by phosphorylation)

PKA/CaM Kinase II phosphorylation causes vesicular dissociation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the two kinds of synaptic plasticity?

A

Depression and Facilitation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is synaptic depression?

A

Depletion of neurotransmitter after repeated stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is synaptic facilitation?

A

Ca2+ builds up as its entry is too fast for removal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which aspects of the PNS can drugs act upon?

A
  • Neurotransmitters (NTs)
  • Synthesis of NTs
  • Storage of NTs
  • Release of NTs
  • Breakdown of NTs
  • Uptake of NTs
  • Activation of receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Draw Cholinergic transmission

A

Well done have a gold star

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the rate limiting step of ACh synthesis?

A

Choline uptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Hemicholium?

A

Blocks choline uptake by binding to transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Trimethylcholine?

A

Acts as a competitive substrate to choline in ACh synthesis

Acetylated to acetyltriethylcholine (released instead of ACh)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Vesamicol?

A

Block the vesicle transport (VAChT)

Inhibition is non-competitive and reversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

β-Bungarotoxin

A

Acts via a phospholipase A2 and localises to the membrane by a K+ channel-binding moiety

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
α-Latrotoxin
Black widow spider venom Targets neurexins, latrophilin receptors, protein tyrosine phosphatase-σ Τetramer forms ion pore = Ca2+ entry
25
Where is acetylcholinesterase found?
Soluble presynaptically and bound to the post synaptic membrane
26
Where is butyrylcholinesterase found?
Predominantly a plasma enzyme, also found in quantities in skin, brain and gut
27
With which Ach receptors does α-bungarotoxin interact?
Binds to brain (α7)5
28
What are the compositions of the striated muscles ACh receptors?
(α1)2β1δε | (α1)2β1δγ
29
What is the composition of the ACh receptors in the autonomic ganglion?
(α3)2(β4)3
30
What is the composition of the ACh receptors in the brain?
(α4)2(β2)3 Some (α3)2(β4)3 (α7)5
31
What are the phase of nicotine action?
Phase I block - Cells are depolarised - VGCs are refractory - Cell unresponsive to stimulation Phase II block - cells repolarise - Neuron becomes electrically re-exitable
32
Trimetaphan
Competitive ACh receptor antagonist
33
Mecamylamine?
Non-competitive ACh receptor antagonist
34
Hexamethonium
Non-competitive ACh receptor antagonist
35
What effect does increasing the chain length have on hexamethonium's action?
Changes its selectivity between ganglion and nmj
36
What were the side effects of hexamethonium?
Loss of sympathetic tone to blood vessels = hypotension Loss of CV reflexes = Fainting Inhibition of secretion = Dry skin and mouth GI paralysis
37
D-Tubocurarine
ACh competitive antagonist = flaccid paralysis
38
Atracurium
ACh competitive antagonist | Ester bond = spontaneous breakdown and hydrolysis by plasma esterases
39
Pancuronium
Competitive antagonist of the ACh receptor
40
Decamethonium
ACh agonist
41
What are the two phases of depolarising blocker action?
Phase I - Depolarising block = spastic paralysis (short lived on focally-innervated muscles) Phase 2 -Desensitisation block in focally-innervated muscles = flaccid paralysis
42
What effect do antiCHE and non-depolarising blockers have on Phase 1 of depolarising blockers action?
Phase 1 is deepened by antiCHE and reversed with non-depolarising blockers
43
What effect do antiCHE and curare-like drugs have on Phase 2 of depolarising blockers action?
Reversed by antiCHE and deepened by curare-like drugs
44
What are the 3 main subtypes of the muscarinic ACh receptor and which G protein type are they coupled to?
M1 - Gq M2 - Gi M3 - Gq
45
McN-A-343
Cell-specific stimulator of muscarinic receptors in ganglionic neurons
46
How do M1 and M3 signal?
Through the generation of IP3 and DAG M1 also inhibits K+ conductance M3 receptor stimulation increases [Ca2+]i
47
How does the M2 receptor function?
Gi inhibits adenylyl cyclase = decrease in cAMP =Decreased phosphorylation of VGCC =Decreased excitability of heart muscle/transmitter release βγ subunit opens GIRK in pacemaker tissue = decreased heart rate
48
Bethanecol?
Muscarinic receptor agonist used for urinary retention
49
Pilocarpine?
Muscarinic receptor agonist used in the treatment of glaucoma (contracts ciliary muscles)
50
Pirenzipine
Selective M1 antagonist | Decrease gastric acid secretion effect on local ganglion rather than M3 receptors of oxyntic
51
Tripitramine
Selective M2 antagonist
52
Darifenacin?
Selective M3 antagonist Decreases bladder activity
53
Atropine
Non-selective muscarinic receptor antagonist Used to dilate eyes (mydriasis) Bronchodilation Decreases GI motility Increased HR
54
Hyoscine (Scopolamine)
Non-selective muscarinic receptor antagonist Used to dilate eyes (mydriasis) Bronchodilation Decreases GI motility Increased HR
55
Ipatropium?
Muscarinic receptor antagonist used in asthma inhalers
56
What is a difference between the structures of AChE and BuChE?
AChE has an anionic and esteratic site | BuChE only has an esteratic site
57
How are the anticholinesterase agents classified?
According to length of action:- Short acting Medium acting Long acting
58
Edrophonium
Short acting AChE inhibitor | Used to diagnose myesthenia gravis
59
Neostigmine
Medium acting AChE inhibitor Binds to esteratic site and carbamoylates the enzyme Used to reverse NMJ blockade after surgery and as an oral treatment to myasthenia gravis (prevent diminishing response)
60
Physostigmine
Medium acting AChE inhibitor Glaucoma treatment
61
Malathion?
Long acting (irreversible) AChE antagonist ^ Parasympathetic activity
62
Dyflos?
Long acting (irreversible) AChE antagonist ^ Parasympathetic activity
63
Pralidoxime?
Causes the dissociation of dyflos/malathion from AChE to prevent poisoning Draw the mechanism bitch
64
What is the pathway for the synthesis of Adr?
Tyrosine Tyrosine hydroxylase (TOH) DOPA DOPA decarboxylase (DDC) Dopamine Dopamine β-hydroxylase (DBH) NA PNMT Adr
65
At what point does the synthesis of Adr move from the cytoplasm to the vacuole?
Dopamine is taken in before being converted to NA
66
α-methyltyrosine
Competitive inhibitor of TOH | rate limiting step therefore reduces the amount of transmitter
67
L-DOPA
By-passes the rate limiting step of DA production Increased DA production in the brain (DA can't be supplemented as it doesnt cross the BBB) Used in the treatment of parkinsons
68
Carbidopa
Peripheral decarboxylase inhibitor Inhibits DDC but cannot enter the brain = reduced side effects of L-DOPA
69
Disulfiram?
Inhibits DBH Clinical used as an inhibitor of aldehyde dehydrogenase
70
MethylDOPA
Released as a false transmitter (MethylNA) for Adr Greater effect on α2 receptors than NA = increased negative feedback
71
How are NA and DA transported into the vesicles?
Transported by VMAT-2, driven by the proton gradient (established by ATP-dependent H+ pump)
72
Reserpine?
Binds to amine binding site of VMAT =blocks uptake Antihypertensive (triggers depression due to CNS -HT depletion)
73
Tyramine
Indirectly acting sympatheticomimetic amine Displaces NA in storage vesicles, NA then transported into synaptic cleft by NET (in exchange for tyramine) Broken down by MAO
74
What are the side effects of tyramine?
Large release of NA = large increase in BP Use of MAO inhibitors increases risk
75
Octopamine
Adr false transmitter From tyramine
76
Ephedrine
Indirectly acting sympatheticomimetic agent Used in nasal sprays
77
Dexamfetamine
Indirectly acting sympatheticomimetic agent
78
Methylphenidate
(Ritalin) Indirectly acting sympatheticomimetic agent Used to treat ADHD
79
MDMA
Indirectly acting sympatheticomimetic agent
80
Tachyphylaxis
Reduction in effectiveness upon repeated administration
81
Guanethidine
Blocks the release of NA Carried into nerve by Uptake 1 Large dose: Indirectly acting sympatheticomimetic amine Low dose: Blocks NA release (hyperpolarisation of nerve terminal)
82
Bretylium
Blocks the release of NA Carried into nerve by Uptake 1 Large dose: Indirectly acting sympatheticomimetic amine Low dose: Blocks NA release (hyperpolarisation of nerve terminal)
83
How do presynaptic Adr receptors work?
Opening of G protein regulated K+ channel = hyperpolarisation
84
What effect do M2 and δ-opioid receptors have on NA release?
They decrease it
85
What are the features of Uptake 1?
High affinity, low capacity NA > Adr Mediated by NET
86
Cocaine?
Blocks Adr transportation by NET
87
Imipramine?
Tricyclic antidepressant Blocks Adr uptake by NET
88
Amitryptyline?
Tricyclic antidepressant Blocks Adr uptake by NET
89
What is NET?
Catecholamine transporter 12 TM domains Na+ dependent
90
What are the features of Uptake 2?
Low affinity, high capacity Adr > NA Carried by ENT (not Na+ dependent) Also transports DA, 5-HT and histamine
91
Normetanephrine
Block Uptake 2 by blocking ENT | metabolite of NA therefore NA uses uptake 1
92
Corticosterone and hydrocortisone
Block ENT
93
What is the role of MAO?
It deamines NA or NM
94
What is the role of COMT?
It methylates catechol OH | either NA, NA aldehyde, DOMA or DOPEG
95
Where is MAO-A found? and what are its substrates?
In the outer mitochondiral membrane In the liver, GI, brain and peripheral nerves NA, Adr, DA and 5-HT
96
Where is MAO-B found? and what are its substrates?
In the outer mitochondrial membrane in the brain DA
97
Tranylcypromine
Nonselective MAO inhibitor Cause depression
98
Clorgiline
MAO-A inhibitor Causes depression
99
Selegine
MAO-B inhibitor Used as a treatment for Parkinson's disease
100
Entacapone
COMT inhibitor used in Parkinson's disease
101
What are the relative affinities of adrenoceptors for their substrates?
α- Na > Adr > isoprenaline | β- isoprenaline > Adr > NA
102
How does the α1 adrenoceptor signal?
Gq PLCs action cause Ca2+ release (via IP3) and activation of PKC (via DAG)
103
What are the principal effects of α1 activation?
``` Vasoconstriction (Ca2+) Uterine smooth muscle constriction GI smooth muscle relaxation (^I[K(Ca)]) Salivary secretion Glycogenolysis (PKC) ```
104
What is the mechanism of α2 signalling?
Gi Gα decreases [cAMP] which in turn deactivated PKA This inhibits VGCC activity Gβγ also inhibits VGCC activity
105
What are the principal effects of α2 activation?
Inhibition of transmission Platelet aggregation Vasoconstriction
106
What is the mechanism of β1 signalling?
Gs Increase in [cAMP] causing increased VGCC activity (via PKA) Also inactivation of myosin light chain kinase (via PKA)
107
What is the mechanism for β2 signalling?
Gs Increase in [cAMP] causing increased VGCC activity (via PKA) Also inactivation of myosin light chain kinase (via PKA)
108
What is the mechanism for β3 signalling?
Gi Decrease in [cAMP] causing a decrease in PKA activity Increase in NO
109
What are the principle effects of β1 activation?
Positive chronotropic and ionotropic effects Relaxation of smooth muscle
110
What are the principal effects of β2 activation?
- Bronchodilation - Vasodilation - Glycogenolysis - Relaxation of smooth muscle in the uterus - Muscle tremor
111
What are the principal effects of β3 stimulation?
Negative chronotropic and ionotropic effects Vasodilation Relaxation of detrusor muscle in the bladder
112
What are the actions of Adr on BP, HR and TPR, and how are they mediated?
Decrease in TPR via α1 and β2 Increase in HR via β1 Increase in systolic and decrease in diastolic pressures
113
What are the actionf of NA on BP, HR and TPR, and how are they mediated?
Increase in TPR Increase in BP Reflex decrease in HR All via α1
114
What are the actions of isoprenaline on BP, HR and TRP, and how are the mediated?
Increase in HR (β1) Decrease in TPR (β2) Increase in systolic and decrease in diastolic
115
Adrenaline?
Used in severe acute conditions Relieves bronchospam in anaphylactic shock (and vasoconstriction) Stimulates heart in acute cardiac failure
116
Xylometazoline
α-adrenoceptor agonist Relieves nasal congestion
117
Pheylephrine
Selective α1-receptor agonist Increase BP in acute hypotension
118
Clonidine
α agonist with some selectivity for α2 Antihypertensive (vasodilation) Vasoconstriction if applied to the periphery (shaving cream) Acts on hind brain (likely to be via the imidazoline I1 receptor)
119
Xylazine
α agonist selective for α2 Sedative effects Action on CNS
120
Isoprenaline
Non selective β agonist | Bronchodilation but increased risk of dysrhythmia
121
Salbutamol/terbutaline
β2-selective agonist Relieves bronchospasm in asthma
122
Salmeterol
Long acting β2-selective agonist
123
Dobutamine
β1-selective agonist Cardiogenic shock or to improve outflow after cardiac surgery
124
Mirabegron
β3-selective agonist Increases bladder capacity by relaxing detrusor muscle
125
Phentolamine
Non selective α antagonist Usually associated with increased HR
126
Prazosin
α1 selective antagonist Antihypertensive agent
127
Phenoxybenzamine
Irreversible antagonist Used to treat phaeochromocytoma
128
Labetalol
α and β antagonist
129
Propranolol
β antagonist nonselective Class IB antidysrhythmic agent
130
Atenolol
β antagonist (β1 selective) Reduced risk of broncospasm Class IB antidysrhythmic agent
131
Ergotamine
Partial α-adrenoceptor agonist Mainly act at 5-HT receptors
132
What is ergotism?
AKA St Anthony's fire Intense vasoconstriction cause by eating fungus from mouldy grain
133
What are the four main ways that drugs can affect noradrenaline release?
1. Directly blocking release 2. By evoking release in the absence of depolarisation (Indirectly acting sympatheticomimetic agents) 3. By acting on presynaptic receptors that indirectly inhibit or enhance release 4. By increasing or decreasing the available stores of NA
134
What is NANC transmission?
Non-adrenergic non-cholinergic transmission Often involves co transmission
135
Is ATP stored in the same or different vesicles to NA?
Same vesicles
136
Are peptides stored in different or the same vesicles to ACh?
Different
137
Who discovered ATPs action as a neurotransmitter?
Drury & Szent-Gyorgy discovered that ATP and other adenine derivatives acted on cells of the heart Burnstock found that ATP satisfied Dale's criteria for a neurotransmitter
138
What are the two main types of purinoceptor? and how are they distinguished?
P1 - Higher affinity for adenosine | P2 - Higher affinity for ATP
139
What are the subtypes of the purinoceptors? and what kind of receptor are they?
P2X (1-7) - Ionotropic P2Y - GPCR P1A1 - GPCR P1A2A - GPCR P1AB - GPCR P1A3 - GPCR
140
What happens as ATP release by a nerve is degraded?
ADP etc. act upon different receptors = different responses
141
What enzyme degrade ATP and where are they found?
Ecto-nucleotidases are found on the cell surface and nucleotidases can be co released with ATP
142
What is the structure of the P2X purinoceptor?
Formed as a trimer of subunits (Homo or hetero) Two TM domains Large extracellular domain with disulphide bonds
143
What is the difference in effects between ATP and NA on the postsynaptic membrane?
``` ATP = Fast depolarisation NA = Slow depolarisation ```
144
What is the role of P2X2 receptors?
Nerve induced contraction of the vas deferens
145
What is the role of P2X4 receptors?
ATP - ^ Force of contraction Up-regulation in the spinal cord - tactile allodynia
146
What is the main role of adenosine?
To signal hypoxic conditions (retaliatory metabolite) Causes vasodilation in smooth muscle and endothelial cells Causes a decreased rate and force of contraction of the heart (reduces O2 demand)
147
What are the signalling mechanisms and principle actions of the A1 receptor?
Gi Decreased HR & force of contraction Bronchoconstriction Presynaptic inhibition of transmitter release Decreased brain glutamate release
148
What are the signalling mechanisms and principle actions of the A2A receptor?
Gs Vasodilation Decreased activation of neutrophils
149
What are the signalling mechanisms and principle actions of the A 2B receptor?
Gs Vasodilation
150
What are the signalling mechanisms and principle actions of the A3 receptor?
Gi/Gq Decreased eosinophil activation in the lungs
151
Caffeine
A1 receptor antagonist Also a PDE inhibitor
152
How is adenosine transmission inactivated?
By transport into cells
153
Dipyramidamole
Blocks uptake and potentiates responses to adenosine
154
What are the features of peptide NANC transmission?
Requires sustained increase in [Ca2+]i for release as peptides-containing vesicles are not found in the active zone Slowly inactivated Produce the late slow epsp
155
What is the synthesis order of a signalling peptide?
Preprohormone Prohormone Active molecule (one precursor can generate several active molecules)
156
Why do peptides not make very good drugs?
Poorly absorbed orally Rapidly degraded Dont cross the BBB
157
Oxytocin
Peptide drug used to induce labour
158
How is NO produced?
Made by Ca2+ dependent enzyme nNOS and eNOS or in a Ca2+ independent manner by iNOS
159
What is the equation for the production of NO?
L-Arginine + O2 + NADPH -> NO + L-citrulline + NADP+
160
How does NO function as a signalling molecule?
Freely diffuses in all directions Activates GC in pre and postjunctional cells PKG causes effect (eg vasodilation)
161
Glyceryl trinitrate
NO donor used to treat angina Taken sublingually
162
Isosorbide dinitrate
Metabolised to isosorbide mononitrate (active) Acts as an NO donor used in the treatment of angina
163
How is NO inactivated?
By binding to haemoglobin or by oxidation to NO2- + NO3-
164
What is the role of NO in the enteric nervous system? Which type of NOS is used?
ENS neurons express nNOS Relax the pyloric sphincter
165
How is penile erection mediated?
Release of NO by NANC nerves =dilation of vessels supplying the corpus spongiosum and cavernosum
166
Sildenafil
Selective inhibitor of PDE 5 used to treat impotence Selectively breaks down cyclic GMP = potentiates NO signallin
167
What is the role of NO in the CNS?
Acts as a retrograde messenger upon activation of NMDA-Rs
168
How is NO used by the immune system?
iNOS in macrophages -NO attacks Fe-S complexes = free Fe = cytotoxicity (excess production is damaging)
169
How is NO involved in septic shock?
Excess NO production = vasodilation and decrease in BP
170
How is NO cytotoxic in the CNS?
Hypoxia = ^ glutamate release = massive influx of Ca2+ = ^ NO production and cell death
171
L-NMMA
No inhibitor Analogue of L-Arginine
172
L-NAME
No inhibitor Analogue of L-Arginine
173
L-NOARG
No inhibitor Analogue of L-Arginine
174
7-NI
Selectively inhibits the NOS of neurons
175
L-NIO
A potent and irreversible inhibitor of iNOS | Shipmanising patients not clinical
176
ADMA
Asymmetric dimethyl arginine Endogenous NOSI Synthesised in post-translational protein methylation Elevated ADMA = poor prognosis

MODA (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions