The Nervous System Flashcards
1
Q
How do you tell the difference between a sympathetic and a parasympathetic nerve?
A
Preganglionic neuron for a parasympathetic nerve is much longer than the preganglionic neuron for a sympathetic nerve
2
Q
What neurotransmitter is released at preganglionic synapse for parasympathetic nerves?
+sympathetic nerves?
A
Acetylcholine for both
3
Q
What neurontransmitter is released at the terminal synapse for a sympathetic nerve?
+parasympathetic nerve?
A
Sympathetic- Noradrenaline
Parasympathetic- Acetylcholine
4
Q
Where do nerves for the sympathetic nervous system emanate from?
A
Thoracolumbar region of the spinal cord
5
Q
Where do nerves for the parasympathetic nervous system emanate from?
A
Cranio and sacral regions of the spinal cord
6
Q
How is neurotransmitter released from a terminal junction?
simple explanation
A
Action potential travels down the axon of the presynaptic nerve where it reaches the terminal region. Depolarisation of terminal region causes voltage dependant Ca2+ channels to open, allowing an influx of Ca2+ which causes vesicles containing neurotransmitter in the terminal region to fuse with the presynaptic membrane and release the neurotransmitter.
7
Q
What is presynaptic autoinhibitory agonism?
A
When the neurotransmitter which was released from the presynapse, comes back to the presynaptic membrane and causes inhibition of further neurotransmitter release.
8
Q
How are neurotransmitter synthesised and stored within the presynapse?
A
A precursor to the neurotransmitter enters the cell, normally through active uptake. Enzyme cascade occurs which turns the precursor to the neurotransmitter. The NT end up in vesicles where they’re stored to protect them from enzymes in the cytoplasm and to increase to concentration of the NT.
9
Q
What can inhibit/stimulate precursor uptake of a presynaptic cell?
A
Hemicholinium inhibits precursor uptake.
An excess of the precursor will increase precursor uptake.
10
Q
What can inhibit precursor turning into enzyme within presynaptic cell?
A
AMPT inhibits the enzymes of the enzyme cascade
11
Q
What can inhibit neurotransmitter release of a presynaptic cell?
A
Reserpine cases leakage of the NT which ultimately inhibits NT release
12
Q
What is the precursor to Dopamine?
A
L-DOPA
13
Q
How is the depolarisation of the terminal end inhibited?
A
Guanethidine is a drug which inhibits terminal region depolarisation of presynaptic cells that release noradrenaline.
14
Q
How is Ca2+ influx into presynaptic cell inhibited?
A
Conotoxin drug
15
Q
What is a ‘dirty drug’?
A
A drug which has multiple receptors in the body it can bind to so its effect within the organism can be wide.
16
Q
What does chlonidine do?
A
Works to inhibit α2 adrenoceptor so can inhibit presynaptic autoinhibitory agonism.
Makes noradrenaline effect last longer as the NT can not be taken up by the presynpase.
17
Q
How is the neurotransmitter terminates?
A
Diffusion (not important considering geometry of synapse)
Enzymes degrade NT to metabolites
Reuptake of NT via presynaptic membrane
18
Q
What drugs can inhibit uptake of neurotransmitter
A
Chlondine works to inhibit α2 adrenoceptor
Cocaine inhibits NA reuptake
Fluoxetine (prozac) inhibits serotonin and NA reuptake
19
Q
What does neostigmine do?
A
Inhibits the AChE by carbamylation of the esteratic site of AChE to provide a medium duration inhibition of AChE
20
Q
What does salbutamol do and act on?
A
It treats asthma
It acts on β2 receptors that are stimulated by noradrenaline.
21
Q
What does phenylephrine do and act on?
A
It is decongestant
It acts on α1 receptors that are stimulated by noradrenaline.
22
Q
What does bromocrotptine do and act on?
A
It treats Parkinson’s Disease
It acts on D2 receptors that are stimulated by dopamine.
23
Q
What does morphine do and act on?
A
It relieves pain
It acts on μ receptors that are stimulated by Enkephalin.
24
Q
What does diazepam do and act on?
A
It treats anxiety
It acts on A receptors that are stimulated by GABA.
25
What does prazosin do and act on?
It reduces blood pressure.
| It acts as an antagonist on α1 receptors that are stimulated by noradrenaline.
26
What does propranolol act on and what is its clinical use?
It is used to treat abnormal cardiac rhythm, myocardial infarction and angina (reduced bloodflow to cardiac muscle) -->(reduces blood pressure overall)
It acts as an antagonist on β2 and β1 receptors.
27
What does atracurium do and act on?
It is a muscle relaxant.
| It acts as an antagonist on nicotinic receptors that are stimulated by ACh.
28
What does atropine do and act on?
It blocks secretions (like saliva), brings about mild tachycardia and dilate pupil.
It acts as an antagonist on muscarinic receptors.
29
What does trifluoperazine do and act on?
It is an antipsychotic drug.
| It acts as an antagonist on D" receptors that are stimulated by Dopamine.
30
What does Botulinum Toxin do and act on?
It stops ACh release.
| It inhibits NT vesicle fusion to membrane.
31
What does Sildenafil do?
It inhibits the breakdown of the second messenger substance cyclic GMP produced by nitric oxide in erectile tissue.
32
What is a putative neurotransmitter?
It 'might' be a neurotransmitter in comparison to an established neurotransmitter.
33
What are the steps of establishing a neurotransmitter?
- Identification of biological activity
- Identification of active principle
- See if the neurotransmitter satisfy criteria for a neurotransmitter
- Identification of physiological roles
34
What is the motor unit?
The motor nerve plus the muscle fibres which it controls.
35
How big is the gap between the nerve and the muscle in a NMJ?
60 nm
36
How is ACh synthesised?
Choline is the precursor to ACh.
| Choline in addition to acetylcoenzyme (AcCoA) by the action of Choline Acetyl Transferase (CAT).
37
What is the structure of ACh?
https://sites.google.com/a/macalester.edu/nerve-agents/_/rsrc/1467895574698/home/acetylcholine-and-vx/Capture%208.JPG?height=148&width=320
38
What is the structure of Choline?
https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=305&t=l
39
What do hemicholiniums do?
Inhibit synthesis of ACh by blocking uptake/reuptake of choline at presynapse.
40
What drug inhibits storage of ACh?
AH5183 (vesamicol)
41
What does Mg2+ do to the presynapse?
It prevents Ca2+ entering the nerve terminal by blocking VOCC
42
What clinical uses does Botulinum toxin have?
'Cosmetic' medicine
Treats hyperhidrosis (excessive sweating)
Treats bladder hyper-reactivity
43
What happens to ACh after it is released?
Once released, a lot of ACh is degraded by acetylcholinesterase (AChE) which is found in the synaptic cleft.
The ACh that makes it to the postsynapse acts as an agonist to nicotinic acetylcholine receptors.
44
AChE breaks down ACh, how?
It breaks down ACh into acetyl and choline. It breaks the ester bond.
45
Describe the function and structure of the nicotinic ACh receptor.
It is activated by nicotine (nicotine is the agonist)
It is formed by five subunits (α,α,β,γ,δ) which form around a non-selective cation channel.
Channel opens when there are two ACh molecules, each bond to one α subunit.
46
What is the end plate potential?
The depolarisation of the muscle membrane produced following activation of the NAChR.
47
What does suxamethonium do?
Acts as an agonist at NAChR. Suxamethonium (succinylcholine) is not broken down by AChE so it lingers at the NMJ producing a prolonged depolarisation.
48
How is succinylcholine broken down?
Not acetylcholine, butyryl-cholinesterase or pseudo-cholinesterase break down succinylcholine.
49
What effects do anticholinesterase have?
The drugs prevent breakdown of ACh so effectively increase concentration of ACh. They reverse the effects of reversible competitive antagonist.
50
Where are the nicotinic activated receptors typically found?
They're found on ganglia.
51
What are Muscarinic receptors?
They are G protein coupled receptors.
| They are like NAChR but they're more sensitive to muscarine in comparison to nicotine.
52
What is pilocarpine?
It is a mimic of ACh.
53
Muscarinic receptors..... Gq linked
.
54
Muscarinic receptors ..... Gi/o linked
.
55
Muscarinic agonist effects list
Cardiovasular: reduces heart rate and cardiac output
Smooth muscle: Increased bladder and bronchial contract
Sweating, lacrimation, salivation and bronchial secretions
Contracts ciliary muscle (Of the eye)
56
What does hyoscine do?
Its a muscarinic antagonist that can pass through the BBB.
It blocks mucous secretions and because it passes the BBB, it has a sedative effect. It is an effective anti-motion sickness drug.
57
What does ipratropium do?
Anti-asthmatic drug.
58
What does tolterodine do?
Anri-muscarinic drug used to treat urinary incontinence (unable to control bladder)
59
What are agonists and antagonists to nicotinic receptors?
Agonists: Nicotine, Lobeline
Antagonist (In ganglia): Hexamethonium, Trimetaphan
Antagonist (In NMJ): Tubocurarine, Pancuronium, Atracurium
60
What is is the difference between AChE and BChE?
AChE is found in the CSF
BChE is found in the tissue and plasma
Both are enzymes that degrade acetylcholine
61
What is within the active site of AChE?
```
There are two regions.
Esteratic site (where ester bond is broken) and anionic site (where the amide group of choline binds).
```
62
What does edrophonium do?
It binds reversibly and briefly to the anionic region of anticholinesterase.
63
What is Ecothiopate?
An irreveribly binding antagonist which binds to AChE's esteratic site.
64
therapeutic effects of anticholinesterases.....
.
65
effects of anticholinesterases....
.
66
What is a disynaptic pathway and what system uses it?
A connection between two neurons involving an intermediate neuron.
The ANS uses it
67
How can the SNS bring about changes to the activity of organs and tissues?
Releasing noradrenaline at the periphery.
| Distributing adrenaline and noradrenaline throughout the body in the bloodstream.
68
What happens when the heart is stimulated by the accelerator nerve?
Increased force of contraction (inotropic effect)
Increased stroke volume (chambers are more emptied)
Heart rate increases (chronotropic effect)
Overall increased cardiac output
69
What happens to the gut after sympathetic stimulation?
Inhibition of digestive processes
Reduced peristalsis (the process that moves food in the digestive tract)
Decreased secretions
Reduced blood supply
Constipation: relaxation of rectum, contraction of internal anal sphincter
70
What happens to the bladder after sympathetic stimulation?
Inhibition of urination
Relaxation of detrusor muscle
Contraction of urethral sphincter
71
What happens to sexual function after sympathetic stimulation?
Ejaculation and detumescence(?)
Contraction of vas deferens
Vasoconstriction
72
What happens to the eye after sympathetic stimulation?
Pupil dilation (radical muscles of the iris contract)
73
What happens to salivary glands after sympathetic stimulation?
Composition of saliva
74
What happens to the respiratory system after sympathetic stimulation?
Bronchodilation
| Increased respiration in exercise
75
What is the adrenal medulla?
It is part of the adrenal gland and is surrounded by adrenal cortex.
It is responsible for releasing adrenaline, noradrenaline and some dopamine into the bloodstream in response to sympathetic stimulation.
76
What are catecholamines?
Hormones made by the adrenal medulla.
| Include adrenaline, noradrenaline and dopamine.
77
How and where do catecholamines form?
The site of catecholamine synthesis is the adrenal medulla. Tyrosine is converted to catecholamines there.
78
What percentage of catecholamines released from the adrenal medulla is noradrenaline and adrenaline?
85% is adrenaline
| 15% is noradrenaline
79
What is the series of reactions to form Dopamine?
Phenylalanine --(phenylalanine hydroxylase)--> tyrosine
Tyrosine --(tyrosine hydroxylase)--> L-Dopa
L-Dopa --(DDC)--> Dopamine
80
What reaction forms noradrenaline?
(pathway that leads to dopamine)
| Dopamine --(dopamine 6 hydroxylase)--> noradrenaline
81
What reaction forms adrenaline?
(pathway that leads to noradrenaline)
| Noradrenaline --(PNMT)--> adrenaline
82
What enzyme catalyses phenylalanine to tyrosine?
Phenylalanine hydroxylase
83
Where and how is adrenaline and noradrenaline 'stored'?
Once synthesised, the catecholamine is moved to chromaffin granules where they're stored as a complex comprised of ATP and a protein called chromogranin and are ready to be secreted.
84
In the synapse, what 5 things can the drug target?
```
Synthesis of the NT
Storage of NT
Release of NT
Removal process of NT
Presynaptic receptors
```
85
What drug can inhibit tyrosine synthesis and what is its clinical use?
a-methyl-p-tyrosine
It is not commonly used in medicine, but it can be used to treat tumors of the adrenal gland (as they produce too many catecholamines)
86
What drug can inhibit dopamine synthesis?
Carbidopa (prevents actions of DDC)
87
What does reserpine do?
Blocks the VMAT so NT is not stored. Non stored NT is broken down which ultimately leads to a reduction in synaptic neurotransmisson
88
What does the VMAT do?
Vesicle monoamine transporter
| It transports free dopamine or noradrenaline to the presynaptic vesicles, ready to be released into the synaptic cleft
89
What is uptake 1?
| What is uptake 2?
.Uptake 1 is when the NT is reabsorbed by the presynapse and is the most important mechanism for terminating NT action (accounts for 80% of NA being terminated)
Uptake 2 is when the NT is not taken up by the presynapse and instead diffuses to extra-neuronal sites where they're taken up by a second transporter process.
90
What is the mechanism of cocaine?
It blocks uptake 1 so enhanced synaptic neurotransmisson (for NA)
NER, DAT and SERT are the receptors that are effected
91
What is MAO
Monoamine oxidase
MAO degrades catecolamines
MAO is closely associated with mitochondria as they protect the body from oxidising amines
92
What happens to NT taken up by uptake 2?
After it is taken up by uptake 2 the noradrenaline or adrenaline is broken down by COMT and the breakdown products are further metabolised by MAO (mostly in the liver and gut wall) to form VMA, which is the end product of metabolism and can be detected in the urine.
93
What happens if the concentration of NA in the presynapse?
If the [NA] id too high in the presynaptic membrane, sympathetic neuron presynaptic ⍺2 adrenoceptors are activated.
⍺2 adrenoceptors mediate a negative feedback control of the release process ensuring that NA release is never excessive.
94
What is the 'cheese reaction'?
The cheese reaction is associated with the presence of too high levels of TYARMINE due MAOIs.
Non-metabolised tyramine enters the circulatory system and leads to the release of NA from neurons. Usually, tyramine is degraded by MAO, but MAOIs inhibit MAOs.
The result is acute hypertension, which leads to severe headches and cerebral haemorrhage.
95
What are 'Indirect Sympathomimetics?
| What are their mechanisms?
Drugs that indirectly cause a sympathomimetic effect. (they cause sympathetic effect without interacting with receptors)
Mechanisms include;
-inhibiting reuptake of NT by interfering with actions of NT transporters
-displacing stored catecholamine transmitter
96
What do amphetamines do?
They enter the presynaptic nerve via uptake 1.
They displace NA from their storage site.
This causes NA to be degraded by MAO or to leak into the synapse.
97
What is the primary and secondary mechanism of amphetamines?
Primary:
- Binds to receptors responsible for uptake 1 of NA
- Influx of amphetamine results in efflux of NA and additionally cause intracellular release of NA from vesicles
- This results in an increase of NT release from the nerve
Secondary:
- Competes with MAO for reuptake
- High concentration of amphetamines inhibit MAO entirely
98
What are side effects of amphetamines?
```
Nervousness
Insomnia
Palpitations
Hypertension
Headaches
Dizziness
Anorexia
Weight Loss
Dry Mouth
```
99
What is the mechanism of tyramine?
Taken up into presynaptic nerve terminal via uptake 1 and causes release of catecholamines.
100
What drugs enhance and diminish the effects of indirect sympathomimetics?
Drugs that inhibit the receptor responsible for uptake 1 diminish the effects indirect sympathomimetic drugs work by entering the cell through uptake 1.
MAOIs enhance the effects of these drugs.
101
```
Indirect sympathomimetics (IS)
What is the effect if the IS has a similar chemical composition to NA/Adrenaline?
```
Bronchodilatation
| β2 adrenoceptor mediated action
102
```
Indirect sympathomimetics (IS)
What is the effect if the IS enters nerve terminal through uptake 1
```
Increase mean arterial BP
| ⍺1 adrenoceptor mediated action
103
```
Indirect sympathomimetics (IS)
What is the effect if the IS inhibits reuptake of NA via uptake 1?
```
Increase heart rate and force
| β1 adrenoceptor mediated action
104
```
Indirect sympathomimetics (IS)
What is the effect if the IS displaces NA/Adrenaline from its storage vesicles
```
Decrease gut motility
| ⍺1 adrenoceptor mediated action
105
What is the mechanism of imipramine?
| What are the side effects
```
Blocks reuptake of noradrenaline (and serotonin) at nerve endings, resulting in an anti-depressive effect.
Side effects include:
-Sodium channel blocker
-Anti-muscarinic
-Anti-histamine
^each has multiple side effects.
```
106
What are direct sympathomimetics?
Drugs that have a direct agonistic effect on the adrenergic receptors
107
What clinical use does isoprenaline have?
Its an agonistic drug used to treat bradycardia.
108
What receptor is at nerve terminals?
⍺2 receptors
109
Where are β1 receptors typically found?
Post synaptic membrane of cardiac cells. Stimulation of these receptors causes and increase on force and rate of contraction.
110
What does isoprenaline do?
Binds directly to β2 receptors of smooth mucles to provoke vasodilation.
Additionally binds directly to β1 receptors of the heart to increase rate and force of contraction.
111
What does adrenaline do to the cardiovascular system?
β2 mediated dilatation in muscle and liver etc but ⍺1
mediated vasoconstriction elsewhere such as skin and gut, causing a fall in diastolic pressure and an increase in systolic pressure, but mean blood pressure stays the same.
112
What does effect does noradrenaline injected intravenously have?
There is stimulation of β2 receptors causing vasoconstriction which causes increased blood pressure. Baroreceptors detect this and there is a reflex reduction in sympathetic activity (negative feedback).
β1 receptors are also stimulated, so force and rate of contraction is increased.
113
What receptors does adrenaline preferably bind to?
⍺1, ⍺2> β1> β2
114
What receptors does noradrenaline preferably bind to?
β1,β2> ⍺1, ⍺2
115
What receptors does isoprenaline preferably bind to?
β1 and β2, no affinity for ⍺1 or ⍺2
116
What receptors does phenylephrine preferably bind to?
⍺1 only
117
What receptors does tizanidine preferably bind to?
⍺2 only
118
What receptors does salbutamol preferably bind to?
β2> β1 and no affinity for ⍺1 or ⍺2
119
What is the clinical use of tizanidine?
It is a muscle relaxant. It binds exclusively to ⍺2 receptors so causes inhibition of synaptic terminal NT release.
120
Where are ⍺1 receptors typically found?
Post-synaptic membrane of all tissues except heart.
121
What is prazosin and what is its clinical use?
It is an ⍺ adrenoceptor antagonists that selectively blocks ⍺1 receptors.
Its clinical use is that its used to treat hypertension.
122
What is metaprolol and what is its clincal use?
It is a β adrenoceptor antagonists that selectively binds to β1 receptors. This makes is 'cardioselective'.
It is used to treat abnormal cardiac rhythm, myocardial infarction and angina (reduced bloodflow to cardiac muscle)
123
How do socially used drugs evoke a pleasure?
Involves activation of dopaminergic reward pathways in the brain that run from ventral tegmental area (VTA) to nucleus accumbens (REWARD PATHWAY)
124
What are ways the reward pathway can be activated?
Directly, where the VTA is directly stimulated.
| Indirectly, where there is dis-inhibition of the VTA (inhibitor of VTA is inhibited).
125
What percentage of people in the UK smoke?
22% of men
17% of women
10 million in total
(are more smoking related statistics needed?)
126
What positive effect does smoking have?
It is a psychoactive stimulant and relaxant.
| It gives a euphoric effect, increased alertness and increased concentration.
127
What is the source of tobacco, heroin and ecstacy?
Tobacco- Tobacco leaf
Heroin- Opium poppy
Ecstacy- Synthetically made, so no source
128
What does nicotine do in the periphery and CNS?
Periphery: Nicotine excites autonomic ganglia to cause adrenaline release from adrenal medulla.
Additionally it causes tachycardia, vasoconstriction and increased blood pressure.
CNS: Causes neuronal excitation, which releases many transmitters including dopamine (euphoria), ACh (concentration) and serotonin (relaxation).
129
Which is more sensitive, muscle nicotinic receptors or neuronal nicotinic receptors?
How much more sensitive is the more sensitive one?
Neuronal is more sensitive than muscle, by about 50x.
130
What are the toxic effects of cigarette smoke?
Carbon monoxide: displaces O2 from haemoglobin to form carboxyhaemoglobin, which causes decreased O2 carriage.
Nicotine: a vasoconstrictor and platelet aggregator, which increases risk of coronary thrombosis.
Tar and irritants (formaldehyde and carcinogenics): Increase incidents of lung cancer
131
Which nicotine receptor has the highest affinity for nicotine?
α4β2 (it is neuronal)
132
What are features of heroin?
Similar effect to morphine, in that it causes psychoactive effects such as euphoria
Converted to morphine in the brain
It is twice as potent as morphine
Can cross BBB faster than morphine
133
What are the toxic effects of morphine?
Mild respiratory depressions (in small doses). This turns to severe respiratory depression if heroin is regularly used. Eventually cause respiratory failure.
Extreme sedation.
134
What 'positive' effects does ecstasy have?
Aiming for euphoria, arousal, empathy, perceptual disturbances, endurance, increased self-confidence
135
What is the mechanism of ecstasy?
The active drug in ecstasy is MDMA
MDMA displaces seratonin from its vesicles, causing it to leak out. MDMA also blocks the reuptake of seratonin into the presynapse which prolongs the effects of seratonin.
Additionally, there is a rise in dopamine and NA in the synaptic cleft.
136
What are the toxic effects of ecstasy?
Short term:
Hyperthermia (high body temp)
Hyponatremia (low [Na+] in blood)
Exhaustion, low mood and high irritability (due to low 5-HT)
Long term:
Depression
Neurotoxicity
