9/16 Flashcards
1
Q
What are heteroreceptors?
A
A receptor on the neuron that responds to something that neuron is not releasing
i.e. a neuron releases norepinephrine, but has a receptor on it that acetylcholine binds to. ACh might slow down or speed up the release of norepinephrine
2
Q
What are autoreceptors?
A
a receptor on a neuron that binds with the same neurotransmitter typically excreted by that neuron.
i.e. neuron normally releases norepinephrine, has a receptor that also binds with norepinephrine and increases or decreases the amount of norepinephrine released.
3
Q
Positive feedback
A
Increases the effect already being produced
4
Q
Negative feedback
A
Decreases the effect already being produced
5
Q
What is the primary pacing node in the heart?
A
SA node
6
Q
What is the sympathetic activity on the heart at beta 1 and 2 receptors?
A
It accelerates the SA node and increases contractility
7
Q
What is the parasympathetic activity on the heart at the muscarinic 2 receptors?
A
decelerates the SA node and decreases contractility
8
Q
What is the sympathetic activity on the blood vessels at beta 2 and alpha1 receptors?
A
Increases blood flow by relaxing skeletal vessels allowing more blood flow, and contracts smooth muscle blood vessels increasing blood pressure
9
Q
What is the parasympathetic activity on the blood vessels on the M3 receptors?
A
relaxes the smooth muscle blood vessels
10
Q
What is the sympathetic activity on the bronchiolar smooth muscle beta2 receptors?
A
Relaxing
11
Q
What is the parasympathetic activity on the bronchiolar smooth muscle M3 receptors?
A
Contracts
12
Q
Skeletal muscles at rest take up about what percent of circulating blood flow?
A
20% (can go up to 80% during physical activity or during sympathetic nervous system stimulation)
13
Q
What is another term for cholinomimetics?
A
parasympathomimetics
14
Q
what do cholinomimetics do?
A
they mimic the activity of the parasympathetic nervous system by mimicking endogenous acetylcholine
15
Q
what is another term for parasympatholytics?
A
antimuscarinics
16
Q
What do antimuscurinics do?
A
they block the effect of the parasympathetic nervous system
17
Q
what are sympathomimetics?
A
they mimic the Sympathetic nervous system
18
Q
what are sympatholytics?
A
alpha and beta blockers, they block the sympathetic nervous system
19
Q
all neurons coming off of the central nervous system release
A
acetylcholine
20
Q
all neurons coming off of the central nervous system in the autonomic nervous system encounter
A
a ganglia which is the next neuron in the chain. this neuron will then release norepinephrine, acetylcholine, or even dopamine depending on the target organ
21
Q
What is the space between the neuron and effector organ cell, muscle, or other neurons called?
A
synapse. very thin space
22
Q
What is another name for the telodendria?
A
synaptic bouton
23
Q
Inputs on a neuron is called a
A
dendtrite
24
Q
the axon hillock generates what?
A
an action potential
25
What is saltatory conduction?
jumping of action potential over the myelin
26
Where is a neurotransmitter stored?
in the synaptic boutons or telodendria
27
Describe information going from the dendrites to the next synapse.
Information comes in through the dendrites
it is sent to the nucleus as a go or no-go
if it's go nucleus becomes active
This activates the axon hillock
Axon hillock generates an action potential
AP goes down the axon
Reaches the telodentria which are capped with synaptic boutons
boutons release neurotransmitter into the synapse
28
Where is saltatory conduction very common?
in the somatic nervous system. If someone throws a ball at your head you want to be able to life your mitt up to catch it
29
Where are neurotransmitters largely made?
in the neuron itself
30
Can one axon have many telodendria?
Yes
31
Where do Telodendria get energy?
from a mitochondria found in the telodendria
32
What are the 2 types of synapses?
chemical and electrical?
33
Where are gap junctions found?
in the heart, this allows the atria and ventricles to contract together
34
What do we do with neurotransmitters after they are released into the synapse?
They will keep signaling if we don't get rid of them.
A lot of synapses have enzymes in them to degrade neurotransmitters
35
What breaks down acetylcholine?
acetylcholine esterase
36
what does acetylcholine esterase break acetylcholine down to?
acetate
choline
37
What happens to acetic acid and choline after acetylcholine esterase breaks down acetylcholine?
They can be reabsorbed into the presynaptic cell to be reassembled into acetylcholine
38
In the CNS we have En Passant synapses, what is this?
swellings in the axons where neurotransmitters can be released into a synapse
39
What are the main stages of synaptic transmission?
AP in synaptic bouton
opening of VG Ca++ channels
Calcium influxes
secretion of neurotransmitter then inactivation of neurotransmitter
activation of receptor 2 options:
1. opening of ion channels
-increased Na+= depolarization (EPSP) and excitation
-increased Cl-= hyperpolarization(IPSP) and inhibition
2. Dissociation of G-protein
-activation of second messenger system
-modulation of ion channel activity
-slow modulation of neural excitability
40
What is EPSP?
excitatory post synaptic potential
41
What is IPSP?
Inhibitory post synaptic potential
42
What are the fates of used neurotransmitters?
It is decreased in the synapse
1. diffuses away
2.degraded by enzymes
3. uptake into pre-synaptic cell
4. uptake into surrounding cell(blood stream, muscle cells etc.)
43
What is an ester?
something that has an r group, carbon, double bond group to oxygen, another bond to oxygen, and another r group
acetylcholine
44
What is a monoamine?
a single amine
norepinephrine
serotinin
dopamine
45
What is an amino acid neurotransmitter?
Glutamate GABA
46
What is a purine neurotransmitter?
adenosine
ATP
47
How is nitric oxide different from the other neurotransmitters?
It can't be stored so it is made as needed
48
What are the 6 classes of neurotransmitters?
1. esters
2. monoamines
3. amino acids
4. purines
5. peptides
6. inorganic gases
49
What is an example of peptide neurotransmitters?
substance P, endorphins
50
What are cholinergic fibers?
specific fibers that release acetylcholine
51
Nicotinic are what kind of channels?
ion channels
fast
52
Muscarinic are what kind of channels?
g protein
slow
53
Where is acetylcholine found?
* almost all preganglionic fibers
* all somatic fibers (skeletal)
* postganglionic
-all parasympathetic
a few sympathetic
**nearly all efferent fibers leaving the CNS**
54
Monoamines are
derivatives of amino acids
55
What are norepinephrine and epinephrine made from?
the amino acid tyrosine
56
What releases norepinephrine and epinephrine
adrenergic or noradrenergic fibers
57
What gives a rewarding or pleasurable sensation?
dopamine
58
Which monoamine is associated with addiction?
dopamine
59
What is associated with depression?
serotonin
60
What is the Lovheim cube?
if you are deficient on any of these 3 neurotransmitters (noradrenaline, dopamine, serotonin) in the CNS, then you can't feel a full range of emotion
61
How does an SSRI work?
It selectively inhibits the reuptake of serotonin, leaving serotonin in the synapse for a longer period of time
62
What are the 3 main amino acid neurotransmitters?
Glutamate
Glycine
Gaba
63
What is the most important excitatory neurotransmitter amino acid in the brain?
Gluta**mate**
mating is exciting
64
Glycine and GABA are both
Inhibitory
produce postsynaptic inhibition
65
What does the poison strychnine do?
blocks the glycine receptor resulting in fatal convulsions d/t not having control over the inhibition
66
What do neuropeptides do?
mediate pain and analgesia
67
Key targets for pharmaceutical intervention features of neurotransmitters at synaptic terminal are
-synthesis
-storage
-release
-activation of receptors
-termination of action
68
One round of acetylcholine at a cholinergic synapse
1. action potential ends in the terminal bouton
2.Terminal bouton becomes depolarized
3. This lets Ca++ in
4. Ca++ binds to vesicles
5. vesicles bind to surface of the cell
6. exocytosis of ACh into the synapse
7. ACh binds to the ACh receptor
8. this opens Na+ channels
9. this depolarizes the postsynaptic cell
10. this influxes Ca++
11. postsynaptic cell depolarizes= muscle contraction.
ACh is now targeted by acetylcholinesterase
ACh is broken down
69
Where is ACh synthesized?
in the cytoplasm of the cell that releases it
70
What is Acetyl-CoA?
a carrier molecule that attaches an acetyl group to choline
71
Where do we get choline?
in our diet
eggs
72
what enzyme combines acetyl-CoA and choline?
choline acetyltransferase ChAT
73
Where is ChAT found?
inside the neuron
74
Where is AChE (Acetylcholine esterase) found?
in the synapse
75
Once ACh is made, where is it stored?
in a vesicle
76
How much ACh is found in a vesicle?
1,000-50,000
77
What is release of ACh dependent on?
extracellular Ca++ coming in and destabilizing the storage vesicles
78
What is CHT?
a choline transporter that takes choline down it's concentration gradient through facilitated diffusion co-transporting Na+ and choline into the cell
79
Once ACh is made it is transported into a vesicle by
**V**essicular **A**cetylcholine **T**ransporter
80
What is a docking molecule?
a protein that anchors a vesicle near the synapse so we can have rapid release of the vesicle
81
what is a collective name of docking molecules?
SNARE complex
like a net
82
Which SNARE proteins are associated with the vesicle?
Syntaxin
SNAP -25
83
Which SNARE protein is a part of the membrane?
**V**esicular **A**ssociated **M**embrane **P**rotein
84
What is Synaptotagmin?
A very important SNARE protein that senses the calcium influx and facilitates the rapid exocytosis of the vesicles filled with ACh
85
What is priming?
it comes after docking of the ACh vesicles.
It is like the cocking of a gun, it is ATP dependent that prepares the vesicle for rapid exocytosis
86
What are the 3 steps of ACh transmission?
docking
priming
fusion
87
What is a choline transporter inhibitor?
hemicholiniums- a molecule used in research
88
How does a calcium channel blocker effect nerve transmission?
It blocks the voltage gated calcium channel meaning Ca++ can't get into the cell. No Ca++ = no activation of synaptotagmin = no exocytosis of ACh = no reaction in the effector cell
89
Cholinergic inhibitors can inhibit other than being a receptor antagonist by
inhibiting some other part of the docking, priming, or fusion process
90
Examples of cholinergic inhibitors that are not direct antagonists?
Hemicholiniums- CHT
Vesamicol- VAT
Caclium channel blocker- vg Ca++ channels
botulinum toxin- vesicle release fusion proteins
sarin (nerve gas)- AChE inhibitor
91
How does Botox cause something to be paralyze?
it blocks the fusion proteins from releasing ACh which means the effector cell never gets activated
92
Sarin (nerve gas) overdoses us on
ACh
93
What is the treatment for Sarin nerve gas?
Atropine
94
In what case would you want to block the AChE?
Myasthenia Gravis- body makes antibodies against acetylcholine receptors causing less and less muscle control
inhibiting AChE therefore increases the amount of ACh in the synapse
95
Tyrosine is a precursor for
DOPA
norepinephrine
epinephrine
96
What happens to Norepinephrine after it is used in the synapse?
It is reuptaken into the neuron by **N**or**E**pinephrine **T**ransporter
or is diffused away from the site
97
After used NE is brought back into the neuron by NET, what happens to it?
can either be redocked into vesicles
or
can be broken down by **M**ono**A**mine **O**xidase
98
What are MAOI's used for clinically?
The treatment for severe depression. The inhibit the breakdown of dopamine, serotonin, NE
99
Why are MAOI's very dangerous?
They can lead to overdose of neurotransmitters and have a lot of drug interactions
100
What is a VMAT?
**V**esicular **M**ono **A**mine **T**ransporter
101
Delete
Me
102
What are the targets for drug actions for adrenergic transmission?
1. Synthesis of neurotransmitter -inhibition of tyrosine
2. storage of neurotransmitter-no current therapeutics
3. vesicle secretion-botox
4. vesicle cycling and endocytosis- no current therapeutics
5. Reuptake of neurotransmitter- SSRI, Cocaine, molly, tricyclic antidepressants
6. biotransformation of neurotransmitter-MAOI
7. Neurotransmitter receptor-agonists, antagonists
103
cholinergic agonist and antagonists bind to which receptors?
nicotinic and muscarinic receptors
104
Why can't you give ACh exogenously?
There are so many AChE in the blood that it is broken down within seconds
105
What are direct acting drugs?
They are agonists
106
What are indirect acting drugs?
antagonists (they block AChE)
107
What are irreversible indirect acting drugs that can affect cholinoreceptors?
Nerve gas and toxins
108
How did muscarinic receptors get their name? (pharm)
from the fungi muscarine
109
What are the symptoms of parasympathetic
Salivation
Lacrimation
Urination
Defecation
Gi motility
Emesis
Myosis -constriction of the pupil
110
What is mycetism?
mushroom poisoning
111
Why is atropine the treatment for mycetism?
It blocks muscarinic receptors
112
Acetocholine is both ___________ But Nicotine only binds to _________ receptors
nicotinic and muscarinic
nicotinic
113
ganglion cells are labeled as
nicotinic
114
The odd number muscarinic receptors (M1,M,3M5) increase _______ which leads to calcium release within the cell
IP3
115
The even number muscarinic receptors (m2&M4) inhibit adenylyl cyclase which
decreases CAMP
116
Drugs that bind to muscarinic receptors are:
esters of choline
alkaloids
117
What are alkaloids?
plant based compounds that are bitter (high pH)
118
If you have a drug that excites or inhibits a muscarinic receptor, they're not going to JUST excite or inhibit M1, or M2, they will target
either all of the odd or all of the even
119
Esters of choline are charged and lipid insoluble molecules and so they
don't cross barriers easily. (can't be given transdermally)
120
Methacholine is used for
diagnosis of asthma
short lived and causes people to have an asthma attack
121
ACh drugs can be used for
pupillary constriction
122
carbachol is used for
decreasing intraocular pressure (constricting the pupil)
123
Bethanechol is used for
bladder dysfunction and reflux disease
stimulates the parasympathetic response
124
What is pilocarpine?
a plant based alkaloid that's chiefly muscarinic
125
What is Arecoline?
nicknamed the betel nut
an alkaloid found in other countries that is used as a stimulant
126
Because we have nicotinic receptors in both the sympathetic and parasympathetic, we can activate
both of them simultaneously, although sympathetic response usually predominates
127
muscarinic effects in the eye?
pupil contraction
128
muscarinic effects in the cardiovascular system
Reduction in PVR and vasodilation
reduces bp
129
What is glaucoma?
Increase in intraocular fluid called aqueous humor which is formed by the ciliary bodies in the ciliary muscle.
130
What does the ciliary muscle do?
it holds the lens in the eye and changes it's shape to focus on something either far away or up close
131
Where does aqueous drainage drain?
Through the canal of schlem
132
Drainage is possible through the canal of schlem because
the iris is fairly flat compared to the cornea, which juts up out from the eye
133
With open angle glaucoma, pts. can ______ drain their aqueous humor into the canal of schlem
easily
134
If a patient with open angle glaucoma has a build up of too much aqueous humor, what can we do to help?
give something that will constrict the pupil and open the angle even more
like bethenicol or methicoline
135
If a patient has closed angle glaucoma the iris is ________ causing a high degree of interocularpressure
bulged forward
136
if we constrict the iris in a patient with closed angle glaucoma,
it may not be enough because the angle is already so closed
137
Closed angle glaucoma can be a medical emergency if we give
atropine
atropine dilates the iris, compressing on the canal of schlem even more and can cause blindness quickly
138
airway tone is important because
we need our airway to have a consistent tone because we don't want smog and smoke particulates to get down deep in the lungs so it is important to decrease the flow and surface area where mucous membranes can bind to that particulate matter
139
what is the parasympathetic response in our lungs?
increased muscle tone
increased mucous secretion
140
what are the parasympathetic responses in the GI tract?
increased gastric secretions and motor activity, sphincters relax
141
what are the parasympathetic responses in the CNS?
brain- mainly muscarinic sites but muscarine doesn't cross very easily, so nicotine has a greater effect.
it's mildly alerting, releases dopamine
142
in large enough doses, nicotine can cause
tremors, emesis, stimulates the respiritaroty center, convulsions, fatal coma
143
If we have something that is going to bind to a nicotinic receptor and keeps it open for a while, we end up with
a depolarization blockage (flaccid paralysis)
this is what succs does.
we've depolarized and can't repolarize because the substance is still there
144
Indirect acting cholinomimetics have what effect on the body?
the same as direct acting cholinomimetics, they just happen a different way by blocking AChE
145
Neostigmine is used to treat
post-op ileus
146
What are the classes of indirect cholinomimetics?
simple alcohols
carbamic acid esters of alcohols
organic derivatives of phosphoric acid
147
alcohols work how long as a cholinomimetics? What is an example of this type of drug?
5-15mins short lived
edrophonium
148
carbamates work how long as a cholinomimetics? What is an example of this type of drug?
neostigmine 0.5-2 hrs
pyridostigmine 3-6 hrs
149
organophosphates work how long as a cholinomimetics? What is an example of this type of drug?
Echothiophate 100 hours
this forms a covalent bond
150
How does an organophosphate work as an indirect cholinomimetic?
It forms a covalent bond with the AChE and hydrolyses it.
Thought of as irreversible
Can be broken if you give pralidoxime within the first few hours
after that the aging makes the covalent bond stronger
151
How is myasthenia gravis diagnosed?
baseline muscle test
2mg iv watch for negative reaction
8mg iv improvement in muscle action= myasthenia gravis
Now we can give longer lasting AChE inhibitors for treatment
152
AChE inhibitors can reverse the effects of paralysis by
increasing the amount of ACh in the synapse
153
Bella donna gives us
atropine intoxication
154
Direct acting muscarinic stimulants act like
muscarine.
Same effect of parasympathetic actions but stronger
155
If you see SLUDGEM give
atropine
156
What does night cap do? A. Phalloides mushroom
inhibits mRNA synthesis and kills in 4-7 days
157
if a person is working out in the field and a plane comes by dumping bug poison, we would look for _____ symptoms and give ______
SLUDGEM
atropine
158
Pralidoxime is useful for
organophosphates
159
atropine is used to combat
extremely high parasympathetic overdose
