Exam 3 - Rochet (CNS/MS Drugs) Flashcards
1
Q
3 main parts of brain
A
hindbrain
midgrain
forebrain
2
Q
main parts of hindbrain
A
medulla
pons, cerebellum
3
Q
main parts of midbrain
A
substantia nigra (SN)
4
Q
main parts of forebrain
A
cerebral cortex
basal ganglia (minus SN)
limbic system
diencephalon
5
Q
what makes up limbic system
A
hippocampus
amygdala
6
Q
what makes up basal ganglia
A
striatum
globus pallidus
subthalamic nucleus
7
Q
what makes up the diencephalon
A
thalamus
hypothalamus
8
Q
is it in the hindbrain, midbrain, forebrain?
medulla
A
hindbrain
9
Q
is it in the hindbrain, midbrain, forebrain?
substantia nigra
A
midbrain
10
Q
is it in the hindbrain, midbrain, forebrain?
pons, cerebellum
A
hindbrain
11
Q
is it in the hindbrain, midbrain, forebrain?
cerebral cortex
A
forebrain
12
Q
is it in the hindbrain, midbrain, forebrain?
basal ganglia
A
forebrain
13
Q
is it in the hindbrain, midbrain, forebrain?
limbic system
A
forebrain
14
Q
is it in the hindbrain, midbrain, forebrain?
diencephalon
A
forebrain
15
Q
is it in the hindbrain, midbrain, forebrain?
hippocampus
A
in limbic system — therefore in FOREBRAIN
16
Q
is it in the hindbrain, midbrain, forebrain?
amygdala
A
in limbic system — therefore in FOREBRAIN
17
Q
is it in the hindbrain, midbrain, forebrain?
hypothalamus
A
in diencephalon — therefore in FOREBRAIN
18
Q
is it in the hindbrain, midbrain, forebrain?
thalamus
A
in diencephalon — therefore in FOREBRAIN
19
Q
what is the overall function of medulla
A
autonomic functions
20
Q
what is overall function of pons
A
a “bridge”
relays signal from forebrain to cerebellum
21
Q
Pons: relays signal from ______ to _______
A
from forebrain to cerebellum
22
Q
main function of cerebellum
A
“little brain”
governs motor coordination for producing SMOOTH movements
23
Q
Medulla does conscious or non-conscious actions?
A
NON-conscious/autonomice
reflexes, respiration, cardiac function etc…
24
Q
_________ undergoes neurodegeneration in spinocerebellar ataxias
A
cerebellum
25
Substantia Nigra: Pars Compacta
| provides _____ to basal ganglia (supplies _______ to the ______
provides INPUT
| supplies DOPAMINE to STRIATUM
26
what are the two parts of substantia nigra
pars COMPACTA
| or pars RETICULATA
27
Substantia Nigra: Pars Reticulata
has ______ function
relays signal from _________ to ______
OUTPUT function
| from basal ganglia; to thalamus
28
Pars Compacta or Pars Reticulata?
| has input function
compacta
29
Pars Compacta or Pars Reticulata?
| has output function
reticulata
30
Pars Compacta or Pars Reticulata?
| provides signal to basal ganglia
compacta
31
Pars Compacta or Pars Reticulata?
| provides signal to thalamus
reticulata
32
Pars Compacta or Pars Reticulata?
| supplies dopamine to striatum
compacta
33
Pars Compacta or Pars Reticulata?
| involved with voluntary motor control
compacta (b/c dopamine)
34
main function of cortex
processing/interpreting information (executive function)
35
other name for cortex
cerebrum
36
main role of basal ganglia
voluntary motor control
| some cognitive functions
37
main role of limbic system
emotions and memory
| emotions - amygdala; memory - hippocampus
38
what is the role of amygdala
emotions
39
what is the role of hippocampus
memory
40
main role of diencephalon
relay station to AND from cortex
regulating internal homeostasis, emotions, hormonal control, and direct regulation
(relaying - thalamus; hypothalamus does the rest (aka lots of regulation)
41
main role of thalamus
relay station to AND from cortex
42
main role of hypothalamus
regulating internal homeostasis, emotions, hormonal control, and direct regulation
43
Decisions are made in "______________" about how to interpret and act on the incoming sensory information
cortico-thalamic loops
44
Schizophrenia is considered a disease of the _______
frontal cortex
45
damage to the cortex can affect what things?
movement, speech, personality
46
T or F: when there is damage to the cortex, drugs are not typically available to treat these deficiencies
True!!
| exception is Schizophrenia tho
47
Afferent or Efferent Neuron Tracts?
| transmit signals from cortex to periphery
efferent
48
Afferent or Efferent Neuron Tracts?
| transmit signals from periphery to cortex
afferent
49
brain is surrounded by layers of membranes collectively known as the ______
meninges
50
3 main layes of meninges
dura
arachnoid
pia
51
Dura, Arachnoid, Pia layer of meninges?
| us closest to bone
dura
| dura = hard next to bone
52
Dura, Arachnoid, Pia layer of meninges?
| is closest to brain
pia
53
Dura, Arachnoid, Pia layer of meninges?
| is the middle layer
arachnoid
54
Dura, Arachnoid, Pia layer of meninges?
| is the outer layer
dura
55
Dura, Arachnoid, Pia layer of meninges?
| is the inner layer
pia
56
what fills the space b/w arachnoid and pia layers?
CSF - cerebrospinal fluid
57
blood enters brain via the ________
carotid artery
58
once carotid artery enters the brain... it branches into what things?
4 arteries total...
opthalmic artery;
anterior, middle, and posterior cerebral arteries
59
CNS consists of ______ and _____ cells
neurons;
| glial cells
60
which is more abundant?
| neurons or glial cells
glial cells
61
3 main glial cells
astrocytes
Oligodendrocytes
Microglia
62
Role of Astrocytes
provide neurons w/ _________ & _______
remove excess __________
support the _________
provide growth factors and anti-oxidants
remove excess GLUTAMATE
support BLOOD BRAIN BARRIER
63
Role of Oligodendrocytes
produce myelin sheath that insulates axons
64
Role of Microglia
Clear debris!!
also provide growth factors
(if too many microglia => inflammation)
65
why is it good astrocytes remove excess glutamate
too much glutamate can damage neurons
66
Astrocytes, Oligodendrocytes, or Microglia?
| remove debris
Microglia
67
Astrocytes, Oligodendrocytes, or Microglia?
| remove excess glutamate
astrocytes
68
Astrocytes, Oligodendrocytes, or Microglia?
| make myelin sheath for axon insulation
oligodendrocytes
69
Astrocytes, Oligodendrocytes, or Microglia?
| support blood brain barrier
astrocytes
70
Astrocytes, Oligodendrocytes, or Microglia?
| provide growth factors
astrocytes (mainly)
| also microglia
71
Astrocytes, Oligodendrocytes, or Microglia?
| provide anti-oxidants
astroyctes
72
Blood Brain Barrier:
| stabilized by ________ in the ______ cell layer of blood vessels in the brain
tight junctions
in endothelial cell layer
73
Neurotransmission is triggered by ______ of the neuron
electrical depolarization (shocking...)
74
Neurotransmission occurs when a influx of ______ changes polarity of membrane
Na+ ions...
75
T or F:
| smaller axon diameter leads to faster firing
false!
| bigger diameter = faster firing
76
depolarizing neurons = excitatory or inhibitory?
excitatory
77
polarizing neurons = excitatory or inhibitory?
inhibitory
78
T or F: action potentials for a SINGLE neuron are always the same magnitude
true!
| "all or none" type thing
79
bundle of axons aka _______
nerve fiber
80
currents carrier by a nerve fiber are higher because of the result of ________
summation
81
what is EPSP
excitatory postsynaptic potential
82
______ neurotransmitters will induce EPSP
excitatory...
83
Excitatory neurotransmitters act on (chronotropic or ionotrpic?) receptor allowing ____ ions to cross the membrane
ionotropic; Na+
84
Inhibitory neurotransmitters induce _________ by allowing ____ ions to cross the membrane
hyperpolarizing; Cl- ions
85
T or F: IPSP can decrease the magnitude of a subsequent EPSP
true!
if lots of hyperpolarizing (hella negative), it can prevent a action potential the next time (aka like refractory period)
86
what are the common amino acid neurotransmitters
GABA
Glycine
Glutamate
87
what are the common non-amino acid neurotransmitters
Ach
DA (dopamine)
NE
Serotonin (5-HT)
88
GABA:
| is a excitatory or inhibitory neurotransmitter?
inhibitory
89
GABA:
| decrease neuronal excitability by doing what?
increasing the influx of Cl- ions into the neuron
90
what are types of GABA receptors?
GABA-A and GABA-B
91
drugs that normally interact with GABA pathways are known as CNS ________
depressants
92
what drug classes are known to be related to the GABA pathway
- Sedative hypnotics (BZDs, Barbituates)
- Anticonvusalnts
- Anxiolytics
93
______ is similar to GABA but it works in the spinal cord
glycine
94
glycine is similar to GABA but it works in the _______
spinal cord
95
GABA-A receptor is a ______
and
GABA-B receptor is a _______
A: ion channel
B: GPCR
96
GABA-A or GABA B receptor is more relevant in seizures
A!
97
Glutamate:
| is a excitatory or inhibitory neurotransmitter?
excitatory
98
Excess glutamate leads to neuronal damage by allowing excessive _____ into neuron
Ca2+ influx
99
what are the glutamate receptors?
AMPA/NMDA
| mGluR
100
Glutamate receptors are ______tropic or ______tropic
metabotropic
or
ionotropic
101
Ach receptors are?
muscarinic (mAchR)
or
nicotinic (nAchR)
102
what parts of the brain does Ach have an effect?
basal forebrain!!
| Pons, Cortex, Basal Ganglia
103
Ach
| is a excitatory or inhibitory neurotransmitter?
excitatory
104
Glutamate works in what parts of the brain?
throughout the whole brain
105
GABA works in what parts of the brain?
throughout the whole brain
106
Ach or DA?
| works in basal forebrain
Ach
107
Ach or DA?
| works in midbrain
DA
108
Dopamine Drug Targets
D1 - D5 GPCR receptors
and
DAT (dopamine transporter)
109
DA neurons arise from where?
VTA and SN
| ```
VTA = ventral tegmental area
(SN = substanta nigra)
```
110
Drugs that block DAT lead to (decrease or increase) in DA?
increase!!
111
what drugs block DAT
amphetamine and cocaine = more dopamine = euphoria = addiction
112
DA Receptors:
D1 like is G___ coupled
D2 like is G____ coupled
D1: Gs
D2: Gi
113
NE works where in the brain?
Pons
114
drug targets for NE
adrenergic receptors (alpha and beta)
and
NET (NE transporter)
115
NET inhibitors are used to treat _______
depression
116
D2 receptor antagonists are used as _______ drugs
Antipsychotics
117
Drug targets for 5-HT
GPCRs and
Gated Ion channel and
SERT (serotonin transporter)
118
5-HT axons arise from a group of cell bodies in the brain stem called __________
Raphe Nuclei
119
5-HT(2A) antagonists are known as _______
atypical antipsychotics
120
5-HT(1D) agonists are used for ______
migraines
121
SERT uptake inhibitors are used for ______
depression (SNRIs??)
122
5-HT(2A) agonists are known as ________
hallucinogenic
(2A - antag used as antipsych...
2A- agonist used to create hallucinogens...)
123
what is Charcot's Triad used for?
its the 3 key signs of MS
124
what makes up Charcot's Triad?
1 - Nystagmus
2 - intention tremor
3 - telegraphic speech
125
what is nystagmus
uncontrolled eye movement
126
what the common symptoms of MS
| Rochet lists 10...
- Visual problems
- Numbness/Tingling
- fatigue/motor weakness
- Problems walking/gait problems
- pain
- spasticity
- dizziness/vertigo
- Sexual dysfunction
- Bladder problems/Constipation
- Emotional/Cognitive changes/depression
127
Viral/bacterial infections may increase risk of MS by activating _________ cells
autoreactive immune
128
What evidence supports the idea that viral/bacterial infections can lead to MS (autoreactive immune cells cause it)
- increased ______ synthesis in CNS of MS pts
- increased ______ to certain viruses
- epidemiological data suggests that _____ infection increases MS risk
IgG;
antibody titers
childhood
129
EBV and MS:
| - sequence similarities b/w EBV and self peptides --> activation of ___________ (aka _________)
activating autoreactive T or B Cells; molecular mimicry
130
Genetic Influences in MS:
| Risk is ______ in twins/siblings and _____ in children/half siblings
higher; lower
131
Genes linked to MS encode the following immune related proteins:
- MHC/HLA______
- interleukin ____ receptor
- interleukin ____ receptor
- MHC/HLA: DR15/Dr6
2(alpha)
7(alpha)
132
List the Clinical Forms of MS:
```
RRMS (relapsing remitting)
SPMS (secondary progressive)
PPMS (primary progressive)
CIS (clinically isolated syndrome)
Marbug Variant
```
133
SPMS:
| has less ________ but does have progressive _____
less inflammation
| progressive decline
134
RRMS or PPMS:
| which one has later onset
PPMS (primary progressive)
| probs bc RRMS has inflammatory episodes surpass symptomatic threshold
135
what is CIS
clinically isolated syndrome;
initial episode of neurologic syndrome > 24 h
involves inflamm. and demyelination in optic nerve/cerebrum,cerebellum, brainstem, or spinal cord
136
what is Marburg Variant of MS
aggressive MS --- hella inflammation; may resemble brain tumor
137
MS consists of what 2 phases
autoimmune and degenerative
138
MS Autoimmune Phase:
| _____ cells present CNS antigens and activate ____ cell responses in the peripheral ________ tissue
Dendritic cells
T cells
lymphoid
139
MS Autoimmune Phase:
| activated B and T cells proliferate and infiltrate CNS (it involves _______ mediated binding and penetration of _____)
involves alpha-4 integrin
penetrate BBB (blood brain barrier)
140
MS Autoimmune Phase:
after re-encountering their specific antigen in CNS, B cells mature into ________ and release ______ to target the antigen on expressing cells
mature into PLASMA CELLS
release IgG antibodies
141
CD8 T Cells or CD4 T Cells?
| interact with target ligands on oligodendrocytes
CD8 T cells
142
CD8 T Cells or CD4 T Cells?
| interact with target ligands on microglia
CD4 T cells
143
CD8 T Cells or CD4 T Cells?
| interact with MHC Class I molecules
CD8 T cells
144
MS Autoimmune Phase:
| T cells being activated leads to what things?
cytokine release + macrophage stimulation --> damage to myelin sheath
145
what cytokines are released by T cells
IFN- gamma
TNA-alpha
perforin
granzyme
146
MS Autoimmune Phase:
| antibodies trigger activation of ________ on oligodendrocytes that result in _____ formation/cell damage
activated COMPLEMENT
| result in PORE
147
MS Autoimmune Phase:
| Macrophages get recruited to the _________ and release _______ that will harm _________
to the inflamm. lesion
release toxins
harm oligodendrocytes
148
Node of Ranvier have ____ channels
vs
Myelin sheath have _____ channels
Ranvier: Na+ Channels
Myelin: K+ Channels
149
T or F: Action potentials travel faster if myelin sheath isn't there
False.... need the sheath for insulation (duh why demyleination is bad..)
150
when there is damage in MS and a lesion has occurred, what two things migrate to the lesion?
neuronal stem cells and OPCs (oligodendrocyte progenitor cells)
151
what is astrogliosis
invasion/propagation of astrocytes resulting in gliotic plaques/scars (done when demyelination occurs)
152
Remyelination in MS:
| 1st Demyelination has to happen, this will cause the activation of what two cells?
microglia and astrocytes
153
Remyelination in MS:
| when astrocytes/microglia get activated the end up releasing what? to recruit what?
pro-migratory factors and mitogens
recruit OPCs
154
3 possible targets/therapeutic interventions in MS
- immune system targets
(T cell binding and BBB penetration; T cell/APC interactions; Cytokines)
- targeting remyelination
- targeting neurodegeneration
155
why is gadolinium (Gd) important to MS
when injected it penetrates the regions where the blood brain barrier is comprosmised
MS lesions are enhanced when GD is given
156
Guillain Barre Syndrome:
| usually preceded by what?(for about 50% of pts)
GI or Respiratory infection
157
Guillain Barre Syndrome:
| Pathophys?
autoimmune attack on peripheral nerves by circulation Abs --> leads to myelination
158
Tx of Guillain Barre Syndrome?
- ventilation (when resp. distress)
- Plasmapheresis (eliminate auto-Abs)
- IV immunoglobulin administration
159
Sx of Guillain Barre Syndrome?
weakness starts in distal muscles/lower extremities goes to upper extremities
can progress to total paralysis w/ death from respiratory failure
160
Progression of Guillain Barre Syndrome can peak in how long?
10 - 14 days
161
what drugs are used for acute MS attacks?
Methylprednisolone
Prednisone
ACTH (adrenocorticotropic hormone)
162
Interferon Beta Drugs:
| first line or second line?
first
163
Interferon Beta Drugs:
| act in the _______ and ______
periphery and BBB
164
Interferon Beta Drugs:
| inhibit what?
inhibit autoreactive lymphocytes
and
inhibit BBB penetration (by decreasing matrix metalloproteinase - MMP)
165
Interferon Beta Drugs:
| efficacious at neutralizing ________
antibodies
166
Glatiramer:
| first line or second line
first line
167
MOA of Glatiramer?
synthetic polypeptide
mimics antigenic properties of myelin basic protein
inhibits T cell - APC/Dendritic interaction
168
MOA of Fingolimod
S1P receptor agonist (sphingosine 1 - phosphate)
169
Fingolimod MOA:
- stimulate ___________
- interference w/ ____________
- stimulate oligodendrocyte survival (remylenination)
| - lymphocyte movement out of lymphoid organs
170
Fingolimoid:
| first or second line?
first line
171
Natalizumab:
| first line or second line?
second
172
MOA of Natalizumab?
Monoclonal Ab specific for a-4 integrin
173
Mitoxantrone:
| first or second line
second line
174
MOA of Mitoxantrone
anthracenedione with CYTOTOXIC activity (reduce lymphocyte numbers)
175
special feature about Mitoxantrone
first cytotoxic drug licenced for SPMS
176
Teriflunomide:
| first or second line agents
uhh.... NEW DRUG! but also used a lot so...?
177
MOA Teriflunomide:
CYTOTOXIC agent that inhibits dihydroorotate dehydrogenase (aka prevents de novo pyrimidine biosynthesis)
178
notable part of dimethyl fumarte's structure?
its simple AF (very small..)
179
MOA for dimethyl fumarate
gets metabolized by esterases in GI tract, blood, tissues and activates Nrf2 mediated cellular anti-ox responses and anti-inflamm. pathyway
180
In Normal Circumstances,
| _______ is an antagonist to Nrf2 by promoting Nrf2 ________
Keap1; ubiquitylation
181
Keap1 dissociates from Nrf2 when cell is exposed to _________ or _____________
electrophilic toxins or oxidative stress
182
for Nrf2 Pathway:
| Keap 1 gets covanlently modified on key ______ residues and then Nrf2 is not ubiquitylated anymore
cysteine
183
for Nrf2 Pathway:
once Nrf2 is not ubiquitlyated anymore it accumulates and enters ________ to activate ________ that are regulated by _________
enters NUCLEUS
to activate gene transcription of genes
regulated by ARE (antiox response element)
184
what genes are under control of ARE?
enzymes for glutathione biosynthesis
and
detoxification
(aka some Phase II enzymes)
185
Glial cells will release _________ and _______ to create neuroprotection and regeneration
release Neurotrophin/antioxidant
186
Nrf2 antiox response pathway induces _______ upregulation in neurons through astrocyte-neuron communication
GSH
187
Firtaegrast: MOA and notable part of struc
MOA: targest a-4 integrin
small molecule
