Exam 3 Flashcards
(425 cards)
1
Q
What are the 3 regions of the brain?
A
Hindbrain
Forebrain
Midbrain
2
Q
What are the components of the hindbrain?
A
Medulla
Pons
Cerebellum
3
Q
What are the components of the midbrain?
A
substantia nigra
4
Q
What are the components of the forebrain?
A
Cerebral cortex
Basal ganglia (striatum, globus pallidus, subthalamic nucleus)
Limbic system (hippocampus, amygdala)
Diencephalon (thalamus, hypothalamus)
5
Q
What structures are associated with the forebrain?
A
“higher” structures
6
Q
What are the functions of the medulla?
A
Autonomic functions (involuntary)
Controls: respiration, cardiac function, vasomotor responses, reflexes (coughing, etc)
7
Q
What are the functions of the pons?
A
Acts as a “bridge” between the cerebellum and the forebrain
-relays signals from the forebrain to the cerebellum
8
Q
What are the functions of the cerebellum?
A
“little brain”
Governs motor coordination for producing smooth movements
9
Q
What is an important point to remember about cerebellum neurodegeneration?
A
Undergoes neurodegeneration in spinocerebellar ataxias
(causes disjointed or jerky movements “ataxias”)
*how we know if this area is damaged
10
Q
What are the two parts of the substantia nigra?
A
SN pars compacta
SN pars reticulata
11
Q
What is the function of the SN pars compacta?
A
Provides INPUT to the basal ganglia
*supplies dopamine to the striatum (goes wrong in Parkinson’s)
-Voluntary motor control and cognitive functions
12
Q
What part of the midbrain is involved in the development of Parkinsons disease?
A
SN pars compacta
-The supply of dopamine by this area to the striatum gets interrupted
-This area undergoes neurodegeneration in Parkinsons
13
Q
What is the function of the SN pars reticulata?
A
Output function
Relays signals from the basal ganglia to the thalamus
14
Q
What is the function of the cortex (cerebrum)?
A
Processing and interpreting information
-decision making, higher level functions
15
Q
What is the function of the basal ganglia?
A
Voluntary motor control
Some cognitive functions
16
Q
What are the two parts of the limbic system?
A
Amygdala
Hippocampus
17
Q
What is the function of the amygdala?
A
Emotions
18
Q
What is the function of the hippocampus?
A
Memory
19
Q
What are the two parts of the diencephalon?
A
Thalamus
Hypothalamus
20
Q
What is the function of the thalamus?
A
“Relay station” to and from the cortex
21
Q
What are the functions of the hypothalamus?
A
Controls involuntary functions
-Internal homeostasis
-Emotions
-Hormonal control
-Direct neural regulation
22
Q
Which structures are associated with controlling involuntary functions?
A
Medulla
Hypothalamus
23
Q
Which structures are associated with controlling voluntary functions?
A
SN pars compacta (movement with intention)
Basal ganglia
24
Q
What is a cortico-thalamic loop?
A
The senses receive information about the environment and pass it through the thalamus to the cortex and then back
-This loop makes decisions about how to interpret and react to the incoming sensory information
25
*What area of the brain is schizophrenia associated with?
Frontal cortex
26
Which of the following brain structures is directly involved in controlling involuntary functions?
A. hypothalamus
B. thalamus
C. medulla oblongata
D. A, B, and C
E. A and C
E.
hypothalamus and medulla
27
What are the 3 functions of astrocytes?
-Provide neurons with growth factors + antioxidants
-Remove excess glutamate
--Support the blood-brain barrier
28
Why is it important for astrocytes to remove glutamate?
Too much glutamate leads to excess calcium which overwhelms mitochondria
-mitochondria spit out free radicals which leads to cell death
(too much glutamate is toxic)
29
What is the function of oligodendrocytes?
Produce myelin sheath that insulates axons
30
What are the 3 functions of microglia?
-Provide growth factors
-Clear debris through phagocytosis
-Neuroinflammation
31
What is an important point to remember about microglia's function?
They are PRO-INFLAMMATORY
32
What is the overarching role of microglia that makes them easier to remember?
They are the "immune cells of the brain"
33
Which of the glial cells make up the blood-brain barrier?
Astrocytes
34
How does the blood-brain barrier act as a barrier?
Cells are held very tight together by tight junctions leaving no spaces between them
-this is what forms the barrier since it is too tight to cross
35
What triggers neurotransmission?
Electrical depolarization of the neuron
(influx of Na+)
36
At the beginning of an action potential, is the inside of the cell positive or negative?
Negative
-why it is below threshold to start
37
True or False: an action potential leading to neurotransmitter release will only occur when threshold is reached or passed
True
38
What causes repolarization?
Action potentials open to move K out of the cell
Cl- moves into cell
-this reestablishes the original negative charge
39
What is an afterpotential?
The action potential dips below resting potential between repolarization and depolarization
(an overshoot of repolarization)
**part of the refractory period
40
How long do action potentials last?
0.2-0.5 msec
41
What is a refractory period?
The period after an action potential when a neuron will not fire again
(hyperpolarized phase)
42
True or False: The magnitude of an action potential will always be the same for a single neuron
True
*the height of the action potential spike on a graph of them will always be the same
43
What happens when we apply an excitatory neurotransmitter?
Action potentials occur more frequently
*depolarizing
44
What happens when we apply an inhibitory neurotransmitter?
Action potentials occur less frequently
*polarizing
45
Why is the current carried by a nerve fiber (bundle of axons) greater?
Summation
46
What are EPSP's?
Excitatory postsynaptic potentials
*weak signals that do not clear the threshold
-induced by excitatory neurotransmitters
47
What are IPSP's?
Inhibitory postsynaptic potentials
*these lower the polarity far below baseline so that it is harder to clear the threshold and produce an action potential
48
How does an excitatory neuron cause an Excitatory Postsynaptic Potential?
Allows Na+ ions to cross the membrane
49
How does an inhibitory neurotransmitter induce hyperpolarization?
Allows Cl- ions to cross the membrane
50
What is hyperpolarization?
When a cell is so negative that it is below the resting potential
51
True or False: an IPSP can decrease the magnitude of an EPSP
True
-because an IPSP makes it harder to reach the threshold
-even though EPSP's do not reach the threshold, they still will lower and farther away from the threshold than normal
52
NOTE
Review lecture 1 slide 20
53
What are the 3 common amino acid neurotransmitters?
GABA*
Glycine
Glutamate*
*= focus in CNS
54
What are the 2 types of GABA receptors?
GABA (A)
GABA (B,C)
55
What type of receptor is GABA (A)?
Ion channel
56
What type of receptor is GABA (B)?
GPCR
57
What is GABA?
The major inhibitory neurotransmitter in the brain
-depresses neuronal excitability (by increasing Cl- influx)
58
What drugs interact with GABA?
CNS depressants
-Sedative hypnotics
-Anticonvulsants
-Anxiolytics
59
What kind of neurotransmitter is GABA?
Inhibitory
-hyperpolarizes the neuron
60
What conditions are affected by GABA?
Epilepsy
Spasticity
Addiction/Alcohol
61
*What is glycine?
Similar to GABA
*but acts in the spinal cord
62
What are the 3 Glutamate Receptors?
AMPA, NMDA (ion channel)
mGluR (GPCR)
63
What is glutamate?
EXCITATORY neurotransmitter in the brain
64
How can excess glutamate cause neuronal damage?
By allowing excessive Ca+ influx into the neuron
(overexcites the neuron, leads to cell death)
65
What disease states are associated with glutamate?
Epilepsy
Schizophrenia
66
Which neurotransmitter (GABA or Glutamate) is excitatory and which is inhibitory?
GABA: inhibitory
Glutamate: excitatory
67
What are the 4 common non-amino acid neurotransmitters?
-Acetylcholine
-Dopamine (DA)
-Norepinephrine
-Serotonin (5-HT)
68
What are the two types of acetylcholine receptors?
Nicotinic
Muscarinic
69
Where do acetylcholine receptors act?
Periphery
-basal forebrain
-pons
-cortex
-basal ganglia
70
*What are examples of drugs that target acetylcholine transmission?
Cholinesterase inhibitors
-Aricept (used in Alzheimer's disease)
71
What disease states are associated with acetylcholine?
Cognitive function/decline
Nicotine dependence
Movement disorders
72
What are the two dopamine receptors?
D1-like (GS coupled)
D2-like (Gi coupled)
73
What are the functions of the D1-like receptor and the D2-receptor?
D1-like: increase cAMP
**Gs coupled
D2-like: decrease cAMP
**Gi coupled
74
Drugs that block dopamine transmission can lead to what?
They increase extracellular dopamine concentrations which can produce euphoria and lead to addiction
(ex: cocaine, amphetamine)
75
Excessive dopaminergic signaling can contribute to which disease state?
Schizophrenia
76
Loss of dopamine neurons in the SN is responsible for which disease state?
Parkinson's disease
77
What drugs interact with the dopamine pathways?
Antipsychotics (D2 receptor antagonists)
D2/D3 and D1 receptor agonists used in Parkinson's disease
78
What disease states are associated with dopamine transmission?
Schizophrenia
Parkinson's disease
Addiction
Depression
ADHD
79
Where does dopamine transmission occur?
Midbrain
-substantia nigra
-pars compacta
-ventral tegmental area (reward + addiction)
80
What are the receptors for norepinephrine?
a1, a2 (GPCR)
81
What are the drug targets of norepinephrine?
a- and B- adrenergic receptors
norepinephrine transporter (NET)
82
Norepinephrine transporter (NET) inhibitors are used to treat what disease state?
Depression
83
Where does norepinephrine transmission occur?
Pons
84
What disease states are associated with norepinephrine transmission?
-Memory
-Depression
-Addiction
-Pain
85
What are the 2 serotonin receptors?
5-HT3
5-HT1,2
86
Where does serotonin transmission occur?
Midbrain
Pons
**raphe nuclei in these areas produce serotonin
87
*What is the function of raphe nuclei?
Give rise to 5-HT axons
88
What drugs interact with 5-HT receptors?
5-HT2A antagonists (atypical antipsychotics)
SERT uptake inhibitors (depression)
5-HT2A agonists (hallucinogenic, ex: LSD)
89
What disease states are associated with serotonin transmission?
-Depression
-Mood disorders/anxiety
-Schizophrenia
90
What is multiple sclerosis (MS)?
An immune-mediated (inflammatory) disorder involving destruction of the myelin sheath surrounding neuronal axons
91
What are some areas in the body that are affected by MS?
-Optic nerve (vision)
-Corticospinal tract (fatigue)
-Cerebellum (walking problems)
-Sensory pathways (pain)
-Vestibular pathways (dizziness)
92
For an environmental insult to cause MS, what age must exposure occur AFTER?
15
93
How can viral or bacterial infections increase the risk of MS?
By activating autoreactive immune cells
-leads to an autoimmune response in genetically susceptible individuals
94
What specific virus may be involved in the development of MS?
Epstein-Barr Virus (EBV)
95
How can Epstein-Barr Virus (EBV) cause MS?
Sequence similarities between EBV and self-peptides can result in activation of autoreactive T or B cells
**molecular mimicry
96
Which antigen is responsible for the molecular mimicry of Epstein-Barr Virus in MS?
Epstein-Barr nuclear antigen (EBNA)
(resembles myelin basic protein, antigens recognize the host's myelin basic protein)
**leads to myelin sheath destruction
97
How does MS demonstrate a gene-environment interaction?
Patients with a particular HLA phenotype have increased risk of developing MS when they also have anti-EBNA antibodies
98
The first time that an inflammatory demyelinating episode surpasses the clinical threshold is known as what?
CIS
Clinically Isolated Syndrome
99
After the CIS, if more inflammatory demyelinating episodes that surpass the clinical threshold occur what are these known as?
RRMS
Relapsing Remitting MS
100
When there are no more inflammatory demyelinating episodes but the underlying MS disease continues to progress this is called what?
SPMS
Secondary Progressive MS
**inflammatory part is less present but damage and symptoms continue
101
What % of MS cases are Relapsing-Remitting MS (RRMS)?
85%
102
What % of MS cases are Primary progressive MS (PPMS)?
15%
103
What is Primary Progressive MS (PPMS)?
Resembles SPMS
-mean age of onset is later (40)
104
True or False:
If a patient has Relapsing-Remitting MS (RRMS) they will never have Primary Progressive MS (PPMS)
True
105
NOTE
See lecture 2 sides 7+8
106
How is the overall clinical presentation of MS in a patient determined?
A combination of the underlying degeneration (uniform/progressive) AND the host's immune reaction to it (intermittent/variable)
107
What are the 2 phases of MS?
Autoimmune
Degenerative
108
Which phase of MS is the disease trigger?
UNCLEAR
109
What is the function of dendritic cells?
Present CNS antigens
110
What is the pathophysiology of MS?
Dendritic cells present CNS antigens and activate T-cells
B and T cells proliferate and infiltrate the CNS using a4-integrin-mediated binding to penetrate the BBB
B cells mature to plasma cells after encountering an antigen, release antibodies
T cells interact with target ligands on MHC molecules, activate, and results in cytokine release and macrophage stimulation
This causes myelin sheath damage
111
What cells do T cells engage with in the MS autoimmune response?
Oligodendrocytes
*destroy these human cells
-antibodies trigger complement activation and cause pore formation and cell damage
-macrophages are recruited and release toxic agents
112
How do macrophages harm the myelin sheath?
The release of toxic agents and phagocytosis
113
Do action potentials travel faster or lower in myelinated regions of axons?
Faster
-due to the insulating effects of myelin
114
What happens to action potentials in the Node of Ranvier?
Action potentials slow down
-current density builds up
(note: this is a zone of demyelination)
115
Voltage-gated Na+ channels in the node of Ranvier are used to do what to action potentials?
Essential for replenishing action potentials
116
How does demyelination affect the propagation speed of action potentials?
Slows them down
117
How does remyelination occur?
Recruits OPCs (oligodendrocyte precursor cells) to the lesion
These turn into myelin-producing oligodendrocytes
118
Why does remyelination typically fail in MS?
Lack of OPCs or failure of OPCs to differentiate
119
What is astrogliosis?
Invasion and propagation of astrocytes that results in irreversible gliotic plaque formation or scars
120
What cells are activated by demyelination?
Microglia
Astrocytes
121
What is the function of microglia and astrocytes in remyelination?
Release pro-migratory factors and mitogens
-These recruit OPCs (oligodendrocyte precursors) to the lesion and stimulate their proliferation
122
What is the key step in remyelination that often fails in MS?
OPC differentiation
123
What are the 2 pathways that demyelinated axons can take?
Remyelination
Degradation
124
What is the function of immunomodulatory therapies in MS?
Interfere with T or B cell activation, proliferation, and binding to the BBB
125
What is the function of rescue strategies in MS?
Remyelination
126
What contrast agent is used to visualize MS brain lesions?
Gadolinium
127
What is Guillain-Barre Syndrome?
Acute, inflammatory neuropathy
-Starts as weakness in distal muscles and lower extremities and can progress to total paralysis with death from respiratory failure in days
-Caused by an autoimmune attack on peripheral nerves resulting in demyelination
128
What are the 3 categories of MS treatment?
1. Treatment of Acute Attacks
2. Disease-Modifying Therapies (DMTs)
3. Symptomatic Therapies
129
What is the goal of disease-modifying therapies with MS?
-Reduce relapse rates
-Slow progression of disability
130
Are disease-modifying MS therapies used to treat relapsing or progressive forms of the disease more?
Relapsing
131
What are the 4 first-line agents for MS?
Interferon B1a (Avonex, Rebif)
Interferon B1b (Betaseron, Extavia)
Glatiramer Acetate (Copaxone)
Fingolimod (Gilenya)
132
What are the 2 second-line agents for MS?
Natalizumab (Tysabri)
Mitoxantrone (Novantrone)
133
What are the 3 new drugs for MS?
Teriflunomide (Aubagio)
Dimethyl fumarate (Tecfidera)
Cladribine (Mylinax)
134
What are the medications used for treatment of acute MS attacks?
Methylprednisolone
Prednisone
Adrenocorticotropic hormone (ACTH)
135
What are the 2 corticosteroids used for acute MS attacks?
Methylprednisolone
Prednisone
136
How do corticosteroids work for treatment of acute MS attacks?
Up-regulate anti-inflammatory genes
Down-regulate pro-inflammatory genes
Alleviate edema in demyelinated areas
137
Where do Interferon B1a and B1b work?
Periphery
BBB
138
What is the function of Interferon B1a and B1b in the periphery?
Inhibit autoreactive lymphocytes
(T cells, dendritic cells)
139
What is the function of Interferon B1a and B1b in the BBB?
Inhibit BBB penetration by decreasing matrix metalloproteinase (MMP)
140
What reduces the efficacy of Interferon B1a and B1b?
neutralizing antibodies
141
What is the MOA of Glatiramer acetate?
Synthetic polypeptide
Mimics antigenic properties of myelin basic protein
**Modulates antigen-presenting cells (dendritic cells) which leads to decreased T cell activation
142
What is the MOA of Fingolimod?
Sphingosine-1-phosphate (S1P) receptor agonist
-stimulates oligodendrocyte survival (remyelination)
[CNS]
-interferes with lymphocyte movement out of lymphoid organs
[Periphery]
143
What is an important side effect to note with Fingolimod?
-Progressive multifocal leukoencephalopathy (PML)
[potentially lethal brain infection]
144
What are considerations to make when deciding which first-line MS treatment to use?
Fingolimod is superior to interferon beta
*BUT Fingolimod has more side effects associated with it
145
What is the MOA of Natalizumab?
*2nd line
Monoclonal antibody specific for a4 integrin*
a4-integrin pairs with B1-integrin to produce "very late antigen" (VLA-4)
Inhibiting VLA-4 binding to its ligand (VCAM-1 on CNS vascular endothelium) interferes with B and T cell movement across the BBB into the CNS
(interferes with binding of B and T cells to the BBB and makes it difficult to cross)
146
What are some side effects to be aware of with Natalizumab?
Progressive multifocal leukoencephalopathy (PML)
Induces neutralizing antibody development which can cause allergic reactions
147
What is the MOA of Mitoxantrone?
*2nd line
Anthracenedione with CYTOTOXIC ACTIVITY
-reduces lymphocyte numbers by causing DNA strand breaks via intercalation
-Delays DNA repair via inhibition of topoisomerase II
148
When should Mitoxantrone be considered for use?
Secondary Progressive MS (SPMS)
**first cytotoxic drug approved for this
Also can be used for induction therapy and then replaced with 1st-line agent
149
Where does Mitoxantrone act?
Periphery
150
What is the MOA of Teriflunomide?
New agent
Cytotoxic agent
-Inhibits proliferation of peripheral lymphocytes (B and T)
151
Where does Teriflunomide act?
Periphery
152
What is the MOA of Dimethyl fumarate, Diroximel fumarate, and Monomethyl fumarate?
New Agents
Metabolized in the GI tract
-Activate Nrf2-mediated cellular antioxidant responses and anti-inflammatory pathways
-Promote remyelination
-Suppress activated T cells and dendritic cells in periphery
153
What is the active form:
Dimethyl fumarate Diroximel fumarate
Monomethyl fumarate
Monomethyl ester
154
Where do Dimethyl fumarate, Diroximel fumarate, and Monomethyl fumarate act?
Periphery
and
CNS
155
What side effect is a concern with Dimethyl fumarate, Diroximel fumarate, and Monomethyl fumarate?
Progressive multifocal leukoencephalopathy (PML)
156
Where does the Nrf2 antioxidant response pathway occur?
In astrocytes
157
What antioxidant degrades Nrf2?
Keap1
158
How does the Nrf2 pathway work?
Normally, Nrf2 is continually targeted for destruction by Keap1
When a cell is exposed to toxins or undergoes oxidative stress, Keap1 is covalently modified and cannot degrade Nrf2
Nf2 accumulates and enters the nucleus where it activates gene transcription regulated by the antioxidant response element (ARE)
These genes are involved in glutathione biosynthesis and detoxification
*Anti-oxidant and Anti-inflammatory
159
What is the MOA of Siponimod, Ozanimod, and Ponesimod?
New drugs
sphingosine-1-phosphate (S1P) receptor agonists
***Same as fingolimod
-oligodendrocyte survival
-remyelination
-interfere with lymphocyte movement out of lymphoid organs
160
When do we use Siponimod, Ozanimod, and Ponesimod?
Relapsing Remitting MS (RRMS)
Secondary progressive MS (SPMS)*
161
What is the MOA of Cladribine?
new drug
*Cytotoxic prodrug
Taken up into cells by purine nucleoside transporters
Damages DNA and interferes with DNA metabolism
-results in cell death and lymphocyte depletion
162
What was the original use of Cladribine?
Chemotherapeutic agent used for leukemia
163
What is an important point to remember about the Cladribine structure?
Prodrug
164
What is Rituximab approved to treat?
Non-Hodgkin lymphomas
Rheumatoid arthritis
165
What MS patients should we consider using Rituximab in?
Primary Progressive MS patients
*effective in some
also for Relapsing Remitting MS (RRMS)
166
What is the MOA of Ocrelizumab?
new drug
Monoclonal antibody that targets CD20 (marker on mature B cells)
*only targets mature B cells, good because we still need B cells
167
What is the name of the antisense oligonucleotide in clinical trials for MS?
ATL1102
168
What is the MOA of ATL1102?
Antisense oligonucleotide that targets VLA-4
*predicted to have the same outcome as natalizumab
(oligonucleotides recognize mRNA and prevent production of protein from them)
169
Which of the following drugs is (are) active in both the periphery and the CNS?
a. dimethyl fumarate
b. natalizumab
c. rituximab
d. teriflunomide
e. none of the above
A. Dimethyl fumarate
170
What are 2important diagnostic criteria for MS?
Dissemination in Time (DIT)
Dissemination in Space (DIS)
171
What is Dissemination in Time (DIT)?
regarding MS diagnosis criteria
Time between evidence of new lesions in subsequent MRIs
(30 days)
*damage that has happened more than once over time is required to diagnose MS
172
What is Dissemination in Space (DIS)?
regarding MS diagnosis criteria
Need to have at least 2 lesions in different areas of the brain at 2 different times to be able to diagnose MS
(damage in more than one place)
173
True or False: having 1 lesion is enough to diagnose as MS
False, need at least 2
174
What is the most common type of MS?
Relapsing Remitting MS
175
How does Secondary Progressive MS present?
Normally is a progression of RRMS
-fewer relapses with continuing disability
176
Who is more likely to be diagnosed with Primary Progressive MS?
Patients diagnosed later in life
177
What is Progressive Relapsing MS (PRMS)?
*Least common form
Steadily worsening disease
Later, clear, acute relapses
May have recovery from acute attacks but no remission between relapses
178
*What is the first choice for MS treatment?
High-dose corticosteroid treatment
(oral or IV based on setting)
179
Which corticosteroid is used IV for MS and what is the dose?
Methylprednisolone
500mg-1000mg IV daily
3-7 days with or without oral taper over 1-3 weeks
180
Why might we give an IV corticosteroid to an MS patient?
Want to blast with anti-inflammatory to bring down lesion and reduce the risk of demyelination
181
What corticosteroid is used outpatient in patients with MS and what is the dose?
Prednisone
1250mg
every other day x 5 doses
no need for taper
*note: 50mg is highest tablet strength, taking a large number of tablets
182
What are the oral MS medications?
Dimethyl fumarate
Diroximel fumarate
Fingolimod**(only 1st line)
Ozanimod
Ponesimod
Siponimod
Teriflunomide
183
What are the injectable MS medications?
Interferon beta-1a
Interferon beta -1b
Peginterferon beta-1a
Glatiramer acetate
184
What are infusion MS medications?
Alemtuzumab
Natalizumab
Ocrelizumab
185
What is the only drug for primary progressive MS?
Ocrelizumab
186
What must all MS patients do to prevent the development of progressive multifocal leukoencephalopathy?
Get tested for JCV antibodies
-disease is caused by reactivation of dormant JCV and causes the myelin sheath to break down
187
What is another important thing all patients with MS should do before starting treatment to prevent their risk of disease?
Get up to date on all vaccines before starting MS treatment because they will be at higher risk for diseases that have vaccines to be deadly after starting treatment
*consider varicella vaccine even if they have never had chicken pox
188
What vaccines are preferred for patients with MS?
Inactivated vaccines
189
What are 3 important counseling points for Dimethyl Fumarate, Diroximel Fumarate, and Monomethyl Fumarate?
-Do not open capsule (do not put on food, do not crush or chew)
-Monitor LFTs (hepatotoxicity)
-Monitor CBC (neutropenia)
190
What are 2 side effects of Dimethyl Fumarate, Diroximel Fumarate, and Monomethyl Fumarate?
Progressive multifocal leukoencephalopathy (PML)
Flushing (can take aspirin before to prevent)
191
When are Sphingosine 1-Phosphate Receptor Modulators contraindicated?
Past arrhythmia diagnosis
192
What are the Sphingosine 1-Phosphate Receptor Modulators?
Fingolimod
Ozanimod
Ponesimod
Siponimod
193
What is an important point to remember when trying to stop Sphingosine 1-Phosphate Receptor Modulators?
Discontinuation can worsen MS symptoms
194
MAO inhibitors should be avoided with which drug?
Ozanimod
195
What testing is required before starting Siponimod?
CYP2C9 genotype testing
196
What side effects may occur with Glatiramer Acetate?
-Lipoatrophy
-Chest pain
-Injection side effects
197
What treatment may be preferred with pregnancy?
Glatiramer acetate
(teratogenic effects are unknown)
198
What side effects are associated with interferons?
*Flu-like symptoms
Psychiatric effects (depression, suicidal thinking)
Elevated LFT
Thyroid dysfunction
199
What assessment should be done before starting interferons?
Mental health assessment
200
What are the 3 monoclonal antibody drugs?
Alemtuzumab
Natalizumab
Ocrelizumab
201
What monoclonal antibodies require REMS program to be done?
Alemtuzumab
Natalizumab
202
What is the only FDA-approved drug for Primary Progressive MS (PPMS)?
Ocrelizumab
203
Complete vaccinations are required at least how long before starting monoclonal antibody treatment for MS?
6 weeks
204
Which MS drug has an absolute contraindication with pregnancy?
Teriflunomide
205
If a patient is taking Teriflunomide and becomes pregnant, what should be done?
Take:
-accelerated elimination cholestyramine
or
-activated charcoal for 11 days
206
What is the single MS drug approved to treat gait abnormalities/walking speed?
Dalfampridine (Ampyra)
-blocks K channels to prevent cell repolarization
-prolongs action potentials
**may increase walking speed
207
Why do we only use ER medications and not IR?
IR dosage form and dose escalation is associated with seizures
*contraindicated in patients with seizure history
208
What are the symptoms of Parkinson's disease?
TRAP
Tremor
Rigidity
Akinesia (slow movement)
Postural Instability (balance, coordination)
-mask-like appearance
-speech and cognitive deficit, depression
209
What causes Parkinson's Disease?
Loss of dopaminergic neurons in the substantia nigra
210
What % of nigral dopamine neurons are lost in Parkinson's disease before motor symptoms present?
50% of nigral dopamine neurons
Or: 70-80% of nerve terminals in striatum
211
Besides loss of dopaminergic neurons, what else is a common characteristic of Parkinson's disease?
Presence of Lewy Bodies
212
What are Lewy Bodies?
Dense, spherical protein deposits
-seen in the brains of Parkinson's patients
-Enriched with fibrillar forms of the protein a-synuclein
213
Where is it suggested that Parkinson's disease may begin?
Brainstem
(because this is the first place Lewy bodies have found to show up in)
214
What area of the brain needs to be affected for classic Parkinson's symptoms to appear?
Substantia nigra
**undergoes neurodegeneration
215
What are the 2 pathways that dopamine neurons signal through?
Direct pathway
Indirect pathway
216
What receptors are involved in the direct pathway of dopamine neuron signaling?
D1 receptors (in the striatum)
217
What receptors are involved in the indirect pathway of dopamine neuron signaling?
D2 receptors (in the striatum)
218
What signaling is favored in signaling from the SNpc to D1 and D2 receptors in the striatum?
Thalamocortical signaling
(this is disrupted in PD)
219
What happens when dopamine is released to the direct and indirect pathways?
Increased signaling from the thalamus to the cortex occurs
-this causes increased motor signaling
220
When the direct or indirect dopamine pathways are interrupted, what is observed?
Interruption of motor functions
221
Antimuscarinics are used in Parkinson's for what purpose?
Adjunct therapy to treat tremor
222
What is the antimuscarinic used in Parkinson's?
Benztropine
223
How do antimuscarinics work in Parkinson's?
Acetylcholine is excitatory and Dopamine is inhibitory
A loss of dopamine results in excess energy in cholinergic pathways
Cholinergic antagonists help compensate for this
*most effective treatments increase dopaminergic transmission
224
What drug is considered the "Gold Standard" of Parkinson's treatment?
L-DOPA
225
What is L-DOPA?
Precursor of dopamine
226
How does L-DOPA differ from dopamine?
It is orally active and can enter the CNS
*dopamine cannot because it has a positive charge at neutral pH
227
What is a common side effect of L-DOPA?
Nausea
228
What drug can be added to L-DOPA in the combination product "Sinemet"?
Carbidopa
229
When we co-administer carbidopa, how much can we decrease the dose of L-DOPA by?
4x
230
Where does carbidopa work?
*Peripherally acting DOPA decarboxylase inhibitor
231
Where in the body do we want L-DOPA converted to dopamine?
Substantia nigra
*but not the periphery because dopamine cannot cross the BBB
232
Will carbidopa cross the BBB?
NO
-has a charge, only works in periphery
233
What are the challenges of L-DOPA treatment?
*On/off oscillations (after years)
*Dyskinesia (right after dose, produces exaggerated motor effects)
Off state (when plasma levels decline, drug may not have an effect)
234
How can we avoid the challenges of L-DOPA treatment?
Administer in a continuous manner instead of pulsatile
(Subq infusion in trials currently)
235
How can we avoid limitations associated with the prodrug conversion of L-DOPA?
L-DOPA must be converted to dopamine by DOPA decarboxylase
-the progressive disease and death of dopamine neurons causes patients to become unresponsive to L-DOPA
**We can use dopamine receptor agonists instead
(because postsynaptic dopamine receptors are still present in the striatum)
236
What are the dopamine receptor agonists?
Apomorphine
Ropinirole
Pramipexole
Rotigotine
237
What kind of receptor agonist is Apomorphine?
Mixed D1/D2 agonist
238
When is Apomorphine used?
Late stages of Parkinson's Disease to provide rapid relief of the off state
239
Why is the usefulness of Apomorphine limited?
It has potent emetic (vomiting) effects
240
What kind of receptor agonists are Ropinirole, Pramipexole, and Rotigotine?
D2/D3 agonists
241
Which Parkinson's drug is a patch?
Rotigotine
242
What are the three MAO-B inhibitors?
Selegiline
Rasagiline
Safinamide (reversible)
243
What is the function of the MAO-B inhibitors?
Inhibit dopamine metabolism
244
Are MAO-B inhibitors reversible or irreversible?
Irreversible
(propargylamines)
245
When are MAO-B inhibitors used?
Can be used as initial monotherapy
Can be used as an adjunct to L-DOPA
246
What is the reversible MAO-B inhibitor?
Safinamide
247
When is Safinamide used?
Adjunct to L-DOPA/Carbidopa
248
What are the COMT inhibitors?
Entacapone
Tolcapone
249
What is the MOA of COMT inhibitors?
Decrease metabolism of L-DOPA in the periphery
Tolcapone: Increases CNS dopamine levels
250
What drugs are included in the combination product Stalevo?
L-DOPA
Carbidopa
Entacapone
251
What is bradykinesia?
Slowness of movement
252
What is the Parkinsonian gait?
Dragging of feet (difficult to get them off the ground)
Width of step shortened
**fall risk
253
What is an important non-motor symptom of Parkinson's disease to remember?
Constipation
**dopaminergic interruption has a variety of roles including gut movement
254
What are some non-pharmacologic therapies for Parkinson's disease?
-Exercise/physical therapy
-Nutritional counseling
-Occupational therapy
-Psychotherapy/support groups
-Speech therapy
255
What is the first step that needs to be done in Parkinson's treatment?
Rule out drug-induced Parkinson's
256
What are the 1st line agents for Parkinson's?
-Dopamine precursor
-Dopamine agonists
-MAO-B inhibitor
257
What are the 2nd line agents for Parkinson's disease?
COMT inhibitors
Amantadine
258
When are dopamine agonists considered first-line?
age < 60 years
Higher risk for dyskinesia
259
Rank the following drugs in order of the MOST efficacy with motor symptoms to LEAST efficacy with motor symptoms:
Dopamine Agonists
Levodopa/Carbidopa
MAOB-I
Most:
Levodopa/Carbidopa
Dopamine Agonists
MAOB-I
260
What are the two types of dopamine agonists?
Non-ergot
Ergot
261
What are the 3 first-line treatment agents for Parkinson's disease?
Dopamine Precursors (L-DOPA, Carbidopa)
Dopamine Agonists
MAO-B inhibitors
262
What are the non-ergot drugs?
Pramipexole
Ropinirole
Rotigotine
Apomorphine
263
What are dopamine agonists used for?
Minimize LD motor fluctuations
264
Which dopamine agonists are rarely used?
Ergots
*have toxicity
265
Which drugs can have Impulse Control Disorder (ICD)?
Dopamine Agonists
266
267
Which drug can cause insomnia because it is metabolized to a stimulant?
Selegiline
268
Which drug group in Parkinsons has a risk of serotonin syndrome?
MAO-B inhibitors
*drug-drug interaction
(these minimize dopamine breakdown but can also inhibit breakdown of other neurotransmitters like serotonin)
269
What are the COMT inhibitors?
Entacapone
Opicapone
Tolcapone
"capone"
270
When are COMT inhibitors used?
As a combination product to manage symptom fluctuation
271
Which drug can cause brown/orange urine discoloration as a side effect?
Entacapone
272
When is Amantadine used?
To manage motor fluctuations in Parkinsons disease
*rarely used monotherapy
273
What is a common side effect of Amantadine?
Confusion/hallucinations
274
What are the anticholinergics used in Parkinsons Disease?
Benztropine
Trihexyphenidyl
275
When are anticholinergics used in Parkinsons disease?
Management of tremor-dominant symptoms in patients <65 years old
276
What medications can worsen Parkinson's disease?
*Dopamine Antagonists*
-Antipsychotics
-Metoclopramide
-Prochlorperazine
-Promethazine
277
NOTE
Review lecture 6 slide 35
278
What gender is more likely to get Alzheimer's disease?
Females
2:1 ratio female:male
279
What is the neuropathology of Alzheimer's disease?
Loss of brain volume
Amyloid plaque formation
Neurofibrillary tangle formation
Synapse loss
280
Where are amyloid plaques located?
Extracellular
281
Where are neurofibrillary tangles located?
Intracellular
282
What are Amyloid Plaques made of?
Amyloid-B peptide (AB)
283
What are neurofibrillary tangles made of?
Hyper-phosphorylated tau
284
Neuropathology associated with Alzheimer's disease typically affects what areas of the brain?
Areas of higher cognitive function:
-Entorhinal cortex
-Hippocampus
-Basal forebrain cholinergic systems
-Neocortex
(these have to do with memory, learning, consolidation, and cognition)
285
Neurons with neurofibrillary tangles and amyloid plaques often develop what?
Destruction of synapses
286
Destruction of synapses causes what?
Reduced levels of neurotransmitters
*Acetylcholine
-Serotonin
-Norepinephrine
-Dopamine
*Also dysregulated glutamate (toxicity)
287
What is the key pathogenic molecule in Alzheimer's disease?
AB or tau?
AB
288
What gene encodes the AB precursor protein?
APP (amyloid precursor protein)
**mutations in this are linked to early onset Alzheimer's
289
What syndrome is associated with Alzheimer's-like symptoms late in life and why?
Down's syndrome
*because the APP gene is located on chromosome 21 and patients with Down's syndrome have an extra copy of this
290
What is the function of B-secretase and y-secretase?
Release AB peptide from APP (amyloid precursor protein)
291
What is the function of a-secretase?
Cleaves APP (amyloid precursor protein) in the middle of the AB segment
-releases non-toxic fragment
***this prevents the release of AB which prevents amyloid plaque formation!
292
What is the difference between AB42 and AB40?
*differ in the number of amino acids in their structure
*AB42 more readily forms amyloid plaques
293
How can mutations in the APP gene lead to greater amyloid plaque formation?
Mutations favor more cleavage by B- or y-secretase
*this leads to more AB42 production over AP40
294
What do the presenilin proteins do?
Cleave AB from APP
*mutations in the gene encoding these lead to early onset Alzheimer's
*mutations lead to production of more AB42 by altering y-secretase cleavage of APP
295
What are the presenilin proteins components of?
y-secretase complex
296
What are the 2 presenilin proteins?
PSEN1 and PSEN2
297
How does AB aggregation effect tau pathology?
Kinase activation leads to tau hyper-phosphorylation
This creates neurofibrillary tangles
Ultimately results in disruption of cytoskeleton and axonal trafficking (synapse transport)
298
Neurofibrillary tangle formation results in what?
Cytoskeletal defects
The cytoskeletal tracks are disrupted leading to defects in axonal transport and synaptic dysfunction
299
What is the function of normal tau?
Binds and stabilizes microtubules
*hyperphosphorylation causes tau to fall off and form tangles
300
How does AB aggregation affect microglial activation?
Increases microglial activation
-microglia release pro-inflammatory cytokines that cause neuroinflammation
-microglia also release reactive nitrogen species and reactive oxygen species that cause oxidative stress
301
What two things are caused by microglial activation?
Neuroinflammation
Oxidative stress
302
Individuals with what gene/allele are more likely to develop Alzheimer's disease?
ApoE4
*note allele 4
303
Inheritance of what Apo allele decreases the risk of developing Alzheimer's?
ApoE2
304
What are the cholinesterase inhibitors used to treat Alzheimer's disease?
Donepezil
Rivastigmine
Galantamine
305
What is the function of Donepezil?
Specific, reversible inhibitor of acetylcholinesterase
306
What is the function of Rivastigmine?
Inhibits acetylcholinesterase AND butyrylcholinesterase
307
What is the function of Galantamine?
Selective, reversible inhibitor of acetylcholinesterase
AND enhances the action of acetylcholine on nicotinic receptors
308
What is the anti-glutamatergic therapy used in Alzheimer's disease?
Memantine
309
How does Memantine work?
NMDA (glutamate receptor) antagonist
-blocks glutamatergic neurotransmission through noncompetitive mechanism
-reduces excitotoxicity (caused by excess glutamate signaling)
310
What are the possible targets for disease-modifying therapy of Alzheimer's disease?
AB generation
AB aggregation
AB clearance
Tau kinase inhibitors
Glutamate-mediated excitotoxicity
Inflammation and Oxidative stress
311
What do the AB antibodies: Aducanumab, Lecanemab, and Donanemab target?
AB clearance
312
What radiolabeled agent is used to visualize Alzheimer's disease?
Florbetapir (18F)
*binds B-amyloid
*visualized by PET scanning
313
What is the radiolabeled agent specific for tau?
Flortaucipir (18F)
314
True or False: Not every dementia patient has Alzheimer's
True
315
What are the characteristics of Vascular Dementia?
-Impaired judgment or executive function
-Result from brain injury associated with vascular disease or stroke
316
What are the characteristics of Dementia with Lewy Bodies (DLB)?
-Combination of cognitive decline and Parkinsonian symptoms
-Visual hallucinations
-Cortical Lewy Bodies
317
What are the characteristics of Frontotemporal Dementia (FTD)?
AKA Pick's Disease
-Disinhibited behavior
-Tau accumulation (Pick's bodies)
318
What percent of patients with epilepsy will experience their first seizure by age 20?
>80%
319
What is the percent chance of having epilepsy after having a single seizure?
20%
320
What is the percent chance of having epilepsy after having 2 seizures?
60%
321
What is the percent chance of having epilepsy after having 3 seizures?
75%
322
What are the types of generalized seizures (non-absence types)?
-Myoclonic
-Tonic
-Clonic
-Atonic
-Tonic-Clonic
323
What is a myoclonic seizure?
Shock-like muscle contraction
(ex: isolated jerking of head, trunk, body)
*isolated jerks
324
What is a tonic seizure?
Rigidity
-results from increased extensor muscle tone
**occur in children
325
What is a clonic seizure?
Rapid, repetitive motor activity
*occur in babies and young children
326
What is an atonic seizure?
Sudden loss of muscle tone
-patient falls if standing
-"drop attacks"
327
What is a tonic-clonic seizure?
Tonic (rigid) phase immediately followed by Clonic (repetitive activity) stage
"Grand Mal" seizure
328
What is the most severe seizure type?
Tonic-Clonic
329
What is a "seizure"?
Paroxysmal disorder of the CNS
-characterized by abnormal cerebral neuronal discharge
**with or without loss of consciousness
330
What is "epilepsy"?
Repeated seizures
*due to damage, irritation, or chemical imbalance in brain
-leads to sudden, excessive, synchronous electrical discharge
331
Where does a seizure originate from?
Gray matter
332
What causes seizures?
Disordered, Synchronous, and Rhythmic firing of brain neurons
"Synchronized Hyperexcitability"
333
What can prolonged seizures cause?
Ischemia
*because the brain uses more energy and oxygen than it can manufacture
334
What are the 3 seizure classifications?
Focal onset
Generalized Onset
Unknown Onset
335
What is the most common classification of seizures?
Focal
336
What is a Focal seizure?
Seizure activity starts in one area of the brain
"focal point"
337
Where do focal seizures commonly start?
Temporal lobe
338
What typically causes Focal seizures?
Some kind of damage to the brain
(disease, trauma, lesion, etc)
339
What is a Focal to Bilateral seizure?
A focal seizure that progresses to a generalized seizure
-typically by projections to the thalamus
340
What is a Generalized seizure?
Involves both brain hemispheres and multiple locations in the brain
341
What is the main cause of a Generalized seizure?
Genetic
342
What is an important point to remember about Generalized seizures?
Patients are unconscious
343
What genes indicate that a patient has epilepsy?
GABRA1
GABRB2+3
GABRG2
SCN1A+B
SCN2A
SCN8A
*GABA receptors and Sodium Channels
344
What does an EEG of a focal seizure look like?
Sharp waves shown only in the electrodes placed where the seizure is coming from on the brain
(less pronounced than generalized, only appears in some rows of the EEG)
345
What does the EEG of a generalized seizure look like?
Shows involvement of both hemispheres
-crazy peaks along the entire EEG in every row
346
What are the two types of focal seizures?
Aware
Impaired Awareness
347
What is the defining factor of Aware type seizures?
No loss of consciousness
348
What seizure types may involve the subject experiencing auras?
Aware Type Focal seizures
+
Impaired Awareness Focal seizures
349
What are the symptoms of an Aura associated with a seizure?
Abdominal discomfort
Sense of fear
Unpleasant smell
Abnormal electrical activity
350
What is a simple partial seizure?
Old term for Aware type focal seizure
351
What is a complex partial seizure?
Old term for Impaired awareness seizure
352
What is a postictal state?
Altered state of consciousness after a seizure
*occurs with impaired awareness focal seizures
353
What type of seizure is an absence seizure?
Generalized
354
What are the two types of Absence seizures?
Typical
Atypical
355
What is a Typical Generalized seizure?
Brief loss of consciousness (10-45 seconds)
-staring or eye flickering, often repetitive
**No convulsions, aura, or postictal period
*Begin abruptly
356
What is an Atypical Generalized seizure?
*Slower onset than typical
**Difficult to control pharmacologically
357
Do tonic-clonic seizures have an aura?
No aura in the tonic phase!
***can have a brief aura if they are focal-to-bilateral tonic-clonic seizures
358
What is Status Epilepticus?
Repetitive seizure activity in which the patient does not regain consciousness between seizures
OR
A single seizure lasting > or = 30mins (after 5 minutes it is considered this)
*note: this is a medical emergency
*convulsions occur
359
What is the therapeutic goal with Status Epilepticus?
Bring seizures under control within 60 mins
360
True or False:
One seizure is considered epilepsy
False
361
When can we gradually withdraw epilepsy drugs?
Patients clinically free of seizures for 2-5 years
362
Which of the following types of convulsions can be preceded by an aura phase?
A. typical absence (petit-mal)
B. primary generalized tonic-clonic
C. focal to bilateral (secondary generalized) tonic-clonic
D. all of the above
C. focal to bilateral (secondary generalized) tonic-clonic
363
What is a "secondarily generalized" seizure?
old term for Focal-to-Bilateral seizure
364
What is a paroxysmal depolarizing shift (PDS)?
A large depolarization that triggers a burst of action potentials
365
What occurs during depolarization?
Influx of cations (ex: Ca+)
-through activation of AMPA and NMDA by glutamate
**Becomes more positive
**Excites the neuron
366
What occurs during hyperpolarization?
Influx of anions (ex: Cl-)
Efflux of K+
*follows depolarization
*Involves activation of GABA receptors
**Becomes more negative
**Inhibits the neuron
367
What are the two ways we can reduce excitation?
Reduce glutamate (excitatory neuron leads to excess movements)
Increase GABA (inhibitory interneuron)
368
Activation of GABA receptors cause what?
Hyperpolarization
**want this with seizures to prevent them
369
Activation of Glutamate causes what?
Depolarization
370
What are AMPA and NMDA?
Glutamate-mediated excitatory receptors
*activation is important in depolarization
371
Which one causes seizures?
Break down of Glutamate
Breakdown of GABA
The breakdown of GABA-mediated inhibition allows action potentials to propagate to distant neurons which causes a spread of seizure activity
-this makes seizures change from focal to secondary generalized
372
What is a potential trigger of status epilepticus?
Sudden discontinuation of AEDs (anti-epileptic drugs)
373
What drugs increase the risk for seizures?
**Alcohol
-Theophylline
-CNS stimulants (coffee)
*Bupropion
*Oral contraceptives
-Withdrawal from depressants
*Clozapine
374
Which of the following occurs during the hyperpolarization phase of a PDS?
A. Influx of Cl- ions resulting from GABA receptor activation
B. Influx of K+ through voltage- and calcium-dependent K+ channels
C. Activation of NMDA receptors
D. All of the above
A. influx of Cl- ions resulting from GABA receptor activation
375
What is the MOA of anticonvulsant drugs?
Stabilize and reduce neuronal excitability
376
What are the 5 ways that anticonvulsant drugs reduce excitability?
1. Decrease sodium influx and prolong inactivation of their channels
2. Reduce calcium influx
3. Enhance GABA-mediated neuronal inhibition
4. Antagonize excitatory transmitters (glutamate!)
5. Other targets (levetiracetam!)
377
What method of reducing excitability by anticonvulsant drugs is most critical for absence seizures?
Reduction of calcium influx
378
What are the excitatory presynaptic targets of anticonvulsant drugs?
Na+ channels
Ca+ channels
379
What are the excitatory post-synaptic targets of anticonvulsant drugs?
NMDA receptors
AMPA receptors
380
What are the inhibitory presynaptic targets of anticonvulsant drugs?
GABA transporter (GAT-1)
GABA transaminase (GABA-T)
381
What are the inhibitory post-synaptic targets of anticonvulsant drugs?
GABA A receptors
GABA B receptors
382
What common structural feature do anticonvulsant drugs share?
Heterocyclic ring structure
383
What drugs are used to treat Focal Seizures and Generalized Tonic-Clonic seizures?
Hydantoins
384
What Hydantoins are used to treat focal and tonic-clonic seizures?
Phenytoin*
Fosphenytoin **injectable prodrug
385
What is the MOA of phenytoin?
Binds and stabilizes the inactive state of Na+ channels
**not isoform selective, works in brain and other body parts
386
What are two important points about phenytoin elimination kinetics?
Dose-dependent
Has non-linear pharmacokinetics
387
What do phenytoin, carbamazepine, and phenobarbital do that can cause drug interactions?
Induce liver cytochrome P450
**increases metabolism of other drugs
388
What are two side effects to remember for phenytoin?
Gingival hyperplasia
Hirsutism
389
What is the MOA of carbamazepine and oxcarbazepine?
Stabilize inactivated state of Na+ channels
390
Which iminostilbene has reduced toxicity?
Oxcarbazepine
(less toxic than carbamazepine)
391
What is the MOA of Lacosamide?
Enhances inactivation of voltage-gated Na+ channels
392
What drugs target Excitatory Presynaptic Na+ Channels?
Phenytoin
Carbamazepine
Lacosamide
393
Where do barbiturates and Benzodiazepines bind?
Allosteric regulatory site on GABA A receptor
(directly bind GABA receptor)
394
What is the MOA of phenobarbital?
Binds an allosteric regulatory site on GABA A receptor
-Increases duration of Cl- channel opening
(enhances GABA signaling)
395
True or False: primidone is more similar to phenytoin than phenobarbital
True
396
What are the benzodiazepines?
Diazepam
Clonazepam
397
What is the MOA of Diazepam and Clonazepam?
Binds an allosteric regulatory site on GABA A receptor
-Increases FREQUENCY of Cl- channel opening
(enhances GABA signaling)
398
What type of treatment are Diazepam and Clonazepam not useful for?
Chronic treatment
(because of tolerance)
399
What is clonazepam useful for?
Acute epilepsy treatment
**Absence seizures
400
What drugs target the inhibitory post-synaptic GABA A receptors?
Phenobarbital
Benzodiazepines
401
What is ataxia?
Impaired coordination
402
What is the MOA of Gabapentin and Pregabalin?
Increase GABA release
Decrease Ca+ influx
Reduce glutamate release
**mimic GABA
403
When is Vigabatrin used?
Adjunct therapy for refractory patients
404
What is the MOA of Vigabatrin?
Irreversible inhibitor of GABA transaminase (GABA-T)
405
What is GABA transaminase (GABA-T)?
Enzyme responsible for degrading GABA
*bad
406
When is Tiagabine used?
Adjunct therapy
407
What is the MOA of Tiagabine?
Inhibits GABA transporter (GAT-1)
408
What is the GABA transporter (GAT-1)?
Transporter responsible for transporting GABA out of the system
*bad
409
What is the function of the NMDA receptor?
Glutamate binding triggers Na+ and Ca+ influx and K+ efflux
410
What is the function of the AMPA receptor?
Glutamate binding triggers Na+ influx and K+ efflux
411
What is the MOA of Felbamate?
NMDA receptor antagonist
412
When is Felbamate used?
3rd line agent for refractory cases
413
What is an important side effect of Felbamate?
Severe hepatitis
414
What is the MOA of Topiramate?
AMPA and Kainate receptor antagonist
415
When is Topiramate used?
Monotherapy or Adjunct
416
What are the succinimides?
Ethosuximide
417
What is the MOA of ethosuximide?
Blocks T-type Ca+ channels
418
What do T-type Ca+ channels do?
Generate the rhythmic discharge of an absence attack
419
Which of the following statements is TRUE?
A. Tiagabine inhibits GABA transaminase
B. Gabapentin increases Cl- influx in postsynaptic neurons
C. Topiramate is an NMDA receptor antagonist
D. Phenytoin is stabilized by the co-administration of carbamazepine
B
420
What two drugs have a risk for seizure recurrence with withdrawal?
Phenytoin
Valproate
421
What is considered "drug-resistant" epilepsy?
Failure of at least two trials of antiseizure medication
422
What type of drug therapy is used with status epilepticus?
IV
423
How many attacks are needed to classify Migraine without Aura?
5 attacks
424
How many attacks are needed to classify Migraine with Aura?
2 attacks
425
