Neuropharmacology Flashcards
1
Q
_____ is a subdivision of pharmacology that studies how drugs affect the brain and behavior
A
Psychopharmacology
2
Q
The transport protein called _____ mediates the delivery of drugs from the brain to the peripheral nervous system
A
p-Glycoprotein
3
Q
p-Glycoprotein is important for the export of ____; it may decrease morphine potency as the drug is pumped out of the brain
A
Opioids
4
Q
Most psychoactive drugs are excreted in the ____ after metabolic transformation
A
Urine
5
Q
What types of drugs are eliminated in the lungs/breath?
A
-Gaseous general anesthetics
-Alcohol (in small amounts)
6
Q
Drugs that are terminated in the ____ are excreted into the intestines and reabsorbed
A
Bile
7
Q
___-___% of a few drugs are excreted in the sweat
A
10-15
8
Q
_____ contain metabolizing enzymes
A
Hepatocytes
9
Q
Cytochrome ____ enzymes are important in drug biotransformation
A
P450
10
Q
CYP3A4 catalyzes ____% of drugs
A
50
11
Q
CYP2D6 catalyzes ____% of drugs
A
20
12
Q
CYP1A2 and CYPE1 each catalyze about ____% of drugs
A
5
13
Q
Metabolic tolerance means that there is ____ of hepatic enzymes
A
Induction
14
Q
With pharmacodynamic tolerance, receptors in the brain adapt to a drug, either decreasing in ____ or ____
A
Number or sensitivity
15
Q
___ ___ is when the removal of drug results in withdrawal symptoms until the brain and body can adapt
A
Physical dependence
16
Q
If someone is on a CNS depressant, when you withdraw the drug, they may have CNS ____ symptoms
A
Excitatory
17
Q
____ are CNS depressants that can be used for alcohol withdrawal symptoms
A
Benzodiazepines
18
Q
_____ is what the drug does to the body, and includes pharmacological and adverse effects
A
Pharmacodynamics
19
Q
Pharmacodynamics requires the drug to interact with ____
A
Receptors
20
Q
Receptors are membrane-spanning proteins with binding sites for ____ ____ and drugs
A
Endogenous neurotransmitters
21
Q
What are types of receptors?
A
-Ion channel receptors (Ex: GABA)
-Carrier or transporter protein
-G protein-coupled receptors (aka middlemen)
-Enzymes (ex: AchE, MAO)
22
Q
Carriers or transporter proteins bind neurotransmitters in the ___ ___ and transport them back into the presynaptic terminal
A
Synaptic cleft
23
Q
Enzymes are involved in the ____ of neurotransmitters and can be blocked by drugs
A
Degredation
24
Q
An ion channel pore ____ when a neurotransmitter or drug binds; more negatively charged Cl ions flow into the neuron (hyperpolarize) to inhibit neuronal function
A
Enlarges
25
Carriers are very important in psychopharmacology; for example, _____ block carrier protein so that there is more serotonin in the synaptic cleft
SSRIs
26
Activation of a G protein, which is a ____-____ receptor, causes the release of intracellular G protein which controls enzyme function in a post-synaptic neuron
Post-synaptic
27
G proteins regulate ____ availability of neurotransmitters in the synapse
Synaptic
28
The ____ is the fundamental unit of the nervous system
Neuron
29
There are over ____ billion neurons in the CNS
100
30
Neurons communicate with thousands of other neurons through ___ signals that are sent at up to 200 mph
Electrical
31
Neurons are the primary site of ____ acting drugs
CNS
32
Drugs may try to mimic concentrations of neurotransmitters or increase the ____ a neurotransmitter stays in the synapse
Time
33
A _____ is a substance that is released at the end of a nerve fiber by the arrival of a nerve impulse and, by diffusing across the synapse, affects the transfer of the impulse to another nerve fiber (or muscle fiber or receptor)
Neurotransmitter
34
____ is a chemical process whereby neurotransmitters are released into the synaptic cleft
Neurotransmission
35
Neurons fire by transmitting electrical signals along its ____
Axon
36
The signal triggers neurotransmitter release from _____
Vesicles
37
Neurotransmitters cross the ____ and bind to receptors on adjacent cells
Synapse
38
The sodium-potassium pump maintains resting membrane potential by pumping ___ potassium in for every ____ sodium out
2; 3
39
The sodium-potassium pump reestablishes resting membrane potential after an ___ ___ has been generated
Action potential
40
_____ means that the sodium channels are open and this makes the cell more positive
Depolarization
41
____ is when the sodium channels close and the potassium channels open; this makes the cell more negative
Repolarization
42
____ action potentials alter resting membrane potential
Graded
43
Depolarization moves membrane potential towards ____, and causes sodium to move into the axon
Positive
44
Hyperpolarization moves membrane potential toward ____, and causes potassium to move out of the axon
Negative
45
A depolarizing ____ potential means that there is not enough stimulus to cause an action potential
Graded
46
In an "all or non" action potential, the individual neuron threshold sets the extent of ____ needed; if it achieves that, it fires
Stimulus
47
In a ___-___ action potential, the electrical current reaches the threshold throughout the axon during the spread of the action potential
Self-propagating
48
Transfer of information from the neuron to the target is via ____ ____
Synaptic transmission
49
An ____ neurotransmitter will depolarize postsynaptic cells
Excitatory
50
An ____ neurotransmitter will hyperpolarize postsynaptic cells
Inhibitory
51
The role of a postsynaptic neuron is to ___ and ___ information
Integrate and process
52
What are 4 examples of monoamine neurotransmitters?
-Acetylcholine
-Norepinephrine
-Serotonin
-Dopamine
53
What are 2 examples of amino acid neurotransmitters?
-Glutamic Acid
-Gamma-amino butyric acid (GABA)
54
What are two examples of neuropeptide neurotransmitters?
-Substance P
-Endogenous opioids
55
Acetylcholine has a primary role in the ____ nervous system
Peripheral
56
Acetylcholine is _____ on skeletal muscle (causes contraction)
Excitatory
57
Acetylcholine is excitatory or inhibitory on ___ ___
Internal organs
58
Acetylcholine is ____ in cognitive disorders such as Alzheimer's
Decreased
59
Norepinephrine is excitatory or inhibitory depending on ____
Receptors
60
Norepinephrine plays a role in...
-Affective disorders
-Learning and memory
-Sleep-wake cycle
61
Serotonin (5-HT) is present in the ___ and ___
Brain and periphery
62
____% of serotonin is in the GI tract, and ___% is in the brain and platelets
90; 10
63
We can get serotonin from dietary ____
Tryptophan
64
Is serotonin usually inhibitory or excitatory?
-Inhibitory
65
Serotonin is involved in...
-Mood
-Sleep Cycle
-Appetite
66
There are multiple serotonin receptor ____
Subtypes
67
Dopamine can be excitatory or inhibitory depending on the ______
Receptor
68
There are ___ distinct dopaminergic systems that differ in the length of neurons
3
69
The short dopaminergic system is found in...
-Retinal and olfactory bulb
70
The intermediate dopaminergic system regulates _____ functions
Hypothalamic
71
The long dopaminergic system is decreased in _____ disease
Parkinsons
72
GABA is a major ____ neurotransmitter in the brain
Inhibitory
73
GABA is synthesized from ____
Glutamate
74
GABA binds to a receptor which results in _____ influx and hyperpolarization of the neuron (non-firing)
Chloride
75
The GABA receptor also binds ____ and ____
Benzodiazepines and Barbituates
76
Glutamate is a major ____ neurotransmitter in the brain
Excitatory
77
Rapid depolarization of neurons results in an ____ firing rate of gltamate
Increased
78
_____ is a main receptor of glutamate
NMDA
79
NMDA antagonists may decrease neuronal damage during a ____
Stroke
80
____ ____ was the first neuropeptide to be isolated
Substance P
81
Substance P can directly ____ motor neurons, similar to excitatory neurotransmitters
Depolarize
82
Substance P may be released in response to ____
Pain
83
Endogenous opioid peptides are substances that bind to stereoselective receptors and possess the pharmacological qualities of ____
Morphine
84
What are three types of endogenous opioid peptides?
-Endorphins
-Enkephalins
-Dynorphins
85
____ are the most potent type of endogenous opioid peptide
Endorphins
86
____ are a type of endogenous opioid peptide that are widely distributed in the CNS
Enkephalins
87
What are two possible pathologies of having "too much" neurotransmission?
-Hyperexcitable neurons fire in the absence of appropriate stimuli (e.g., seizure disorder)
-Too many neurotransmitters binding to postsynaptic receptors (e.g., psychosis)
88
What is a possible pathology of having "too little" neurotransmission?
-Too few neurotransmitters binding to postsynaptic receptors (e.g., depression, Parkinson's)
89
What four things could cause decreased neurotransmission?
-Decreasing synthesis of neurotransmitters
-Increases neurotransmitter metabolism
-Promoting increased neuronal uptake
-Blocking access to post synaptic receptors (e.g., administer an antagonist)
90
What six things could cause increased neurotransmission?
-Increasing neurotransmitter synthesis
-Increased neurotransmitter release
-Prolonging time of the neurotransmitter in the synapse
-Administering neurotransmitter precursors that are taken up and metabolized to active neurotransmitter molecules
-Inhibiting the enzymes that degrade neurotransmitters
-Administering agonists that act as post-synaptic receptors
91
In what three ways can drugs alter neurotransmitters?
-Increasing or decreasing neurotransmitter synthesis or release
-Increasing or decreasing neurotransmitter concentration in the synaptic cleft
-Increasing or decreasing neurotransmitter action on post-synaptic membranes
92
The two most important amino acid neurotransmission systems in the CNS involve ____ (the main inhibitory neurotransmitter) and _____ (the main excitatory neurotransmitter)
GABA; glutamate
93
Neurotransmitters alter the ____ of one or more ion-selective channels
Conductance
94
Inhibitory neurotransmitters trigger a selective ____ current
Outward
95
Excitatory neurotransmitters cause a net ____ current
Inward
96
An inhibitory neurotransmitter hyperpolarizes membranes by inducing a net outward current by promoting either an influx of ___ (ex: chloride) or an efflux of ___ (ex: potassium)
Anions; cations
97
Opening of the chloride or potassium channels also decreases the membrane ____ and thereby lowers the 0Vm response to excitatory currents
Resistance
98
The decreased membrane resistance results in lower ____
Responsiveness
99
Excitatory neurotransmitters depolarize membranes by inducing a net inward current by enhancing inward current (ex: opening a sodium channel) or decreasing outward current (ex: closing a potassium channel); potassium channel closure also increases the resting membrane potential and renders the cell more ____ to excitatory postsynaptic currents
Responsive
100
GABA has _____ distribution and has influence on many neuronal circuits and functions
Widespread
101
GABA affects what processes?
-Arousal and attention
-Memory formation
-Anxiety
-Sleep
-Muscle tone
102
GABA disfunction can cause widespread neuronal ____, like with epilepsy
Hyperactivity
103
Synthesis of GABA is mediated by ___ ___ ___
Glutamic acid decarboxylase
104
GABA is made from the ____ of glutamate
Decarboxylation
105
The synthesis of GABA requires vitamin ____
B6
106
GABA is stored in ___-___ vesicles and released into the synaptic cleft in response to an action potential
Pre-synaptic
107
Termination of GABA neurotransmission depends on the removal of GABA from the extracellular space which is done by...
-GABA transporters (neurons in CNS)
-GABA transaminase (converts within other cells)
108
In one pathway for glutamate synthesis, a-ketoglutarate is produced by the Kreb's cycle serves as a substrate for ____ ____ which seductively transaminates intraneuronal alpha-ketoglutarate to glutamate
GABA transaminase
109
Alternatively, glutamate is converted to GABA by ____ ___ ____, changing the major excitatory neurotransmitter to the majority inhibitory transmitter
Glutamic acid decarboxylase
110
What are the two types of GABA receptors?
-Ionotropic GABA receptors (GABAa and GABAc)
-Metabotropic GABA receptors (GABAb)
111
Metabotropic GABA receptors are ___-___ coupled receptors
G-protein
112
Which type of GABA is the most abundant in the CNS?
GABAa
113
GABAa has ___ different subtypes
16
114
Different subunit combinations display distinct distributions at the ___ and ___ levels; GABA subtypes play distinct roles in specific neural circuits
Cellular and tissue
115
Most subtypes consist of ___ alpha, ___ beta, and ___ gamma subunit
2, 2, 1
116
GABAa has a ____ structure
Pentameric
117
Activation of GABA receptor requires the binding of ____ GABA molecules to the receptor, one to each of the subunits
2
118
Each subunit of the GABAa receptor has four membrane-spanning regions and a ____ loop in the extracellular N-terminal domain
Cysteine
119
There are five subunit of GABAa receptors that surround a central ____-selective ion pore that opens in the presence of GABA
Chloride
120
GABAa receptors contain a number of ____ sites where drugs can bind
Regulatory
121
The response of GABAa receptors can vary depending on the ____ ___ composition
Receptor subunit
122
Prolonged occupation of the agonist sites by GABA also leads to GABAa receptor _____, which results in an inactive agonist-bound state
Desensitization
123
Low levels of GABA can also cause a baseline ____ current in many neurons
Inhibitory
124
____ is when open chloride channels attenuate the change in membrane potential caused by excitatory synaptic currents
Shunting
125
Increasing concentrations of GABA induce both greater chloride currents and more rapid receptor ______
Desensitization
126
Activity of GABAa receptors can be allosterically modulated by ____ like DHEA
Neurosteroids
127
Neurosteroids alter receptor function by binding to _____ sites on the receptor protein to either activate or inhibit GABAa
Allosteric
128
GABAc is ionotropic and has ___ subunits that are not in GABAa
3
129
GABAc receptors are ___-___ chloride channels
Ligand-gated
130
GABAc receptors are limited to the ____
Retina
131
Are there any drugs that target GABAc receptors?
No
132
GABAb receptors are ___ ___-coupled receptors
G protein
133
GABAb receptors have a ____ rate of activation and deactivation compared to GABAa
Slower
134
GABAb receptors have a slow ___ ___ signal transduction mechanism
Second messenger
135
GABAb receptors activate G proteins that are either coupled to K+ or Ca2+ channels directly or are linked to ___ ___ systems such as adenylyl cyclase or phospholipase C
Second messenger
136
The increased K+ efflux leads to slow, long-lasting _____ postsynaptic potentials
Inhibitory
137
The reduced Ca2+ influx may enable GABAb autoreceptors to inhibit ____ neurotransmitter release
Presynaptic
138
Activation of potassium channels ____ neuronal firing; it drives the neuronal transmembrane voltage toward "resting" potentials that reduce the frequency of action potential initiation
Inhibits
139
The majority of drugs affecting GABAergic neurotransmission act on the ionotropic _____ receptor
GABAa
140
Binding of drugs to the GABA receptors causes...
-Sedation
-Anxiolysis
-Hypnosis
141
Some drugs inhibit the reuptake of GABA to increase synaptic concentration at GABAa; an example of a disorder where this would be important is ____
Epilepsy
142
_____ is a selective GABAb receptor agonist that works in the spinal cord
Baclofen
143
Baclofen stimulates downstream second messengers to act on ___ and ___ channels
Calcium and potassium
144
Baclofen is effective for mild ____
Spasticity
145
Baclofen modulates ___ and ___, and it is being investigated as a therapy for drug addiction
Pain and cognition
146
Baclofen has a modest volume of distribution and does not readily cross the ___-___ barrier
Blood-brain
147
Elimination of GABA is ___% renal, and ___% liver
85; 15
148
The half-life of Baclofen is ___ hours
5
149
What are some adverse effects of Baclofen?
-Sedation
-Somnolence
-Ataxia
150
If someone has decreased renal function, they may experience Baclofen _____
Toxicity
151
Is there any tolerance with oral baclofen?
No
152
Tolerance with interthecal Baclofen increases over ___-___ years
1-2
153
What are some withdrawal symptoms of Baclofen?
-Acute hyperelasticity
-Rhabdomyolysis
-Pruritis
-Delirium
-Fever
-Multi-organ failure
-Coagulation abnormalities
-Shock
-Death
154
____ neurotransmission exists throughout the CNS
Glutamatergic
155
Glutamatergic neurotransmission is involved with...
-Development of elevated pain sensation
-Cerebral neurotoxicity
-Synaptic changes involved with certain types of memory formation
156
The synthesis of glutamatergic neurotransmission occurs via what two distinct pathways?
-Ketoglutarate via Krebs cycle converted in CNS and nerve terminals
-Glutaminase converts glutamine in nerve terminals
157
Glutamate is release via ____-dependent exocytosis of transmitter-containing vesicles
Calcium
158
Glutamate is removed from the synaptic cleft by ___ ___ ___ located on presynaptic nerve terminals
Glutamate reuptake transporters
159
What are the two subgroups of glutamate receptors?
-Ionotropic
-Metabotropic
160
_____ glutamate receptors mediate fast excitatory synaptic responses
Ionotropic
161
When activated, neurotransmission permits the flow of ___, ___, and in some instances, ___ ions across the plasma membranes
Sodium, potassium, and calcium
162
What are the 3 types of gated ion channels?
-AMPA (may have a role in neuronal damage)
-Kainate (spinal cord- pain transmission)
-NMDA
163
All three ionotropic glutamate receptors are ____ complexes composed of the same or different subunits
Tetrameric
164
____ glutamate receptors contain 7 transmembrane-spanning domains coupled via G proteins to various effector mechanisms
Metabotropic
165
___ subtypes of metabotropic glutamate receptors exist
8
166
The 8 subtypes of metabotropic glutamate receptors all belong to 1 of 3 groups that are categorized by...
-Sequence homology
-Signal transduction mechanism
-Pharmacology
167
What are the three ways to terminate glutamatergic neurotransmission?
-Transmitter reuptake by the presynaptic terminal
-Transmitter diffusion out of the synaptic cleft
-Receptor desensitization
168
Increased release or decreased reuptake of glutamate in pathological states can lead to a ____ feedback cycle known as excitotoxicity
Positive
169
Excitotoxicity is defined as neuronal death caused by excessive cellular ____
Excitation
170
What diseases cause excitotoxicity?
-Neurodegenerative disease (ALS, dementia, Parkinson's)
-Stroke, trauma
-Hyperalgesia
-Epilepsy
171
What are examples of NMDA receptor agonist drugs?
-Riluzole (ALS)
-Memantine (non-competitive Alzheimer's)
-Amantadine (non-competitive Parkinson's- with Levadopa)
172
In animals, inhibition of AMPA receptor activation prevents ____ onset
Seizure
173
NMDA receptor antagonists decrease seizure ____ and ____
Intensity and duration
