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Advanced Pharmacology > Neuropharmacology > Flashcards

Neuropharmacology Flashcards

1
Q

_____ is a subdivision of pharmacology that studies how drugs affect the brain and behavior

A

Psychopharmacology

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2
Q

The transport protein called _____ mediates the delivery of drugs from the brain to the peripheral nervous system

A

p-Glycoprotein

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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

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4
Q

Most psychoactive drugs are excreted in the ____ after metabolic transformation

A

Urine

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5
Q

What types of drugs are eliminated in the lungs/breath?

A

-Gaseous general anesthetics
-Alcohol (in small amounts)

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6
Q

Drugs that are terminated in the ____ are excreted into the intestines and reabsorbed

A

Bile

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7
Q

___-___% of a few drugs are excreted in the sweat

A

10-15

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8
Q

_____ contain metabolizing enzymes

A

Hepatocytes

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9
Q

Cytochrome ____ enzymes are important in drug biotransformation

A

P450

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10
Q

CYP3A4 catalyzes ____% of drugs

A

50

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11
Q

CYP2D6 catalyzes ____% of drugs

A

20

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12
Q

CYP1A2 and CYPE1 each catalyze about ____% of drugs

A

5

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13
Q

Metabolic tolerance means that there is ____ of hepatic enzymes

A

Induction

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14
Q

With pharmacodynamic tolerance, receptors in the brain adapt to a drug, either decreasing in ____ or ____

A

Number or sensitivity

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15
Q

___ ___ is when the removal of drug results in withdrawal symptoms until the brain and body can adapt

A

Physical dependence

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16
Q

If someone is on a CNS depressant, when you withdraw the drug, they may have CNS ____ symptoms

A

Excitatory

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17
Q

____ are CNS depressants that can be used for alcohol withdrawal symptoms

A

Benzodiazepines

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18
Q

_____ is what the drug does to the body, and includes pharmacological and adverse effects

A

Pharmacodynamics

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19
Q

Pharmacodynamics requires the drug to interact with ____

A

Receptors

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20
Q

Receptors are membrane-spanning proteins with binding sites for ____ ____ and drugs

A

Endogenous neurotransmitters

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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)

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22
Q

Carriers or transporter proteins bind neurotransmitters in the ___ ___ and transport them back into the presynaptic terminal

A

Synaptic cleft

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23
Q

Enzymes are involved in the ____ of neurotransmitters and can be blocked by drugs

A

Degredation

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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

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25
Q

Carriers are very important in psychopharmacology; for example, _____ block carrier protein so that there is more serotonin in the synaptic cleft

A

SSRIs

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26
Q

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

A

Post-synaptic

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27
Q

G proteins regulate ____ availability of neurotransmitters in the synapse

A

Synaptic

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28
Q

The ____ is the fundamental unit of the nervous system

A

Neuron

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29
Q

There are over ____ billion neurons in the CNS

A

100

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30
Q

Neurons communicate with thousands of other neurons through ___ signals that are sent at up to 200 mph

A

Electrical

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31
Q

Neurons are the primary site of ____ acting drugs

A

CNS

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32
Q

Drugs may try to mimic concentrations of neurotransmitters or increase the ____ a neurotransmitter stays in the synapse

A

Time

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33
Q

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)

A

Neurotransmitter

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34
Q

____ is a chemical process whereby neurotransmitters are released into the synaptic cleft

A

Neurotransmission

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35
Q

Neurons fire by transmitting electrical signals along its ____

A

Axon

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36
Q

The signal triggers neurotransmitter release from _____

A

Vesicles

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37
Q

Neurotransmitters cross the ____ and bind to receptors on adjacent cells

A

Synapse

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38
Q

The sodium-potassium pump maintains resting membrane potential by pumping ___ potassium in for every ____ sodium out

A

2; 3

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39
Q

The sodium-potassium pump reestablishes resting membrane potential after an ___ ___ has been generated

A

Action potential

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40
Q

_____ means that the sodium channels are open and this makes the cell more positive

A

Depolarization

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41
Q

____ is when the sodium channels close and the potassium channels open; this makes the cell more negative

A

Repolarization

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42
Q

____ action potentials alter resting membrane potential

A

Graded

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43
Q

Depolarization moves membrane potential towards ____, and causes sodium to move into the axon

A

Positive

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44
Q

Hyperpolarization moves membrane potential toward ____, and causes potassium to move out of the axon

A

Negative

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45
Q

A depolarizing ____ potential means that there is not enough stimulus to cause an action potential

A

Graded

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46
Q

In an “all or non” action potential, the individual neuron threshold sets the extent of ____ needed; if it achieves that, it fires

A

Stimulus

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47
Q

In a ___-___ action potential, the electrical current reaches the threshold throughout the axon during the spread of the action potential

A

Self-propagating

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48
Q

Transfer of information from the neuron to the target is via ____ ____

A

Synaptic transmission

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49
Q

An ____ neurotransmitter will depolarize postsynaptic cells

A

Excitatory

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50
Q

An ____ neurotransmitter will hyperpolarize postsynaptic cells

A

Inhibitory

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51
Q

The role of a postsynaptic neuron is to ___ and ___ information

A

Integrate and process

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52
Q

What are 4 examples of monoamine neurotransmitters?

A

-Acetylcholine
-Norepinephrine
-Serotonin
-Dopamine

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53
Q

What are 2 examples of amino acid neurotransmitters?

A

-Glutamic Acid
-Gamma-amino butyric acid (GABA)

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54
Q

What are two examples of neuropeptide neurotransmitters?

A

-Substance P
-Endogenous opioids

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55
Q

Acetylcholine has a primary role in the ____ nervous system

A

Peripheral

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56
Q

Acetylcholine is _____ on skeletal muscle (causes contraction)

A

Excitatory

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57
Q

Acetylcholine is excitatory or inhibitory on ___ ___

A

Internal organs

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58
Q

Acetylcholine is ____ in cognitive disorders such as Alzheimer’s

A

Decreased

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59
Q

Norepinephrine is excitatory or inhibitory depending on ____

A

Receptors

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60
Q

Norepinephrine plays a role in…

A

-Affective disorders
-Learning and memory
-Sleep-wake cycle

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61
Q

Serotonin (5-HT) is present in the ___ and ___

A

Brain and periphery

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62
Q

____% of serotonin is in the GI tract, and ___% is in the brain and platelets

A

90; 10

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63
Q

We can get serotonin from dietary ____

A

Tryptophan

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64
Q

Is serotonin usually inhibitory or excitatory?

A

-Inhibitory

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65
Q

Serotonin is involved in…

A

-Mood
-Sleep Cycle
-Appetite

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66
Q

There are multiple serotonin receptor ____

A

Subtypes

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67
Q

Dopamine can be excitatory or inhibitory depending on the ______

A

Receptor

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68
Q

There are ___ distinct dopaminergic systems that differ in the length of neurons

A

3

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69
Q

The short dopaminergic system is found in…

A

-Retinal and olfactory bulb

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70
Q

The intermediate dopaminergic system regulates _____ functions

A

Hypothalamic

71
Q

The long dopaminergic system is decreased in _____ disease

A

Parkinsons

72
Q

GABA is a major ____ neurotransmitter in the brain

A

Inhibitory

73
Q

GABA is synthesized from ____

A

Glutamate

74
Q

GABA binds to a receptor which results in _____ influx and hyperpolarization of the neuron (non-firing)

A

Chloride

75
Q

The GABA receptor also binds ____ and ____

A

Benzodiazepines and Barbituates

76
Q

Glutamate is a major ____ neurotransmitter in the brain

A

Excitatory

77
Q

Rapid depolarization of neurons results in an ____ firing rate of gltamate

A

Increased

78
Q

_____ is a main receptor of glutamate

A

NMDA

79
Q

NMDA antagonists may decrease neuronal damage during a ____

A

Stroke

80
Q

____ ____ was the first neuropeptide to be isolated

A

Substance P

81
Q

Substance P can directly ____ motor neurons, similar to excitatory neurotransmitters

A

Depolarize

82
Q

Substance P may be released in response to ____

A

Pain

83
Q

Endogenous opioid peptides are substances that bind to stereoselective receptors and possess the pharmacological qualities of ____

A

Morphine

84
Q

What are three types of endogenous opioid peptides?

A

-Endorphins
-Enkephalins
-Dynorphins

85
Q

____ are the most potent type of endogenous opioid peptide

A

Endorphins

86
Q

____ are a type of endogenous opioid peptide that are widely distributed in the CNS

A

Enkephalins

87
Q

What are two possible pathologies of having “too much” neurotransmission?

A

-Hyperexcitable neurons fire in the absence of appropriate stimuli (e.g., seizure disorder)
-Too many neurotransmitters binding to postsynaptic receptors (e.g., psychosis)

88
Q

What is a possible pathology of having “too little” neurotransmission?

A

-Too few neurotransmitters binding to postsynaptic receptors (e.g., depression, Parkinson’s)

89
Q

What four things could cause decreased neurotransmission?

A

-Decreasing synthesis of neurotransmitters
-Increases neurotransmitter metabolism
-Promoting increased neuronal uptake
-Blocking access to post synaptic receptors (e.g., administer an antagonist)

90
Q

What six things could cause increased neurotransmission?

A

-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
Q

In what three ways can drugs alter neurotransmitters?

A

-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
Q

The two most important amino acid neurotransmission systems in the CNS involve ____ (the main inhibitory neurotransmitter) and _____ (the main excitatory neurotransmitter)

A

GABA; glutamate

93
Q

Neurotransmitters alter the ____ of one or more ion-selective channels

A

Conductance

94
Q

Inhibitory neurotransmitters trigger a selective ____ current

A

Outward

95
Q

Excitatory neurotransmitters cause a net ____ current

A

Inward

96
Q

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)

A

Anions; cations

97
Q

Opening of the chloride or potassium channels also decreases the membrane ____ and thereby lowers the 0Vm response to excitatory currents

A

Resistance

98
Q

The decreased membrane resistance results in lower ____

A

Responsiveness

99
Q

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

A

Responsive

100
Q

GABA has _____ distribution and has influence on many neuronal circuits and functions

A

Widespread

101
Q

GABA affects what processes?

A

-Arousal and attention
-Memory formation
-Anxiety
-Sleep
-Muscle tone

102
Q

GABA disfunction can cause widespread neuronal ____, like with epilepsy

A

Hyperactivity

103
Q

Synthesis of GABA is mediated by ___ ___ ___

A

Glutamic acid decarboxylase

104
Q

GABA is made from the ____ of glutamate

A

Decarboxylation

105
Q

The synthesis of GABA requires vitamin ____

A

B6

106
Q

GABA is stored in ___-___ vesicles and released into the synaptic cleft in response to an action potential

A

Pre-synaptic

107
Q

Termination of GABA neurotransmission depends on the removal of GABA from the extracellular space which is done by…

A

-GABA transporters (neurons in CNS)
-GABA transaminase (converts within other cells)

108
Q

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

A

GABA transaminase

109
Q

Alternatively, glutamate is converted to GABA by ____ ___ ____, changing the major excitatory neurotransmitter to the majority inhibitory transmitter

A

Glutamic acid decarboxylase

110
Q

What are the two types of GABA receptors?

A

-Ionotropic GABA receptors (GABAa and GABAc)
-Metabotropic GABA receptors (GABAb)

111
Q

Metabotropic GABA receptors are ___-___ coupled receptors

A

G-protein

112
Q

Which type of GABA is the most abundant in the CNS?

A

GABAa

113
Q

GABAa has ___ different subtypes

A

16

114
Q

Different subunit combinations display distinct distributions at the ___ and ___ levels; GABA subtypes play distinct roles in specific neural circuits

A

Cellular and tissue

115
Q

Most subtypes consist of ___ alpha, ___ beta, and ___ gamma subunit

A

2, 2, 1

116
Q

GABAa has a ____ structure

A

Pentameric

117
Q

Activation of GABA receptor requires the binding of ____ GABA molecules to the receptor, one to each of the subunits

A

2

118
Q

Each subunit of the GABAa receptor has four membrane-spanning regions and a ____ loop in the extracellular N-terminal domain

A

Cysteine

119
Q

There are five subunit of GABAa receptors that surround a central ____-selective ion pore that opens in the presence of GABA

A

Chloride

120
Q

GABAa receptors contain a number of ____ sites where drugs can bind

A

Regulatory

121
Q

The response of GABAa receptors can vary depending on the ____ ___ composition

A

Receptor subunit

122
Q

Prolonged occupation of the agonist sites by GABA also leads to GABAa receptor _____, which results in an inactive agonist-bound state

A

Desensitization

123
Q

Low levels of GABA can also cause a baseline ____ current in many neurons

A

Inhibitory

124
Q

____ is when open chloride channels attenuate the change in membrane potential caused by excitatory synaptic currents

A

Shunting

125
Q

Increasing concentrations of GABA induce both greater chloride currents and more rapid receptor ______

A

Desensitization

126
Q

Activity of GABAa receptors can be allosterically modulated by ____ like DHEA

A

Neurosteroids

127
Q

Neurosteroids alter receptor function by binding to _____ sites on the receptor protein to either activate or inhibit GABAa

A

Allosteric

128
Q

GABAc is ionotropic and has ___ subunits that are not in GABAa

A

3

129
Q

GABAc receptors are ___-___ chloride channels

A

Ligand-gated

130
Q

GABAc receptors are limited to the ____

A

Retina

131
Q

Are there any drugs that target GABAc receptors?

A

No

132
Q

GABAb receptors are ___ ___-coupled receptors

A

G protein

133
Q

GABAb receptors have a ____ rate of activation and deactivation compared to GABAa

A

Slower

134
Q

GABAb receptors have a slow ___ ___ signal transduction mechanism

A

Second messenger

135
Q

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

A

Second messenger

136
Q

The increased K+ efflux leads to slow, long-lasting _____ postsynaptic potentials

A

Inhibitory

137
Q

The reduced Ca2+ influx may enable GABAb autoreceptors to inhibit ____ neurotransmitter release

A

Presynaptic

138
Q

Activation of potassium channels ____ neuronal firing; it drives the neuronal transmembrane voltage toward “resting” potentials that reduce the frequency of action potential initiation

A

Inhibits

139
Q

The majority of drugs affecting GABAergic neurotransmission act on the ionotropic _____ receptor

A

GABAa

140
Q

Binding of drugs to the GABA receptors causes…

A

-Sedation
-Anxiolysis
-Hypnosis

141
Q

Some drugs inhibit the reuptake of GABA to increase synaptic concentration at GABAa; an example of a disorder where this would be important is ____

A

Epilepsy

142
Q

_____ is a selective GABAb receptor agonist that works in the spinal cord

A

Baclofen

143
Q

Baclofen stimulates downstream second messengers to act on ___ and ___ channels

A

Calcium and potassium

144
Q

Baclofen is effective for mild ____

A

Spasticity

145
Q

Baclofen modulates ___ and ___, and it is being investigated as a therapy for drug addiction

A

Pain and cognition

146
Q

Baclofen has a modest volume of distribution and does not readily cross the ___-___ barrier

A

Blood-brain

147
Q

Elimination of GABA is ___% renal, and ___% liver

A

85; 15

148
Q

The half-life of Baclofen is ___ hours

A

5

149
Q

What are some adverse effects of Baclofen?

A

-Sedation
-Somnolence
-Ataxia

150
Q

If someone has decreased renal function, they may experience Baclofen _____

A

Toxicity

151
Q

Is there any tolerance with oral baclofen?

A

No

152
Q

Tolerance with interthecal Baclofen increases over ___-___ years

A

1-2

153
Q

What are some withdrawal symptoms of Baclofen?

A

-Acute hyperelasticity
-Rhabdomyolysis
-Pruritis
-Delirium
-Fever
-Multi-organ failure
-Coagulation abnormalities
-Shock
-Death

154
Q

____ neurotransmission exists throughout the CNS

A

Glutamatergic

155
Q

Glutamatergic neurotransmission is involved with…

A

-Development of elevated pain sensation
-Cerebral neurotoxicity
-Synaptic changes involved with certain types of memory formation

156
Q

The synthesis of glutamatergic neurotransmission occurs via what two distinct pathways?

A

-Ketoglutarate via Krebs cycle converted in CNS and nerve terminals
-Glutaminase converts glutamine in nerve terminals

157
Q

Glutamate is release via ____-dependent exocytosis of transmitter-containing vesicles

A

Calcium

158
Q

Glutamate is removed from the synaptic cleft by ___ ___ ___ located on presynaptic nerve terminals

A

Glutamate reuptake transporters

159
Q

What are the two subgroups of glutamate receptors?

A

-Ionotropic
-Metabotropic

160
Q

_____ glutamate receptors mediate fast excitatory synaptic responses

A

Ionotropic

161
Q

When activated, neurotransmission permits the flow of ___, ___, and in some instances, ___ ions across the plasma membranes

A

Sodium, potassium, and calcium

162
Q

What are the 3 types of gated ion channels?

A

-AMPA (may have a role in neuronal damage)
-Kainate (spinal cord- pain transmission)
-NMDA

163
Q

All three ionotropic glutamate receptors are ____ complexes composed of the same or different subunits

A

Tetrameric

164
Q

____ glutamate receptors contain 7 transmembrane-spanning domains coupled via G proteins to various effector mechanisms

A

Metabotropic

165
Q

___ subtypes of metabotropic glutamate receptors exist

A

8

166
Q

The 8 subtypes of metabotropic glutamate receptors all belong to 1 of 3 groups that are categorized by…

A

-Sequence homology
-Signal transduction mechanism
-Pharmacology

167
Q

What are the three ways to terminate glutamatergic neurotransmission?

A

-Transmitter reuptake by the presynaptic terminal
-Transmitter diffusion out of the synaptic cleft
-Receptor desensitization

168
Q

Increased release or decreased reuptake of glutamate in pathological states can lead to a ____ feedback cycle known as excitotoxicity

A

Positive

169
Q

Excitotoxicity is defined as neuronal death caused by excessive cellular ____

A

Excitation

170
Q

What diseases cause excitotoxicity?

A

-Neurodegenerative disease (ALS, dementia, Parkinson’s)
-Stroke, trauma
-Hyperalgesia
-Epilepsy

171
Q

What are examples of NMDA receptor agonist drugs?

A

-Riluzole (ALS)
-Memantine (non-competitive Alzheimer’s)
-Amantadine (non-competitive Parkinson’s- with Levadopa)

172
Q

In animals, inhibition of AMPA receptor activation prevents ____ onset

A

Seizure

173
Q

NMDA receptor antagonists decrease seizure ____ and ____

A

Intensity and duration

Advanced Pharmacology (10 decks)

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