Module 7 - Neuropharm - CG Flashcards
1
Q
What is the primary excitatory neurotransmitter in the CNS?
A
Glutamate
2
Q
Which two sources can produce glutamate?
A
Glucose metabolism in the Kreb’s Cycle and GABA metabolism in glial cells.
3
Q
What are the two most important glutamate receptors?
A
AMPA and NMDA receptors.
4
Q
What enzyme converts glutamine into glutamate?
A
Glutaminase.
5
Q
How is glutamate inactivated at the synapse?
A
It is rapidly taken up by neighboring glial cells and converted back into glutamine by
glutamine synthetase.
6
Q
What is excitotoxicity, and which neurotransmitter is primarily involved?
A
Excitotoxicity is excessive stimulation by glutamate leading to neuronal damage or death
due to high intracellular calcium levels.
7
Q
Which ion channel is regulated by NMDA receptors?
A
A non-specific ion channel that allows Na+ and Ca2+ to enter while allowing K+ to leave.
8
Q
Why is NMDA receptor activity important for long-term potentiation (LTP)?
A
It is necessary for memory formation and synaptic plasticity.
9
Q
What neurotransmitter is the primary inhibitor in the CNS?
A
GABA (Gamma-Aminobutyric Acid).
10
Q
What enzyme synthesizes GABA from glutamate?
A
Glutamic Acid Decarboxylase (GAD).
11
Q
How is GABA inactivated after release?
A
Reuptake into glial cells or presynaptic neurons, followed by metabolism via GABA
transaminase (GABA-T).
12
Q
Which ion does the GABA-a receptor primarily regulate?
A
Chloride (Cl-).
13
Q
What class of drugs modulates GABA-a receptors to enhance inhibition?
A
Benzodiazepines (BDZs).
14
Q
Which neurotransmitter imbalance is implicated in epilepsy?
A
Excess glutamate or insufficient GABA.
15
Q
What is the mechanism of action of valproic acid in seizure treatment?
A
It inhibits GABA transaminase (GABA-T), increasing GABA activity.
16
Q
What role do enkephalins play in pain modulation?
A
They act on opioid receptors to inhibit pain signals.
17
Q
What is the primary receptor for enkephalins?
A
The mu-opioid receptor.
18
Q
Which drug is a competitive antagonist for opioid receptors?
A
Naloxone.
19
Q
What is the function of the AMPA receptor?
A
It mediates fast excitatory synaptic transmission by allowing Na+ and K+ flux.
20
Q
What is the role of serotonin (5-HT) in pain modulation?
A
It is involved in descending pain inhibition by promoting enkephalin release.
21
Q
What is cortical spreading depression (CSD), and what condition is it associated with?
A
CSD is a wave of neuronal depolarization linked to migraines.
22
Q
Which two neurotransmitters are co-released with glutamate in pain pathways?
A
Substance P (SP) and Calcitonin Gene-Related Peptide (CGRP).
23
Q
What is the gate theory of pain modulation?
A
The concept that non-painful stimuli (A-beta fiber activation) can inhibit pain signals via
inhibitory interneurons.
24
Q
How do benzodiazepines enhance GABA activity?
A
They increase chloride ion conductance at the GABA-a receptor, enhancing inhibitory
effects.
25
What is the relationship between chronic pain and central sensitization?
Prolonged excitatory signaling leads to a lowered threshold for pain perception, causing pain without actual tissue damage.
26
What are the key roles of glutamate in the nervous system?
Learning, memory, epilepsy, and Huntington’s Disease.
27
How does glutamate contribute to memory formation?
It activates NMDA receptors, which play a key role in long-term potentiation (LTP), essential
for memory storage.
28
What is the role of AMPA receptors in synaptic transmission?
They mediate fast excitatory synaptic transmission by allowing Na+ and K+ flux.
29
Why is calcium (Ca2+) influx through NMDA receptors tightly regulated?
Excess calcium can cause excitotoxicity, leading to neuronal damage and cell death.
30
What is the difference between AMPA and NMDA receptors in glutamate signaling?
AMPA receptors mediate fast synaptic transmission, while NMDA receptors require
depolarization to remove the Mg2+ block and allow Ca2+ influx.
31
How does excessive glutamate lead to neurodegeneration?
Overactivation of NMDA receptors leads to excessive Ca2+ influx, triggering cell damage
and apoptosis.
32
What is the function of excitatory amino acid transporters (EAATs)?
They regulate glutamate levels by removing it from the synaptic cleft to prevent
excitotoxicity.
33
How do astrocytes contribute to glutamate recycling?
They take up glutamate and convert it to glutamine via glutamine synthetase, which neurons then use to regenerate glutamate.
34
What is the primary inhibitory neurotransmitter in the brain, and what is its main function?
GABA; it reduces neuronal excitability and helps regulate anxiety and sleep.
35
How do GABA-T inhibitors help treat seizures?
By inhibiting GABA transaminase (GABA-T), they increase GABA levels, enhancing inhibition
and preventing excessive neuronal firing.
36
What is the main difference between GABA-a and GABA-b receptors?
GABA-a receptors are ionotropic (control Cl- influx), while GABA-b receptors are metabotropic (linked to second messenger systems).
37
What is the role of benzodiazepines in anxiety treatment?
They enhance GABA-a receptor activity, increasing chloride ion influx and leading to greater neuronal inhibition.
38
Why do benzodiazepines require both GABA and a benzodiazepine to bind for full receptor activation?
BDZs are allosteric modulators, meaning they enhance GABA’s effects but cannot activate
the receptor alone.
39
What are common side effects of benzodiazepines?
Sedation, dizziness, dependency, and memory impairment.
40
What is the relationship between GABA and glutamate in the brain?
They have opposing roles; glutamate is excitatory, while GABA is inhibitory, and they are
metabolically linked.
41
What is the function of enkephalins in the nervous system?
They modulate pain perception by acting on opioid receptors, reducing pain signals.
42
What are the three main types of opioid receptors?
Mu (μ), Delta (δ), and Kappa (κ).
43
What are the effects of activating the mu-opioid receptor?
Analgesia, respiratory depression, euphoria, and sedation.
44
How does naloxone work to reverse opioid overdoses?
It is a competitive antagonist at opioid receptors, displacing opioids and blocking their
effects.
45
How do opioids cause respiratory depression?
They inhibit respiratory centers in the brainstem by increasing K+ conductance and reducing neuronal excitability.
46
What neurotransmitters are involved in the transmission of pain signals?
Glutamate, Substance P (SP), and Calcitonin Gene-Related Peptide (CGRP).
47
What is Substance P’s role in pain transmission?
It binds NK-1 receptors and enhances pain signaling and neurogenic inflammation.
48
How does the gate control theory of pain work?
Non-painful stimuli (A-beta fibers) activate inhibitory interneurons, reducing pain signal
transmission in the dorsal horn.
49
How does enkephalin contribute to the gate control theory of pain?
It inhibits pain signals by reducing neurotransmitter release from nociceptive neurons.
50
What are the two types of pain fibers, and how do they differ?
• A-delta fibers: Myelinated, fast conduction, sharp localized pain.
• C-fibers: Unmyelinated, slow conduction, dull aching pain.
51
What is neurogenic inflammation?
Inflammation triggered by neurotransmitter release from primary afferent nociceptors,
including Substance P and CGRP.
52
How does serotonin (5-HT) modulate pain perception?
It enhances descending inhibition by promoting enkephalin release, reducing pain
transmission.
53
How do SSRIs affect pain perception?
They increase serotonin levels, which can enhance descending pain inhibition.
54
What is cortical spreading depression (CSD), and why is it significant?
A wave of neuronal depolarization linked to migraines, triggered by excessive glutamate
release.
55
What role do calcium pumps play in preventing excitotoxicity?
They actively remove excess intracellular Ca2+ to maintain neuronal homeostasis.
56
How does excessive glutamate release contribute to chronic pain?
It leads to central sensitization, making neurons hyperexcitable and increasing pain
perception.
57
What is the primary mechanism of chronic pain?
Central sensitization, where prolonged excitatory signaling lowers the pain threshold, leading to persistent pain perception.
58
How does chronic inflammation contribute to central sensitization?
It maintains a heightened state of excitability in dorsal horn neurons, making pain perception more intense.
59
What is the role of the periaqueductal gray (PAG) in pain modulation?
It activates descending pain inhibition pathways that release serotonin and norepinephrine.
60
How do opiates reduce pain at the spinal cord level?
They inhibit Ca2+ influx presynaptically (reducing neurotransmitter release) and increase K+
efflux postsynaptically (hyperpolarization).
61
Why can prolonged opioid use lead to hyperalgesia?
It causes increased sensitivity to pain due to receptor desensitization and changes in
neurotransmitter balance.
62
What is the function of norepinephrine in pain modulation?
It contributes to descending pain inhibition by activating opioid-releasing interneurons.
63
What neurotransmitters are involved in the descending pain modulation system?
Serotonin (5-HT), norepinephrine (NE), and enkephalins.
64
What is central biasing in pain perception?
The brain’s ability to modulate pain perception based on past experiences and emotional
factors.
65
How does glutamate contribute to epilepsy?
Excessive glutamate activity leads to overexcitation of neurons, increasing the likelihood of
seizures.
66
What role does glutamate play in Huntington’s Disease?
Excess glutamate release causes excitotoxicity, leading to the degeneration of GABAergic
neurons in the caudate nucleus.
67
How does GABA contribute to anxiety disorders?
Reduced GABA activity leads to increased neuronal excitability, contributing to heightened
anxiety.
68
What are the two main types of GABA receptors, and how do they differ?
• GABA-a: Ionotropic, controls Cl- influx, leads to fast inhibition.
• GABA-b: Metabotropic, uses second messenger systems for slower inhibition.
69
What is the function of GABA transporters (GATs)?
They remove GABA from the synaptic cleft to terminate its action.
70
What is the mechanism of action of barbiturates?
They enhance GABA-a receptor activity, prolonging Cl- channel opening for stronger
neuronal inhibition.
71
Why are benzodiazepines considered safer than barbiturates?
They only enhance GABA’s effect rather than directly opening Cl- channels, reducing
overdose risk.
72
How does alcohol affect GABA neurotransmission?
It enhances GABA-a receptor activity, leading to sedative and depressant effects.
73
What is the role of AMPA receptors in synaptic plasticity?
They mediate fast excitatory transmission and play a role in synaptic strengthening and LTP.
74
How do NMDA receptors contribute to synaptic plasticity?
They allow Ca2+ influx, which activates intracellular signaling pathways crucial for memory
formation.
75
How does magnesium (Mg2+) regulate NMDA receptor activity?
It blocks the NMDA receptor channel at resting membrane potential, requiring depolarization to be removed.
76
What are the consequences of excessive NMDA receptor activation?
Increased Ca2+ influx leads to excitotoxicity, neuronal damage, and possible neurodegeneration.
77
How does memantine work as a treatment for Alzheimer’s disease?
It blocks NMDA receptors to prevent excessive Ca2+ influx and reduce excitotoxicity.
78
What is the function of EAAT transporters in glutamate regulation?
They remove excess glutamate from the synaptic cleft to prevent excitotoxicity.
79
How does glycine interact with NMDA receptors?
It acts as a co-agonist, necessary for NMDA receptor activation alongside glutamate.
80
What happens when GABA levels are too low?
Increased neuronal excitability, leading to anxiety, insomnia, and potentially seizures.
81
What is the function of GABA-T inhibitors in seizure treatment?
They prevent GABA breakdown, prolonging its inhibitory effect.
82
What role does Substance P play in inflammation?
It promotes vasodilation, increased vascular permeability, and activation of immune cells.
83
How does CGRP contribute to migraines?
It is a potent vasodilator involved in the pathophysiology of migraine headaches.
84
What is the primary function of the periaqueductal gray (PAG)?
It is a key structure in descending pain modulation, activating inhibitory pathways.
85
How do opioids affect neurotransmitter release at the spinal cord level?
They inhibit presynaptic Ca2+ influx, reducing the release of excitatory neurotransmitters like glutamate and Substance P.
86
Why does opioid tolerance develop over time?
Repeated opioid use leads to receptor desensitization and downregulation, reducing drug effectiveness.
87
What is opioid-induced hyperalgesia?
A condition where prolonged opioid use paradoxically increases pain sensitivity.
88
How do NSAIDs reduce pain and inflammation?
They inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
89
How does serotonin contribute to descending pain modulation?
It enhances inhibitory interneuron activity, reducing pain signal transmission.
90
What is the relationship between norepinephrine and pain control?
It enhances descending inhibition by activating opioid-releasing interneurons.
92
How do antidepressants like SSRIs and SNRIs help in chronic pain?
They enhance serotonin and norepinephrine activity, boosting descending pain inhibition.
93
What is the significance of central sensitization in chronic pain?
It leads to heightened pain perception due to persistent excitatory neurotransmitter activity.
94
How does the spinal cord regulate pain before reaching the brain?
Through inhibitory interneurons that modulate nociceptive transmission in the dorsal horn.
95
What is the primary pathway for pain perception in the brain?
The spinothalamic tract, which transmits pain signals to the thalamus and cortex.
96
What is the main function of the dorsal horn in pain processing?
It serves as the first synaptic relay for nociceptive information, where pain signals can be
modulated.
97
How does ketamine work as an analgesic?
It blocks NMDA receptors, preventing excessive excitatory signaling and reducing pain
perception.
98
What neurotransmitters are involved in descending pain control?
Serotonin (5-HT), norepinephrine (NE), and enkephalins.
99
How does touch-based therapy like massage modulate pain?
It activates A-beta fibers, engaging the gate control mechanism to inhibit pain signals.
100
How does stress influence pain perception?
Chronic stress increases cortisol levels, which can enhance excitatory neurotransmission
and lower pain tolerance.
101
How does acupuncture modulate pain perception?
It stimulates endogenous opioid release, reducing pain transmission.
102
What is the role of TRPV1 receptors in pain sensation?
They detect heat and capsaicin, contributing to pain signaling and neurogenic inflammation.
103
What are endozepines, and what is their function?
E ndogenous benzodiazepine-like compounds that modulate GABA-a receptor activity.
104
How do cannabinoids influence pain perception?
They act on CB1 receptors to inhibit neurotransmitter release, reducing pain signaling.
105
Why are GABAergic drugs used in muscle relaxation?
They enhance inhibition in the spinal cord, reducing muscle tone and spasms.
106
How does glutamate contribute to addiction?
It plays a role in synaptic plasticity, reinforcing drug-seeking behavior through NMDA
receptor activation.
107
Why is NMDA receptor activation important in opioid withdrawal?
It contributes to hyperexcitability and withdrawal symptoms when opioid inhibition is
removed.
108
What are the two primary excitatory neurotransmitters in the brain?
Glutamate and aspartate.
109
What is the role of glutamate in reflexes?
It mediates excitatory signaling in the afferent limb of reflex arcs.
110
Why is glutamate considered the most important neurotransmitter for cognition?
It is essential for synaptic plasticity, learning, and memory.
111
How does glutamate interact with astrocytes?
Astrocytes take up excess glutamate and convert it into glutamine for recycling.
112
What happens when glutamate transporters (EAATs) are dysfunctional?
Excess glutamate accumulates, increasing the risk of excitotoxicity and neurodegeneration.
113
What is the relationship between glutamate and schizophrenia?
Hypofunction of NMDA receptors is associated with cognitive deficits in schizophrenia.
114
What are the primary inhibitory neurotransmitters in the CNS?
GABA and glycine.
115
How do benzodiazepines affect sleep?
They enhance GABAergic inhibition, promoting sedation and sleep.
116
How does alcohol withdrawal cause seizures?
Chronic alcohol use enhances GABA activity, and withdrawal causes a rebound excitability
due to reduced inhibition.
117
Why does GABA deficiency contribute to movement disorders?
Lack of GABAergic inhibition leads to excessive motor activity, as seen in Huntington’s
Disease.
118
What is the function of the GABA-b receptor?
It inhibits neurotransmitter release via G-protein-coupled mechanisms, leading to prolonged inhibition
119
What is the role of glutamate in stroke-induced brain damage?
Ischemia leads to excessive glutamate release, causing excitotoxicity and neuronal death.
120
How does memantine differ from other NMDA receptor antagonists?
It is a low-affinity antagonist that blocks excessive NMDA activity without disrupting normal
function.
121
What is the effect of chronic stress on glutamate signaling?
It increases glutamate release, leading to synaptic remodeling and potential neurotoxicity
122
What role does dopamine play in regulating glutamate and GABA balance?
Dopamine modulates excitatory and inhibitory transmission in the basal ganglia to control
movement.
123
What is the primary function of opioid peptides like enkephalins?
They inhibit pain transmission in the spinal cord and brain.
124
How does morphine produce analgesia?
It binds to mu-opioid receptors, inhibiting neurotransmitter release and reducing pain
signaling.
125
How do chronic pain conditions alter neurotransmitter function?
They lead to increased glutamate and Substance P activity, along with reduced inhibitory
control.
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