Neuropharmacology Flashcards
exam (157 cards)
1
Q
alpha1-R
A
stimulatory
2
Q
alpha2-R
A
inhibitory
3
Q
GABAA-R
A
inhibitory
4
Q
NMDA-R and nACh-R
A
excitatory
5
Q
potency
A
activity of drug in terms of concentration of drug required
6
Q
thalamus is associated with
A
pain, altertness
7
Q
Basal ganglia (striatum) associated with
A
movement
8
Q
hippocampus associated with
A
long term memory and episodic memory, stress response
9
Q
amygdala associated with
A
emotional memories
10
Q
Nucleus accumbens (striatum) associated with
A
reward and motivation
11
Q
Dorsolateral PFC
A
executive function, problem solving
12
Q
orbitofrontal PFC
A
emotions, impulsivity, decision making
13
Q
cingulate PFC
A
formation, processing of memories
14
Q
hypothalamus associated with
A
sleep, appetite
15
Q
spinal cord associated with
A
pain
16
Q
inhibitory neurotransmitter
A
GABA
17
Q
Effect of GABA
A
sedation
18
Q
Effect of NE
A
mood, arousal, cognition, wakefulness
19
Q
Effect of 5HT
A
mood, arousal, cognition wakefulness, anxiety, impulsivity
20
Q
Effect of DA
A
arousal, cognition, reward, movement, impulsivity, addiction
21
Q
Dopaminergic pathways
A
Mesolimbic, VTA to striatum
Mesocortical, VTA to PFC
Nigrostritial, Substantia nigra to striatum
22
Q
Mesolimbic dysregulation
A
Addiction , reward pathway
23
Q
Mesocortical dysfunction
A
negative symptoms in schizophrenia
24
Q
Nigrostriatial dysfunction
A
movement control, EPS
25
Effect of histamines
wakefulness, executive function
26
Effect of ACh
arousal, sleep, learning, memory
27
CSTC loop modulates
attention, emotion, impulsivity, motor activity
28
Positive symptoms of schizophrenia
characteristics that should not be there eg delusions, hallucination.
29
Negative symptoms of schizophrenia
lack of normal characteristics
30
symptoms of schizophrenia
positive- and negative symptoms, affective symptoms, cognitive function, aggressive symptoms
31
Hyperactive mesolimbic pathway in schizophrenia according to DA hypothesis
positive symptoms
32
Hypoactive mesocortical pathway in schizophrenia according to DA hypothesis
cognitive, affective, negative symptoms
33
Dopamine hypothesis of schizophrenia
disturbed and hyperactive DA transmission
34
Positive symptoms glutamate hypothesis of schizophrenia
Hyperactive mesolimbic DA transmission, due to insufficient GABA feedback to VTA leading to excessive glutamate in VTA, excessive DA in N-Acc
35
Negative symptoms glutamate hypothesis of schizophrenia
Hypoactive mesocoritcal DA transmission
36
Hypoactiva tuberofudibular pathway
Hyperprolactinemia
37
Glutamate hypothesis
NMDA-R dysfunction, compromises GABA feedback causing increased glutaminergic neuron activity. Too much uncoordinated information
38
Glutamate hypothesis : positive symptoms
Hypoactive NMDA-R on GABA neurons leads to increased glutamate in VTA, leading to excessive DA stimulation in mesolimbic DA pathway
39
Glutamate hypothesis: negative symptoms
Hypoactive NMDA-R on GABA neurons leads to increased glutamate in VTA, this leads to excessive stimulation on pyramidal neurons which inhibits mesocortical DA neurons
40
Nigrostrial pathway (substantia nigto to striatum)
EPS
41
Serotonin hypothesis of schizophrenia
increased 5HT in striatum and PFC
42
Conventional anti psychosis
D2 antagonists eg haloperidol.
| Dampens positive symptoms (limbic), do not alleviate negative systems.
43
Side effects of conventional psychotics:
Hyperprolactinemia, EPS
44
Types of EPS:
Parkinsonism = parkinson like symptoms like tremor
Akathasia: inability to remain motionless
Dystonia: sustained muscle contractions
Dyskinesia: involuntary movements
45
Role of 5HT-R
5HT1A: depression, anxiety, cognition
5HT2A: sleep, hallucinations, inhibits DA release in nigrostriatal pathway
5HT2C: obesity, mood, cognition
46
5HT2A-R
on GABA neurons inhibit DA transmission in nigrostrial pathway,
stimulate mesolimbic DA transmission by stimulating glutamate neurons
47
5HT1A-R
autoreceptor inhibits 5HT release, less 5HT2A stimulated DA release. Stimulate striatal DA by decreasing 5HT transmission
48
Atypical antipsychotics
reduced EPS tendency, 5HT2A-antagonism, 5HT1A antagonism, D2 rapid dissociation , D2-R partial
only partially normalize negative, cognitive and affective symptoms
49
side effects atypical antipsychotics
Broad antagonism:
alpha1: sedation, dizziness, orthostatic hypotension
H1: weight gain
M1: blurred vision mouth
50
5HT2C antagonism
weight gain, increased cortical DA and NE, mesolimbic DA disinhibition
51
Symptoms of depression
depressed mood, apathy, weight changes, sleep disturbance, guilt, psychomotor, fatigue
52
reduced positive affect
depressed mood, anhedonia, apathy, decreased enthusiasm
| = DA and NE deficits
53
increased negative affect
depressed mood, ruminative thoughts, guilt, disgust
| =5HT deficits
54
Monoamine hypothesis
depression due to deficient brain monoamine transmission
55
Activity in different brain regions in depression
increased in amygdala, acc, ofc
| decreased in striatum
56
Anhedonia
due to reduced response of N.Acc to positive stimuli
57
Dysregulated HPA axis in depression
decreased negative feedback by GR, increase CRH and ACTH and thereby cortisol. Cortisol facilitate mesolimbic DA release which leads negative bias and cognitive deficits
58
default mode network
active during passive rest and mind wandering
self-appraisal, self-evaluation
hyperactive in depression
59
task positive network
active during tasks
60
SNRI and NRI effect
SNRI decrease negative affects
| NRI increase positive affects
61
VMPFC involved in
emotional response, self-confidence, self-criticism
62
DLPFC involved in
problem solving, sustained attention, cognitive flexibility
63
Acc
selective attention
64
amygdala
associative emotional memory
65
hippocampus
conscious long term memory, attribute context to stimuli
66
Neuroinflammatory hypothesis of depression
increased production of inflammatory markers
67
Neurogenesis hypothesis
antidepressants increase BDNF production which leads to neurogenesis
68
GABA-glutamate hypothesis of depression
depressed has Reduced GABA, increased glutamate in CSF
| NMDA-R inhibition disinhibit glum release causing more AMPA transmission
69
Reboxetine (NRI)
normalize impaired memory of positive words
70
NE regulate 5HT transmission through
alpha1 and alpha2 receptors
71
adrenergic autoreceptor
alpha2
72
5HT regulate NE through
5HT2A (increase DA and NE in PFC) and 5HT2C receptors (reduce DA and NE in PFC)
73
TCAs
effective,
side effects due to alpha1 (orthostatic hypotension), M1/M3 (blurred vision, dry mouth constipation) and H1 antagonism (sedation, weight gain), voltage gated Na+ channels (cardiac arrhythmia, seizures)
74
SSRI
fluoxetine, setraline, citalopram
| may cause apathic recovery by increasing 5HT, the negative affect is improved but positive affects isn't.
75
SNRI
venlaflaxine
| improves positive affects better than SSRI
76
NDRI
methylphenidate, amphetamine
less sexual side effects
may be nAchR-antagonist
77
NRI
reboxetine, amoxetine
78
Other targets
melatonin-R agonists (agomelatine), NaSSA (mirtazapine)
79
MAO-I
inhibits MAO enzymes
reversible or irreversible
tyramine risk of hypertensive crisis
if given with SERT can cause serotonin syndrome
80
5HT reduce mesolimbic and cortical DA
through 5HT2C-R in Acc (GABA, descending glutamate)
81
Delayed action of ADs
due to autoreceptor desensitization:
- chronic NET inhibition can desensitize terminal alpha2-R
- chronic SERT can desensitize 5HT1A and 5HT1B/D autoreceptors. 5Ht transmission is attenuated by increased 1A stimulation, chronic stimulation leads desensitized 1A-R causing firing to normalize.
82
AMPA and NMDA ratio
chronic AD treatment cause decrease in NMDA-R sensitivity, which increase AMPA expression. ADs shifts toward AMPA
83
side effects of SERT inhibition
anxiety: 5HT2A/C overactivation
suicidal: changes in 5HT2A transmission
sexual: 5HT1B/C
nausea: 5HT3
84
psilocybin in despression
fast acting, long lasting, blast 5HT2A-r stimulation
85
symptoms of anxiety
Fear and worry (sleep, concentration, fatigue, arousal, panic attacks)
86
Regulation of fear
overreactive connections between amygdala and Acc+OFC
87
Fear expression
expressed by motor avoidance (amygdala and PAG), increased cortisol (heart disease, diabetes), increasing respiration rate (PBN via amygdala), increased HR and BP (LC and amygdala)
88
characterization of anxiety disorders
excessive and aberrant responding under conditions of threat. Inflated estimates of probability and consequences = judgement bias
can be triggered by traumatic memories hippocampus activating amygdala
89
Fear is amygdala centered
emotional response to actual threat/stressor, quick, on-set, brief
panic, phobia
90
anxiety is CSTC centered
sustained emotional response to unpredictable threat
| anxious misery, obsessions
91
Cause of fear and worry
amygdala hyperactivity causing glutamate release
| BDZ, alpha2delta, SERT, 5HT1A-R reduce this
92
GAD (anxiety based)
generalized and persistent anxiety - not restricted to particular circumstances.
symptoms are nervousness, sweating, trembling
intolerance of uncertainty
dysregulated HPA axis, elevated cortisol, low GABAA-R
treated with: SSRI, SNRI alpha2delta ligands, 5HT1A-R partial agonist
93
PD (fear based)
recurrent panic attacks not restricted to particular circumstances
chest pain, choking, dizziness
No HPA dysregulation
SSRI, SNRI, alpha2delta ligands
avoidance maintained by cognitive appraisal
94
Phobia (fear based)
anxiety evoked in well-defined situations
focused on individual symptoms
SSRI, SNRI, alpha2delta ligands
beta-blockers may dampen blushing, tremor, nausea
95
PTSD (anxiety based)
reexperiencing and avoiding traumatic memories
traumatic stressor is criteria
due to decreased alpha2R sensitivity leading to increased cortical NE
sensitized HPA -> low cortisol
SNRI, SSRI, alpha-delta ligands, alpha1 antagonists prevents nightmares
96
OCD
recurrent obsessive thoughts, compulsive rituals, if resisted anxiety gets worse
97
buspirone is partial 5HT1A agonist
-
98
NE hyperactivation in anxiety
= anxiety, panic, tremor,
| treat with alpha1 or beta blockers
99
Fear extinction
progressive reduction of response to stimuli as VMPFC learns new context for feared stimuli. Produces GABA inhibition by activating glutamate neurons
100
fear conditioning
stressfull stimuli is relayed to amygdala and integrated with input from VMPFC and hippocampus. Amygdala may remember stimuli and increase efficiently of glutamate neurontransmission making future response more efficiently triggered.
101
MDMA in anxiety
reduce sense of fear by increasing 5HT2A-R, Ne, DA, alpha2 activation
102
Rem sleep is characterized by
motor atonia = due to sleep specific ACh activated inhibitory circuit
103
brain region allowing sleep
hypothalamus filtering out sensory transmission
104
wakepromoting neurotransmitters
5HT, NE, Ach, histamine
105
sleep promoting neurotransmitters
MCH, GABA, ACh, adenosine
106
high firing neurotransmitters in REM
ACh
107
high firing neurotransmitters in awake
ACh, 5HT, NE, H
108
Adenosine hypothesis
increases sleep. Accumulating extra cellular concentration during wakefulness. The increased concentration inhibits waker,oyinh cells, when this activity is sufficiently decreased sleep is induced. Concentration decrease during sleep.
109
Orexin neurons
```
located in lateral hypothalamus.
fire in awake, silent in asleep.
induce behavioral arousal
excites Ach neurons in wakefullness, 5HT, H, Ne all involved in wakefullness
= Arousal
```
110
MCH (melanin concentrating hormone)
in lateral hypothalamus
| increase REM duration, release GABA
111
wake promoting regions
LC, TMN, raphe
112
melatonin
SCN passes information onto pineal gland which synthesize and secrete melatonin, inhibited by light exposure
increases sleepiness, master clock for timing
113
insomnia
disruption of thalamic filters i CSTC loops
-> local thalamic GABA transmission deficient at night = massive sensory input
OR
stress activating HPA axis, increasing cortisol blocks sleep
114
consequences of sleep deprivation
increased BP, mood changes, elevated metabolic rate hyperalgesia
115
Sleep wake switch
in hypothalamus.
VLPO is sleep switch mediated by GABA
TMN is wake switch mediated by Histamine
116
Drugs for insomnia
GABAA-PAMs (BDZ, barbiturates, z-drugs), histamine drugs (H1 antagonism), melatonin (M1/M2 agonism)
117
EDS
problem with sleep/wake switch
| treated with wakefulness drugs like orexin agonists
118
Drugs causing sedation
histamine, anticholinergic, alpha adrenergic, 5Ht enhancers, melatonin-R agonists
119
Restless leg syndrome,e
cause of insomnia
urge to move legs, relieving pain, worsening at rest
ion deficiency
alpga2 agonistst, Da agonists, opioids, BDZ
120
sleep disturbance indicators
high NE and CRH
121
REM sleep behavior disorder
vigorous and injurious behavior in REM sleep,
122
Narcolepsy treatment
treated with GHB, midnafinil, amphetamine,
123
function of sleep
maintain healthy immune system (comprises immune system), metabolism (risk of metabolic syndrome), healthy cognition.
124
function of sleep
maintain healthy immune system (comprises immune system), metabolism (risk of metabolic syndrome), healthy cognition.
125
symptoms of ADHD
hyperactivity, impulsivity, sustained attention, selective attentive
126
selective attention in ADHD due to
unability to activate ACC this recruiting other regions (dysfunctional CSTC-loop)
127
Motor activity in ADHD due to
regulation by PFMC
| dysfunctional CSTC-loop
128
Sustained attention in ADHD due to
regulation by DLPFC
| dysfunctional CSTC-loop
129
Impulsivity in ADHD due to
regulation by OFC
| dysfunctional CSTC-loop
130
Insufficient NE/DA in ADHD
distracted, impulsive, poor judgement, impaired working memory,
131
Excessive NE/DA in ADHD
stressed, hyperactive, distractible, inattentive
132
Fine tuning signal-to-noise ratio in ADHD
hypofrontality in PFC for executive functioning.
NE increase sensitivity for relevant stimuli, DA decrease sensitivity for irrelevant stimuli
alpha2 and D1 receptors on dendritic spines gate incoming signals.
If HCN channel is open, signal leaks and is lost.
NE keeps channel closed, DA opens channel.
133
default mode network in ADHD
interrups task positive network during attention tasks
134
treatment of ADHD
methylphenidate, ampetamine, amoxetine, guanfacine, stimulants (normalize mesolimbic DA, reduce amygdala)
135
Reuptake transporters in PFC
low DAT, high NET
136
Reuptake transporters in NAcc
low NET, high DAT
137
Gate control theory
Abeta-fibers can disrupt sensation of pain, by exciting neurons that can inhibit pain carrying neurons by releasing GABA
138
Neuropathic pain
pain caused by lesion or disease of somatosensory nervous system
139
Abeta fibers
non-noxious, mechanical stimuli (myelinated)
140
Adelta fibers
noxious, chemical stimuli (myelinated)
141
C fibers
noxious, heat and chemical stimuli (unmyelinated)
142
Delaying discount in ADHD
decay of subjective experience of reward value, if reward delivery is delayed
- delays faster in impulsive
- challenges ability to tolerate delayed gratification.
lack of DA response to stimuli can cause distress and delayed gratification.
(less striatal response to reward anticipation in DA, more to reward delivery)
143
segmentral central sensitization
can increase pain as chronic firing in dorsal horn leads to exaggerated or prolonged response to inputs
144
suprasegmentral central sensitization
from peripheral injury
- thalamus or cortex amplifies pain
- pain can occur without peripheral input
145
Desccending NE and 5HT
can inhibit pain
146
treatment of neuropathic pain
TCA, SSRI, SNRI, anticonvulsants
147
inherent reward
intrinsic
148
not inherent reward
extrinsic
149
Intensifying hedonic experiences
DA release in NAcc
| can be stimulated by coke, my-opioid R
150
repeated opioid use
cause down regulation of my-opioid-R leading my tolerance and dependence
151
BDZ in addiction
disinhibit reward circuit, chronic use down regulate GABAA-R = tolerance and dependence
152
Alcohol
PAM at GABAA-R, chronic intake down regulate expression extrasynaptically -> leading to decreased excitability of neurons, chronic reduce baseline GABA transmission and increase glutamate,
stimulate my-opioid-R, Cb1 activation
153
Gateway hypothesis
alcohol, nicotine, cannabis are gateway drugs increasing risk of moving on to harder drugs
154
diagnostic criteria for addiction
impaired control, social impairment, risky use of substance, pharmacological criteria
155
Tolerance
reduction in drug effect, requiring increased dose to maintain effective dose
156
Dependence
response to a drug whereby removal gives unpleasant symptoms
157
Addiction
drug taker feels compelled to use drug and suffers from anxiety when separated
