Neuropharm Final Flashcards
(260 cards)
1
Q
what is pharmacology?
A
the scientific study of the actions of drugs and their effects on a living organism
2
Q
define pharacokinetics
A
how substances are distributed through the body
3
Q
define pharmacodynamics
A
interactions of the substance with a receptor
4
Q
define neuropharmacology
A
drug-induced changes in nervous system functions
5
Q
define psychopharmacology
A
drug-induced changes in mood, thinking, and behavior
6
Q
define neuropsychopharmacology
A
drug-induced changes in the nervous system that influence behavior
7
Q
what is a drug action?
A
a specific molecular change
drug binds to its target (receptor)
8
Q
what is a drug effect?
A
a more widespread/systemic change
9
Q
what are therapeutic effects?
A
desirable drug effects
10
Q
what are side effects?
A
undesirable drug effects?
11
Q
what are specific drug effects?
A
results from interactions btwn a drug and its target
12
Q
what are nonspecific drug effects?
A
include mood, expectations, perceptions, attitudes
13
Q
what is pharmacokinetics?
A
mechanisms involved in delivering a drug to its target, where it can have pharmacological effect
-administration
-absorption
-distribution
-elimination
—–metabolism and excretion
14
Q
what is bioavailability?
A
the amount of drug in the blood that is free to act on a specific target
–depends on absorption, distribution, elimination
15
Q
what are pharmacodynamics?
A
interactions btwn the drug and its target; mechanisms of drug action
16
Q
describe lipid-receptor interaction
A
–dynamic and reversible
–in a constant state of binding and breaking away
–follows the law of mass action
17
Q
how do you determine non-specific binding?
A
a very high concentration of unlabeled ligand is added, outcompeting the hot radioligand for specific binding sites
18
Q
what is an agonist?
A
drug that mimics the effect of the endogenous transmitter
19
Q
what is a partial agonist?
A
drug that cannot produce the full agonist response
20
Q
what is an antagonist?
A
drug that block the effect of the endogenous transmitter
21
Q
what is receptor affinity?
A
how tightly the receptor holds onto the drug
—lock and key mechanism
22
Q
what is drug potency?
A
the amount of drug necessary to produce a desired level of effect
23
Q
what is drug efficacy?
A
the maximum response produced by a drug
24
Q
what is a competitive antagonist?
A
“compete” w the agonist for binding to the agonist binding site
***high affinity for the agonist binding site, but no efficacy
25
what is a non-competitive antagonist?
bind to a site different from the agonist binding site
***negative allosteric modulation
26
a competitive antagonist shifts the dose-response curve to the _____?
right
27
what is another name for the myelencephalon?
medulla
28
what is another name for the mesencephalon?
midbrain
29
what brain structures make up the metencephalon?
cerebellum and pons
30
what brain structures make up the diencephalon?
thalamus and hypothalamus
31
what brain structures make up the telencephalon?
neocortex, basal ganglia, limbic system
32
describe ligand-gated ion channels
--ionotropic
--fast transmission
--no intermediate chemical steps
--directly changes membrane permeability
33
describe G protein-coupled receptor
--metabotropic
--slow activation
--long-lasting effects
--alters intracellular biochemistry
34
terminal autoreceptors are _____-modulating
release
35
somatodendritic autoreceptors are _______-modulating
activity
36
the morris water maze is a test of ________
spatial learning
37
the open field test is a measure of _______
motor activity
38
the delayed-response tests is a measure of ______
working memory
39
the light-dark box measures ________
unconditioned anxiety
40
the elevated plus-maze measures ________
unconditioned anxiety
41
the forced swim test measures _______
behavioral dispair
42
the sucrose preference test is a measure of _______
anhedonia, the inability to derive pleasure from normally pleasurable events
43
drug self-administration measures _______
reinforcement value of substances
44
define breaking point
point at which effort required exceeds reinforcing value-- the higher the breaking point, the higher the abuse potential
45
drug discrimination studies measure _____
how an animal experiences a drug
46
what are the ionotropic receptors for ACh?
nicotine
curare
47
what are the metabotropic receptors for ACh?
muscarine
atropine
48
what is the rate-limiting step of ACh synthesis?
choline uptake into nerve terminal
49
what does vesamicol do?
blocks VAChT
reduces amount of ACh released when the neurons fire
50
what does black widow spider venom do to ACh release?
massive release of ACh in the PNS
--muscle pain, tremors, nausea, vomiting, salivation, copious sweating
51
what does botulinum toxin do to ACh release?
inhibits ACh release
52
which drug is used to treat glaucoma?
physostigmine
53
which drug is used to treat myasthenia gravis?
neostigmine and pyridostigmine
54
does physostigmine cross the BBB?
yes!
55
do neostigmine and pyridostigmine cross the BBB?
nope!
56
what are the reversible AChE inhibitors?
donepezil and rivastigmine
57
what are organophosphates?
irreversible AChE inhibitors
***insecticides
***nerve agents
58
describe the nAChR
5 subunits are arranged around a central pore
-each subunit has 4 TMDs
59
homomeric nACh receptor is permeable to which ion?
calcium!
60
what is an agonist for nAChR?
nicotine
61
what is an antagonist for nAChR?
curare
62
describe the mAChR
M1-M5
63
what is an agonist for mAChR?
muscarine
64
what is an antagonist for mAChR?
atropine
scopolamine
65
what does ACh do in cognition?
memory consolidation
sensory attention
behavioral arousal
66
deficits in ACh signaling are involved in _______
dementia
67
mACh receptor antagonists are ______ and impair performance on ______
amnestic
learning tasks
68
ACh synthesis
choline + acetyl CoA
----choline acetyltransferase
acetylcholine
----acetylcholinesterase
choline + acetic acid
69
what is the most abundant excitatory neurotransmitter in the brain?
glutamate!
70
glutamate synthesis
glutamine
----glutaminase
glutamate
----glutamine synthetase
glutamine
71
what is the most abundant inhibitory neurotransmitter in the brain?
GABA
72
ionotropic glutamate receptors
NMDA
AMPA
KA
73
metabotropic glutamate receptors
group 1 (1 and 5)
group 2 (2 and 3)
group 3 (4, 6, and 7)
74
which iGlu receptors are permeable to ca2+?
NMDA
AMPA lacking GlueA2
75
properties of NMDA receptors
ligand-gated ion channels, requiring co-agonists glu and gly
voltage gated
--removal of Mg2+ block
76
GABA a ionotropic receptors
permeable to Cl- leading to hyperpolarization
two alpha, two beta, and one gamma subunit
77
what is a GABA binding site agonist
muscimol
78
what is a GABA binding site competitive antagonist
bicucculine
79
GABA b receptors are ______
metabotropic
80
what do postsynaptic GABAb receptors do
open k+ ion channels
inhibition of AC/ decrease cAMP
81
what do presynaptic GABAb receptors do
autoreceptors, heteroceptors
inhibition of Ca2+ channels
inhibition of AC/ decrease cAMP
82
what are positive allosteric modulators for GABA a
benzodiazepines
barbiturates
neurosteroids, EtOH, Anesthetics
83
what are negative allosteric modulators of GABAa
pictrotoxin
84
behavioral effects due to a-1
sedation (Ambien)
85
behavioral effects due to a-2/3
anxiolytic (Xanax)
86
behavioral effects of a-5
amnestic
87
how do you obtain tyrosine?
In diet
88
catecholamines synthesis
tyrosine --(TH/Fe2+, O2, BH4)---> L-DOPA --(AADC/vitamin b6)--> dopamine --(DBH/cu2+, o2, ascorbic acid)--> norepinephrine --(SAM)--> epinephrine
89
what is the rate-limiting step in catecholamine synthesis?
TH
90
AMPT
TH inhibitor
91
Reserpine
irreversible VMAT inhibitor
92
tetrabenazine, deutetrabenazine, valbenazine
reversible VMAT inhibitor
93
6-OHDA and MPTP
DA neurotoxins
94
amphetamine
catecholamine releaser and reuptake blocker
95
cocaine
catecholamine reuptake blocker
96
what is a noradrenergic alpha2 autoreceptor agonist
clonidine
97
what is a noradrenergic alpha 2 autoreceptor antagonist
yohimbine
98
where is the nigro-striatal pathway located and what is it in control of?
substantia nigra
activation, motivation, cognition
99
where is the mesolimbic system located and what is it in charge of?
VTA
behavioral arousal, reward learning
100
where is the mesocortical system located and what is it in charge of?
VTA
attention, working memory
101
where is the tuberohypophyseal system located and what is it in charge of?
hypothalamus
prolactin release
102
what do the D1 and D5 receptors do?
increase cAMP
Gs coupled
stimulate adenylyl cyclase activity
103
what do D2, D3, D4 receptors do?
decreases cAMP
Gi coupled
inhibit adenylyl cyclase activity
increase gk, hyperpolarize
104
methylphenidate
catecholamine reuptake blocker
105
apomorphine
nonselective D1 and D2 receptor agonist
106
SKF 383393
D1 receptor agonist
107
DETQ
D1 receptor positive allosteric modulator
108
Quinpirole
D2/D3 receptor agonist
109
bromocroptine, pramipexole, ropinirole, rotigotine
D2/D3 receptor agonist
110
SCH 23390
D1 receptor antagonist
111
Haloperidol
D2 receptor antagonist
112
DA regulates _______ along a continuum
behavioral activation
113
reducing da synthesis ______ behavioral activation?
impairs
114
what happens when reserpine blocks VMAT
sedation in animals
depression in humans
115
what happens when AMPT blocks TH activity
associated with relapse into depression following positive response to antidepressant medication
116
what happens following a bilateral central lesion?
sensory neglect
motivational deficits
parkinsonian motor deficits
117
what happens after a unilateral 6-OHDA lesion to the SNpc
loss of DA input to lesion side, however DA continues to release behavior on intact side
118
adrenergic agonists in the LH promote ______
wakefulness
119
adrenergic input to the PFC can improve or impair _______
working memory
120
how do a2-AR agonists like guanfacine and clonidine affect performance of delayed task resonse?
improve
121
does a1-AR have a high or low affinity for NE?
low
122
serotonin synthesis
tryptophan --(TPH2/fe2+, 02, BH4)--> 5-HTP --(AADC/ vitamin B6)--> 5-HT
123
what is the rate limiting step in serotonin synthessi
TPH
124
what happens with TRP depletion
induces symptoms in people with major depression
125
what does PCPA do?
blocks 5-HT synthesis by irreversibly inhibiting TPH
126
5-HT is loaded into vesicles by ______
VMAT2
127
what kind of receptors at 5-HT 1B/1D
terminal autoreceptors
128
what kind of receptors are 5-HT1A receptors
somatodendritic
129
what do 5-HT 1b/1d terminal autoreceptors do
inhibit 5-HT release
decrease Ca2+ influx
decrease cAMP
130
what do 5-HT 1a somatodendritic autoreceptors do
opens K+ channels, hyperpolarizing Vm
decrease neural activity
important in psychopharmacology of SSRIs
131
SERT
5-HT transporter
target of SSRI, cocaine, and MDMA
132
MAO-A
enzymatic degradation
5-HIAA is major metabolite
133
para-chloroamphetamine and fenfluramine
5-HT releaser
134
MDMA
5-HT releaser
135
buspirone
5-HT1a partial agonist
136
what other condition is MDMA used for?
PSTD
137
where are majority of 5-HT neurons found in the CNS?
raphé nuclei
138
8-OH-DPAT
5-HT1a full agonist
139
WAY-100635
5-HT1a antagonist
140
DOI
5-HT2a agonist
141
LSD
5-HT2a agonist
142
katanserin and ritanserin
5-HT2a antagonist
143
triptans
5-HT1b/1d agonists
144
lasmiditan
5-HT1f agonist
145
how is territorial aggression tested on animals
resident-intruder tests
146
impaired 5-HTergic signaling ______ behavioral aggression
increases
147
what is the 5-HT Deficiency Hypothesis
impaired 5-HTergic signalling increases behavioral aggression
148
5-HT1a _______ are anxiolytic
partial agonists
149
5-HT1b and 5-HT2c agonists do what to behavior?
reduce feeding
150
what is addiction?
a chronic, relapsing behavioral disorder
151
describe the impulsive stage of addiction cycle
binge intoxication
pleasurable effects
abstinence neutral affect
reward craving
152
describe the compulsive stage of drug addiction
prolonged intoxication
relief
protracted abstinence negative affect
relief craving
153
what are the rewarding properties of drug abuse
the positive experience associated with the drug
the "high"
154
what are the positively reinforcing properties of drug abuse
consuming the drug strengthens whatever preceding behavior was performed
how hard an animal will work for a drug
155
rewarding properties of drugs are commonly evaluated using which two animal tests?
place conditioning
electrical self-stimulation
156
withdrawal from ethanol _____ threshold for electrical self-stimulation of reward pathway
increases
157
how is relapse to drug use modeled
reinstatement
158
how is reinstatement performed in animals?
CS's, stress, or drug exposure
159
describe the impulsive stage
driven by positive reinforcement, drug reward properties
activation of the reward circuit
160
describe compulsive stage
driven by negative reinforcement; removal of negative stimuli
recruitment of anti-reward circuitry
161
what brain regions are in reward pathway
VTA
Nuc. Acc
162
what brain regions are involved in antireward pathway
CaA, BNST
LC
163
PFC dysfunction in addiction is characterized by
intrusive thoughts
craving
poor impulse control
164
cocaine-HCl
oral, intranasal, IV
vulnerable to heat
165
free base cocaine
dissolve in H2O, NaHCO3
heat & dry = "crack"
166
lipophillic cocaine
easily crosses BBB
167
metabolites for cocaine
benzoylecgonine
coc+EtOH --> cocaethylene
168
what are the drug actions for cocaine
inhibit NT transporters
--high affinity for NET and SERT
increased DA release independent of DAT
--inhibition of NET in PFC drives excitation of VTA
169
m/AMPH drug actions
enters DA nerve terminals by DAT uptake, provoking release from synaptic vesicles into cytoplasm
DAT functions in reverse, releasing DA into extracellular fluid
170
what are the behavioral effects of cocaine?
1. euphoric high
2. behavioral activation (repetitive stereotyped behaviors, locomotion, rearing, sniffing)
3. sympathetic arousal (tachycardia, vasoconstriction, hypertension, hyperthermia)
171
psychostimulant microinjection into the Nuc. Acc. induces what behavioral effect?
increase locomotor behavior
172
psychostimulant microinjection into dorsal striatum induces what behavioral effect?
increase stereotyped behaviors
173
6-OHDA lesion in Nuc. Acc induces which behavioral effect?
decreased locomotor
174
6-OHDA lesion in dorsal striatum induces which behavioral effect?
decreased stereotyped behaviors
175
true or false: COC-insensitive DAT-ki mice do not self-administer cocaine
true
176
Do D1 KO mice self-administer cocaine?
no
177
do D2 or D3 KO mice self-administer cocaine?
yes
178
once-daily, intermittent administration of cocaine results in _______
sensitization
179
continuous cocaine administration results in _______
tolerance
180
what does chronic cocaine use do to the brain?
decreased gray matter volume
hypofunction of PFC
181
what are the names of natural opiates?
morphine, codeine, thebaine
182
postsynaptic inhibition of endogenous opioids
opens k+ channels
183
axoaxonic inhibition of endogenous opioids
close Ca2+ channels
184
presynaptic inhibition of endogenous opioids
reduce transmitter release
185
what are the PNS effects of opioids?
pinpoint pupils
vomiting
cough suppression
constipation
186
how does death by opioids occur?
respiratory depression
cardiac depression
187
what are the three symptoms of "opioid overdose triad"
pinpoint pupils, unconsciousness, respiratory depression
188
what do 6-OHDA lesions do to self-administration for opioids?
reduce, but not stop completely
189
injection of naloxone into which brain structure produces the physiological symptoms of WD?
LC/ PAG
190
injection of naloxone into which brain structure produces the aversive properties of WD?
N.Acc
191
ethanol synthesis
alcohol --(alcohol dehydrogenase/NAD)--> acetaldehyde --(aldehyde dehydrogenase/NAD)--> acetic acid --(oxidation reaction)--> carbon dioxide
192
in acute tolerance, effects of alcohol are _____ during the elimination phase
reduced
193
how does EtOH interact w GABA receptors?
increases Cl- flux through GABAa receptors
194
how does EtOH interact w glutamate receptors?
EtOH inhibits iGlu receptors, decreasing release.
195
how do blackouts occur?
acute EtOH inhibits NMDA receptors and decreases LTP
196
what is wet brain
EtOH induced excitotoxic damage
197
chronic EtOH associated with _____ of alpha1 and ______ of alpha 4 and 6
down-regulation
up-regulation
198
what are the two THC metabolites?
11-OH-THC
THC-COOH
199
what is the half life of THC
20-30 hours
200
what are the two endocannabinoids
anandamide
2-AG
201
anandamide
CB1 partial agonist
degraded by FAAH
202
2-AG
full, nonselective CB1 and 2 agonist
degraded by MAGL
203
what converts DAG to 2-AG
DAG Lipase
204
retrograde signaling by endocannabinoids is involved in ______
synaptic plasticity
205
what are CP-55,940 and WIN 55,212-2
full CB1 and 2 agonists
206
what is SR 141716A
selective CB1 antagonist
207
what is Epidiolex
first FDA-approved drug that contains a purified drug substance derived from cannabis
--lennox-gastaut syndrome
--dravet syndrome
208
CB1-R in VTA
hyperpolarize IN
decrease GABA release
increase VTA firing
increase dopamine release
209
prazosin
alpha1-AR antagonist
increases peripheral vasodilation
reduces nightmares in PTSD
210
propranolol
beta-AR antagonist
negative chronotropic and negative ionotropic effects on heart
reduces performance anxiety in social anxiety disorder
211
5-HT1a autoreceptors
dorsal and median raphé
inhibit neuronal firing and 5-HT release
agonists are anxiolytic
212
5-HT postsynaptic receptors
hippocampus and amygdala
emotional and cognitive aspects
agonists are anxiogenic
213
short allele
smaller amygdala and sgACC volume
increased amygdala activity
greater symptom severity in anxiety disorders
214
early elevated 5-HT
short allele is low-expressing
SERT KO are more anxious
215
what are benzodiazepines
positive allosteric modulators of GABA a receptors
216
long-acting BZD
metabolites are psychoactive
librium
valium
217
short(er)-acting BZD
metabolized in one step
xanax
ativan
klonopin
218
short-acting BZD
rohypnol
versed
219
neurontin and Lyrica
anticonvulsants
block active calcium channels
reduces excitatory neurotransmission
off-label use
220
how to view anhedonia in animal models
sucrose preference
221
how to view anxiety in animal models
novelty-suppressed feeding
222
what is the specific action of TCAs
inhibit NET and SERT
223
what are the HAM side effects and how are they caused?
***caused by off-target sites antagonism
H1- sedation/fatigue, weight gain
a-AR - hypotension, arrhythmia
mACh - dry mouth, constipation, dizzy
224
fluoxatine
"activating"
5-HT2c antagonist
225
sertraline
"activating"
DAT blockade
226
paroxetine
anxiolytic
NET blocker
anti-cholinergic
227
lexapro
the purest SSRI
228
trazodone and nefazodone
multi-action AD, used for sedative properties
serotonin antagonist and reuptake inhibitor
sedating (H1) effective in insomnia
antagonism reduces SSRI side effects, though priapism is possible
229
effexor
SNRI
selectively boosts DA in PFC
230
duloxetine
SNRI
AD in absence of pain
231
fetzima
SNRI
232
which two dual-action ADs have the lowest incidence of sexual dysfunction?
wellbutrin and mirtazapine
233
viibryd
5-HT1a partial agonist
234
trintellix
5-HT1a antagonist
235
zulresso
PPD
positive modulator for GABAa receptors
continuous IV infusion over 60 hours
236
spravato
nasal spray used in conjunction w AD
237
acute AD administration _____ release of 5-HT
reduces
238
ketamine
non-competitive NMDA receptor antagonist
239
what is necessary for ketamine to be an effective AD?
dendritic spines
240
what is the name of the phenothiazine
chlorpromazine
241
what is the name of a butyrophenone
haloperidol
242
describe neuroleptics
D2 receptor antagonists
effective antipsychotics
significant side effects
****EFFECTIVE IN TREATING POSITIVE SYMPTOMS
243
nigrostriatal pathway function w neuroleptics
EPS side effects
244
meso-limbic pathway function w neuroleptics
antipsychotic efficacy
245
tubero-hypophyseal pathway function w neuroleptics
endocrine side effects
246
clozapine
effective atypical antipsychotic for 1/3 people non-responsive to neuroleptics
EPS side effects are less severe
reduces risk of suicide
247
side effects of clinical use of clozapine
loss of WBCs
substantial weight gain
reduced seizure threshold
248
what do atypical antipsychotics have high affinity for
5-HT2a antagonists
249
2 pips and a rip
D2 partial agonist
5-HT1a partial agonist
adjunct in MDD
abilify
rexulti
250
peens and dones
depressive episodes in BD
quetiapine
lurasidone
251
T/F: CRF acts as both a hormone and a neurotransmitter
true
252
T/F: inhibitions of the LC can elicit alerting and fear responses in animals
false
253
T/F: the role of serotonin is not entirely clear bc some serotonin receptor subtypes can have opposite effects on anxiety
true
254
T/F: barbiturates are not commonly used for the treatment of insomnia bc they can induce dependence and can be lethal in overdose
true
255
T/F: some BZD, such as valium and librium, are long-acting anxiolytics bc they have active metabolite
true
256
In general, the addiction potential of a drug is positively correlated with its
a. duration of action
b. speed of onset
c. ability to cause relapse
d. all of the above
b. speed of onset
257
T/F: drug self administration studies typically produce a dose-response curve that is sigmoid shape
false
258
an increased threshold for electrical self-stimulation during withdrawal from alcohol is generally interpreted to indicate a(n)
a. state of intoxication
b. increase sensitivity of the reward circuit
c. state of craving
d. decrease in sensitivity of the reward circuit
d. decrease in sensitivity of the reward circuit
259
Koob and Le Moal propose that after repeated bouts of intoxication and withdrawal, drug use is driven by
a. rewarding properties of the drug
b. negative reinforcement
c. prefrontal cortex deficits
d. the reward circuitry
b. negative reinforcement
260
which of the following structures are part of the proposed circuitry involved in the rewarding and reinforcing effects of abused drugs?
a. amygdala
b. PFC
c. nuc. acc.
d. ventral pallidum
e. all of the above
e. all of the above
