Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuropsychopharmacology > Whole bloody module > Flashcards

Whole bloody module Flashcards

1
Q

Benzodiazepines

A

Diazepam, Flunitrazepam

Positive allosteric modulators of GABAa Receptor

Bonds to BZ site, on alpha-gamma interface, dependant on H101 residue

Does not bind to alpha-4,6 isoforms as residue it R101

Anxiolytic, insomnia, epilepsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Barbiturates

A

Pentobarbital

Positive Allosteric Modulator of GABAaR, agonist at higher doses

Anxiolytic, anticonvulsant, insomnia, epilepsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Bicuculline

A

GABAaR competitive antagonist

Excitatory, mimics epilepsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

a1-GABAaR

A

Mediates sedation, anti-convulsion and addiction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

a2-GABAaR

A

Anxiolytic, muscle relaxant, additive?

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

a3-GABAaR

A

Muscle relaxant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

a5-GABAaR

A

Amnesia (Cognition), muscle relaxant

NAMs promote cognition

Expressed extrasynaptically in hippocampal CA1 neurons, media’s tonic current

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

L655,708 (a5IA or R0493851)

A

Binds to a1,2,3,5 GABAaRs

NAM/IA of a5-GABAaR, no affect on a1,2,3

Benzodiazepine antagonist of a1,2,3

Cognitive enhancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

GABA phasic and tonic inhibition

A

Phasic Mediated by synaptic GABAaRs by triggered neurotransmitter release
(Seen as individual spikes or hyperpolarisation)

Tonic mediated by extrasynaptic GABAaRs, and also GABAbRs to some extent, residual GABA in ECF mediates this
(Seen as a constant hyperpolarisation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

H101R Mutation

A

Causes loss of benzodiazepine-sensitivity in a1,2,3,5-GABAaRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

R101H Mutation

A

Causes gain of benzodiazepine-sensitivity in a4,6-GABAaRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Heat hyperalgesia

A

Paw withdrawal upon exposure to defined radiant heat,

Measure paw withdrawal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Mechanical sensitisation

A

Mechanical stimulus used, Von Frey filaments of varying size used to spike foot. Measures paw withdrawal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cold allodynia

A

Time spent lifting, shaking or licking paw after drop of acetone on an injured paw

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

a2-GABAaRs expressed densely in:

A

Lamina II/III

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Inflammatory pain model

A

Zymosan A

Injected into hind paw, assessed by measuring paw withdrawal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Neuropathic (chronic) pain Model

A

Sciatic nerve tie off

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

L838,417

A

GABAa selective PAM

Acts as partial agonist/PAM of a2,3,5-GABAaR

NAM/IA of a1-GABAaR

Analgesic, anxiolytic

No sedative effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How to assess affinity and efficacy of GABA drugs?

A

Transcription with particular GABAaR DNA, then either:

Measure binding affinity by homogenising and using radioligand binding assay

Measure efficacy by using whole-cell-clamp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Tests for Anxiety

A

Elevated plus maze
Light/dark maze

Common component of many neurological disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Tests for fear

A

Cued fear conditioning (amygdala)
Contextual fear conditioning (amygdala and hippocampus)

PTSD, phobias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Tests for attention (human)

A

Wisconsin Card Sort
Behavioural flexibility test

Schizophrenia, ADHD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Test for attention (mouse)

A

Attentional set-shifting

Dependant of prefrontal cortex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Depression

A

Learned helplessness

Tail suspension test
Forced swim test

Dependant on anterior cingulate cortex

Depression, bipolar disorder, OCD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Locomotor Activity

A

Activity box

Parkinson’s disease, muscular atrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Locomotor coordination

A

Rotarod
Skilled reaching
Balance beam

Parkinson’s disease, Huntington’s disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Sensory perception

A

Von Frey Test
Temperature sensitivity

Pain in Parkinson’s disease, chronic pain (neuropathic pain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Learning

A

Morris water maze
Radial arm maze
Pair-associated learning

Autism, amnesia, Alzheimer’s disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Memory

A

Spontaneous alteration
Novel object recognition

Autism, amnesia, Alzheimer’s disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Procedural memory

A

How?

Striatum dependant

Not usually effected in most neurological disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Declarative memory

A

What?

Semantic (facts)

Episodic (events)

Usually affected by Parkinson’s disease, Alzheimer’s disease and dementia

Dependant on hippocampus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Translational

A

Trained to mimic human test

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Naturalistic

A

Uses relevant or innate skill or preference of the animal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Radial arm maze

A

Reference memory - which arms are baited

Working memory - which arms have already been visited in the current trial

Require food and animal scent controls

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Barnes Maze

A

Holes around edge with one leading to home box

Controls for odour and scent required, as well as proximal cues (objects) for animal to reference

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Morris Watermaze

A

Opaque water with one platform

Naturalistic and rats swim to escape cold water

No scent controls required
Proximal cues required

Human analogue is being shown a position on a computer screen, then entering a 3D arena eg tent, and placing object on the same spot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Pair Associated Learning (human)

A

Pairs shown, humans must recall other object after being shown one half

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Pair associates learning (mouse, naturalistic)

A

Choice trial

Mouse searches arena with hole in it and eventually finds ‘food x’, mouse repeated this and finds ‘food y’ at different location
Mouse can then be cues by food x or food y to go to the specific burial spot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Pair associated learning (mouse, translational)

A

Mouse is trained to use touchscreen exactly the way humans do,

Require a lot of training

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Phase I trials

A

Safety in healthy humans

1-2 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Phase II trails

A

Efficacy of treatment

2-5 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Phase III trials

A

Large scale study of efficacy and safety

3-10 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Phase IV trials

A

Ongoing review of safety in the very long term in real patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Drug discovery phase

A

High-throughput screening of compounds on target receptor

Narrowing down and refinement of successful candidates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Preclinical development

A

Pharmacokinetic optimisations

46
Q

What scale to use for plotting concentrations?

A

Logarithmic

47
Q

How to shiver logarithmic concentrations?

A

Serial dilution

48
Q

High-Throughput Screening

A

Thousands to millions of chemicals in library

Screening of ligands hypotheses to have an effect by computational studies

TR-FRET used with europium labelled antibody

~1% hit rate

49
Q

TR-FRET

A

Time resolved fluorescent energy transfer

50
Q

Z’ factor

A

Tests robustness of assay

Z>0.6 = excellent
0.6>Z>0.3 = workable
Z<0.3 = not workable
51
Q

Assays should be:

A

SRRM

Simple
Robust
Relevant
Miniaturisable

52
Q

How to identify a ligand’s mechanism?

A

Concentration-response curve and compare it to natural ligand

53
Q

Fraction bound =

A

Fraction bound = [D]/([D] + Kd)

54
Q

Linear regression:

Y =

A

Y = 1/(1+(Kd/x))

55
Q

How to calculate geometric mean:

A

GM = ‘cube route’(a x b x c)

56
Q

pKd =

A

pKd = -log(Kd)

57
Q

siRNA

A

Can knockdown expression of genes

58
Q

First order elimination

A

Is a straight line on log plot

59
Q

Kel =

A

Kel = ln(2)/(t1/2)

60
Q

Volume of distribution

Vd =

A

Represents what volume the drug would have to be distributed in to give the observed plasma concentration

Vd (L) = dose (mg) / concentration (mg/L)
Usually related to body weight!

Vd (L/kg) = dose (mg/kg) / concentration (mg/L)

0.05L/kg = blood volume
0.3kg/L = extracellular water volume
0.5-2L/kg = broad distribution
>2L = accumulation in tissue

61
Q

Clearance

Cl =

A

Cl = Kel , Vd

Therefore
Cl = (ln(2) . Vd) / (t1/2)

62
Q

Free drug hypothesis

A

Pharmacological activity is dependant on free drug

Things affecting free drug conc are:
Membrane
Lipids
Protein

63
Q

Partition coefficient
Kp =
Kp u.u =

A

Kp = brain conc / plasma conc
If over 1 then higher concentration in brai

Kp u.u = unbound brain conc / unbound blood conc

Better measure of brain penetration as it takes into account brain has 20x more lipid and half the amount of protein, so free drug can be affected greatly

64
Q

Transcellular

A

Flow through cell

More hydrophobic compounds, active transport can contribute

65
Q

Paracellular

A

Flows through gap between cells,

Usually small molecular molecule/ions, hydrophilic compounds

In BBB this gap is very tight due to tight junctions formed by caludins and occludins, so it is inhibited

66
Q

The effect of CSF?

A

Quite negligible as blood:CSF interface is 5000x smaller than blood:brain

67
Q

Blood Brain Barrier

A

Important to protect ionic concentrations in CNS to maintain neuronal function.

Complex structure of endothelial, astrocyte and pericyte cells

Allows distribution of very small molecules such as dissolved gasses

Has active uptake mechanisms for glucose and amino acids

68
Q

P-Glycoprotein (P-gp)

A

Endothelial ATPases which active pump molecule back out to prevent transcellular permission

Only on apical side of cell (blood)

69
Q

PAMPA assay

A

Parallel artificial membrane permeability assay

Uses hexadecane membrane

Can be converted to use a cell monolayer

70
Q

Measuring P-gp activity

A

MDCK cells expressing P-gp monolayer used to separate two fluids, Concert measured on each side to calculate an efflux ratio

Passive diffusion should have ratio of ~1, if P-gp is pumping it out (higher conc in apical fluid), then ratio will be >1

71
Q

Measuring CNS penetration in humans

A

Conc in CSF approx equal to conc in brain ISF, as there are minimal barriers, it can give a good indication

Only accurate if active transport does not take place
Sampling is invasive

72
Q

Positron Emission

A

Proton from unstable parent nucleus degrades into a neutron (beta decay), emitting a positron and neutrino.

Electron and positron collide and annihilate one another, this emits two antiparallel photons (gamma waves)

PET detector reads photos emitted, signal requires co-incident if both photons - it allows for mapping of location

Isotopes that decay by beta positive decay include: C11, N13, O15, F18

Short lived, therefore radioisotopes have to be prepared on site.

73
Q

Epilepsy definition

A

Group of CNS disorders in which recurrent seizures occurs due to chronic underlying processes, affecting motor, sensory and autonomic outputs

Seizures are paroxysmal events, due to abnormal synchronous discharges from a population of CNS neurons

74
Q

Idiopathic epilepsy (primary)

A

Cannot be ascribed to particular cause or incident

Eg benign neonatal convulsions or juvenile myoclonic epilepsy

75
Q

Symptomatic epilepsy (secondary)

A

Associated with trauma, neoplasm (abnormal growth), infection, developmental abnormalities, cerebrovascular disease.

76
Q

Generalised epilepsy

A

Eg grand mal or petit mal

77
Q

Focal epilepsy

A

Eg partial seizures

78
Q

EEG use

A

Electroencephalograph, records brain waves

79
Q

Simple partial seizure

A

No impairment of consciousness, can be confined to single muscle group/limb.

Brain locus is identifiable

KCNA1 mutation

Treated with:
Gabapentin - Ca v channel alpha2-delta, increases GABA biosynthesis by up GAD and up BCAT
Vigabatrin - inhibits GABA transaminase, half life of biological activity longer than elimination half life and levels of GABA-T take up to 6 days to recover

80
Q

Complex partial seizures

A

Consciousness impaired, confusion and stumbling, with automatisms resembling ticks

Treated with:
Gabapentin - Ca v channel alpha2-delta, increases GABA biosynthesis by up GAD and up BCAT
Vigabatrin - inhibits GABA transaminase , half life of biological activity longer than elimination half life and levels of GABA-T take up to 6 days to recover

81
Q

Partial seizures secondary generalised

A

Partial seizure followed immediately my generalised tonic-clonic seizure

Treated with:
Gabapentin - Ca v channel alpha2-delta, increases GABA biosynthesis by up GAD and up BCAT
Vigabatrin - inhibits GABA transaminase, half life of biological activity longer than elimination half life and levels of GABA-T take up to 6 days to recover

82
Q

Generalised tonic-clonic seizures

A

Aka grand mal

Tonic rigidity followed by tremor
Clinic phase relaxations are longer causing muscle jerking

Treated by:
Levetiracetam - binds to synaptic vesicles glycoprotein SV2A and inhibits presynaptic Ca2+ channels reducing neurotransmitter release

83
Q

Absence seizure

A

Aka petit mal

10-45s, up to 100 a day.
Altered consciousness, mild clonic spasms may occur.
Automatisms May confuse diagnosis with complex partial.
Start in childhood and patients often suffer mental retardation.

Treated by:
Ethosuxamide - inhibit T type Ca2+ channels in thalamic neurons, inhibit Na+ v channels
Valproate - increase Na+ channel inactivation, inhibit T type Ca2+ channels, inhibit GABA breakdown

84
Q

Atonic seizure

A

Sudden loss of posture leading to collapse

85
Q

Myoclonic seizure

A

Isolated clonic jerks associated with multiple spikes in EEG, rhythmic series of clonic seizures

Treated by:
Ethosuxamide - inhibit T type Ca2+ channels in thalamic neurons, inhibit Na+ v channels
Levetiracetam - binds to synaptic vesicles glycoprotein SV2A and inhibits presynaptic Ca2+ channels reducing neurotransmitter release

86
Q

Infantile Spasms

A

Syndrome of bilateral attacks of tied recurrent myoclonic jerks.
90% of patients have attacks before 1 year of age

87
Q

Status Epilipticus

A

Continuous or repetitive seizure over 30 mins in durations
Inadequate treatment results in brain damage or death
Can occur by non-compliance with treatment program, or by medicated patients suffering fever/infection which can lower serum drug conc
Can be induced by sudden withdrawal of benzodiazepines or barbiturates

88
Q

Epileptic recruitment of surrounding neurons

A

Raised K+ conc in ECF causing depolarisation
Raised Ca2+ in presyanptic terminal causing neurotransmitter release
Depolarisation-induced NMDAR activation increasing intracellular Ca2+ conc

89
Q

Maximal shock test

A

Model for partial and tonic-clonic
Also, pilocarpine (mAChR antagonist) administered for 14 days
Ameliorated by phenytoin

90
Q

Pentylenetetrazol-induced clonic seizure

A

GABAaR antagonist

Model for generalised seizures, especially absence

91
Q

Minimal metrazol-induced Seizures

A

Model myoclonic seizures

92
Q

Electrical kindling

A

Model for complex partial seizures

Repeated focal electrical stimulation

93
Q

Mouse models

A

Star-gazer
Lethargic
Tottering

Models for generalised seizures (similar to PTZ)

94
Q

Juvenile Myoclonic epilepsy

A

nAChR alpha7 subunit

95
Q

Autosomal dominant nocturnal frontal lobe epilepsy

A

nAChR alpha 4, beta 2 subunit

96
Q

Generalised epilepsy with Febrile seizures

A

GABAaR alpha 1, gamma 2, delta subunits

97
Q

Generalised epilepsy with Febrile seizures with broader APs

A

Na+ channel 1A, 1B, 2A subunits

98
Q

Benign familial neonatal convulsions

A

KCNQ2/3

99
Q

Partial epilepsy/episodic atoxia

A

KCNA1

100
Q

Only inhibitory neurons have:

A

GAD - GABA decarboxylase

101
Q

Clonazepam

A

Benzodiazepine used against absence and some tonic and clonic/myoclonic seizures

102
Q

Additional mechanism for epilepsy to occur and be treated:

A

BBB leakage allows albumin to enter brain ISF, bind to astrocyte TGFb, results in downregulation of inward-rectifying K+ channels, causing hyperexcitability

Decreased expression of glutamate transporters EAAT-1,2 occurs in brain after seizure

Seizure can induce inflammation by cytokines production and brain-derived neurotrophic factor (BDNF) can sustain hyperactivity

E-prostanoid-2 receptor antagonists can help prevent neuronal injury after status epilipticus

Astrocytic adenosine kinase degrades adenosine, which is a neuron derives-anticonvulsant, this can be inhibited

mTOR inhibition with rapamycin

Seizure induced expression of P-glycoprotein can limit effectiveness of drug therapy

103
Q

Phenytoin

A

Block tetanus firing through increasing Na+ channel inactivation

Reduced neurotransmitter release

104
Q

Carbamazepine

A

Block titanic firing through increased Na+ channel inactivation

Potentiates GABA response

Tricyclic antidepressant

105
Q

Valproate

A

Block titanic firing through increased Na+ channel inactivation

Inhibit T-type Ca2+ channel

Inhibit GABA breakdown

Used against absence seizures

106
Q

Ethosuxamide

A

Inhibits T-type Ca2+ channel

Inhibits Na+ v channels

Used to treat absence and myoclonic seizures

107
Q

Lamotrigine

A

Na+ v channel blocker

Inhibits release of excitatory amino acids
Phenytoin, primidone, carbamazepine reduce t1/2, valproate increases t1/2

108
Q

Topiramate

A

Blocks Na+ channels

Inhibits Kainate receptors

Enhances GABA action

Also anti-migraine

109
Q

Gabapentin

A

Ca v channel alpha2-delta,

Increases GABA biosynthesis by up GAD and up BCAT

Little protein bound or metabolised (interacts with cimetidine, Mg and Al antacids

Used to treat partial seizures with or without secondary generalisations

Also use in chronic pain management

110
Q

Vigabatrin

A

inhibits GABA transaminase

half life of biological activity longer than elimination half life and levels of GABA-T take up to 6 days to recover

Reduces plasma conc of primidone

Used to treat partial seizures

111
Q

Levetriacetam

A

Binds to synaptic vesicle protein SVA2

Inhibits presynaptic Ca2+ channels

Reduces neurotransmitter release

Used to treat partial onset, myoclonic or tonic-clonic seizures

112
Q

Acetazolamide

A

Carbonic anhydride inhibitor

Reduces local pH to decreased NMDAR activity

Used to treat menstrual related epilepsy and refractory epilepsy

Neuropsychopharmacology (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions