Brainscape's Knowledge GenomeTM

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


See full index

Pharm 2A > Conditions and their neurotransmitter systems > Flashcards

Conditions and their neurotransmitter systems Flashcards

1
Q

What is myasthenia gravis

A

muscle weakness due to block of ACh at the NMJ

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

What neurotransmitter system is primarily involved in epilepsy

A

GABA/glutamate

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

What is epileptiform activity

A

overexcitability of a single neuron - may be due to up-regulation of glutamatergic transmission or down-regulation of GABAergic transmission

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

What is paroxysmal depolarising shift

A

extended depolarisation at each action potential firing - easier for subsequent action potential firing (similar to activation of NMDA receptor)

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

What are the 6 possible sites for pharmacological intervention for epilepsy

A
  1. Block initiation at the focus
  2. Block propagation - spread of activity
  3. Increase GABAergic transmission
  4. Reduce glutamatergic transmission
  5. decrease neuronal action potential firing
  6. Inhibit neurotransmitter release (e.g. calcium channels)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what causes necrosis

A

sodium and calcium ion influx causes osmotic imbalance, leading to cell lysis and release of cell contents including glutamate and inflammatory mediators

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

what is primarily responsible for excitoxicity

A

elevated extracellular glutamate -> persistent neuronal depolarisation

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

what causes apoptosis

A

calcium ion influx leads to mitochondria impairment, resulting in decreased ATP, free radical production and release of cytochrome C (an apoptosis initiator)

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

What is ischaemic stroke

A

blockage of a cerebral artery

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

What is haemorrhagic stroke

A

rupture of cerebral artery

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

What are the three major processes that occur in ischaemic stroke

A
  1. inflammation
  2. free radical production
  3. rise in extracellular glutamate concentration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is used to treat ischaemic stroke and what is its usable time window

A

Tissue plasminogen activator (TPA) - first 3h

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

How does TPA help treat ischaemic stroke

A

converts plasminogen to plasmin which breaks down clots

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

What does ischaemia lead to

A

Ischaemia leads to a core in which neurons undergo irreversible necrotic cell death - the core is surrounded by a penumbra of tissue which is susceptible to cell death over a period of 2-3h

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

Why is targeting glutamate receptors alone in the treatment of stroke a problem

A

hard to separate the effects of the drugs on abnormal glutamatergic transmission in disorder from effect on receptors required for normal physiological activity

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

What neurotransmitter system is involved in ALS

A

glutamate

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

How is glutamate involved in ALS

A

selective loss of glial cell glutamate transporter - reduced uptake of glutamate in regions of CNS containing cell bodies of motor neurons

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

What is ALS

A

Amyotrophic Lateral Sclerosis: characterised by progressive muscular weakness, leading to paralysis and eventually death

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

How does genetics affect ALS

A

superoxide dismutase mutation (SOD1) leads to protein aggregations in motor neurons in the spinal cord

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

What environmental toxin is a cause of excitotoxic neurodegeneration

A

domoic acid

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

What are the effects of domoic acid

A

atrophied hippocampus

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

What is domoic acid

A

Natural product isolated from marine diatoms from west coast USA and Canada and is a potent AMPA/Kainate receptor agonist that can cross the BBB - causes neuronal cell death

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

What are the major causes of epilepsy

A

birth and perinatal injuries
congenital malformations
genetic
vascular insults
head trauma
chronic drug/alcohol abuse
neoplasia
infection
idiopathic

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

What are some seizure triggers

A

altered blood glucose and pH
stress
fatigue
flashing lights and noise
no apparent cause

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

What are the categorisations of seizures

A

simple - no loss of consciousness
complex - impairment of consciousness/awareness

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

What are partialised seizures

A

involves one hemisphere of the brain
- may affect movement, sensory experience, mood and behaviour
- temporal lobe - may get stereotypic movements and strong emotional responses

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

What is ‘Jacksonian epilepsy’

A

in motor cortex: repetitive jerky movements on one side which spreads

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

What are the 5 types of generalised seizures

A

Atonic, tonic, myoclonic, tonic-clonic, absence

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

What are atonic seizures

A

loss of muscle tone

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

What are tonic seizures

A

increased muscle tone

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

What are myoclonic seizures

A

jerking movement

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

What are tonic-clonic seizures

A

stiffness and jerking

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

What are absence seizures

A

loss of awareness

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

How is Alzheimer’s Disease diagnosed

A

Mini-Mental State Exam
PET/SPECT MRI - changes in brain metabolism/blood flow
Altered CSF tau (high) and beta-amyloid (low) proteins (spinal tap/lumbar puncture)

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

How is Alzheimer’s disease identified post-mortem

A

brain atrophy
cerebral ventricles symmetrically dilated
neurofibrillary tangles
senile plaques containing beta-amyloid core
neuronal and synaptic loss

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

What are the causes of Alzheimer’s Disease

A

majority idiopathic
small percentage hereditary
- mutations associated with processing of beta-amyloid
- chromosome 21 in particular (and also 1, 10, 14, 19)
- early onset

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

What are the hypothesised causes of Alzheimer’s Disease pathology

A

Cholinergic dysfunction
Glutamatergic dysfunction
Amyloid hypothesis
Tau hypothesis
Neuroinflammation

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

How do beta-amyloid plaques form

A

Abnormal cleavage of amyloid precursor protein leading to excess amyloid accumulation

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

What is the role of tau

A

stabilises microtubules
important for transporting molecules and organelles around neuron

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

How is tau affected in AD

A

tau is hyperphosphorylated and dissociates from microtubules, leading to misfolding and aggregation into neurofibrillary tangles

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

What are the direct mechanisms possibly involved in tau hyperphosphorylation

A
  • upregulation of abberant activation of tau kinases
  • down regulation of phosphatases
  • mutations
  • covalent modifications of tau
  • others
40
Q

What are the indirect mechanisms possibly involved in tau hyperphosphorylation

A

beta-amyloid-mediated toxicity
oxidative stress
inflammation
others

41
Q

What are the toxic gains-of-functions due to tau

A

NFTs made of hyperphosphorylated tau sequester normal tau
NFTs become physical obstacles to the transport of vesicles and other cargoes

42
Q

How is chromosome 21 associated with AD

A

APP gene - Down syndrome sufferers carry and extra gene copy and exhibit AD-like disorders by age 40

43
Q

What is the major AD genetic risk factor

A

APOE4

44
Q

What is APOE4

A

major serum lipoprotein involved in cholesterol metabolism -> leads to excess amyloid buildup in the brain before AD symptoms arise

45
Q

What are the future strategies for AD therapy

A
  1. cholinergics
  2. reduce beta-amyloid production
  3. increase beta-amyloid clearance
  4. stop or reverse plaque formation
  5. increase cell survival
  6. cell replacement
  7. reduce oxidative stress
  8. neuroimmune modulation
46
Q

What are strategies for decreasing amyloid peptides

A
  1. vaccination therapy
  2. beta- and gamma- secretase inhibitors
  3. statins
  4. clioqionol
  5. NSAIDS
47
Q

How do statins help in AD therapy

A

increases processing of APP by alpha-secretase, leading to decreased production of beta-amyloid peptides

48
Q

How does clioquinol help in AD therapy

A

decreases Cu/Zn interaction with beta-amyloid peptides, leading to amyloid plaques being cleared

49
Q

How do NSAIDS help in AD therapy

A

modulate the way gamma-secretase cleaves amyloid beta fragments
inhibits the production of AB42 peptide

50
Q

What are the motor symptoms of Parkinson’s Disease

A

bradykinesia, Parkinsonian gait, reduced arm swing, rigidity, freezing, postural instability, asymmetric resting tremor

51
Q

What are some non-motor symptoms of Parkinson’s Disease

A

Depression, anxiety
upper airway obstruction, abnormalities of ventilatory control
muscular weakness and aches
constipation
forced closure of the eyelids
difficulty speaking, excessive salivation, difficulty swallowing
increased sweating

52
Q

What is the neuropathological cause of Parkinson’s Disease

A

Death of neurons in substantia nigra leads to dopamine depletion in the striatum

53
Q

What is the basal ganglia

A

a group of nuclei associated with the control of movement

54
Q

What are the components of the basal ganglia

A

Globus pallidus (GPe, GPi)
Substantia nigra (SNr, SNc)
Subthalamic nucleus (STN)
Striatum (Caudate nucleus, Putamen)

55
Q

How does the basal ganglia function

A
  • receives excitatory inputs from across the cortex
  • output is inhibitory - acts as a brake on motor function
56
Q

What is the direct pathway in the basal ganglia circuit diagram for motor control

A

activation of D1 receptors inhibit GPi -> thalamus is disinhibited -> more movement

57
Q

What is the indirect pathway in the basal ganglia circuit diagram for motor control

A

D2 receptor -> inhibition of GPe -> inhibition of STN (more excitable) -> excites GPi -> reduces movement

58
Q

How does Parkinson’s Disease affect the pathways in the basal ganglia circuit

A

indirect > direct -> less movement

59
Q

What are the neuronal changes in Parkinson’s Disease

A

dopamine depletion in the striatum due to neurodegeneration of dopaminergic neurons
formation of Lewy bodies (inclusions containing alpha-synuclein)

60
Q

What genes are associated with Parkinson’s Disease

A

PARK 1/4
PARK 3 and 15
PINK1 and LRRK2

61
Q

How does PARK 1/4 affect Parkinson’s Disease patients

A

encodes alpha-synuclein

62
Q

How does PARK 3 and 5 affect Parkinson’s Disease patients

A

associated with Lewy body formation

63
Q

How does PINK1 and LRRK2 affect Parkinson’s Disease patients

A

encode serine/threonine kinase proteins, localised to mitochondria

64
Q

What are the 4 categories of treatment options for Parkinson’s Disease

A
  1. Preventative
  2. Symptomatic
  3. Non-motor management
  4. Restorative (still under clinical trials)
65
Q

What are the symptoms of Huntington’s Disease

A

chorea/uncontrollable movements, unsteadiness of gait, difficulty in eating, swallowing, walking, dementia, anxiety, depression, mania

66
Q

What is Huntington’s Disease caused by

A

mutation of huntingtin (Htt) gene

67
Q

What is the pathology of Huntington’s disease

A

Neurodegenerative, leading to shrinkage and thinning of cerebral cortex
striatum grossly atrophied early
major loss of GABAergic medium spiny interneurons -> reduced activation of indirect pathway

68
Q

How do mHtt genes differ from normal Htt genes

A

mHtt contains an expansion of glutamine (CAG) repeats

69
Q

Why is mHtt pathology restricted to medium spiny interneurons

A

mHtt binds to the small GTP binding protein Rhes which is selectively expressed in MSNs

70
Q

What diseases are associated with CAG expansion repeats

A

Huntington’s Disease
Spinobulbar muscular atrophy
Dentatorubral-pallidouysian atrophy
Spinocerebellar ataxias

71
Q

How do mHtt inclusions form

A

Extra long and sticky glutamine sequence -> propensity to create extra H bonds -> misfolding of fragment -> aggregate and go out of solution

72
Q

What are toxic effects of mHtt inclusions

A

transcriptional alteration
metabolic dysfunction
proteasome impairment
stress response abnormalities

73
Q

What are the potential targets for causes of polyglutamine diseases

A

genetically reduce mHtt expression
protease inhibition
native conformation stabilisation
aggregation inhibition
reversing cellular defects (by promoting neuronal cell health)

74
Q

How can mHtt expression be reduced genetically

A

CRISPR Cas9 to remove some glutamine to <35
RNAi bind mHtt mRNA leading to degradation
Antisense oligonucleotides (ASOs) - synthetic DNA strands complimentary to pre-mRNA stopping translation

74
Q

How does RNAi cross the BBB

A

viral vector

75
Q

What is RDoC

A

Research Domain Criteria - symptoms-based classification of psychiatric disorders recognising overlap between conditions and need to target treatments to specific domains

76
Q

What are the five categories in the RDoC

A

negative valence
positive valence
cognitive
social
arousal & regulation

77
Q

What are the possible causes of pathological anxiety

A
  • brain regions responsible for fear response not shut down (inhibited)
  • disruption of serotonergic (5-HT) system which also provides inhibitory inputs to NA system
  • disruption of the NA system (arousal)
78
Q

What are the different types of anxiety

A

General anxiety disorder
social anxiety disorder
phobias
panic disorder
post-traumatic stress disorder
obsessive compulsive disorder
body dysmorphic disorder

79
Q

What receptors are involved in the 5-HT brake

A

presynaptic alpha2 autoreceptor
postsynaptic alpha2 heteroreceptor

80
Q

What receptors are involved in the 5-HT accelerator

A

alpha1 receptor
presynaptic alpha 2 autoreceptor

81
Q

How does increased synaptic [monoamine] cause increased anxiety

A

activation of somatodentritic autoreceptors (5-HT1A, alpha2 adrenoceptors) -> decreased neuronal firing
activation of presynaptic autoreceptors (5-HT1B/D, alpha2 adrenoceptors) -> decreased neurotransmitter release

82
Q

What symptoms of schizophrenia are primary targets for drug treatment

A

delusions
hallucinations
disorganised thoughts
abnormal behaviours

83
Q

What are some symptoms of schizophrenia which could be worsened by antipsychotics

A

blunted emotions
anhedonia
poverty of speech
attention impairment
loss of motivation
new learning
memory
executive function
depression
anxiety
impulse control

84
Q

What are symptoms of muscarinic acetylcholine receptor activation

A

dry mouth, blurred vision, constipation

85
Q

What are symptoms of histamine receptor activation

A

sedative

86
Q

What are symptoms of adrenergic alpha receptor activation

A

postural hypotension

87
Q

What are side effects of 5-HT2A receptor activation

A

agonists -> propsychotic effects

88
Q

What are side effects of 5-HT2C

A

metabolic effects

89
Q

What are the neurochemical theories in schizophrenia

A
  1. Hyperdopaminergic dysfunction
  2. Serotonergic dysfunction
  3. Glutamate hypofunction
90
Q

How are dopamine receptors involved in schizophrenia

A

Amphetamine-induced DA release can cause acute psychoses

91
Q

How is serotonin involved in schizophrenia

A

Drugs which block 5-HT2 receptor exhibit clinical efficacy
5-HT2A agonists induce hallucinations
5-HT2 receptors modulate glutamate and dopamine level

92
Q

How is glutamate involved in schizophrenia

A

NMDA antagonists induce psychotic symptoms

93
Q

What is the hypothesis behind ADHD

A

dysregulation between cortical and sub-cortical neurotransmission

94
Q

How do 5-HT and DA interact

A

Raphe innervation of substantia nigra
5-HT2 modulation of DA in nucleus accumbens

95
Q

How do NA and 5-HT interact

A

LC innervation of raphe numbers (alpha1)
NA inhibition (alpha2) at 5-HT terminals

96
Q

What are the important brain neurotransmitters involved in addiction

A

dopamine
glutamate
serotonin

97
Q

What is the reward pathway

A

Ventral Tegmental Area (VTA) to Nucleus Accumbens
Increased dopamine release in response to positive outcomes

98
Q

What receptors/transporters do drugs of abuse act on

A

Dopamine transporter
NA transporter
5-HT transporter, 5-HT2A receptor
NMDA receptor
nicotinic ACh receptor
A1, A2A, A2B and A3 adenosine receptors
CB1 receptor

99
Q

How does the mu opioid receptor affect dopamine

A

activation inhibits the GABAergic inhibitory interneurone -> disinhibition increases dopamine release at dopaminergic neurone in VTA

Pharm 2A (10 decks)

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