Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharm 2A > Conditions and their neurotransmitter systems > Flashcards

Conditions and their neurotransmitter systems Flashcards

(102 cards)

Start Studying
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
What are the categorisations of seizures
simple - no loss of consciousness complex - impairment of consciousness/awareness
24
What are partialised seizures
involves one hemisphere of the brain - may affect movement, sensory experience, mood and behaviour - temporal lobe - may get stereotypic movements and strong emotional responses
25
What is 'Jacksonian epilepsy'
in motor cortex: repetitive jerky movements on one side which spreads
26
What are the 5 types of generalised seizures
Atonic, tonic, myoclonic, tonic-clonic, absence
27
What are atonic seizures
loss of muscle tone
28
What are tonic seizures
increased muscle tone
29
What are myoclonic seizures
jerking movement
30
What are tonic-clonic seizures
stiffness and jerking
31
What are absence seizures
loss of awareness
32
How is Alzheimer's Disease diagnosed
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)
33
How is Alzheimer's disease identified post-mortem
brain atrophy cerebral ventricles symmetrically dilated neurofibrillary tangles senile plaques containing beta-amyloid core neuronal and synaptic loss
34
What are the causes of Alzheimer's Disease
majority idiopathic small percentage hereditary - mutations associated with processing of beta-amyloid - chromosome 21 in particular (and also 1, 10, 14, 19) - early onset
35
What are the hypothesised causes of Alzheimer's Disease pathology
Cholinergic dysfunction Glutamatergic dysfunction Amyloid hypothesis Tau hypothesis Neuroinflammation
36
How do beta-amyloid plaques form
Abnormal cleavage of amyloid precursor protein leading to excess amyloid accumulation
37
What is the role of tau
stabilises microtubules important for transporting molecules and organelles around neuron
38
How is tau affected in AD
tau is hyperphosphorylated and dissociates from microtubules, leading to misfolding and aggregation into neurofibrillary tangles
39
What are the direct mechanisms possibly involved in tau hyperphosphorylation
- upregulation of abberant activation of tau kinases - down regulation of phosphatases - mutations - covalent modifications of tau - others
40
What are the indirect mechanisms possibly involved in tau hyperphosphorylation
beta-amyloid-mediated toxicity oxidative stress inflammation others
41
What are the toxic gains-of-functions due to tau
NFTs made of hyperphosphorylated tau sequester normal tau NFTs become physical obstacles to the transport of vesicles and other cargoes
42
How is chromosome 21 associated with AD
APP gene - Down syndrome sufferers carry and extra gene copy and exhibit AD-like disorders by age 40
43
What is the major AD genetic risk factor
APOE4
44
What is APOE4
major serum lipoprotein involved in cholesterol metabolism -> leads to excess amyloid buildup in the brain before AD symptoms arise
45
What are the future strategies for AD therapy
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
What are strategies for decreasing amyloid peptides
1. vaccination therapy 2. beta- and gamma- secretase inhibitors 3. statins 4. clioqionol 5. NSAIDS
47
How do statins help in AD therapy
increases processing of APP by alpha-secretase, leading to decreased production of beta-amyloid peptides
48
How does clioquinol help in AD therapy
decreases Cu/Zn interaction with beta-amyloid peptides, leading to amyloid plaques being cleared
49
How do NSAIDS help in AD therapy
modulate the way gamma-secretase cleaves amyloid beta fragments inhibits the production of AB42 peptide
50
What are the motor symptoms of Parkinson's Disease
bradykinesia, Parkinsonian gait, reduced arm swing, rigidity, freezing, postural instability, asymmetric resting tremor
51
What are some non-motor symptoms of Parkinson's Disease
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
What is the neuropathological cause of Parkinson's Disease
Death of neurons in substantia nigra leads to dopamine depletion in the striatum
53
What is the basal ganglia
a group of nuclei associated with the control of movement
54
What are the components of the basal ganglia
Globus pallidus (GPe, GPi) Substantia nigra (SNr, SNc) Subthalamic nucleus (STN) Striatum (Caudate nucleus, Putamen)
55
How does the basal ganglia function
- receives excitatory inputs from across the cortex - output is inhibitory - acts as a brake on motor function
56
What is the direct pathway in the basal ganglia circuit diagram for motor control
activation of D1 receptors inhibit GPi -> thalamus is disinhibited -> more movement
57
What is the indirect pathway in the basal ganglia circuit diagram for motor control
D2 receptor -> inhibition of GPe -> inhibition of STN (more excitable) -> excites GPi -> reduces movement
58
How does Parkinson's Disease affect the pathways in the basal ganglia circuit
indirect > direct -> less movement
59
What are the neuronal changes in Parkinson's Disease
dopamine depletion in the striatum due to neurodegeneration of dopaminergic neurons formation of Lewy bodies (inclusions containing alpha-synuclein)
60
What genes are associated with Parkinson's Disease
PARK 1/4 PARK 3 and 15 PINK1 and LRRK2
61
How does PARK 1/4 affect Parkinson's Disease patients
encodes alpha-synuclein
62
How does PARK 3 and 5 affect Parkinson's Disease patients
associated with Lewy body formation
63
How does PINK1 and LRRK2 affect Parkinson's Disease patients
encode serine/threonine kinase proteins, localised to mitochondria
64
What are the 4 categories of treatment options for Parkinson's Disease
1. Preventative 2. Symptomatic 3. Non-motor management 4. Restorative (still under clinical trials)
65
What are the symptoms of Huntington's Disease
chorea/uncontrollable movements, unsteadiness of gait, difficulty in eating, swallowing, walking, dementia, anxiety, depression, mania
66
What is Huntington's Disease caused by
mutation of huntingtin (Htt) gene
67
What is the pathology of Huntington's disease
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
How do mHtt genes differ from normal Htt genes
mHtt contains an expansion of glutamine (CAG) repeats
69
Why is mHtt pathology restricted to medium spiny interneurons
mHtt binds to the small GTP binding protein Rhes which is selectively expressed in MSNs
70
What diseases are associated with CAG expansion repeats
Huntington's Disease Spinobulbar muscular atrophy Dentatorubral-pallidouysian atrophy Spinocerebellar ataxias
71
How do mHtt inclusions form
Extra long and sticky glutamine sequence -> propensity to create extra H bonds -> misfolding of fragment -> aggregate and go out of solution
72
What are toxic effects of mHtt inclusions
transcriptional alteration metabolic dysfunction proteasome impairment stress response abnormalities
73
What are the potential targets for causes of polyglutamine diseases
genetically reduce mHtt expression protease inhibition native conformation stabilisation aggregation inhibition reversing cellular defects (by promoting neuronal cell health)
74
How can mHtt expression be reduced genetically
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
How does RNAi cross the BBB
viral vector
75
What is RDoC
Research Domain Criteria - symptoms-based classification of psychiatric disorders recognising overlap between conditions and need to target treatments to specific domains
76
What are the five categories in the RDoC
negative valence positive valence cognitive social arousal & regulation
77
What are the possible causes of pathological anxiety
- 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
What are the different types of anxiety
General anxiety disorder social anxiety disorder phobias panic disorder post-traumatic stress disorder obsessive compulsive disorder body dysmorphic disorder
79
What receptors are involved in the 5-HT brake
presynaptic alpha2 autoreceptor postsynaptic alpha2 heteroreceptor
80
What receptors are involved in the 5-HT accelerator
alpha1 receptor presynaptic alpha 2 autoreceptor
81
How does increased synaptic [monoamine] cause increased anxiety
activation of somatodentritic autoreceptors (5-HT1A, alpha2 adrenoceptors) -> decreased neuronal firing activation of presynaptic autoreceptors (5-HT1B/D, alpha2 adrenoceptors) -> decreased neurotransmitter release
82
What symptoms of schizophrenia are primary targets for drug treatment
delusions hallucinations disorganised thoughts abnormal behaviours
83
What are some symptoms of schizophrenia which could be worsened by antipsychotics
blunted emotions anhedonia poverty of speech attention impairment loss of motivation new learning memory executive function depression anxiety impulse control
84
What are symptoms of muscarinic acetylcholine receptor activation
dry mouth, blurred vision, constipation
85
What are symptoms of histamine receptor activation
sedative
86
What are symptoms of adrenergic alpha receptor activation
postural hypotension
87
What are side effects of 5-HT2A receptor activation
agonists -> propsychotic effects
88
What are side effects of 5-HT2C
metabolic effects
89
What are the neurochemical theories in schizophrenia
1. Hyperdopaminergic dysfunction 2. Serotonergic dysfunction 3. Glutamate hypofunction
90
How are dopamine receptors involved in schizophrenia
Amphetamine-induced DA release can cause acute psychoses
91
How is serotonin involved in schizophrenia
Drugs which block 5-HT2 receptor exhibit clinical efficacy 5-HT2A agonists induce hallucinations 5-HT2 receptors modulate glutamate and dopamine level
92
How is glutamate involved in schizophrenia
NMDA antagonists induce psychotic symptoms
93
What is the hypothesis behind ADHD
dysregulation between cortical and sub-cortical neurotransmission
94
How do 5-HT and DA interact
Raphe innervation of substantia nigra 5-HT2 modulation of DA in nucleus accumbens
95
How do NA and 5-HT interact
LC innervation of raphe numbers (alpha1) NA inhibition (alpha2) at 5-HT terminals
96
What are the important brain neurotransmitters involved in addiction
dopamine glutamate serotonin
97
What is the reward pathway
Ventral Tegmental Area (VTA) to Nucleus Accumbens Increased dopamine release in response to positive outcomes
98
What receptors/transporters do drugs of abuse act on
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
How does the mu opioid receptor affect dopamine
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.
© 2025 Bold Learning Solutions. Terms and Conditions