Brainscape's Knowledge GenomeTM

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


See full index

PHAR0002 > CNS Disorders (Lecture 18) > Flashcards

CNS Disorders (Lecture 18) Flashcards

1
Q

What (2) things do we need to know to treat CNS disorders?

A
  1. The pathophysiological mechanism
  2. The symptomatic pathway - the transmitter pathway for impaired function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 2 treatment strategies for schizophrenia?

A
  1. Affecting dopaminergic transmission
    Antagonism of D2 (metabotrophic, postsynaptic) receptors
    Which decreases the effects of excess dopamine signalling
    E.g. Chlorpromazine
  2. Affecting serotonergic transmission
    ‘Atypical antipsychotics’ - antagonise D2 & 5-HT2A receptors
    This also works on negative symptoms
    E.g. Clozapine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are 2 drugs used in the treatment of schizophrenia and what pathways do they affect?

A

Chlorpromazine - dopaminergic transmission

Clozapine - serotonergic transmission

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

What is the treatment strategy for Alzheimer’s disease?

A

No cure

Increasing ACh signalling in the brain can provide some minor symptomatic improvements

Done through AChE inhibitors

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

What is the precursor for dopamine synthesis?

A

L-DOPA

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

What is the pathophysiology of schizophrenia ?

A

A GAIN & LOSS of function disorder - causes positive & negative symptoms

Characterised by excess dopamine
Altered serotonin & glutamate signalling likely upstream of excess dopamine

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

Is Parkinson’s disease a loss or gain of function disorder?

A

Loss of function (neurodegenerative) disorder

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

What is Parkinson’s disease caused by?

A
  1. Reduced dopamine signalling due to progressive dopamine neuronal death in substansia nigra (80% loss before symptomatic)
  2. Drug treatment for schizophrenia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Is Alzheimer’s disease a loss or gain of function disorder?

A

Loss of function (neurodegenerative) disorder

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

What are the 2 pathological hallmarks of AD?

A

Extracellular beta-amyloid plaques

Intracellular neurofibrillary tangles (tau protein)

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

What is the pathophysiology of AD?

A

2 pathological hallmarks: extracellular beta-amyloid plaques & intracellular neurofibrillary tangles (tau protein)
Accumulation of these protein deposits is followed by synapse loss and neuronal death - causing gross atrophy of brain tisse starting in the temporal lobe

Mechanism of neuronal death is unclear

AD patients have lower brain ACh levels & loss of cholinergic neurones

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

What is the relationship between AD and dementia?

A

AD is the most common form of dementia - progressive impairment of cognition & memory (60-70% of cases)

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

Is epilepsy a loss or gain of function disorder and what is it caused by?

A

A GAIN of function disorder caused by increased glutamatergic and / or decreased GABAergic signalling

The imbalance in excitation / inhibition in the brain causes seizures

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

What type of disorder is epilepsy?

A

A motor disorder

Causes abnormal activity in movement control circuitry

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

What is the pathophysiological mechanism of strokes?

A

Neuronal death (ischemia / haemorrhage)

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

What is the symptomatic pathway of strokes?

A

No specific pathway (localised legion)

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

What is the treatment strategy for strokes?

A

None - neurones cannot be restored

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

What is the pathophysiological mechanism of AD?

A

Amyloid plaques & tau tangles (still under research)

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

What is the symptomatic pathway for AD?

A

(Reduced) cholinergic signalling in the CNS (cortex)

20
Q

What is the treatment strategy for AD?

A

Symptomatic treatment - through increasing ACh signalling in the brain, using AChE inhibitors
(Very limited due to side effects)

21
Q

What happens if you reduce dopamine signalling (below the normal level) in the treatment of schizophrenia?

A

Causes Parkinson’s disease

22
Q

What happens if you over-stimulate D2 receptors (in the treatment of Parkinson’s disease) ?

A

Causes schizophrenia

23
Q

What conditions are caused by a LOSS of function / decreased activity?

A

Depression
Parkinson’s
AD
Negative symptoms of schizophrenia

24
Q

What conditions are caused by a GAIN of function / increased activity?

A

Epilepsy
Anxiety
Pain
Positive symptoms of schizophrenia

25
Q

What causes Parkinson’s disease?

A

A loss of neurones in the substansia nigra, causing a reduction of dopamine in the brain

26
Q

What are the symptoms of Parkinson’s disease?

A

Primarily a MOTOR disorder - symptoms of tremor & rigidity (can’t initiate movement)

In late stages - disruption to emotion, motivation & cognitive function

27
Q

What are the recent findings surrounding the treatment of AD?

A

Lecanemab (antibody therapy)
Targets amyloid accumulation directly - decreases amyloid plaques
Thus slows the onset / progression of symptoms of cognitive decline

28
Q

What are the positive symptoms of schizophrenia?

A

Positive symptoms (caused by increased activity):
Hallucinations (mostly auditory)
Paranoia
Delusions

29
Q

What are the negative symptoms of schizophrenia?

A

Negative symptoms (caused by decreased activity):

Flat affect - lack of emotional expressiveness / response to stimuli

Anhedonia - loss of pleasure / interest in activities

Reduced speech

Catalonia - state of abnormal motor behaviour characterised by immobility, extreme rigidity, or repetitive, purposeless movements

30
Q

Describe the motor & non-motor seizures in epilepsy

A

Motor:
Clonic - repeated rhythmical jerking of the body
Tonic-clonic - person becomes unconscious, body goes stiff, body jerks and shakes

Non-motor (absence):
Individual becomes unconscious for a short time

31
Q

What are the 3 types of focal onset seizures?

A
  1. Focal to bilateral tonic-clonic - seizures that spread to both sides of the brain
  2. Focal aware - awareness during seizure, knowledge of self & environment, consciousness intact
  3. Focal impaired awareness - affect a bigger part of one hemisphere of the brain than focal aware, consciousness is affected
32
Q

What are the 4 targets of drugs for modulating synaptic transmission?

A
  1. Synthesis
  2. Release
  3. Effects (on target neurone)
  4. Removal
33
Q

How can drugs increase / decrease synthesis of NT in the modulation of synaptic transmission?

A

Increase - add more precursor

Decrease - inhibit enzymes

34
Q

How can drugs increase / decrease release of NT in the modulation of synaptic transmission?

A

Increase - agonists

Decrease - antagonists of presynaptic receptors

35
Q

How can drugs increase / decrease effects of NT in the modulation of synaptic transmission?

A

Increase - with agonists

Decrease - with antagonists of postsynaptic receptors

36
Q

How can drugs decrease removal of NT in the modulation of synaptic transmission?

A

Decrease by inhibition of re-uptake / metabolism of transmitter

37
Q

What are the 4 main types of epilepsy?

A
  1. Focal
  2. Generalised
  3. Combination focal & general
  4. Unknown

*a person’s seizure determines which type of epilepsy they have

38
Q

What are the 3 major treatment strategies to increase dopamine signalling in the treatment of Parkinson’s disease?

A
  1. Add L-DOPA precursor - increase dopamine synthesis
    - increasing L-DOPA alone is ineffective as most is converted to dopamine in the periphery which cannot cross the blood-brain barrier
    - AADC inhibitors (e.g. Carbidopa) used in addition to prevent the conversion of L-DOPA to dopamine so that it can cross the blood-brain barrier
  2. Use D2 receptor agonists - mimic effects of dopamine in the brain by binding to dopamine receptors
    - e.g. pramipexole, ropinirole, bromocriptine
  3. Decrease metabolism (i.e. removal) of dopamine
    - (central) COMT inhibitors (e.g. tolcapone)
39
Q

What are the 2 treatment strategies for epilepsy and what do they target?

A
  1. Increase inhibition - target GABA
  2. Decrease excitation - target glutamate
40
Q

How is inhibition increased in the treatment of epilepsy (target GABA)? (3 ways)

A
  1. Barbiturates (e.g. Phenobarbital) to open Cl- channels to cause hyperpolarisation
  2. Benzodiazepines (e.g. Diazepram) for positive modulation of GABA-A receptor (more subtle affect)
  3. Block GABA re-uptake (e.g. Tiagabine)
41
Q

How is excitation decreased in the treatment of epilepsy (target glutamate) ?

A
  1. Block presynaptic Ca2+ channels = less release of glutamate (e.g. Gabapentin)
  2. Block postsynaptic Na+ channels = preventing AP generation (e.g. Carbamazepine)
42
Q

Outline CNS disorders

A

They can be simplistically considered to be caused by a GAIN or LOSS of function
If this gain / loss can be mitigated or reversed then it may be possible to treat the disorder

43
Q

What is the pathophysiological mechanism of Parkinson’s disease?

A

Neuronal death (dopaminergic neurones)

44
Q

What is the symptomatic pathway of Parkinson’s disease?

A

Reduced signalling in the nigrostriatal dopamine pathway

45
Q

What is the treatment strategy for Parkinson’s disease?

A

Delay / symptomatic

Increasing dopamine signalling

46
Q

Why is the efficacy of AChE inhibitors limited?

A
  1. Short duration of action (short half-life)
  2. Limited selectivity - can result in unwanted side effects - dose needs to be low enough not to affect autonomic & motor function in the periphery
  3. Central vs. Peripheral affects - some can cross blood-brain barrier, others can’t
  4. Tolerance - can build from prolonged use
  5. Adverse effects - inc. nausea, diarrhoea, muscle weakness

PHAR0002 (20 decks)

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