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L2 pharmacology > CNS 3 - Antipsychotics > Flashcards

CNS 3 - Antipsychotics Flashcards

1
Q

What are neuroleptics?

A

Antipsychotics

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2
Q

What are the 4 main amine neurotransmitters in the CNS?

A
  • Noradrenaline
  • Dopamine
  • 5HT (serotonin)
  • Acetylcholine
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3
Q

What kind of signalling do antipsychotics target?

A

Dopamine

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4
Q

What kind of signalling do antidepressants target?

A

Serotonin and some noradrenaline

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5
Q

What kind of behaviours are the amine neurotransmitters associated with?

A

High level behaviours e.g. cognition, emotions, awareness

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6
Q

Where is the main source of noradrenergic neurons in the brain?

A

Locus coeruleus

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7
Q

What is the locus coeruleus associated with? (2)

A
  • Wakefulness and alertness (arousal)
  • Mood
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8
Q

Why is noradrenaline an aerosol neurotransmitter?

A

Presynaptic and postsynaptic terminal not closely associated so noradrenaline is released like an aerosol and have a broad influence

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9
Q

What are alpha 1 adrenoreceptors in the brain associated with? (3)

A
  • Motor control
  • Cognition
  • Fear
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10
Q

Where are alpha 1 adrenoreceptors found in the brain?

A

Widely distributed

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11
Q

What are alpha 2 adrenoreceptors found in the brain associated with? (3)

A
  • Blood pressure regulation
  • Sedation
  • Analgesia
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12
Q

Where are beta 1 adrenoreceptors found in the brain? (3)

A
  • Cortex
  • Striatum
  • Hippocampus
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13
Q

What are beta 1 adrenoreceptors found in the brain associated with? (2)

A
  • Initiating movement
  • Learning
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14
Q

Which G protein are beta 1 receptors coupled to?

A

Gs

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15
Q

Which G protein are alpha 2 receptors coupled to?

A

Gi

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16
Q

Which G protein are alpha 1 receptors coupled to?

A

Gq

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17
Q

What are the 3 dopaminergic pathways in the brain?

A
  • Nigrostriatal pathway
  • Mesocortical and mesolimbic pathways
  • Tuberohypophyseal pathway
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18
Q

Where are the cell bodies in the nigrostriatal pathway located?

A

Substantia nigra

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19
Q

Where do the neurons in the nigrostriatal pathway extend to?

A

Striatum

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20
Q

What is the nigrostriatal pathway associated with?

A

Fine motor control

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21
Q

What pathway degenerates in Parkinson’s disease?

A
  • Nigrostriatal pathway
  • Loss of dopaminergic neurons in the substantia nigra
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22
Q

Where are the cell bodies in the mesolimbic and mesocortical pathways located?

A

Ventral Tegmental Area

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23
Q

Where do the neurons in the mesolimbic and mesocortical pathways extend to?

A

Cortex

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24
Q

What are the mesolimbic and mesocortical pathways associated with? (3)

A
  • Behavioural effects
  • Pleasure-euphoria-reward (motivation)
  • Compulsion
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25
Which pathway is associated with addicition and attention deficit disorders?
Mesolimbic and mesocortical pathways
26
Where are the cell bodies in the tuberohypophyseal pathway located?
Hypothalamus
27
Where do the neurons in the tuberohypophyseal pathway extend to?
Pituitary
28
What is the tuberohypophyseal pathway associated with?
Pituitary hormone secretion e.g. prolactin
29
Which amino acid is dopamine synthesised from?
Tyrosine
30
What is the rate limiting step in dopamine synthesis?
Conversion of tyrosine to DOPA by tyrosine hydroxylase
31
How is dopamine synthesised?
- Tyrosine converted to DOPA by tyrosine hydroxylase - DOPA converted to dopamine by DOPA decarboxylase
32
How is Parkinson's disease treated?
L-dopa drug which can cross the blood-brain barrier and is converted into dopamine by DOPA decarboxylase to increase dopamine concentrations in the brain
33
Why can't dopamine itself be given to Parkinson's patients?
Dopamine can't cross the blood-brain barrier but L-dopa can
34
What enzymes will be expressed in dopaminergic neurons? (2)
- Tyrosine hydroxylase - DOPA decarboxylase
35
What enzymes will be expressed in noradrenergic neurons? (3)
- Tyrosine hydroxylase - DOPA decarboxylase - Dopamine beta hydroxylase
36
What is dopamine the precursor molecule for?
Noradrenaline
37
What is noradrenaline the precursor molecule for?
Adrenaline
38
Which enzyme do dopaminergic neurons NOT express?
Dopamine beta hydroxylase
39
What kind of receptors are dopamine receptors?
G protein coupled
40
How is dopamine action terminated?
- Dopamine reuptake transporters - Breakdown by MAO or COMT enzymes
41
What are the 2 main products of dopamine metabolism?
- HVA - DOPAC
42
Why are HVA and DOPAC important?
Their levels are measured in the clinic to determine if there are issues with dopaminergic transmission in a patient
43
Which dopamine receptors are coupled to Gs? (2)
- D1 - D5
44
Which dopamine receptors are coupled to Gi? (3)
- D2 - D3 - D4
45
Where in the brain are D1 receptors found?
Cortex
46
What inhibitory effects do D2 receptors have aswell as the normal Gi inhibition of adenylate cyclase? (2)
- Activate K+ channels to prevent APs - Inhibit Ca2+ channels to prevent Ca2+ influx
47
How are D2 receptors autoinhibitory?
They reduce excitability of dopaminergic neurons and reduce dopamine release
48
Where in the brain are D2 receptors found?
Pituitary
49
What does inhibition of D2 receptors in the pituitary cause?
Increased prolactin secretion
50
How do amphetamines work?
- Taken up into neurons and displace dopamine and noradrenaline from vesicles - Dopamine and noradrenaline build up in the cytosol which causes the reuptake transporters to work in reverse to get rid of it - Causes increased dopaminergic and noradrenergic signalling independent of APs
51
How does cocaine work?
- Inhibits the reuptake transporters for dopamine and noradrenaline - Causes increased dopaminergic and noradrenergic signalling independent of APs
52
What are the effects of taking amphetamines/cocaine? (3)
- Increased motor activity - Activation of reward pathways - Euphoria
53
What are therapeutic uses for amphetamines/cocaine? (2)
- Increase wakefulness in narcolepsy - Increase focus in ADHD
54
What are the 2 types of schizophrenia symptoms?
- Positive - Negative
55
What are the positive symptoms of schizophrenia? (8)
- Hallucinations - Delusions - Paranoia - Attention deficits - Bizarre behaviour - Aggression - Stereotyped movements - Catatonia
56
What are the negative symptoms of schizophrenia? (4)
- Blunting of emotions - Withdrawal from society - Anhedonia - Reluctance to perform everyday tasks
57
What kind of symptoms are seen in young schizophrenia patients?
Mainly positive symptoms, negative symptoms increase with age
58
What may accompany schizophrenia symptoms? (4)
- Cognitive defects (attention, memory) - Anxiety - Depression - Suicide attempts
59
What are risk factors for developing schizophrenia? (3)
- Abnormalities which disrupt normal brain development - Genetic predisposition - Consumption of cannabis in adolescence
60
How are the positive symptoms of schizophrenia treated?
D2 antagonists
61
How does ketamine work?
NMDA receptor antagonist
62
What signalling pathways other than dopamine might be involved in schizophrenia? (2)
- Glutamate (NMDA antagonists produce psychotic symptoms e.g. ketamine) - Serotonin (5HT2A agonists produce psychotic symptoms e.g. LSD)
63
How does LSD work?
5HT2A receptor agonist
64
Which pathway is overactive in schizophrenia? (3)
- Mesolimbic pathway - Increased D2 activity - Associated with positive symptoms
65
Which pathway has decreased activity in schizophrenia? (3)
- Mesocortical pathway - Decreased D1 activity - Associated with negative symptoms
66
What is the evidence for the dopamine theory of schizophrenia? (4)
- Amphetamines increase dopaminergic signalling and cause schizophrenic-like behaviour - Parkinson's patients treated with L-dopa have hallucinations as a side effect - D2 agonists induce stereotypic behaviours in animals - Dopamine antagonists control positive symptoms
67
What does reserpine do?
- Blocks dopamine storage - Depletion of amine transmitters
68
How do antipsychotic drugs work?
D2 receptor antagonists
69
What occupancy of D2 receptors is needed to decrease positive symptoms?
80%
70
What are the 2 types of antipsychotics?
- First generation (typical/conventional) - Second generation (atypical)
71
What are examples of first generation antipsychotics? (2)
- Haloperidol - Chlorpromazine
72
What are the problematic side effects of first generation antipsychotics? (2)
- Motor disturbances (Parkinson's like) - Prolactin secretion
73
What are examples of second generation antipsychotics? (2)
- Clozapine - Risperidone
74
Why are second generation antipsychotics favoured over first generation?
Fewer extrapyramidal side effects
75
What are some unwanted side effects of antipsychotics? (4)
- Irreversible dyskinesia - Weight gain - Hypotension - Sedation

L2 pharmacology (9 decks)

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