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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
Q

Which pathway is associated with addicition and attention deficit disorders?

A

Mesolimbic and mesocortical pathways

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26
Q

Where are the cell bodies in the tuberohypophyseal pathway located?

A

Hypothalamus

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27
Q

Where do the neurons in the tuberohypophyseal pathway extend to?

A

Pituitary

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28
Q

What is the tuberohypophyseal pathway associated with?

A

Pituitary hormone secretion e.g. prolactin

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29
Q

Which amino acid is dopamine synthesised from?

A

Tyrosine

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30
Q

What is the rate limiting step in dopamine synthesis?

A

Conversion of tyrosine to DOPA by tyrosine hydroxylase

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31
Q

How is dopamine synthesised?

A
  • Tyrosine converted to DOPA by tyrosine hydroxylase
  • DOPA converted to dopamine by DOPA decarboxylase
32
Q

How is Parkinson’s disease treated?

A

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
Q

Why can’t dopamine itself be given to Parkinson’s patients?

A

Dopamine can’t cross the blood-brain barrier but L-dopa can

34
Q

What enzymes will be expressed in dopaminergic neurons? (2)

A
  • Tyrosine hydroxylase
  • DOPA decarboxylase
35
Q

What enzymes will be expressed in noradrenergic neurons? (3)

A
  • Tyrosine hydroxylase
  • DOPA decarboxylase
  • Dopamine beta hydroxylase
36
Q

What is dopamine the precursor molecule for?

A

Noradrenaline

37
Q

What is noradrenaline the precursor molecule for?

A

Adrenaline

38
Q

Which enzyme do dopaminergic neurons NOT express?

A

Dopamine beta hydroxylase

39
Q

What kind of receptors are dopamine receptors?

A

G protein coupled

40
Q

How is dopamine action terminated?

A
  • Dopamine reuptake transporters
  • Breakdown by MAO or COMT enzymes
41
Q

What are the 2 main products of dopamine metabolism?

A
  • HVA
  • DOPAC
42
Q

Why are HVA and DOPAC important?

A

Their levels are measured in the clinic to determine if there are issues with dopaminergic transmission in a patient

43
Q

Which dopamine receptors are coupled to Gs? (2)

A
  • D1
  • D5
44
Q

Which dopamine receptors are coupled to Gi? (3)

A
  • D2
  • D3
  • D4
45
Q

Where in the brain are D1 receptors found?

A

Cortex

46
Q

What inhibitory effects do D2 receptors have aswell as the normal Gi inhibition of adenylate cyclase? (2)

A
  • Activate K+ channels to prevent APs
  • Inhibit Ca2+ channels to prevent Ca2+ influx
47
Q

How are D2 receptors autoinhibitory?

A

They reduce excitability of dopaminergic neurons and reduce dopamine release

48
Q

Where in the brain are D2 receptors found?

A

Pituitary

49
Q

What does inhibition of D2 receptors in the pituitary cause?

A

Increased prolactin secretion

50
Q

How do amphetamines work?

A
  • 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
Q

How does cocaine work?

A
  • Inhibits the reuptake transporters for dopamine and noradrenaline
  • Causes increased dopaminergic and noradrenergic signalling independent of APs
52
Q

What are the effects of taking amphetamines/cocaine? (3)

A
  • Increased motor activity
  • Activation of reward pathways
  • Euphoria
53
Q

What are therapeutic uses for amphetamines/cocaine? (2)

A
  • Increase wakefulness in narcolepsy
  • Increase focus in ADHD
54
Q

What are the 2 types of schizophrenia symptoms?

A
  • Positive
  • Negative
55
Q

What are the positive symptoms of schizophrenia? (8)

A
  • Hallucinations
  • Delusions
  • Paranoia
  • Attention deficits
  • Bizarre behaviour
  • Aggression
  • Stereotyped movements
  • Catatonia
56
Q

What are the negative symptoms of schizophrenia? (4)

A
  • Blunting of emotions
  • Withdrawal from society
  • Anhedonia
  • Reluctance to perform everyday tasks
57
Q

What kind of symptoms are seen in young schizophrenia patients?

A

Mainly positive symptoms, negative symptoms increase with age

58
Q

What may accompany schizophrenia symptoms? (4)

A
  • Cognitive defects (attention, memory)
  • Anxiety
  • Depression
  • Suicide attempts
59
Q

What are risk factors for developing schizophrenia? (3)

A
  • Abnormalities which disrupt normal brain development
  • Genetic predisposition
  • Consumption of cannabis in adolescence
60
Q

How are the positive symptoms of schizophrenia treated?

A

D2 antagonists

61
Q

How does ketamine work?

A

NMDA receptor antagonist

62
Q

What signalling pathways other than dopamine might be involved in schizophrenia? (2)

A
  • Glutamate (NMDA antagonists produce psychotic symptoms e.g. ketamine)
  • Serotonin (5HT2A agonists produce psychotic symptoms e.g. LSD)
63
Q

How does LSD work?

A

5HT2A receptor agonist

64
Q

Which pathway is overactive in schizophrenia? (3)

A
  • Mesolimbic pathway
  • Increased D2 activity
  • Associated with positive symptoms
65
Q

Which pathway has decreased activity in schizophrenia? (3)

A
  • Mesocortical pathway
  • Decreased D1 activity
  • Associated with negative symptoms
66
Q

What is the evidence for the dopamine theory of schizophrenia? (4)

A
  • 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
Q

What does reserpine do?

A
  • Blocks dopamine storage
  • Depletion of amine transmitters
68
Q

How do antipsychotic drugs work?

A

D2 receptor antagonists

69
Q

What occupancy of D2 receptors is needed to decrease positive symptoms?

A

80%

70
Q

What are the 2 types of antipsychotics?

A
  • First generation (typical/conventional)
  • Second generation (atypical)
71
Q

What are examples of first generation antipsychotics? (2)

A
  • Haloperidol
  • Chlorpromazine
72
Q

What are the problematic side effects of first generation antipsychotics? (2)

A
  • Motor disturbances (Parkinson’s like)
  • Prolactin secretion
73
Q

What are examples of second generation antipsychotics? (2)

A
  • Clozapine
  • Risperidone
74
Q

Why are second generation antipsychotics favoured over first generation?

A

Fewer extrapyramidal side effects

75
Q

What are some unwanted side effects of antipsychotics? (4)

A
  • Irreversible dyskinesia
  • Weight gain
  • Hypotension
  • Sedation

L2 pharmacology (9 decks)

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