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3922 > 16 - Antipsychotics > Flashcards

16 - Antipsychotics Flashcards

1
Q

What is schizophrenia

A

Disorder of higher cognitive function

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2
Q

What kind of abnormalities in the brain lead to schizophrenia

A

Structural

Neurochemical

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3
Q

What are some risk factors for schizophrenia (5)

A 
Genes
Prenatal factors
Early-life stress
Drugs
Stressful life events
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4
Q

What are the positive symptoms of schizophrenia (3)

A

Hallucinations
Delusions
Disorganised thought and speech

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5
Q

What are the negative symptoms of schizophrenia (4)

A

Flattened affect
Alogia
Avolution/apathy
Anhedonia

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6
Q

What are the cognitive symptoms of schizophrenia

A

Impaired memory

Impaired executive function

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7
Q

What are some physical treatments for schizophrenia

A

Frontal lobotomy

Electroconvulsion therapy

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8
Q

What are indications of antipsychotics

A

Treatment of psychosis and symptoms of schizophrenia

Treatment of schizophrenia in ‘treatment resistant patients who fail to respond to other antipsychotic drugs’

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9
Q

What was the first antihistamine

A

Chlorpromazine

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10
Q

What do antipsychotics antagonist

A

D2 receptors

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11
Q

What is the correlation between therapeutic efficacy and affinity for D2 receptors

A

Linear

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12
Q

When is clinical efficacy of D2 drugs achieved

A

Receptor occupancy up to 80%

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13
Q

What are arguments for ‘excess levels of dopamine increase neurological activity leading to schizophrenia’ 1.

A
  1. Amphetamines and other dopamine-releasing drugs induce a state resembling the positive symptoms of schizophrenia
  2. Antipsychotic drugs antagonise D2 receptors
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14
Q

What are arguments against the ‘excess dopamine’ hypothesis 1.

A
  1. No evidence of increased dopamine turnover in schizophrenic brain
  2. Inconsistent changes in concentrations post-mortem
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15
Q

What are arguments for increased dopamine receptors in schizophrenia 2.

A
  1. Increased dopamine receptors are found in schizophrenia brain
  2. Increased binding and affinity of DA in schizophrenic brain
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16
Q

What are arguments against increased dopamine receptors in schizophrenia 2.

A

Antipsychotics upregulate DA receptors

17
Q

What is the dopamine hypothesis of schizophrenia 3.

A

Elevated presynaptic striatal dopamininergic function is the final common pathway in psychosis

18
Q

What is the dopamine hypothesis of schizophrenia 4.

A

GABAergic deficit in hippocampus underlies DA dysregulation in the nucleus accumbens and medial prefrontal cortex

19
Q

What are some presynaptic DA abnormalities

A

1) DA levels, synthesis or release are elevated in key brain areas
2) Deficiencies in other neurotransmitters lead to DA dysregulation
3) D2 receptors are supersensitive, blockade reduces overactivity and alleviates psychosis

20
Q

What do the different dopamine pathways mediate

A

Mesolimbic - therapeutic
Nigrostriatal - movement side effects
Tuberoinfundibular - endocrine

21
Q

What are the three major classes of

first generation antipsychotics

A
  1. Phenothiazines
  2. Butyrophenones
  3. Thioxanthenes
22
Q

What are major classes of second generation antipsychotics

A 
Diazepines
Dibenzothiapines
Benzamides
Benzisoxazols
Quinolinone derivative
23
Q

Which antipsychotics have better therapeutic efficacy (2)

A

Atypical antipsychotics
Fewer side effects
Effective in ‘treatment resistant’ patients

24
Q

What are the receptor actions of atypical antipsychotics

A

High-affinity of 5HT2 receptors

Moderate affinity for adrenergic and D3 receptors

25
Q

Which receptors do clozapine and olanzapine have high affinity for

A

D4 receptors

26
Q

How quickly does clozapine dissociate fro receptors

A

Rapidly

27
Q

How do antipsychotics work in the short term

A

Block D2 autoreceptors increasing DA release
Block supersensitive D2 postsynaptic receptors, decreasing DA inhibiti)n
(More chance of cell firing:

28
Q

How do antipsychotics work in the long term

A

Upregulation of presynaptic D2 receptors reduces DA release
Blockade of D2 receptors and upregulation of these receptors restores homeostasis
(Restores ‘normal cell firing’)

29
Q

What is first line treatment for schizophrenia

A

Atypical antipsychotic (olanzapine)

30
Q

What are 4 arguments for glutamate role in schizophrenia

A
  1. PCP (NMDA receptor antagonist precipitates symptoms of schizophrenia, both positive and negative)
  2. NMDA receptor knockdown mice show symptoms of schizophrenia
  3. Changes in glutamate receptor and transporter expression in prefrontal cortex and temporal lobes
  4. Reduced pyramidal cell dendrites and dendritic spines
31
Q

What are some novel approaches to schizophrenia drugs (5)

A
  • Enhancing glutamatergic activity (glycine transporter blockers and site partial agonists)
  • Increasing GABAergic tone (Sodium valproate and benzodiazepines as adjunct therapy)
  • Ratio fo D2/5-HT affinities
  • D2/5-HT2A with 5HT7 antagonism
  • Cannabidiol

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