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pr3136 ca1 > L5 Antipsychotics > Flashcards

L5 Antipsychotics Flashcards

1
Q

What are the 5 symptom domains of schizophrenia?

A
  1. pos
  2. neg
  3. anx/dep
  4. aggressive
  5. cognitive
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2
Q

What kind of symptoms are most distressing for an individual with schizophrenia?

A

Negative symptoms. In contrast, positive phases are characterised by lack of insight (self-awareness of abnormal behaviour)

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3
Q

Examples of positive symptoms of schizophrenia (4)

A
  1. Delusions, often paranoid
  2. Hallucinations eg. exhortatory voices
  3. Thought disorder including feeling that thoughts are controlled by an outside agency
  4. Abnormal behaviours eg. stereotypical or aggressive behaviour
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4
Q

What kind of symptoms are most disturbing to others, usually leading to first referral to a psychiatrist and detection of schizophrenia?

A

Positive symptoms, abnormal behaviours added

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5
Q

Examples of negative symptoms of schizophrenia (2)

A
  1. Withdrawal from social contacts

2. Flattening of emotional responses

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6
Q

As the disease progresses, which kind of symptoms generally dominates?

A

Negative symptoms, normal behaviours subtracted

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7
Q

Why is cognitive dysfunction an important symptom of schizophrenia?

A

Predicts level of social and vocational functioning and hence, treatment outcome, better than positive symptoms
- Persistent core feature of the disease, not iatrogenic

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8
Q

What are some evidences suggesting that schizophrenia might be a neurodevelopmental disorder?

A
  • Onset in late adolescence/early adulthood is consistent with neurodevelopmental abnormality involving cortio-cortical pathways
  • Evidence of enlarged ventricles, abnormalities in laminar organisation of cortical cells
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9
Q

Neurochemical theories (3)

A

Primarily theories of the positive symptoms

  1. Dopamine Theory
  2. 5-HT (Serotonin) Theory
  3. Glutamate Theory
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10
Q

What is the most important basis for pharmacotherapy of schizophrenia?

A

All antipsychotic drugs are D2 antagonists - the dopamine theory

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11
Q

What is the dopamine theory?

A

Amphetamine produces symptoms similar to acute schizophrenia

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12
Q

What are the dopamine pathways of the brain? (4)

A
  1. Nigrostriatal
  2. Mesolimbic
  3. Mesocorticol
  4. Tuberoinfundibular
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13
Q

What is the MOA for many of the newer antipsychotics?

A

5-HT2 antagnosim - the serotonin theory

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14
Q

What is the serotonin theory?

A

LSD, a 5-HT2 agonist, produces symptoms similar to acute schizophrenia

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15
Q

What is the glutamate theory?

A

Drugs that block the NMDA receptor channel eg. phencyclidine (PCP) and ketamine, produce symptoms similar to acute schizophrenia

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16
Q

Which typical antipsychotic has a better side effect profile? Chlorpromazine or Haloperidol

A

Haloperidol

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17
Q

What are the side effects of chlorpromazine?

A
  • M1: dry mouth, constipation, blurred vision
  • H1: sedation, weight gain
  • a1: postural hypotension, dizziness
18
Q

What causes the EPS of D2 antagonist drugs?

A

Action on the extrapyrimidal motor pathways, almost simulating the same deficit as Parkinson’s

19
Q

Which of dyskinesia/akathisia correlates directly with duration on medication?

A

Akathisia, not dyskinesia

20
Q

What is the EPS side effect that occurs in 20-40% of patients on typical antipsychotics?

A

Tardive dyskinesia and akathisia

21
Q

Why is tardive dyskinesia and akathisia often irreversible?

A

Most probably de to upregulation or supersensitivity of dopamine receptors in the nigrostriatal system

22
Q

What is dyskinesia?

A

Repetitive and stereotyped involuntary movements of face, tongue, and limbs

23
Q

What is akathisia?

A

Involuntary movements and compulsion to act, associated with restlessness, anxiety, and agitation

24
Q

Examples of typical antipsychotics (4)

A

Chlorpromazine, haloperidol, trifluoperazine, fluphenazine

25
Q

What defines atypicality of antipsychotics?

A

Less severe EPS

  • not greater affinity at 5-HT2 or D4 receptors
  • not mixed antagonism at a-adrenoceptors, H1 histamine receptors, muscarinic acetylcholine receptors, and 5-HT2 receptors
26
Q

What is the ‘core’ of most atypical antipsychotics?

A

SDA: serotonin-dopamine antagonism (5HT2A, D2)

27
Q

What was the clinical use of clozapine limited by?

A

Agranulocytosis - develops in only approx 1% of patients on clozapine but can be fatal!

28
Q

What was the prototypical atypical antipsychotic drug?

A

Clozapine

29
Q

What did the clozapine-induced agranulocytosis adverse effect led to?

A

Development of compounds related to clozapine but without this adverse effect ie. olanzapine

30
Q

What is special about amisulpride?

A

Atypical pattern of receptor affinities for an atypical antipsychotic: no SDA!!!

  • selective D2/D3 antagonist, recently reported to have 5-HT7 antagonism
  • no 5HT2 antagonism
31
Q

Which of the atypical antipsychotic drugs has the fewest side effect?

A

Amisulpride - due to selectivity for D2/D3 receptors + absensce of a-adrenoceptor block, antihistaminergic, and anticholinergic side effects

32
Q

What is a notable side effect of amisulpride?

A

Increases prolactin release

33
Q

In presence of agonist, partial agonists have ________ effects?

A

antagonistic

34
Q

What is an additional adverse effect of atypical antipsychotic?

A

New onset or exacerbation of diabetes, does not reverse when drug is stopped

35
Q

Which atypical antipsychotic drug is an exception that does not induce hyperglycaemia and diabetes?

A

Amisulpride

- effect is strong for clozapine, olanzapine, risperidone

36
Q

Which of the atypical antipsychotic had been used in the treatment of anorexia nervous experimentally?

A

Olanzapine

37
Q

Does chlorpromazine (typical antipsychotic) cause weight gain?

A

No, H1 and a-adrenoceptor hypotheses do not explain this weight gain ADR of atypical antipsychotics

38
Q

How does a higher D2 to D1 antagonism ratio result in less EPS in atypical antipsychotics?

A

Should confer less complete blockade of dopaminergic function in the striatum as D2 antagonism will increase dopamine release

39
Q

Examples of atypical antipsychotics that are more effective against negative smx

A

clozapine, olanzapine, risperidone

40
Q

Examples of atypical antipsychotics that may ameliorate cognitive dysfunction

A

clozapine, risperidone

41
Q

Examples of atypical antipsychotics that are better at mood stabilisation

A

clozapine, olanzapine, risperidone

42
Q

Examples of atypical antipsychiatric

A

amisulpride, aripiprazole, clozapine, olanzapine, risperidone

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