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Pharmacotherapeutics > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

What are the general symptoms of schizophrenia?

A
  • Periods of acute presentation with positive symptoms (abnormal behaviors added) are interspersed with periods during which the negative symptoms (normal behaviors subtracted) predominate.
  • As the disease progresses, the negative symptoms become more dominant
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2
Q

Positive symptoms of schizophrenia

A
  • Delusions (often paranoia)
  • Hallucinations (e.g. exhortatory voices)
  • Thought disorder including feelings that thoughts are controlled by an outside agency.
  • Abnormal behaviours (e.g. stereotypical or aggressive behaviors).
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3
Q

Negative symptoms of schizophrenia

A
  • Withdrawal from social contacts

- Flattening of emotional responses

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4
Q

Possible cognitive dysfunction from schizophrenia

A
  • Impairment of selective attention and working memory.
  • Important because it predicts level of social vocational functioning.
  • Persistent feature of the disease, not iatrogenic (caused by the physican or medication).
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5
Q

Genetic factors that cause schizophrenia

A
  • Incomplete hereditary tendency (50% risk in monozygotic twin of affected individual).
  • Suspect chromosomal regions that prognosticate susceptibility to schizophrenia include:
    » DISC1, neuregulin-1, dysbindin-1 and catechol-O-methyl transferase (COMT).
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6
Q

Environmental factors that cause schizophrenia

A
  • Maternal viral infections during pregnancy

- Obstetric complications

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7
Q

What causes schizophrenia in late adolescents / early adults?

A

Neurodevelopmental abnormality involving myelination of cortico-cortical pathways.
» Evidence of enlarged ventricles, abnormalities in laminar organization of cortical cells, pointing to a possible neurodevelopmental disorder.

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8
Q

What are the different neurochemical theories?

A
  1. Dopamine Theory
    - Amphetamine produces symptoms similar to acute schizophrenia.
    - Basis for pharmacotherapy: All antipsychotic drugs are D2 antagonists, with drugs that are stronger on D2 receptor antagonism resulting in higher clinical efficacy.
    - Dopamine increases in acute schizophrenia. This results in impaired emotion, cognition and attention span.
    - Dopamine Pathways of the Brain
    » Nigrostriatal: part of the extrapyramidal motor system
    » Mesolimbic: reward and emotion
    » Mesocortical: cognition and attention
    » Tuberoinfundibular: regulates prolactin secretion
  2. 5-HT (Serotonin) Theory
    - LSD acts primarily as a 5-HT2 agonist, produces symptoms similar to acute schizophrenia.
    - Many of the newer atypical antipsychotics have 5-HT2 antagonism.
  3. The Glutamate Theory
    - Drugs which block the NMDA receptor channel (e.g. phencyclidine (PCP) and ketamine) produce symptoms similar to acute schizophrenia.
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9
Q

Names of typical antipsychotics

A

Chlorpromazine, Haloperidol

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10
Q

Names of atypical antipsychotics

A

Amisulpride, clozapine, olanzapine and risperidone, aripiprazole

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11
Q

Similarities between typical and atypical antipsychotics

A

Control positive symptoms of schizophrenia

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12
Q

Differences between typical and atypical antipsychotics

A

Atypical antipsychotics produce less EPS than typical ones.

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13
Q

What are examples of extrapyramidal side effects?

A
  1. Acute dystonias
    - Parkinsonism-like syndrome (e.g. cogwheel rigidity and tremor at rest).
    - Caused by D2 antagonism in the nigrostriatal pathway.
  2. Tardive dyskinesia and akathisia
    - Develop slowly (tardive) over months or years of treatment.
    - Repetitive and stereotyped involuntary movements of face, tongue and limbs (dyskinesia).
    - Involuntary movements and compulsion to act with restlessness, anxiety and agitation (akathisia).
    - Akathisia correlates directly with duration on medication, but not dyskinesia.
    - Caused by the upregulation or supersensitivity of dopamine receptors in the nigrostriatal system due to changes in dopamine pathways over time.
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14
Q

Chlorpromazine side effects

A
  1. M1 receptor: Dry mouth, constipation, blurred vision
  2. H1 receptor: Sedation, weight gain
  3. α1 receptor: postural hypotension, dizziness
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15
Q

Characteristics of atypical antipsychotics

A
  • Greater affinity at 5-HT2 receptors
  • Greater affinity at D4 receptors
  • Mixed antagonism at α-adrenoreceptors, H1 histamine receptors, muscarinic acetylcholine receptors and 5-HT2 receptors.
  • Serotonin-dopamine antagonism (SDA) is the “core” of most atypical antipsychotics.
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16
Q

Clozapine side effects

A
  • M1 receptor: dry mouth, constipation, blurred vision
  • H1 receptor: sedation, weight gain
  • α1 receptor: postural hypotension, dizziness
  • Clozapine-induced agranulocytosis
    » Clinical use of clozapine is limited by agranulocytosis.
    » Agranulocytosis develops in only approximately 1% of patients on clozapine but can be fatal.
    » Regular blood counts are required to ensure that patient does not develop agranulocytosis.
    »> Olanzapine: compound related to clozapine but without the adverse effect.
17
Q

Adverse effects of atypical antipsychotics

A
  1. Dry mouth, constipation, blurred vision
  2. Postural hypotension, reflex tachycardia
  3. Sedation
  4. New onset or exacerbation of diabetes
  5. Drug-induced weight gain
18
Q

Which drugs are likely to cause dry mouth, constipation, blurred vision?

A

clozapine and olanzapine

anticholinergic side effects

19
Q

Which drugs are likely to cause postural hypotension, reflex tachycardia?

A

risperidone

α1-adrenoceptor antagonism

20
Q

Which drugs are likely to cause sedation?

A

clozapine and olanzapine

histamine H1 receptor antagonism

21
Q

Which drugs are likely to cause new onset or exacerbation of diabetes?

A

Olanzapine (most prone), clozapine
Risperidone (diabetes does not reverse when drug is stopped)
Antisulpride is an exception

22
Q

Which drugs are likely to cause weight gain?

A

clozapine, olanzapine, and risperidone

23
Q

What are the adverse effects of amisulpride?

A
  • Few side-effects due to selectivity for D2/D3 receptor antagonism.
  • Absence of α-adrenoreceptor block, antihistaminergic, and anticholinergic side-effects.
  • Adverse effects on mammary glands and tissues:
    » Increased prolactin secretion due to the blockage of dopamine receptors in the anterior pituitary gland.
    » Breast swelling, pain and lactation.
    » Presents as gynecomastia in males.
24
Q

Which drugs have the strongest D1 receptor affinity?

A

clozapine, olanzapine

25
Q

Which drugs have the strongest D2 receptor affinity?

A

haloperidol, risperidone

26
Q

Which drugs have the strongest D3 receptor affinity?

A

amisulpride

27
Q

Which drugs have the strongest alpha adrenoreceptor affinity

A

risperidone

28
Q

Which drugs have the strongest H1 receptor affinity?

A

clozapine, olanzapine

29
Q

which drugs have the strongest muscarinic/cholinergic receptor affinity?

A

clozapine

30
Q

Receptor affinity of amisulpride

A

Amisulpride is a selective D2/D3 antagonist - may have 5-HT7 antagonism as well

31
Q

Why do atypical antipsychotics produce less EPS?

A
  • Potent 5-HT2A receptor antagonism (clozapine, olanzapine)
  • High D3 to D2 antagonism ratio favors actions on the nucleus accumbens over the striatum (clozapine).
  • High D4 to D2 antagonism ratio favors actions in the prefrontal cortex over the striatum (clozapine).
  • High D2 to D1 antagonism ratio reduces impact of antagonism in the striatum (amisulpride, risperidone).
    » Confer less complete blockade of dopaminergic function in the striatum as D2 antagonism will increase dopamine release
32
Q

Additional benefits of atypical antipsychotics

A
  • Some are more effective against negative symptoms of schizophrenia than typical antipsychotics.
    » Clozapine, olanzapine, risperidone
  • Some may ameliorate cognitive dysfunction
    » Clozapine, risperidone
  • Some may be better at mood stabilization than typical antipsychotics.
    » Clozapine, olanzapine, risperidone

Pharmacotherapeutics (28 decks)

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