Psychopharmacology Treatments of Psychotic Disorders Flashcards

1
Q

What are key pathways affected by dopamine in the brain?

A
  • Mesocortical
    • Projects from ventral tegmentum (brain stem) to the cerebral cortex
    • Is where negative symptoms and cognitive disorders (lack of executive function) arise
    • Problem for psychotic patient is too little dopamine
  • Mesolimbic
    • Projects from dopaminergic cell bodies in ventral tegmentum to the limbic system
    • Is where positive symptoms come from (hallucinations, delusions, thought disorders)
    • Problem for psychotic patient is too much dopamine
  • Nigrostriatal
    • Projects from dopaminergic cell bodies in substantia nigra to the basal ganglia
    • Involved in movement regulation
    • Dopamine suppresses acetylcholine activity
      • Dopamine hypoactivity can cause Parkinsonian movements (such as rigidity, bradykinesia, tremors) and akathisia and dystonia
  • Tuberoinfundibular
    • Projects from hypothalamus to anterior pituitary
    • Remember dopamine release inhibits/regulates prolactin release
    • Blocking dopamine in this pathway will predispose patient to hyperprolactinemia (gynecomastia, galactorrhea, decreased libido, menstrual dysfunction)
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2
Q

Where do the following pathways project from and to:

  • mesocortical
  • mesolimbic
  • nigrostriatal
  • tuberoinfundibular
A
  • Mesocortical
    • Projects from ventral tegmentum (brain stem) to the cerebral cortex
  • Mesolimbic
    • Projects from dopaminergic cell bodies in ventral tegmentum to the limbic system
  • Nigrostriatal
    • Projects from dopaminergic cell bodies in substantia nigra to the basal ganglia
  • Tuberoinfundibular
    • Projects from hypothalamus to anterior pituitary
      *
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3
Q

Where do the negative and positive symptoms of psychosis come from (what pathways)?

A
  • Negative symptoms
    • Mesocortical
  • Positive symptoms
    • Mesolimbic
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4
Q

In the following pathways is the problem for the psychotic patient too much or too little dopamine:

  • mesocortical
  • mesolimbic
A
  • Mesocortical
    • Problem for psychotic patient is too little dopamine
  • Mesolimbic
    • Problem for psychotic patient is too much dopamine
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5
Q

What is the nigrostriatal pathway involved in?

A
  • Involved in movement regulation
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6
Q

What does dopamine do in the nigrostriatal pathway?

A
  • Projects from dopaminergic cell bodies in substantia nigra to the basal ganglia
  • Involved in movement regulation
  • Dopamine suppresses acetylcholine activity
    • Dopamine hypoactivity can cause Parkinsonian movements (such as rigidity, bradykinesia, tremors) and akathisia and dystonia
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7
Q

What effect does dopamine hypoactivity have on the nigrostriatal pathway?

A
  • Nigrostriatal
    • Projects from dopaminergic cell bodies in substantia nigra to the basal ganglia
    • Involved in movement regulation
    • Dopamine suppresses acetylcholine activity
      • Dopamine hypoactivity can cause Parkinsonian movements (such as rigidity, bradykinesia, tremors) and akathisia and dystonia
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8
Q

What are examples of Parkinsonian movements?

A
  • Dopamine hypoactivity can cause Parkinsonian movements (such as rigidity, bradykinesia, tremors) and akathisia and dystonia
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9
Q

How does dopamine release affect prolactin release?

A
  • Tuberoinfundibular
    • Projects from hypothalamus to anterior pituitary
    • Remember dopamine release inhibits/regulates prolactin release
    • Blocking dopamine in this pathway will predispose patient to hyperprolactinemia (gynecomastia, galactorrhea, decreased libido, menstrual dysfunction)
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10
Q

What does blocking dopamine in the tuberoinfundibular pathway cause?

A
  • Tuberoinfundibular
    • Projects from hypothalamus to anterior pituitary
    • Remember dopamine release inhibits/regulates prolactin release
    • Blocking dopamine in this pathway will predispose patient to hyperprolactinemia (gynecomastia, galactorrhea, decreased libido, menstrual dysfunction)
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11
Q

What are the 2 classes of antipsychotics?

A
  • Typicals
    • High potency D2 dopamine receptor antagonist
      • As result higher risk of extrapyramidal side effects
      • Drugs – Fluphenazine, Haloperidol and Pimozide
    • Low potency D2 dopamine receptor antagonist
      • Tender to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects such as sedation, hypotension
      • Drugs – Chlorpromazine
  • Atypicals
    • Serotonin-dopamine 2 antagonists (SDAs)
    • Atypical as affect both
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12
Q

What are the different kinds of typical antipsychotics?

A
  • High potency D2 dopamine receptor antagonist
    • As result higher risk of extrapyramidal side effects
    • Drugs – Fluphenazine, Haloperidol and Pimozide
  • Low potency D2 dopamine receptor antagonist
    • Tender to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects such as sedation, hypotension
    • Drugs – Chlorpromazine
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13
Q

What kind of side effects are associated with high potency typical antipsychotics?

A
  • High potency D2 dopamine receptor antagonist
    • As result higher risk of extrapyramidal side effects
    • Drugs – Fluphenazine, Haloperidol and Pimozide
  • Low potency D2 dopamine receptor antagonist
    • Tender to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects such as sedation, hypotension
    • Drugs – Chlorpromazine
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14
Q

What are examples of high potency typical antipsychotics?

A
  • Drugs – Fluphenazine, Haloperidol and Pimozide
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15
Q

What side effects are associated with low potency typical antipsychotics?

A
  • Tender to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects such as sedation, hypotension
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16
Q

What is an example of a low potency typical antipsychotic?

A
  • Drugs – Chlorpromazine
17
Q

What is the mechanism of action of typical antipsychotics?

A

D2 dopamine receptor antagonist

18
Q

What is the mechanism of action of atypical antipsychotics?

A
  • Serotonin-dopamine 2 antagonists (SDAs)
19
Q

What side effects are atypical antipsychotics associated with?

A

Both extrapyramidal and cardiotoxic/anticholinergic

20
Q

What are the most commonly used antipsychotics?

A
  • Risperidone
    • Side effects – extrapyramidal side effects, hyperprolactinaemia, weight gain and sedation
  • Olanzapine
    • Side effects – hypertriglyceridemia, hypercholesterolemia, hyperglycaemia, hyperprolactinaemia, abnormal LFTs
  • Quetiapine
    • Side effects – abnormal LFTs, weight gain, hypertriglyceridemia, hypercholesteraemic, hyperglycaemia, orthostatic hypotension (most likely to cause)
  • Aripiprazole
    • Unique mechanism of action as D2 partial agonist so less cardio side effects
    • Side effects – akathisia/activation
21
Q

For risperidone:

  • side effects
A
  • Side effects – extrapyramidal side effects, hyperprolactinaemia, weight gain and sedation
22
Q

For olanzapine:

  • side effects
A
  • Side effects – hypertriglyceridemia, hypercholesterolemia, hyperglycaemia, hyperprolactinaemia, abnormal LFTs
23
Q

For quetiapine:

  • side effects
A
  • Side effects – abnormal LFTs, weight gain, hypertriglyceridemia, hypercholesteraemic, hyperglycaemia, orthostatic hypotension (most likely to cause)
24
Q

For aripiprazole:

  • mechanism
  • side effects
A
  • Unique mechanism of action as D2 partial agonist so less cardio side effects
  • Side effects – akathisia/activation
25
Q

How do you pick first line antipsychotic?

A

How to pick which first line agent:

  • Efficacy similar, based on side effect profile
  • Good rule of thumb, 1/3 good response, 1/3 some response and 1/3 poor response
26
Q

What antipsychotic is used for treatment resistance?

A
  • Clozapine
    • Side effects – agranulocytosis so required weekly bloods for 6 months, seizures, sedation, weight gain, abnormal LFTs, hypertriglyceridemia, hypercholesterolemia, hyperglycaemia
27
Q

For clozapine:

  • side effects
A
  • Side effects – agranulocytosis so required weekly bloods for 6 months, seizures, sedation, weight gain, abnormal LFTs, hypertriglyceridemia, hypercholesterolemia, hyperglycaemia
28
Q

What are indications for antipsychotics?

A
  • Schizophrenia
  • Schizoaffective disorder
  • Bipolar disorder for mood stabilisation and/or when psychotic features present
  • Psychotic depression
  • Augmenting agent in treatment resistant repressive and anxiety disorders
29
Q

What are the general side effects of antipsychotics?

A
  • Tardive dyskinesia
    • Involuntary muscle movements
  • Neuroleptic malignant syndrome
    • Severe muscle rigidly, fever, altered mental status, autonomic instability, elevated WBC
  • Extrapyramidal side effects (EPS)
    • Acute dystonia, Parkinson syndrome, Akathisia
    • Can treat these effects with anticholinergics such as benztropine, or dopamine facilitation such as Amantadine or beta blockers such as proponalol
30
Q

What is tardive dyskinesia?

A
  • Tardive dyskinesia
    • Involuntary muscle movements
31
Q

What are clinical features of neuroleptic malignant syndrome?

A
  • Neuroleptic malignant syndrome
    • Severe muscle rigidly, fever, altered mental status, autonomic instability, elevated WBC
32
Q

What are clinical features of extrapyramidal side effects?

A
  • Extrapyramidal side effects (EPS)
    • Acute dystonia, Parkinson syndrome, Akathisia
33
Q

How can extrapyramidal side effects be treated?

A
  • Extrapyramidal side effects (EPS)
    • Acute dystonia, Parkinson syndrome, Akathisia
    • Can treat these effects with anticholinergics such as benztropine, or dopamine facilitation such as Amantadine or beta blockers such as proponalol
34
Q

What are indications for anxiolytics?

A

Indications:

  • Panic disorder
  • Generalised anxiety disorder
    • Often used in combination with SSRIS or SNRIs
  • Substance-related disorders and their withdrawal
  • Insomnias
  • Parasomnias
35
Q

What are examples of benzodiazepines?

A

Drugs:

  • Alprazolam (Xanax)
  • Chloridiaze poxide (Libtrium)
  • Clonazepam (Klonopin)
  • Diazepam (Valium)
36
Q

What are indications for benzodiazepines?

A

Indications:

  • Insomnia
  • Parasomnias
  • Anxiety disorders
  • CNS depressant withdrawal protocols
37
Q

What are side effects of benzodiazepines?

A

Side effects:

  • Dependence
  • Somnolence
  • Cognitive deficits
  • Amnesia
  • Disinhibition
  • Tolerance