Psychotic Disorders Flashcards

1
Q

What does the dopamine hypothesis suggest?

A

Psychosis is due to excess DA activity in the mesolimbic pathway. Theory is supported by iatrogenic psychosis caused by drugs that increase DA activity in the brain

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2
Q

How does the mesolimbic pathway work?

A

Its the pathway responsible for rewards, motivation, emotions and positive schizo symptoms. D2 antagonism decreases positive symptoms.

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3
Q

How does the mesocorticol pathway work?

A

It responds to cognition and executive functions, emotions and mood. Hypofunction of thus pathway leads to negative symptoms. Serotonin 2 antagonism leads to decrease in cognitive and negative symptoms

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4
Q

How does the nigrostrital pathway work?

A

Its the pathway responsible for motor planning and appropriate movement. D2 antagonism cause EPSEs and Tardive Dyskinesia

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5
Q

How does the tuberinfundibular pathway work?

A

Dopaminergic projections in hypothalamus. It inhibits prolactin release. D2 antagonism causes hyperprolactinemia.

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6
Q

What is the serotonin hypothesis for schizophrenia?

A

Serotonin 2A receptors activation modulates release of DA, NA, glutamate. 2A antagonists provides an antipsychotic effect.

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7
Q

What are some of the limitations of dop. Hypothesis?

A

Cognitive, Negative symptoms, Drug-Induced Psychosis, that is not dopamine related.

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8
Q

What are some symptoms of schizophrenia?

A

Postive - psychosis, hallucinations, delusions
Negative - social withdrawal, anhedonia, lack of motivation
Cognitive - diorganised speech and thoughts.

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9
Q

What are the catergories of antipsychotics?

A

1st generation - potent D2 antagonists
2nd generation - Serotonin 2 and D2 antagonists
3rd generation - Dopamine partial agonists.

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10
Q

What is the relationship of D2 occupancy and EPSEs?

A

The higher the % of binding to dopamine receptors, the more likely the patient is likely to experience EPSEs. Hyperprolactinaemia is also seen in this way.

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11
Q

What are side effects of 1st generation antipsychotics relating to neurotransmitters?

A

H1 - sedation, weight gain
Alpha1 - postural hypotension
M- anticholinergic SE

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12
Q

List 4 examples of 1st generation agents

A

Chlorpromazine, Flupenthixol, Haloperidol, Pimozide, Sulpiride.

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13
Q

What is the MOA of 2nd generation agents?

A

Block 5HT2A receptors, also 5HT2C, 1D and 5HT1 (Agonism) and also block dopamine 2 receptors to a lesser extent.

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14
Q

What are 5 examples of 2nd generation agents?

A

Clozapine, Quetiapine, Risperidone, Ziprasidone, Olanzapine

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15
Q

What is the MoA of 3rd generation agents?

A

They are partial D2 agonists, 5HT2a antagonists and partial 5HT1a agonist effects.

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16
Q

Why was brexipiprazole brought to the market?

A

Aripiprazole is very effective but may cause agitation, anxiety and insomnia

17
Q

What are the pharmacokinetics of aripiprazole?

A

Time to peak plasma concentrations: 3-5 hours
Half-life 75 hours.
Highly plasma protein bound (99%)
Hepatically metabolized CYP3A4, CYP2D6

18
Q

What are the possible benefits of 5HT-1 agonism?

A

Anxiolytic, antidepressant, improves cognition.

19
Q

Which antipsychotics cause metabolic abnormalities?

A

Clozapine, Olanzapine cause weight gain, increase lipids, and increase in glucose.

20
Q

What are some cardiovascular effects?

A

Postural hypotension- chlorprozamine, clozapine and risperidone.
Soms agents (haloperidol and ziprasidone and quetiapine.) Cause QT prolongation

21
Q

How is antipsychotic-induced EPSEs reduced?

A

Decrease dose of antipsychotic, recommend an anticholinergic agent (biperidin), amantidine, may add benzodiazepine.

22
Q

What is neuroleptic malignant syndrome?

A

More common with typical antipsychotics, symptoms include severe muscle rigidity, fever, leukocytosis, increased creatine kinase levels. Its due to excessive rapid blockade of D2 receptors.

23
Q

What is the treatment neuroleptic malignant syndrome?

A

Dopamine agonist, muscle relaxants, reduce fever, consider atypical agent.