- What is the glutamate disorder hypothesis?

1. NMDA receptor antagonists can manifest select aspects of schizophrenia 2. Agents that modulate glycine modulatory site NMDA/AMPA receptor reduce some cognitive symptoms of schizophrenia 3. Cognitive symptoms may be due to low activity of NMDA/AMPA receptor on GABA inhibitor interneurons in prefrontal cortex

Antipsychotics Flashcards by Zachary Harbin

What are some indications of antipsychotics?

Recurrent suicidal behavior

- Hallucinations/Delusions associated with Parkinson Disease psychosis

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What is the dopamine hypothesis?

Chlorpromazine serendipitously found to have antipsychotic activity
Direct/indirect DA-agonists provoke psychotic reactions in non-schizophrenics and exacerbate symptoms in schizophrenics
PET studies have revealed alterations in DA-mediated transmission in schizphrenics

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What are positive symptoms of schizophrenia?

Hallucinations
Delusions
Disorganized speech/thinking
Agitation
Abnormal motor behavior

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What is the anatomy of the mesolimbic pathway in schizophrenia?

Projections from the ventral tegmental area to the nucleus accumbens

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What is the physiology of the mesolimbic pathway schizophrenia?

Motivation
Emotions
Reward
Positive symptoms of schizophrenia

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What is the anatomy of the mesocortical pathway in schizophrenia?

Projections from the ventral tegmental area to the cortex

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What is the physiology of the mesocortical pathway in schizophrenia?

Cognition and executive functions

- Emotions and affect

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What are the implications of the mesolimbic pathway in schizophrenia?

D2 antagonists reduce positive symptoms of schizophrenia

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What are the implications of the mesocortical pathway in schizophrenia?

Hypofunction of the mesocortical pathway might be related to cognitive and negative symptoms in schizophrenia

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What are the negative symptoms of schizophrenia?

Apathy
Avolition
Alogia
Cognitive deficits
Social withdrawal

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What is the anatomy of the nigrostriatal pathway and EPS?

Projections from substantia nigra to striatum

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What is the physiology of the nigrostriatal pathway and EPS?

Stimulation of purposeful movement

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What are the implications of the nigrostriatal pathway and EPS?

D2 antagonism induces extrapyramidal symptoms (pseudoparkinsonism)

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What is the anatomy of the tuberoinfundibular pathway and prolactin release?

Hypothalamus to infundibular region

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What is the physiology of the tuberoinfundibular pathway and prolactin release?

Dopamine is released into the portal circulation connecting the median eminence with the anterior pituitary gland
Dopamine tonically inhibits prolactin release

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What are some implications of the tuberoinfundibular pathway and prolactin release?

D2 antagonism increases prolactin levels

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What are the four dopaminergic pathways?

Mesolimbic pathway
Mesocortical pathway
Nigrostriatal pathway
Tuberoinfundibular pathway

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What is the schizophrenia hypotheses?

Limits to dopamine hypothesis
1. Does not account for all cognitive deficits/negative symptoms associated with schizophrenia
2. Does not fully explain role of other neurotransmitters or other receptors

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What is the glutamate disorder hypothesis?

NMDA receptor antagonists can manifest select aspects of schizophrenia
Agents that modulate glycine modulatory site NMDA/AMPA receptor reduce some cognitive symptoms of schizophrenia
Cognitive symptoms may be due to low activity of NMDA/AMPA receptor on GABA inhibitor interneurons in prefrontal cortex

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What is the early-life neurodevelopmental disorder hypothesis?

Youth/adolescence genetic/environmental impact during pivotal neurodevelopmental stages leads to later-life symptoms and presentation of worsening impacts

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What do the therapeutic choices start with when treating psychotic disorders?

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Previous dosing history

- Tolerance to known side effects

What is the minimum therapy necessary in order to evaluate response to therapy?

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2-3 weeks

- Max benefit may take several months

What is the best for rapid response in treating psychotic disorders?

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Injectable versions

- Acute high doses are not universally beneficial

When is favorable prognosis seen in treating psychotic disorders?

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Shorter duration and less severe symptoms of disease prior to diagnosis/treatment]
Strong, positive pre-illness functionality

What is the MOA of first generation antipsychotics (FGAs)?

- Primarily block dopamine type-2 post synaptic receptors (D2>> 5-HT)

What else does FGAs do?

- Also block one or more other receptors (primarily inducing SE's) 1. Muscarinic 2. Histaminic 3. Alpha-adrenergic 4. D2 receptors in nigrostriatal and tuberoinfundibular

What are the muscarinic side effects of FGAs?

- Dry mouth - Constipation - Urinary retention - Blurred vision - Sedation

What are the alpha adrenergic side effects of FGAs?

- Orthostatic hypotension | - Dizziness/syncope

What are the histamine side effects of the FGAs

- Sedation

What are some other side effects of FGAs?

- Rick of QT prolongation and seizure activity

What are some dopamine associated side effects of FGAs?

- Hyperprolactinemia (amenorrhea/galactorrhea/gynecomastia/decreased libido) - Extrapyramidal symptoms/Tardive dyskinesia

What are some treatments for extrapyramidal symptoms (EPS)?

1. Anticholinergic agents (benztropine and trihexyphenidyl) | 2. Antihistamine agents (diphenhydramine)

What are some treatment for tardive dyskinesia (TD)?

1. Selective vesicular monoamine transporter 2 (VMAT2) inhibitors (valbenazine and deutetrabenazine)

What is the MOA of second generation antipsychotics (SGAs)?

- Not only block dopamine type 2 post synaptic receptors they also block 5HT - They are stronger 5HT blockers than D2

What are the four broad categories of SGAs?

1. 5HT-2A/DA receptor antagonists 2. Partial DA/5HT-1A receptor agonists 3. Multi-acting receptor target agents 4. Inverse serotonin agonist/antagonist

What are some 5HT-2A/DA receptor antagonist drugs?

- Iloperidone - Lurasidone - Paliperidone - Risperidone - Ziprasidone

What are some partial DA/5HT-1A receptor agonist drugs?

- Aripiprazole | - Brexpiprazole

What are some multi acting receptor target agents?

- Asenapine - Clozapine - Olanzapine - Quetiapine - Lumateperone

What are some inverse serotonin agonist/antagonists?

- Primavanserion

What are some side effects of SGAs?

- Weight gain - Metabolic effects - QT prolongation/ECG changes - Stroke

What is monitored during antipsychotic treatment?

- Serum glucose - Lipids - Weight - BP - Waist circumference and personal/family histories of metabolic and CV disease (if possible)

What are some ways to monitor antipsychotics?

- GASS - AIMS - BARS - SAS

What are some rare side effects of SGAs?

- Agranulocytosis (clozapine) - Drug reaction with eosinophilia and systemic symptoms (DRESS) (olanzapine) - Neuroleptic Malignant Syndrome (NMS)

What is the treatment of Neuroleptic Malignant Syndrome?

- Dantrolene (malignant hyperthermia)

What may be needed after dose escalation or when switching agents?

- Combination of antipsychotic therapy may be necessary clinically

What is the best for acute agitation?

- Injectable and ODT or SL versions

What is the best treatment of multi-drug resistant disease of psychotic diseases?

- Clozapine

What is critical in treatment of psychotic disorders?

- Adherence

How can non-adherence be managed?

- Long acting injectable agents (LAIAs)

What are some LAIAs?

- Haloperidol - Fluphenazine - Risperidone - Olanzapine - Aripiprazole

Antipsychotics Flashcards

(50 cards)