Psychotic Disorders Flashcards
What does the dopamine hypothesis suggest?
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
How does the mesolimbic pathway work?
Its the pathway responsible for rewards, motivation, emotions and positive schizo symptoms. D2 antagonism decreases positive symptoms.
How does the mesocorticol pathway work?
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
How does the nigrostrital pathway work?
Its the pathway responsible for motor planning and appropriate movement. D2 antagonism cause EPSEs and Tardive Dyskinesia
How does the tuberinfundibular pathway work?
Dopaminergic projections in hypothalamus. It inhibits prolactin release. D2 antagonism causes hyperprolactinemia.
What is the serotonin hypothesis for schizophrenia?
Serotonin 2A receptors activation modulates release of DA, NA, glutamate. 2A antagonists provides an antipsychotic effect.
What are some of the limitations of dop. Hypothesis?
Cognitive, Negative symptoms, Drug-Induced Psychosis, that is not dopamine related.
What are some symptoms of schizophrenia?
Postive - psychosis, hallucinations, delusions
Negative - social withdrawal, anhedonia, lack of motivation
Cognitive - diorganised speech and thoughts.
What are the catergories of antipsychotics?
1st generation - potent D2 antagonists
2nd generation - Serotonin 2 and D2 antagonists
3rd generation - Dopamine partial agonists.
What is the relationship of D2 occupancy and EPSEs?
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.
What are side effects of 1st generation antipsychotics relating to neurotransmitters?
H1 - sedation, weight gain
Alpha1 - postural hypotension
M- anticholinergic SE
List 4 examples of 1st generation agents
Chlorpromazine, Flupenthixol, Haloperidol, Pimozide, Sulpiride.
What is the MOA of 2nd generation agents?
Block 5HT2A receptors, also 5HT2C, 1D and 5HT1 (Agonism) and also block dopamine 2 receptors to a lesser extent.
What are 5 examples of 2nd generation agents?
Clozapine, Quetiapine, Risperidone, Ziprasidone, Olanzapine
What is the MoA of 3rd generation agents?
They are partial D2 agonists, 5HT2a antagonists and partial 5HT1a agonist effects.
Why was brexipiprazole brought to the market?
Aripiprazole is very effective but may cause agitation, anxiety and insomnia
What are the pharmacokinetics of aripiprazole?
Time to peak plasma concentrations: 3-5 hours
Half-life 75 hours.
Highly plasma protein bound (99%)
Hepatically metabolized CYP3A4, CYP2D6
What are the possible benefits of 5HT-1 agonism?
Anxiolytic, antidepressant, improves cognition.
Which antipsychotics cause metabolic abnormalities?
Clozapine, Olanzapine cause weight gain, increase lipids, and increase in glucose.
What are some cardiovascular effects?
Postural hypotension- chlorprozamine, clozapine and risperidone.
Soms agents (haloperidol and ziprasidone and quetiapine.) Cause QT prolongation
How is antipsychotic-induced EPSEs reduced?
Decrease dose of antipsychotic, recommend an anticholinergic agent (biperidin), amantidine, may add benzodiazepine.
What is neuroleptic malignant syndrome?
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.
What is the treatment neuroleptic malignant syndrome?
Dopamine agonist, muscle relaxants, reduce fever, consider atypical agent.
