Antipsychotic Agents PSYCH Flashcards
Developmental model for psychosis
Mesocortical pathway is hypoactive & Mesolimbic pathway is hyperactive
• Development of hypo-frontality
o Prefrontal cortex is supposed to inhibit VTA
o Initially drugs blocked D2 receptors in VTA – Nac circuit
o Unfortunately, the PFC – VTA circuit also uses D2 so you make the PFC control of VTA worse
o Also drugs that block D2 also increase prolactin because dopamine inhibits prolactin
o Also loss of dopamine produces Parkinson like muscular syndromes
Neurodegenerative Model
• Glutamatergic dysregulation leads to apoptosis i.e. neurodegeneration
o Effect seen after PCP use and psychosis
o NMDA antagonists produce + and - deficits
What is a typical antipstychotic
- D2 blockers
* Cholinergic so cause extrapyramidal symptoms: Movement & Parkinsonian
Name 4 typical antipsychotics
- Chlorpromazine
- Perphenazine
- Haloperidol
- Fluphenazine
Most potent & least typical antipsychotic
Lowest: • Chlorpromazine
Highest: • Fluphenazine
How long for typical antiP drugs to take effect
Months for insight & cognitive improvement
Days for improved behavior, sleep & confusion
Side effects of typical antiP at low dose
- Dry mouth, blurred vision, constipation, urinary retention, hypotension, sedation, weight gain
- Less acute dystonia, NMS
- Parkinsonism, Akathisia, tardive dyskinesia
- Prolactin elevation
Side effects of typical antiP at high dose
- More acute dystonia, NMS
- Parkinsonism, Akathisia, tardive dyskinesia
- Prolactin elevation
Neurological side effects in atypical antiP
- 1-5 days: Acute dystonia (spasms)
- 5-30 days: Parkinsonism
- 5-60 days: Akathisia (motor restlessness)
- Months: Tardive dyskinesia * perioral tremor
What is neuroleptic maligant synndrome
Excess D2 syndrome (sympathetic activation)
- Fever
- Rigidity
- Elevated CPK
- Tachycardia
- Abnormal blood pressure
- Tachypnea
- Altered consciousness
- Diaphoresis
What are atypical/novel antipsytoics
D2 agonist
Often serotonin agonist
What is the most effective atypical/novel antipsytoics
Clozapine
Benefits of atypical antiP over typical
- Useful in affective psychosis
- Suicidal patients
- Fewer neurological SE
- Less likely to cause relapse s because it does not block D2 so you restore prefrontal functioning
- Improved efficacy
Clozapine
Use
Impact of suicide attempts
Hematological SE
Other Side Effect
Use
Impact of suicide attempts
Decreased
Hematological SE
• Agranulocytosis
Other Side Effect • Fewer EPS • Minimal prolactin elevation • Seizures • Myocarditis • Tachycardia • Drooling • Sedation • Liver function reduced
Mechanism of atypical antiP, respiradone, olanzapine & quetiapine?
• 5HT & D2 receptor blocker
