Psychotic Disorders

Question 1

chlorpromazine (Thorazine), thioridazine (Mellaril)

Answer 1

Psychotic Disorders
Typical Antipsychotic (1st Generation) 
• Low Potency 
- more likely to have additional effects at histamine, acetylcholine, and adrenergic receptors
MOA 
- Dopamine-2 (D2) Receptor Antagonists
o Blockade of receptors prevents Dopamine (DA) binding
Pros 
• Effective for psychotic symptoms (positive sx of schizophrenia)
Cons
• Possibly worsen other symptoms, such as negative symptoms (pts may already be low in dopamine à lower more by using dopamine blockers)
• Adverse effects
ADE
• *Neuroleptic Malignant Syndrome
• Anticholinergic effects 
• Orthostatic Hypotension
• Sedation  
BLACK BOX
o Black box warning for increased mortality in elderly patients with dementia related psychosis
D/I
• Cytochrome P450

Question 2

*haloperidol (Haldol), *fluphenazine (Prolixin), pimozide (Orap)

Answer 2

Psychotic Disorders
Typical Antipsychotic (1st Generation) 
• High Potency
- more selective for D2 receptors
MOA 
= Dopamine-2 (D2) Receptor Antagonists
o Blockade of receptors prevents Dopamine (DA) binding
Pros 
• Effective for psychotic symptoms (positive sx of schizophrenia)
Cons
• Possibly worsen other symptoms, such as negative symptoms (pts may already be low in dopamine à lower more by using dopamine blockers)
• Adverse effects
ADE
• *Early Onset Extrapyramidal Symptoms
• *Neuroleptic Malignant Syndrome
• *Hyperprolactinemia 
• *Heart related effects
• Anticholinergic effects 
• Orthostatic Hypotension
• Sedation  
BLACK BOX
o Black box warning for increased mortality in elderly patients with dementia related psychosis
D/I
• Cytochrome P450

Question 3

aripriprazole (Abilify), cariprazine (vraylar), clozapine

Answer 3

Psychotic Disorders
Atypical Antipsychotic (2nd Generation)
• ***Clozapine is preferred in treatment refractory patients
MOA
= Atypicals have an “atypical” mechanism of action
o D2 antagonists AND 5-HT2A (serotonin) antagonists
• Blockade of 5-HT2A prevents DA inhibition à DA functions “normally”
Pros
o Also effective for psychotic symptoms (positive sx)
o Theoretically less worsening of negative symptoms
Cons
o Adverse effects
o In practice, the theoretical benefits with regards to their unique mechanism have been limited (haven’t seen huge benefit in negative sx)
ADE
• *Weight gain and Metabolic Syndrome
• Anticholinergic effects
• Orthostatic Hypotension
• Sedation
ADE clozapine
o *Constipation, higher risk seizures, agranulocytosis, sialorrhea
BLACK BOX
o Black box warning for increased mortality in elderly patients with dementia related psychosis
• Clozapine = **Black box warnings for agranulocytosis, seizures, myocarditis, and other cardiac and respiratory effects
D/I
• Cytochrome P450