Drug- induced physchoses
- Anticholinergic drugs
- Benzodiazepines
- Antipsychotic agents
- Dopaminergic agents
- Corticosteroids
- Withdrawal from sedatives/alcohol
Positive Symptoms vs. Negative Symptoms
Positive symptoms: Symptoms that you would expect to be present in patients with Psychosis/depression -Delusions -Hallucinations -Disorganized thoughts/speech
Negative Symptoms:
Harder to detect Symptoms that you would NOT expect to find in healthy patients, but find in mentally ill patients:
- > Anhedonia (inability to feel pleasure)
- > Flattened affect
- > Apathy
Important OLDER Antipsychotics
1) Chlorpromazine -> low potency
2) Perphenazine, Thiothizene -> Medium potency
3) Haloperidol -> HIGH potency
Antipsychotics/Neuroleptics MOA:
1) Blockade of dopamine (D2) receptors
- > Older agents
2) Plus/minus blockade of serotonin (5HT2A) receptors
- > Newer agents (aka: atypicals)
4 dopamine tracts in the brain (these are the targets to block Dopamine activity):
1) Mesolimbic tract
2) Nigrostriatal tract
3) Mesocortical tract
4) Tuberoinfundibular tract
People with psychosis (ie Schizophrenia) have overactivity of one of these tracts
mesolimbic
antipsychotic (positive symptoms)
mesocortical
antipsychotic (negative symptoms)
nigrostriatal
extrapyramidal movements
tuberoinfundibular
prolactin release
Consequences of Blocking Mesolimbic Dopaminergic Pathway
Antipsychotic (pos symptoms)
Consequences of Blocking Mesocortical Dopaminergic Pathway
Antipsychotic (neg symptoms)
Consequences of Blocking Nigrostriatal Dopaminergic Pathway
Extrapyramidal movements
Consequences of Blocking Tuberoinfundibular Dopaminergic Pathway
Prolactin Release
Blocking dopamine at the pituitary -> more Prolactin is released (off target effect of these drugs)
Common ADVERSE reactions when using Antipsychotics:
1) Hyperprolactinemia
- > Galactorrhea, amenorrhea, gynecomastia, reduced libido
- > Less with newer agents
2) Postural HYPOTENSION
- > anti psychotic drugs BLOCK K+ channels
- > the potential for K+ to be released from the cell is inhibited
- > AL contrario -> STIMULANTS tend to stimulate Alpha 1 receptors and lead to higher BP
3) QT prolongation
- > IN some more than others
Anti Psychotic drugs and QT interval
Anti psychotic drugs lead to a LONGER QT interval because they block the K+ channel
-> (K+ CANT LEAVE the cell to reset the negative cell potential inside)
Common Adverse Reactions to Antipsychotic drugs
1) Extrapyramidal Syndromes (EPS)
-> Dystonias, akathesia, parkinsonism
-> Seen less with newer agents (atypicals)
-> Treat by lowering dose, changing drug
-> Drug therapy:
Benztropine (Cogentin)
Trihexyphenidyl (Artane)
2) Acute dystonic reaction
-> Oculogyric crisis, torticollis
-> Give single injection of ANTICHOLINERGIC agent:
(For example: Benztropine 1-2 mg)
-> Followed by oral therapy
3) Tardive Dyskinesia (TD)
- > Persistent EPS
- > Elderly at greater risk
STRATEGIES:
- Use min. effective doses for min. duration
- Gradual dose reduction
- Change to atypical agent
- Vitamin E? (kind of sucks, not actually that effective)
4) Neuroleptic Malignant Syndrome
- > Hyperpyrexia, rigidity, autonomic instability, delirium
- > Uncommon, but can be LETHAL
- > More likely w/high doses
- > Onset - any time
- > Stop drug & control rigidity
- > Supportive care, dantrolene, bromocriptine
“Typical” Antipsychotics
Low Potency
- > Chlorpromazine (Thorazine)
- > Thioridazine (Mellaril)
Medium Potency
- > Perphenazine (Trilafon)
- > Thiothixene (Navane)
- > Trifluoperazine (Stelazine)
High Potency
- > Haloperidol (Haldol)
- > Fluphenazine (Prolixin)
Top 5 Most Commonly Prescribed “Atypical” Antipsychotics
- Clozapine (Clozaril)
- Risperidone (Risperdal) (also: paliperidone - Invega)
- Olanzapine (Zyprexa)
- Quetiapine (Seroquel)
- Aripiprazole (Abilify)
Atypical Antipsychotics Adverse Effects/ Concerns
1) Increases in weight, blood glucose & lipids
2) Includes hypotension & miscellaneous others (somnolence, dizziness, increased LFTs (Liver Function Tests), CYP450 interactions)
3) Increase in Prolactin & EPS tend to be limited to higher doses
Clozapine (Clozaril)
Atypical Antipsychotic Drug
Role:
- May be of use if treatment refractory
- Or if there are EPS (Extrapyramidal syndromes) with other agents
- Usually dosed 3 times/day
Adverse effects: - Little EPS or increase in prolactin - Sedation and WEIGHT GAIN QUITE COMMON - Also may see sialorrhea (drooling) - Seizures in 1-4% - More common with higher doses - Agranulocytosis in about 1% (Requires frequent CBC monitoring)
Risk factors:
- > Women > men
- > Elderly
- > Ashkenazi Jewish descent
- > Between weeks 6-18 of treatment
Notes on Atypical Antipsychotics
Risperidone
-> Lower cost than most other atypicals
Olanzapine
-> Clozapine derivative
Quetiapine
-> Cataracts?
Aripiprazole
-> Fewer metabolic side effects
Clozapine vs. Olanzapine
Olanzapine -> no Choloride group, slightly modified chemical groups
- > OVERALL safer drug for the bone marrow
- > might not be quite as effective as Clozapine, but doesn’t cause Agranulocytosis
Treatment Considerations for Atypical Antipsychotics
Time to effect:
-> Some symptoms improve rapidly
-> MOST IMPROVE SLOWLY
(Over weeks to months)
Duration of treatment:
-> Most require prolonged maintenance
(Need to balance against SEs)
-> Abrupt discontinuing of taking the drug can increase relapse risk
Risk of Treating Dementia-related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared to placebo.
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Neuroreceptors and Ntts19
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Childhood disorders10
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Psychostimulants24
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Theories15
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Personality disorders29
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Sleep15
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Antiphsychotics25
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schizophrenia29
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eating disorders23
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somatic symptoms30
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midterm review15
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depression14
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Bipolar disorders10
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Antidepressents31
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mood stabilizers25
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Anxiety disorders24
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Neurocognitive Disorder I: Dementia38
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neurocognitive II: delirium28
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Anxiolytics and Sedatives32
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anticonvulsants21
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final review20
