Antipsychotics Flashcards
What are the indications for use of antipsychotics?
ie what conditions are they used to treat
Schizophrenia
Schizoaffective disorder
Bipolar disorder:
(for mood stabilisation and/or when psychotic features are present)
Psychotic depression
Resistant depression (augmenting agent)
Resistant anxiety (augmenting agent)
What chemical in le brain do antipsychotics affect?
Dopamine
Antagonists - so reduce the amount of dopamine in certain pathways of the brain
What are the key dopamine pathways in the brain?
Mesocortical
Mesolimbic
Nigrostriatal
Tuberoinfundibular
What is the mesocortical dopamine pathway?
What abnormality causes psychotic symptoms?
Mesocortical
- ventral tegmentum (brainstem) to the cerebral cortex
- This pathway is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise
- this is due to too little dopamine
What is the Mesolimbic pathway?
What abnormalities cause psychosis?
Mesolimbic
- dopaminergic cell bodies in the ventral tegmentum (brainstem) to the limbic system
- Too much dopamine is responsible for positive symptoms of psychosis (hallucinations, delusions, disordered thought)
What is the Nigrostriatal pathway?
In a healthy patient - what is this pathway involved in?
What abnormalities does abnormal dopamine levels cause?
Nigrostriatal
- dopaminergic cell bodies of substantia nigra (midbrain/mesencephalon) to the basal ganglia
- Involved in movement regulation -using ACh (which dopamine suppresses)
- Dopamine hypoactivity (when treating with antipsychotics) can impact movement regulation - which leads to Parkinsonian movements
Dopamine hypoactivity in the Nigrostriatal pathway can lead to dysfunctional movement regulation
What would you see in a patient with this dyregulation?
Parkinsonian movements (extrapyramidal side effects)
Rigidity
Bradykinesia
Tremors
Akathisia (restless legs)
Dystonia
What is the tuberoinfundibular pathway?
What side effects can be seen when blocking dopamine that are linked to this pathway?
Give the specific features of this
Tuberoinfundibular
- hypothalamus to anterior pituitary
- antipsychotic use (blocking dopamine) in this pathway predisposes patients to hyperprolactinaemia:
gynecomastia
galactorrhea
decreased libido
menstrual dysfunction
What are the groups of antipsychotics?
What are the subgroups and some exampled of eacg
Typical & Atypical
Typical - D2 receptor antagonists
Atypical - serotonin-dopamine 2 antagonists (SDAs)
What are the types of Typical antipsychotics?
Give some examples
What side effects are associated with each type?
Typical antipsychotics
1) High potency - high affinity for D2:
- associated w/ extrapyramidal side effects (parkinsonian)
- Eg - Fluphenazine, Haloperidol, Pimozide
2) Low potency - lower affinity for D2:
- associated w/ cardiotoxic and anticholinergic adverse effects including sedation, hypotension
- Eg - chlorpromazine and thioridazine
The Atypical Antipsychotics are serotonin-dopamine 2 antagonists (SDAs)
Which pathways do they affect in the brain?
Affect sertonin and dopamine neurotransmission in all 4 of the key dopamine pathways:
- Mesocortical
- Mesolimbic
- Nigrastriatic
- Tuberoinfundibular
What are the main atypical antipsychotics?
Risperadone - (Risperdal)
Olanzapine - (Zyprexa)
Quetiapine - (Seroquel)
Aripiprazole - (Abilify)
Clozapine - (Clozaril) - if resistant
First 4 are all first line and are chosen depending on side effect profile and preparation
What is Risperidone?
What side effects can it cause?
Atypical antipsychotic - although functions more like a typical antipsychotic at higher doses
Side effects:
- extrapyramidal - dose dependant
- hyperprolactinaemia - sexual dysfunction etc
- weight gain & sedation
What is Olanzapine?
What side effects can it cause?
Atypical antipsychotic
May cause:
- severe weight gain
- hypertryglyceridaemia, hypercholesterolaemia, hyperglycaemia
- hyperprolactinaemia
- abnormal LFTs
What is Quetiapine?
Side effects?
Atypical antipsychotic
May cause:
- orthostatic hypotension
- abnormal LFTs
- weight gain
- hyper: triglycerides, cholesterol, glycaemia
What is Aripiprazole (Abilify)?
What are its benefits?
Side effects?
Atypical antipsychotic - unique mechanism as a partial D2 agonist
This means its less associated with extrapyramidal side effects, no QT prolongation, no sedation, no weight gain
Side effects:
- akathisia/activation
- interactions with fluoxetine, paroxetine
What antipsychotics are useful for immediate sedation?
Why is this?
ie in an emergency situation with a psychotic patient
Olanzapine (Zyprexa)
Aripiprazole (Abilify)
Available in immediate release IM form
What is clozapine?
Clozapine (Clozaril)
Tablet only Antipsychotic used for treatment resistant psychosis (ie if first lines do not work)
Very effective but with quite bad potential side effects
What are the side effects of clozapine?
Agranulocytosis:
- patients on clozapine require weekly bloods for 6 months, then fortnightly bloods for 6 months
Increased risk of seizures (esp if on lithium)
Most sedation, weight gain and abnormal LFTs
Hyper: triglycerides, cholesterol, glycaemia & risk of hyperosmolar coma and death
What specific groups of adverse affects can be caused by any of these antipsychotics (typical and atypical)?
Already mentioned a lot but for some reason this has its own slide so must be important
Tardive dyskinesia (esp w/ typical antipsychotics)
involuntary muscle movements
Neuroleptic malignant syndrome (NMS)
characterized by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and lfts
Extrapyramidal side effects (EPS)
acute dystonia, Parkinson syndrome, Akathisia
What agents are available to treat EPS?
Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine
Dopamine facilitators such as Amantadine
Beta-blockers such as propranolol
Watch for anticolinergic side effects
