Pharmacology of Psychotic Disorders Flashcards
What are some of the dopamine pathways in the brain that can be implicated in the development of psychotic disorders?
Mesocortical
Mesolimbic
Nigrostriatal
Tuberoinfundibular
Where is the mesocortical pathway? How can it become implicated in psychotic disorders?
From ventral tegmentum (brain stem) to cortex
Too little dopamine in this area can cause negative symptoms of psychotic disorders
Where is the mesolimbic pathway? How can it become implicated in psychotic disorders?
Dopaminergic cell bodies in the ventral tegmentum to the limbic system
Too much dopamine here can cause the positive symptoms of psychotic disorders (hallucinations etc.)
Where is the nigrostriatal pathway? How can it become implicated in psychotic disorders?
From the substantia nigra to the basal ganglia
Dopamine Hypoactivity in this area can cause Parkinsonian movements (rigidity, bradykinesia, tremors), akathisia and dystonia
What happens if you block dopamine in the tuberoinfundibular pathway?
Dopamine release inhibits the relase of prolactin
Therefore reducing dopamine in this area will lead to hyperprolactinaemia
gynecomastia, galactorrhoea, decreased libido, menstrual dysfunction
What is the mechanism of typical antipsychotics? Some examples of typical antipsychotics?
D2 dopamine receptor antagonists
Bind to the dopamine receptors with high affinity
Fluphenazine, Haloperidol, Pimozide
What sort of side effects may be caused by typical antipsychotics?
Reduce the effect of dopamine so can lead to Parkinsonian side effects
What is the mechanism of atypical antipsychotics?
Serotonin-dopamine 2 antagonists
Affect both serotonin and dopamine transmission
What are some examples of atypical antipsychotics?
Risperidone
Olanzapine
Aripiprazole
How effective are atypical antipsychotics?
1/3 good response
1/3 some response
1/3 poor response
What drug is used when psychosis is treatment resistant after 2+ psychotics? Why is it not first line?
Clozapine
Very effective but usually avoided due to its extreme side effect profile
What are some of the side effects of clozapine?
Agranulosis (0.5 - 2%) Significant sedation and weight gain Abnormal LFTs Risk of seizures (esp. when with lithium) Hypertriglyceridaemia hypercholesterolaemia hyperglycaemia
Due to the agranulosis that can occur with clozapine, what is necessary when starting the drug?
Weekly bloods for 6 months
Followed by bloods every 2 weeks for 6 months
How effective is clozapine?
Among the treatment resistant cases:
1/3 good response
1/3 some response
1/3 poor response
What are some of the significant adverse affects associated with antipsychotics?
Tardive Dyskinesia (involuntary muscle movements)
Neuroleptic malignant syndrome (muscle rigidity, altered mental status, autonomic instability, elevated WBC, CPK and LFTs)
Extrapyrimidal side effects
What are some of the extrapyrimdal side effects that may be noticed when taking antipsychotics?
Acute dystonia
Parkinson syndrome
Akathisia (inner restlessness and mental distress)
What are some pharmacological agents to help with the extrapyrimidal side effects seen when taking antipsychotics?
Anticholinergics
Dopamine facilitators
Beta-blockers
What is the most common symptom of psychosis? What does this mean pharmacologically?
Lack of insight
Patients won’t be compliant with drugs and will relapse. Estimated only around 30% of patients are compliant
After around the third episode of schizophrenia what tends to occur? How can this be combatted?
After about 3 epiodes there is a significant decline in cognitive functioning, IQ, and increased presence of negative symptoms in the patient
Consider a long acting intramuscular antipsychotic (can be taken monthly / 3 monthly)
In general what tend to be the side effects of typical antipsychotics?**
Extrapyrimidal symptoms
akathesia
tardive dyskenesia
In general what tend to be the side effects of Atypical antipsychotics?**
Metabolic effects:
- weight gain
- hypercholesterolaemia
- hyperglycemia
Treatment resistant psychosis?
CLOZAPINE
What are anxiolytics?
Used to treat anxiety disorders and substance misuse disorders
Often used in combination with SSRIs and SNRIs for anxiety disorders
What are benzodiazepines used to treat?
Insomnia
Parasomnia
Alcohol withdrawal
Anxiety disorders
