L5 Antipsychotics Flashcards
What are the 5 symptom domains of schizophrenia?
- pos
- neg
- anx/dep
- aggressive
- cognitive
What kind of symptoms are most distressing for an individual with schizophrenia?
Negative symptoms. In contrast, positive phases are characterised by lack of insight (self-awareness of abnormal behaviour)
Examples of positive symptoms of schizophrenia (4)
- Delusions, often paranoid
- Hallucinations eg. exhortatory voices
- Thought disorder including feeling that thoughts are controlled by an outside agency
- Abnormal behaviours eg. stereotypical or aggressive behaviour
What kind of symptoms are most disturbing to others, usually leading to first referral to a psychiatrist and detection of schizophrenia?
Positive symptoms, abnormal behaviours added
Examples of negative symptoms of schizophrenia (2)
- Withdrawal from social contacts
2. Flattening of emotional responses
As the disease progresses, which kind of symptoms generally dominates?
Negative symptoms, normal behaviours subtracted
Why is cognitive dysfunction an important symptom of schizophrenia?
Predicts level of social and vocational functioning and hence, treatment outcome, better than positive symptoms
- Persistent core feature of the disease, not iatrogenic
What are some evidences suggesting that schizophrenia might be a neurodevelopmental disorder?
- Onset in late adolescence/early adulthood is consistent with neurodevelopmental abnormality involving cortio-cortical pathways
- Evidence of enlarged ventricles, abnormalities in laminar organisation of cortical cells
Neurochemical theories (3)
Primarily theories of the positive symptoms
- Dopamine Theory
- 5-HT (Serotonin) Theory
- Glutamate Theory
What is the most important basis for pharmacotherapy of schizophrenia?
All antipsychotic drugs are D2 antagonists - the dopamine theory
What is the dopamine theory?
Amphetamine produces symptoms similar to acute schizophrenia
What are the dopamine pathways of the brain? (4)
- Nigrostriatal
- Mesolimbic
- Mesocorticol
- Tuberoinfundibular
What is the MOA for many of the newer antipsychotics?
5-HT2 antagnosim - the serotonin theory
What is the serotonin theory?
LSD, a 5-HT2 agonist, produces symptoms similar to acute schizophrenia
What is the glutamate theory?
Drugs that block the NMDA receptor channel eg. phencyclidine (PCP) and ketamine, produce symptoms similar to acute schizophrenia
Which typical antipsychotic has a better side effect profile? Chlorpromazine or Haloperidol
Haloperidol
What are the side effects of chlorpromazine?
- M1: dry mouth, constipation, blurred vision
- H1: sedation, weight gain
- a1: postural hypotension, dizziness
What causes the EPS of D2 antagonist drugs?
Action on the extrapyrimidal motor pathways, almost simulating the same deficit as Parkinson’s
Which of dyskinesia/akathisia correlates directly with duration on medication?
Akathisia, not dyskinesia
What is the EPS side effect that occurs in 20-40% of patients on typical antipsychotics?
Tardive dyskinesia and akathisia
Why is tardive dyskinesia and akathisia often irreversible?
Most probably de to upregulation or supersensitivity of dopamine receptors in the nigrostriatal system
What is dyskinesia?
Repetitive and stereotyped involuntary movements of face, tongue, and limbs
What is akathisia?
Involuntary movements and compulsion to act, associated with restlessness, anxiety, and agitation
Examples of typical antipsychotics (4)
Chlorpromazine, haloperidol, trifluoperazine, fluphenazine
What defines atypicality of antipsychotics?
Less severe EPS
- not greater affinity at 5-HT2 or D4 receptors
- not mixed antagonism at a-adrenoceptors, H1 histamine receptors, muscarinic acetylcholine receptors, and 5-HT2 receptors
What is the ‘core’ of most atypical antipsychotics?
SDA: serotonin-dopamine antagonism (5HT2A, D2)
What was the clinical use of clozapine limited by?
Agranulocytosis - develops in only approx 1% of patients on clozapine but can be fatal!
What was the prototypical atypical antipsychotic drug?
Clozapine
What did the clozapine-induced agranulocytosis adverse effect led to?
Development of compounds related to clozapine but without this adverse effect ie. olanzapine
What is special about amisulpride?
Atypical pattern of receptor affinities for an atypical antipsychotic: no SDA!!!
- selective D2/D3 antagonist, recently reported to have 5-HT7 antagonism
- no 5HT2 antagonism
Which of the atypical antipsychotic drugs has the fewest side effect?
Amisulpride - due to selectivity for D2/D3 receptors + absensce of a-adrenoceptor block, antihistaminergic, and anticholinergic side effects
What is a notable side effect of amisulpride?
Increases prolactin release
In presence of agonist, partial agonists have ________ effects?
antagonistic
What is an additional adverse effect of atypical antipsychotic?
New onset or exacerbation of diabetes, does not reverse when drug is stopped
Which atypical antipsychotic drug is an exception that does not induce hyperglycaemia and diabetes?
Amisulpride
- effect is strong for clozapine, olanzapine, risperidone
Which of the atypical antipsychotic had been used in the treatment of anorexia nervous experimentally?
Olanzapine
Does chlorpromazine (typical antipsychotic) cause weight gain?
No, H1 and a-adrenoceptor hypotheses do not explain this weight gain ADR of atypical antipsychotics
How does a higher D2 to D1 antagonism ratio result in less EPS in atypical antipsychotics?
Should confer less complete blockade of dopaminergic function in the striatum as D2 antagonism will increase dopamine release
Examples of atypical antipsychotics that are more effective against negative smx
clozapine, olanzapine, risperidone
Examples of atypical antipsychotics that may ameliorate cognitive dysfunction
clozapine, risperidone
Examples of atypical antipsychotics that are better at mood stabilisation
clozapine, olanzapine, risperidone
Examples of atypical antipsychiatric
amisulpride, aripiprazole, clozapine, olanzapine, risperidone
