Antipsychotics Flashcards
Schizophrenia:
- Acute or chronic?
- Time of onset
- Consequence on individual
- Chronic disease
- Onset in late adolescence/ early adulthood
- Highly disabling to social and vocational functioning
The five symptom domains of schizophrenia
- Positive sx
- Negative sx
- Anxiety/depression
- Aggressive sx
- Cognitive sx
(focus on positive and negative sx)
Examples of “Positive sx” in schizophrenia and its “function” in the disease
- Delusion
- Hallucinations
- Abnormal behaviours (E.g. stereotypical)
- Thought disorder, incl. feeling that thoughts are controlled by outside agency
Function: Presentation of these sx most disturbing, leads to referral to psychiatrist and detection of schizo
Negative sx in Schizophrenia and its impact on the patient
- Withdrawal from social contacts
- Flattening of emotional responses
Impact: Negative sx most distressing (while positive sx characterised by lack of insight)
As Schizo progresses, which of the five symptoms of schizophrenia becomes dominant?
Negative sx
In 10% schizo cases, suicide occurs. Why is this so?
Schizo is frequently associated with depression
What are some possible secondary causes of negative sx?
- Depression
- Extrapyramidal sx (EPS)
- Environmental deprivation
- Positive sx
What are some examples of cognitive dysfunction of schizo. What is the cause of cognitive dysfunction in schizo patients?
- Impaired selective attention (unable to focus and retain info)
- Impaired working memory
Cause: The disease itself (i.e. persistent core feature of disease, no iatrogenic)
Why is the level of cognitive dysfunction important in treatment of schizo?
Helps predict level fo social and vocational functioning, hence treatment outcome. It is a better predictor than positive sx.
Factors that may lead to Schizo
- Genetic factors (mutationof various genes)
2. Environmental factors: related to neurodevelopmental abnormalities (e.g. maternal viral infections during preg)
What are some possible evidence showing “neurodevelopmental abnormalities” in Schizo Patients?
- Onset in late adolescence/ early adulthood
- Myelination of cortico-cortical pathways is abnormal
- Enlarged ventricles, abnormalities in laminar organisation of cortical cells
State the three neurochemical theories of Schizo. What characteristic of Schizo do these theories attempt to explain?
- Dopamine Theory
- 5-HT Theory
- Glutamate Theory
These theories proposed are primarily theories of positive sx
Describe Dopamine Theory. How did dopamine theory come about?
D2 receptor activity is associated with Schizo
- Amphetamine, a dopaminergic, produces sx of acute schizo
- Drugs are D2 antagonists
Four dopamine pathways of the Brain and their functions. What pathways are the proposed drug targets?
- Nigrostriatal: Part of extrapyramidal motor system (affected in PD)
- Mesolimbic: Reward and emotion
- Mesocortical: Cognition and attention
- Tuberoinfundibular: Prolactin secretion into blood circulation
Drug targets: 2 and 3
Describe the 5-HT Theory in Schizo
- Lysergic acid diethylamide (LSD), a 5-HT2 agonist, produces sx similar to acute Schizo
- Many atypical antipsychotics have 5-HT2 antagonism
- Hence excess 5-HT is associated with Schizo
Describe the Glutamate Theory in Schizo
- Drugs blocking NMDA receptor chanel (e.g. PCP, ketamine) produce sx similar to acute Schizo
- Hence NMDA receptor associated with Schizo
- No clinically useful drugs yet
One of the most widely used TYPICAL antipsychotic
Haloperidol
Some examples of ATYPICAL antipsychotics
- Amisulpride
- Clozapine
- Olanzapine
- Risperidone
Similarity between Typical and Atypical antipsychotics
Control positive symptoms
One important difference between Atypical Antipsychotics over Typical Antipsychotics
Atypical produce less extrapyramidal SE
Other than D2 receptor, what are other receptor that Chlorpromazine binds to, hence its side effects and loss in popularity as an atipsychotic?
- M1 receptor: Parasympatholytic effects (dry mouth, constipation, blurred vision)
- H1 receptor: Sedation, Weight gain
- Alpha-1 receptor: postural hypotension, dizziness (body unable to respond to orthostatic changes)
Advantage of Haloperidol over Chlorpromazine
- Haloperidol does not block M1 and H-1 receptor
- Hence less SE
Three examples of extrapyramidal SE in antipsychotic drugs. What is the mechanism leading to these SE?
- Acute Dystonias (involuntary contraction of muscles)
- Tardive Dyskinesia (involuntary stiff and jerky movements)
- Akathisia (inner restlessness)
Mechanism: Actions on extrapyramidal motor pathways (affects basal ganglia –> Striatum and substantia nigra)
Describe acute dystonias caused by antipsychotics. During treatment, when does it occur? How does it occur? Is it reversible?
- Parkinsonism-like syndrome (e.g. cogwheel rigidity, tremor at rest)
- Occurs within first few weeks of treatment and reversible when drug is stopped
- May be caused by D2 antagonism in nigrostriatal pathway
