Antipsychotics Flashcards
Schizophrenia
Life time incidence of schizophrenia is estimated at about 1 in 100 (i.e. 1% of people will suffer from it at some point in their life).
Prevalence of schizophrenia is estimated at about 1 in 300 (i.e. 0.3 % of people suffer from schizophrenia at any one time).
Chronic disease.
Onset in late adolescence / early adulthood.
Highly disabling to social & vocational functioning
Schizophrenia SNS
1) positive symptoms
2) negative symptoms
3) anx/dep
4) aggressive symptoms
5) cognitive symptoms
Periods of acute presentation with positive symptoms are interspersed with periods during which the negative symptoms predominate.
As the disease progresses the negative symptoms generally become more dominant.
Positive symptoms of schizophrenia
(abnormal behaviours added)
Delusions (often paranoid).
Hallucinations (e.g. exhortatory voices).
Thought disorder including feeling that thoughts are controlled by an outside agency.
Abnormal behaviours (e.g. stereotypical or aggressive behaviours).
Usually it is the presentation of positive symptoms that is most disturbing to others and leads to first referral to a psychiatrist and detection of schizophrenia.
Negative symptoms of schizophrenia
Withdrawal from social contacts.
Flattening of emotional responses.
For the individual with schizophrenia the negative symptoms are often the most distressing.
In contrast, the positive phases are characterised by lack of insight (self-awareness of abnormal behaviour
Schizophrenia is also frequently associated with depression, resulting in suicide in about 10 % of cases.
Can be
Primary deficit of the illness
Secondary to depression
Secondary to extrapyramidal symptoms (EPS)
Secondary to environmental deprivation
Secondary to positive symptom
Cognitive dysfunction
Impairment of selective attention.
Impairment of working memory.
Only recently recognized to be a persistent core feature of the disease, not iatrogenic (caused by the physician/medication).
Important because it predicts level of social and vocational functioning, and hence treatment outcome, better than positive symptoms.
Aetiology of Schizophrenia
Genetic factors:
Incomplete hereditary tendency.
50 % risk in monozygotic twin of affected individual.
Genetic studies have established linkage to various chromosomal regions.
Genes for susceptibility to schizophrenia have been elusive, but some candidate genes have been identified in the suspect chromosomal regions e.g.
DISC1, neuregulin-1, dysbindin-1, and catechol-Omethyl transferase (COMT).
Not all schizophrenics share the same mutations of susceptibility genes.
Environmental factors:
Various theories relating to possible neurodevelopmental abnormalities:
Maternal viral infections during pregnancy?
Obstetric complications?
● Onset in late adolescence / early adulthood is consistent with neurodevelopmental abnormality involving myelination of cortico-cortical pathways.
● Evidence of enlarged ventricles, abnormalities in laminar organization of cortical cells. A neurodevelopmental disorder?
Theories of schizophrenia
Dopamine Theory
5-HT (Serotonin) Theory
Glutamate Theory
Neurochemical theories proposed are primarily theories of the positive symptoms.
Dopamine Theory
The Dopamine Theory
● Amphetamine produces symptoms similar to acute schizophrenia.
● Most important as basis for pharmacotherapy:
●All antipsychotic drugs are D2 antagonists.
D2 Receptor Antagonism Correlates with Clinical Efficacy
Dopamine Pathways of the Brain
Nigrostriatal Pathway
• Substantia nigra to dorsal striatum.
• Involved in voluntary movement
Mesocortical/Mesolimbic Pathways
• Ventral tegmental area (VTA) to prefrontal cortex and limbic (emotional) brain.
• Involved in emotion, cognition, and attention.
• Dopamine increased in acute schizophrenia
A) nigrostriatal: part of extrapyramidal motor system
B) mesolimbic: reward and emotion
C) mesocortical: cognition and attention
D) tuberoinfundibular: pathway from hypothalamus to anterior pituitary regulates prolactin secretion into the blood circulation.
The 5-HT (Serotonin) Theory
The 5-HT (Serotonin) Theory
Lysergic acid diethylamide (LSD), which acts primarily as a 5-HT2 agonist, produces symptoms similar to acute schizophrenia.
Many of the newer atypical antipsychotics have 5-HT2 antagonism.
The Glutamate Theory
The Glutamate Theory
● Drugs which block the NMDA receptor channel, e.g. phencyclidine (PCP) and ketamine, produce symptoms similar to acute schizophrenia.
● Gaining popularity in schizophrenia research again but still has not produced any clinically useful drugs.
Antipsychotic Drugs
Typical Antipsychotics
- Chlorpromazine
- Haloperidol
Atypical Antipsychotics
- amisulpride,
- clozapine,
- olanzapine &
- risperidone.
- Aripiprazole
Typical Antipsychotics
Control positive symptoms of schizophrenia.
Produce extrapyramidal side-effects (EPS).
Chlorpromazine was the first antipsychotic drug
Like the TCAs, derived from antihistamine drugs.
Revolutionised psychiatric care of schizophrenics.
Haloperidol remains one of the most widely used antipsychotic drugs.
Chlorpromazine
Typical Antipsychotics
(antiD2)
M1: Dry mouth, constipation, blurred vision
H1: sedation, weight gain
A1: Postural hypotension,dizziness.
D2: EPS (Acute Dystonias, Tardive Dyskinesia, Akathisia)
Haloperidol
Typical Antipsychotics
(antiD2)
A1: Postural hypotension,dizziness.
D2: EPS (Acute Dystonias, Tardive Dyskinesia, Akathisia)
