Antipsychotics

Question 1

Aetiology of Schizophrenia

Answer 1

• Incomplete hereditary tendency
• Genetic studies have established linkage to various chromosomal regions
• Genes for susceptibility to schizophrenia elusive, but some candidate genes identified in the suspect chromosomal regions
• Not all schizophrenics share the same mutations of susceptibility genes
• Environmental factors
  (eg. maternal viral infections during pregnancy may incr risk)
• Onset in late adolescence/early adulthood is consistent with neurodevelopmental abnormality involving the myelination of cortico-cortical pathways
• Evidence of enlarged ventricles, abnormalities in laminar organization of cortical cells

Question 2

Symptoms of Schizophrenia

Answer 2

1) +ve symptoms (addition of abnormal behaviours)
- Delusions, hallucinations, thought disorders (including feeling that thoughts are controlled by an outside agency), abnormal behaviours

2) -ve symptoms
- Withdrawal from social contacts, flattening of emotional responses
- -> -ve symptoms often the most depressing
- -> in contrast, +ve phases are characterised by lack of insight

Question 3

What kind of symptoms are the neurochemical theories primarily a theory of?

Answer 3

Positive symptoms

Neurochemical theories:

1) *Dopamine theory
2) 5-HT Serotonin theory
- newer atypical antipsychotics have 5-HT2 antagonism
3) Glutamate theory

Question 4

Pharmacotherapy of antipsychotics

Answer 4

D2 Antagonist

Question 5

Dopamine pathways of the brain

Answer 5

1) Nigrostriatal Pathway (> related to Parkinson’s disease)
- Part of Extrapyramidal Motor System involved in voluntary movement

2) *Mesolimbic & Mesocortical Pathways
- Mesolimbic: Involved in emotion
- Mesocortical: Involved in cognition & attention
- -> Dopamine increased in acute schizoprenia

3) Tuberoinfundibular Pathway
- Regulates prolactin secretion

Question 6

Features of typical antipsychotic drugs

Answer 6

• Control (+) symptoms

- Produce extrapyramidal side-effects (EPS )

Question 7

List eg. of Typical Antipsychotics

Answer 7

• Chlorpromazine
• Fluphenazine
• Haloperidol
• Trifluoperazine

Question 8

Side effects of Typical Antipsychotics

Answer 8

Eg. Haloperidol
- Postural hypot/s, dizziness (alpha-1 antagonism)

Eg. Chlorpromazine
(+) Sedation, weight gain (H1 antagonism)
(+) Dry mouth, constipation, blurred vision (M1 antgonism)

Question 9

What does the extrapyramidal pathway involve?

Answer 9

Basal ganglia, striatum & substantia nigra

Question 10

What are the extrapyramidal side effects?

Answer 10

1) Acute Dystonias
- Parkinson-like syndrome (cogweel rigidity & tremor @ rest)
- Caused by D2 antagonism in the nigrostriatal pathway (connects substantia nigra -> striatum)
- Occurs within 1st few weeks of treatment, reversible when drug is stopped

2) Tardive Dyskinesia & 3) Akathisia
- Repetitive & involuntary movements of face, tongue & limbs
- Develop slowly over years, correlated with duration of use
- IRREVERSIBLE