Antipsychotics

Question 1

How are symptoms classified in schizophrenia?

Answer 1

Five symptom domains:

1. positive symptoms
2. negative symptoms
3. anx/dep
4. aggressive symptoms
5. cognitive symptoms

Question 2

Describe the presentation of symptoms in schizophrenia.

Answer 2

Periods of acute presentation of positive symptoms interspersed with periods during which the neg symptoms predominate.

As disease progresses, neg symptoms become more dominant.

Question 3

What are some positive symptoms of schizophrenia?

Answer 3

• Delusions (often paranoid)
• Hallucinations
• Thought disorder
• Abnormal behaviours (e.g. aggressive behaviours)

Question 4

What are some negative symptoms of schizophrenia and how do they arise?

Answer 4

• Withdrawal from social contacts
• Flattening of emotional responses

Could be due to:

• Primary deficit of the illness
• Secondary to environmental deprivation
• Secondary to positive symptoms
• Secondary to depression
• Secondary to extrapyramidal symptoms

Question 5

Why is recognition of cognitive dysfunction important in schizo pts?

Answer 5

Cognitive dysfunction includes impairment of selective attention and working memory. These symptoms predict level of social and vocational functioning, and hence treatment outcomes, better than pos symptoms.

Question 6

What is the usual age of onset of schizophrenia?

Answer 6

Late adolescence to early adulthood

Question 7

Aetiology of schizophrenia

Answer 7

1. Genetic
   - incomplete hereditary tendency
   - some genes for susceptibility to schizo have been identified, but not all pts have same mutations of susceptibility genes
2. Environmental
   - various theories relating to possible neurodevelopmental abnormalities ➝ e.g. maternal viral infx during pregnancy, obstetric complications
   - abnormalities involving myelination of cortico-cortical pathways
   - evidence of enlarged ventricles, abnormal laminar organisation of cortical cells

Question 8

What are the neurochemical theories for schizo?

Answer 8

1. Dopamine theory (dopaminergic overactivation)
2. 5-HT theory (too much serotonin)
3. Glutamate theory (deficiency in glutamate activity)

Question 9

What is the diff between typical and atypical antipsychotics?

Answer 9

Atypical produces less extrapyramidal side effects than typical.

Question 10

What are extrapyramidal side effects?

Answer 10

EPS are motor side effects such as acute dystonias and tardive dyskinesia & akathisia.

Extrapyramidal pathway involves the basal ganglia, including striatum and substantia nigra. EPS arise due to D2 blockade of nigrostriatal pathway by antipsychotics.

Question 11

Differentiate the presentation of acute dystonia vs tardive dyskinesia and akathisia.

Answer 11

Acute dystonia: Parkinsonism-like syndrome (cogwheel rigidity, tremors at rest)
VS
Dyskinesia: Repetitive and stereotyped involuntary movements of face, tongue and limbs
VS
Akathisia: Involuntary movements and compulsion to act associated with restlessness, agitation and anxiety

Question 12

Onset of acute dystonia vs tardive dyskinesia and akathisia

Answer 12

Acute dystonia - within first few weeks of treatment, reversible when drug is stopped.

Tardive and akathisia - develops over months or years, often irreversible. Akathisia correlates directly with duration on meds.

Question 13

Cause of acute dystonia vs tardive dyskinesia and akathisia

Answer 13

Acute dystonia - D2 antagonism in nigrostriatal pathway

Tardive and akathisia - upregulation of supersensitivity of dopamine receptors in nigrostriatal pathway

Question 14

Which receptors do chlorpromazine target and what are the associated /therapeutic side effects?

Answer 14

1. D2 antagonist - reduce dopamine activity, treat pos symptoms
2. mAChR antagonist - dry mouth, constipation, blurred vision
3. Histamine H1 antagonist - sedation, weight gain
4. alpha1-adrenergic antagonist - postural hypotension, dizziness

Question 15

Why does haloperidol have fewer side effects than chlorpromazine?

Answer 15

Haloperidol targets fewer receptors - only D2 and alpha1

Question 16

List a few key typical antipsychotics.

Answer 16

chlorpromazine, fluphenazine, haloperidol, trifluoperazine

Question 17

Clinical use of clozapine is limited by which serious adverse effect?

Answer 17

Agranulocytosis - rare but fatal. Regular blood counts needed to monitor pts.

Question 18

What are common adverse effects of atypical antipsychotics?

Answer 18

1. Anticholinergic effects due to mAChR antagonism (esp clozapine and olanzapine)
2. Postural hypotension and reflex tachycardia due to alpha1-adrenergic antagonism (esp for risperidone)
3. Sedation due to histamine H1 receptor antagonism (esp clozapine and olanzapine)

Question 19

Amisulpride is selective for which receptors?

Answer 19

D2 and D3

Question 20

How are the side effects of amisulpride diff from other atypical antipsychotics?

Answer 20

Amisulpride doesn’t block alpha-adrergic, histamine H1 or mACh receptors.

Causes adverse effects on mammary glands and tissues:

• due to increased prolactin secretion due to block of dopamine receptors in anterior pituitary gland (part of tuberoinfundibular system).
• breast swelling, pain and lactation
• gynaecomastia in males

Question 21

What are some additional side effects of atypical antipsychotics?

Answer 21

1. New onset or exacerbation of diabetes
   - effect is strong for clozapine, olanzapine and risperidone
   - for risperidone higher chance of diabetes not reversing when drug is stopped
2. Weight gain
   - esp clozapine, olanzapine and risperidone

Question 22

Why do atypicals produce less EPS?

Answer 22

• Potent 5-HT2A receptor antagonism vs weak D2 antagonism ➝ lower EPS and higher efficacy against neg symptoms (clozapine and olanzapine)
• High D4 to D2 antagonism ratio favours actions in prefrontal cortex over striatum (clozapine)
• High D3 to D2 antagonism ratio favours action on the nucleus accumbens over striatum (amisulpride)
• High D2 to D1 antagonism ratio reduces impact of antagonism in the striatum (amisulpride, risperidone)

Question 23

What are some additional benefits of atypical antipsychotics?

Answer 23

Some more effective against neg symptoms and may be better at mood stabilisation than typicals

• clozapine, olanzapine, risperidone
• but effect on neg symptoms still weak, only relevant for pts who start out with severe neg symptoms

Some may ameliorate cognitive dysfunction better than typicals
- clozapine, risperidone