Antipsychotics

Question 1

Describe the mode of action of antipsychotics. What is the difference between typicals and atypicals?

Answer 1

MOA: D2 receptor antagonists - therapeutic effects due to action on dopaminergic neurones of mesolimbic pathway.

Atypicals are weaker dopamine antagonists (decreased extra-pyramidal effects) but tend to have more serotonergic activity. Typicals bind more to muscarinic and histaminic Rs.

Question 2

Suggest examples of antipsychotics you would prescribe someone with SZP

Answer 2

Atypical antipsychotics 1st line, e.g.

• ARIPIPRAZOLE - tends to have fewer side effects but ?less efficacious
• RISPERIDONE
• QUETIAPINE
• AMISULPIRIDE
• CLOZAPINE - most efficacious but greater risk of agranulocytosis so reserved for Tx-resistant SZP

Typical antipsychotics 2nd line due to s/e, e.g.

• CHLORPROMAZINE
• HALOPERIDOL
• FLUOPENTIXOL
• SULPIRIDE

Question 3

which side effects are associated with antipsychotics?

Answer 3

1. extra-pyramidal symptoms
2. hyperprolactinaemia
3. sexual dysfunction
4. cardiovascular effects, e.g. tachycardia, arrhythmias (eg. haloperidol and prolonged QT), hypotension
5. hyperglycaemia and weight gain
6. neuroleptic malignant syndrome
7. blood dyscrasias

Question 4

describe and explain the different types of extra-pyramidal effects

Answer 4

Caused by dopamine antagonism in substantia nigra

1. parkinsonism
   - tremor, bradykinesia, parkinosonias gait
   - more common in adults/elderly
   - may appear gradually
   - remits on drug withdrawal and may be suppressed by antimuscarinic drugs
2. acute dystonias
   - e.g. torticollis, oculogyric crisis
   - more common in children or young adults
   - appear after only a few doses
3. tardive dyskinesia
   - rhythmic, involuntary movements of tongue, face and jaw
   - usually develop on long-term therapy or with high dosage
   - may be irreversible
4. akathisia

Question 5

explain why hyperprolactinaemia can be a side effect. what are the possible effects?

Answer 5

Dopamine inhibits prolactin release so dopamine antagonism in tubulo-infundibular pathway can cause increased prolactin release.

Can cause:

• sexual dysfunction
• gynaecomastia
• galactorrhoea
• impaired glucose tolerance

Question 6

suggest specific side effects of clozapine

Answer 6

1. agranulocytosis
2. reduced seizure threshold
3. myocarditis
4. constipation/paralytic ileus
5. hypersalivation

Question 7

what monitoring is required for a patient starting on an antipsychotic?

Answer 7

• FBC, lipid profile, LFTs, UandEs and HbA1c - baseline, at 3 mths and annually
• weight - baseline, at 3 mths and annually
• prolactin - baseline, at 6 mths and annually
• ECG - baseline