Antipsychotics

Question 1

Uses of antipsychotic

Answer 1

Psychotic symptoms – delusions and hallucinations
• Mania
• Acute behavioural disturbance
• Antidepressant augmentation

Question 2

Mechanism of antipsycotics

Answer 2

• Dopamine antagonists – D2 and others. Some 5HT effects, particularly in atypicals.
• Act on multiple dopamine pathways
o Mesolimbic – antipsychotic action (dopamine hypothesis of schizophrenia)
o Nigrostriatal – extrapyramidal movement pathway
o Pituitary temporofundibular system – prolactin.
• Some muscarinic, 5HT, histamine and adrenergic effects.

Question 3

Typical antipsychotics

Answer 3

• Phenothiazines:
o Chlorpromazine – sedative, moderate anticholinergic side effects, moderate EPSE
o Levomepromazine
o Pipothiazine
o Trifluoroperozine
• Butrophenones
o Haloperidol – sedative, fewer anticholinergic side effects, EPSE common
• Tioxanthines
o Flupentixol – good for depressive component
o Zuclopenthixol – good for aggressive component
• Sulpiride – less EPSE

Question 4

EPSEs

Answer 4

o Parkinsonism in 20-40%. Tremor, cogwheel rigidity, bradykinesia. Anticholinergic drugs.
o Akathisia in 20-40%. Subjective restlessness. Does not respond to anticholinergics.
o Dystonia – serious muscle spasms. IM anti-cholinergic (pro-cyclidine)
o Tardive dyskinesia – choreo-athetoid orofacial movements. Serious, long term, involuntary, difficult to treat.

Question 5

Atypicals

Answer 5

• Olanzapine
• Quetiapine – prolactin neutral
• Amisulpiride – EPSE, prolactin
• Risperidone – EPSE, prolactin
• Aripiprazole – partial dopamine agonist. Less metabolic side effects.
• Clozapine – most effective antipsychotic
• Asenapine – new, 5-HT2A, dopamine receptor antagonist.

Question 6

Side effects of atypicals

Answer 6

o Hyperprolactinaemia – pituitary dopamine blockade. Leads to amenorrhoea, galactorrhoea, gynaecomastia, sexual dysfunction (osteoporosis). Possibly increased breast cancer risk. Consider prolactinoma if >3000.
o Anti-adrenergic – sedation, postural hypotension
o Anticholinergic.
o Cardiac arrhythmias – prolonged QT – sudden cardiac death.

Question 7

Antipsychotic pharmacokinetics

Answer 7

• Well absorbed, mainly from the jejunum.
• Some first pass effect
• Highly protein bound

Question 8

Antipsychotic DDIs

Answer 8

• Potentiate the effects of other sedatives.

* May delay the metabolism of other drugs.

Question 9

Antipsychotic contraindications

Answer 9

• Myasthenia gravis, Addison’s, glaucoma

* Clozapine – bone marrow depression

Question 10

Antipsychotic monitoring

Answer 10

• Metabolic
o Weight, BMI, waist, BP, glucose, lipids.
o Baseline, 3 month and every 12 months
• ECG
o Recommended before starting antipsychotics.
o Dual antipsychotics
o Multiple QTc prolonging medications
• Clozapine monitoring
o FBC weekly and then monthly. 0.5% risk of agranulocytosis.
o Clozapine levels.

Question 11

Antipsychotic depot

Answer 11

• Increase compliance and bioavailability
• Side effects more difficult to control.
• Haloperidol decanoate Haldol
• Flupenthixol decanoate (depixol)
• Fluphenazine decanoate (modecate)
• Risperidone (Risperdal consta)
• Paliperidone
• Olanzapine

Question 12

Neuroleptic malignant syndrome

Answer 12

• Rare idiosyncratic response to antipsychotics and other psychotropics.
• Medical emergency – 10% mortality.
• EPSE – muscle rigidity, akinetic mutism, stupor.
• Autonomic dysfunction – hyperpyrexia, tachycardia, unstable blood pressure, excessive sweating, salivation, urinary incontinence.
• Creatinine kinase increased
• Complications – renal failure, pneumonia, thromboembolism.