Antipsychotics and clozapine flashcards
20 high-yield MRCP Part 1 cards from the Intellect Medicos Psychiatry course. Try to answer each question before you open it — then study them properly with spaced repetition, which brings each card back just before you would forget it.
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A 19-year-old was given IM haloperidol in the emergency department 6 hours ago. His eyes are now fixed upwards and his neck is twisted painfully to one side. What is the first-line treatment?
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Procyclidine (an anticholinergic), given IM or IV.
Why? This is acute dystonia (oculogyric crisis and torticollis), which occurs within hours to days of starting a dopamine blocker.
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A patient feels inwardly restless and cannot sit still 1 week after starting an antipsychotic. After reducing the dose or switching, which drug is first line?
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Propranolol (a benzodiazepine is an alternative).
Why? This is akathisia, which appears days to weeks after starting.
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A man on haloperidol for many years develops lip-smacking, chewing movements and tongue protrusion. What is the first step in management?
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Stop or reduce the antipsychotic, and consider switching (the course notes favour clozapine).
Why? This is tardive dyskinesia, which appears after months to years and is often irreversible.
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Which atypical antipsychotic is classically linked with hyperprolactinaemia?
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Risperidone.
Why? It strongly blocks D2 receptors in the tuberoinfundibular pathway, where dopamine normally inhibits prolactin. Effects include galactorrhoea, amenorrhoea and sexual dysfunction.
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What is the most serious haematological adverse effect of clozapine?
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Agranulocytosis (severe neutropenia).
Why? It is why clozapine can only be prescribed with registration on a monitoring service and regular full blood counts.
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How often is the full blood count checked on clozapine?
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Weekly for the first 18 weeks, then every 2 weeks until 1 year, then every 4 weeks.
Why? The risk of neutropenia and agranulocytosis is highest in the first few months of treatment.
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Which cardiac complication of clozapine typically occurs in the first 2 months of treatment?
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Myocarditis.
Why? It presents with tachycardia, fever, chest pain or heart failure. Cardiomyopathy can occur later. Clozapine must be stopped if it is suspected.
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A patient stable on clozapine stops smoking. What happens to the clozapine level, and why?
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It rises, because cigarette smoke induces CYP1A2; stopping smoking slows clozapine metabolism.
Why? Levels can rise sharply within days, risking toxicity (sedation, seizures). The dose often needs reducing, guided by plasma levels.
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A man started haloperidol 5 days ago. He is now confused with temperature 39.8 °C, generalised 'lead-pipe' rigidity, sweating, labile BP and CK 14,000 U/L. What is the most likely diagnosis?
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Neuroleptic malignant syndrome.
Why? A dopamine-blocker reaction that develops over days with hyperthermia, severe rigidity, autonomic instability and a very high CK. It can occur with typical or atypical antipsychotics.
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What is the first-line management of neuroleptic malignant syndrome?
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Stop the antipsychotic and give supportive care (IV fluids, cooling, often HDU/ICU); consider dantrolene or bromocriptine if severe.
Why? IV fluids also protect against AKI from rhabdomyolysis. Dantrolene relaxes muscle; bromocriptine is a dopamine agonist that reverses the blockade.
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First-generation (typical) antipsychotics mainly block ______ receptors; second-generation (atypical) drugs additionally block serotonin 5-HT2A receptors.
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dopamine D2
Why? Typicals cause more extrapyramidal effects; atypicals cause more metabolic effects (weight gain, glucose, lipids).
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First-generation (typical) antipsychotics mainly block dopamine D2 receptors; second-generation (atypical) drugs additionally block ______ receptors.
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serotonin 5-HT2A
Why? Typicals cause more extrapyramidal effects; atypicals cause more metabolic effects (weight gain, glucose, lipids).
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Which two antipsychotics cause the most weight gain and metabolic disturbance?
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Clozapine and olanzapine.
Why? Both cause marked weight gain, hyperglycaemia and hyperlipidaemia, so metabolic monitoring is essential.
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Which baseline investigation does the BNF recommend before starting haloperidol?
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An ECG (and correction of any electrolyte disturbance).
Why? Haloperidol prolongs the QT interval and can cause torsades de pointes. It is contraindicated with QTc prolongation, uncorrected hypokalaemia, Parkinson's disease and dementia with Lewy bodies.
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What is the mechanism of action of aripiprazole?
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A partial agonist at dopamine D2 receptors (also acts on 5-HT1A and 5-HT2A receptors).
Why? Partial agonism explains why it rarely raises prolactin and causes little weight gain.
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Six weeks after starting haloperidol, a man has a resting tremor, cogwheel rigidity, a mask-like face and slow movements. What is the first step in management?
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Reduce the dose or switch to an atypical antipsychotic; an anticholinergic such as procyclidine can be used if needed.
Why? This is drug-induced parkinsonism, which typically appears after weeks of dopamine blockade.
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After starting an antipsychotic, how often should weight be checked (NICE)?
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Weekly for the first 6 weeks, then at 12 weeks, at 1 year and then annually.
Why? Fasting glucose or HbA1c and lipids are checked at baseline, 12 weeks, 1 year and then annually; pulse and BP at 12 weeks, 1 year and annually.
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Which serious risks led the MHRA to warn against antipsychotics in older people with dementia?
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Increased risk of stroke and of death.
Why? Antipsychotics should be used for behavioural symptoms in dementia only when there is severe distress or risk of harm, at the lowest dose and for the shortest time, with regular review.
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Which potentially fatal gastrointestinal adverse effect of clozapine must be screened for at every review?
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Gastrointestinal hypomotility: severe constipation, faecal impaction and paralytic ileus.
Why? Clozapine's strong anticholinergic effect slows the gut. Ask about bowel habit and treat constipation early; avoid other anticholinergic drugs.
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On clozapine, below what neutrophil count must the drug be stopped immediately (a 'red' result)?
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Neutrophils below 1.5 × 10⁹/L.
Why? This suggests developing agranulocytosis; a total white count below 3.0 × 10⁹/L also triggers action. Stop clozapine, check FBC daily, and look for infection; neutropenic sepsis is treated urgently.