Antipsychotics are licensed for a wide variety of conditions. Which of the following are licensed indications for some antipsychotics
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Tourette syndrome
Hiccoughs
Nausea and vomiting
Attention deficit hyperactivity disorder
Personality disorder
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Correct
1. Tourette syndrome
Antipsychotics such as haloperidol are licensed for Tourette syndrome.
2. Hiccoughs
Some antipsychotics (eg chlorpromazine, haloperidol and perphenazine) are licensed for intractable hiccough.
3. Nausea and vomiting
The antipsychotic prochlorperazine is widely used for controlling nausea and vomiting; others licensed for nausea and vomiting include chlorpromazine and haloperidol (both for use in restricted circumstances), perphenazine and trifluoperazine. The antiemetics domperidone and metoclopramide are D2 antagonists but they are not antipsychotics.
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4. Attention deficit hyperactivity disorder
Antipsychotics are not licensed for attention deficit hyperactivity disorder.
5. Personality disorder
Antipsychotics are not licensed for the treatment of personality disorder.
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Which of the following antipsychotics are usually considered ‘atypical’ or ‘second-generation’ antipsychotics?
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Paliperidone
Aripiprazole
Clozapine
Sulpiride
Amisulpride
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1. Paliperidone
Paliperidone, an active metabolite of risperidone, is a benzisoxazole derivative and a so-called second-generation antipsychotic.
2. Aripiprazole
Aripiprazole is a second-generation dihydrocarbostyril antipsychotic. Because aripiprazole is a partial agonist at the dopamine D2 receptor, it has sometimes been referred to as a 'third-generation antipsychotic'.
3. Clozapine
Clozapine, a dibenzodiazepine derivative, is regarded as the prototype 'atypical' or 'second-generation' antipsychotic.
5. Amisulpride
Although amisulpride is chemically related to sulpiride—both being substituted benzamides—amisulpride is considered to be an 'atypical' or 'second-generation' antipsychotic.
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4. Sulpiride
Although sulpiride is chemically related to amisulpride—both being substituted benzamides—sulpiride is considered to be a 'conventional' or 'first-generation' antipsychotic.
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Antipsychotics can affect various physiological systems in addition to their intended target of action. Which of the following physiological systems is NOT thought to be directly affected by antipsychotics? Select the single best answer.
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Rarely, antipsychotics can be toxic to bone marrow, producing anaemia, neutropenia and thrombocytopenia. (The agranulocytosis of clozapine is not thought to occur by bone marrow suppression but through another mechanism).
Correct
Motor fibres in the spinal cord consist of the corticospinal tract which, along with the corticobulbar tract, forms the pyramidal tracts subserving voluntary movement. These neurones are not directly affected by antipsychotics.
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The extrapyramidal motor system contains elements of the nigrostriatal pathway which are directly inhibited by the D2 antagonism of antipsychotics. The extrapyramidal system is responsible for involuntary movement and the coordination of movement; inhibition of this system by antipsychotics can produce extrapyramidal side effects.
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Antipsychotics can antagonise the D2 receptors in the hypothalamic temperature regulation system, leading to problems with temperature control.
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Antagonism of D2 receptors in the anterior pituitary prevents dopamine-mediated inhibition of prolactin secretion, leading to risk of hyperprolactinaemia.
All of the following are considered extrapyramidal side effects of antipsychotics, EXCEPT (select the single best answer):
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The extrapyramidal side effects of antipsychotics are caused by the antagonism of D2 receptors in the extrapyramidal motor systems of the brain. The four main types of extrapyramidal side effects are tardive dyskinesia, acute dystonia, akathisia and parkinsonism. More than one may be present at the same time.
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The extrapyramidal side effects of antipsychotics are caused by the antagonism of D2 receptors in the extrapyramidal motor systems of the brain. The four main types of extrapyramidal side effects are tardive dyskinesia, acute dystonia, akathisia and parkinsonism. More than one may be present at the same time.
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The extrapyramidal side effects of antipsychotics are caused by the antagonism of D2 receptors in the extrapyramidal motor systems of the brain. The four main types of extrapyramidal side effects are tardive dyskinesia, acute dystonia, akathisia and parkinsonism. More than one may be present at the same time.
Correct
Catatonia is a neuromotor and behavioural syndrome characterised by rigidity, stereotyped movements, posturing and repetitive movements or actions. It is associated with psychiatric disorders such as schizophrenia and severe depression or bipolar disorder.
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The extrapyramidal side effects of antipsychotics are caused by the antagonism of D2 receptors in the extrapyramidal motor systems of the brain. The four main types of extrapyramidal side effects are tardive dyskinesia, acute dystonia, akathisia and parkinsonism. More than one may be present at the same time.
Which of the following is NOT a typical feature of neuroleptic malignant syndrome? Select the single best answer:
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Neuroleptic malignant syndrome is a rare but potentially fatal disorder which typically occurs within two weeks of starting an antipsychotic or altering the regimen. It is characterised by raised temperature, muscle rigidity, altered mental status and autonomic instability (eg irregular pulse, blood pressure variation, excessive sweating). Skeletal muscle breakdown can raise creatine kinase level.
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Neuroleptic malignant syndrome is a rare but potentially fatal disorder which typically occurs within two weeks of starting an antipsychotic or altering the regimen. It is characterised by raised temperature, muscle rigidity, altered mental status and autonomic instability (eg irregular pulse, blood pressure variation, excessive sweating). Skeletal muscle breakdown can raise creatine kinase level.
Correct
Myoclonus1 is a common feature of serotonin syndrome rather than of neuroleptic malignant syndrome. Neuroleptic malignant syndrome is a rare but potentially fatal disorder which typically occurs within two weeks of starting an antipsychotic or altering the regimen. It is characterised by raised temperature, muscle rigidity, altered mental status and autonomic instability (eg irregular pulse, blood pressure variation, excessive sweating). Skeletal muscle breakdown can raise creatine kinase level.
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The enzyme creatine kinase (formerly known as creatine phosphokinase, CPK), is raised in muscle disease and in athletes. Skeletal muscle breakdown associated with neuroleptic malignant syndrome can also raise creatine kinase. Neuroleptic malignant syndrome is a rare but potentially fatal disorder which typically occurs within two weeks of starting an antipsychotic or altering the regimen. It is characterised by raised temperature, muscle rigidity, altered mental status and autonomic instability (eg irregular pulse, blood pressure variation, excessive sweating).
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Neuroleptic malignant syndrome is a rare but potentially fatal disorder which typically occurs within two weeks of starting an antipsychotic or altering the regimen. It is characterised by raised temperature, muscle rigidity, altered mental status and autonomic instability (eg irregular pulse, blood pressure variation, excessive sweating). Skeletal muscle breakdown can raise creatine kinase level.
An 18-year-old is admitted to A&E having been detained by the police. He was running down a motorway naked screaming about his ‘mind being controlled by the Apple Corporation’. The admitting A&E doctor prescribed haloperidol 10 mg by intramuscular injection. You are asked to review the patient two hours later and find him grimacing and lying in a contorted position on the bed. The most likely explanation for this is:
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Parkinsonism is associated with the use of antipsychotics, but it follows chronic rather than acute use. Parkinsonism most commonly affects older individuals.
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Psychomotor retardation is a reduction in voluntary movement and slowing down of thought that is usually associated with affective disorders such as severe depressive illness.
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Catatonia is a neuromotor and behavioural syndrome characterised by rigidity, stereotyped movements, posturing and repetitive movements or actions. It is associated with psychiatric disorders such as schizophrenia and severe depression or bipolar disorder. Although catatonia is possible in this scenario, given the history of recent injection of high dose of high-potency antipsychotic, another explanation is more likely.
Correct
Injection of a high dose of haloperidol, a relatively high-potency antipsychotic, can produce acute dystonia, especially in an individual who has not previously taken an antipsychotic. Acute dystonia is a sustained muscular contraction, often manifesting as grimacing, rigid body posture and subjective feeling of distress. Acute dystonias are caused by D2 antagonism in the nigrostriatal pathway and tend to occur rapidly, within the first days of treatment and often within hours.
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Tardive dyskinesia is associated with the use of antipsychotics, but it follows chronic rather than acute use.
Which of the following may be appropriate treatment options for the above scenario:
Intramuscular benzodiazepine eg lorazepam
Oral antimuscarinic eg orphenadrine
Oral dopamine agonist eg bromocriptine
Intramuscular antimuscarinic eg procyclidine
Intramuscular serotonin antagonist eg ondansetron
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2. Oral antimuscarinic eg orphenadrine
The treatment of acute dystonia may require antimuscarinic (anticholinergic) therapy. This may be given by the oral route or, where this is not possible, by the parenteral route.
4. Intravenous antimuscarinic eg procyclidine
The treatment of acute dystonia may require antimuscarinic (anticholinergic) therapy. This may be given by the oral route or, where this is not possible, by the parenteral route.
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1. Intramuscular benzodiazepine eg lorazepam
A benzodiazepine can sedate the patient and relax muscles, but it is not specific treatment for acute dystonia. An intramuscular benzodiazepine must be used with caution when a parenteral antipsychotic has been used recently, and would not be recommended in acute dystonia because breathing difficulties may result. (It should be borne in mind that absorption of lorazepam from the intramuscular injection site may be slower than absorption from lorazepam given orally.)
3. Oral dopamine agonist eg bromocriptine
There has been scientific interest in the use of oral dopamine agonists for acute dystonia, but none is licensed for this use and dopamine agonists may aggravate the symptoms of schizophrenia.
A patient was started on an antipsychotic two weeks ago, in line with current guidelines. On medication review she complains of nausea (but no vomiting). Which of the following could be appropriate management (select the single best answer):
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As the patient has recently started antipsychotic therapy, she should already be on the lower end of the licensed dose range, so halving the dose in response to nausea would not be recommended.
Correct
The patient should generally be advised that nausea associated with initiation of antipsychotic therapy is relatively common and usually abates within a short period (ie should improve within two weeks). Specialist advice may be necessary if the patient is finding the nausea particularly troublesome..
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Metoclopramide is a dopamine antagonist; use of a dopamine antagonist antiemetic is not recommended because it may increase the risk of antipsychotic side effects and possibly cause extrapyramidal symptoms.
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Prochlorperazine is a dopamine antagonist; use of a dopamine-antagonist antiemetic is not recommended because it may increase the risk of antipsychotic side effects and possibly cause extrapyramidal symptoms.
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Nausea and vomiting often occur at the start of antipsychotic treatment and this should not be a reason for stopping treatment, especially if nausea and vomiting are not very troublesome.
A 21-year-old lady with schizophrenia is prescribed risperidone. Her condition responds well to treatment with clear improvement in symptoms. However, her blood tests reveal persistent and marked elevation of circulating prolactin. On medication review, you discuss with the clinical team switching to an alternative antipsychotic. Which of these alternative antipsychotics might be appropriate option in this case?
Haloperidol
Quetiapine
Clozapine
Aripiprazole
Amisulpride
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2. Quetiapine
Quetiapine is considered to be a relatively prolactin-sparing antipsychotic.
4. Aripiprazole
Aripiprazole is considered to be a relatively prolactin-sparing antipsychotic.
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1. Haloperidol
Haloperidol is relatively likely to produce hyperprolactinaemia, so it would not be appropriate for this case.
3. Clozapine
Clozapine is prolactin-sparing, but it is licensed for use only in treatment-resistant schizophrenia or when the patient is intolerant of other antipsychotics. So, it would not be recommended as second-line choice in this scenario.
5. Amisulpride
Amisulpride is relatively likely to produce hyperprolactinaemia, so it would not be appropriate for this case.
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Which of the following can increase the risk of clinically significant arrhythmia associated with antipsychotic-induced QT-interval prolongation?
Other medicines
Hypokalaemia
Congenital QT interval prolongation
Family history of sudden cardiac death
Congestive cardiac failure
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1. Medicines
Concomitant use of two or more medicines that prolong the QT interval could potentially increase the risk of arrhythmia; such medicines include antiarrhythmic drugs (eg amiodarone and disopyramide), macrolide antibiotics (eg erythromycin), and methadone.
2. Hypokalaemia
Hypokalaemia predisposes patients to prolongation of the QT interval. Hypokalaemia can occur as a consequence of certain disorders or as a side-effect of drugs such as loop and thiazide diuretics, corticosteroids, and parenteral amphotericin.
3. Congenital QT interval prolongation
Organic heart disease such as congenital long QT syndrome increase the risk of prolonging ventricular repolarisation or of torsades de pointes.
4. Family history of sudden cardiac death
Patients who have a family history of sudden death may be at increased risk of QT-interval prolongation and arrhythmias.
5. Congestive cardiac failure
Congestive cardiac failure is among several organic heart disorders that may prolong the QT interval. Medicines such as antipsychotics that prolong the QT interval should therefore be avoided or used very cautiously in such patients.
Which of the following cardiovascular disorders are associated with antipsychotic use?
Cardiomyopathy
Cerebrovascular accident
Myocarditis
Tetralogy of Fallot
Short QTc syndrome
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1. Cardiomyopathy
Clozapine is associated with cardiomyopathy; it generally develops some time after starting treatment.
2. Cerebrovascular accident
Antipsychotics have been associated with thromboembolic disorders; in elderly patients with dementia the risk of stroke may be increased three-fold.
3. Myocarditis
Clozapine is associated with myocarditis; it most often occurs in the first two months of treatment.
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4. Tetralogy of Fallot
Tetralogy of Fallot can be caused by environmental or genetic factors. Drugs (eg isotretinoin) have been linked with this congenital heart defect but there is no convincing evidence linking antipsychotics to tetralogy of Fallot.
Tetralogy of Fallot comprises: (a) a hole in the wall (septum) between the two ventricles; (b) narrowing of the valve at the top of the right ventricle (pulmonary valve) that allows blood to enter the pulmonary artery on its way to the lungs; (c) mis-positioned aorta such that the blood vessel lies directly above the hole between the ventricles; and (d) thickening of the muscle around the right ventricle (right ventricular hypertrophy).
5. Short QTc syndrome
Antipsychotics are associated prolongation (rather than shortening) of QT interval, which represents an interference with the electromechanical function of the heart and which can lead to arrhythmia and death.
Short QTc syndrome is linked to genetic factors. Its severity may vary from ECG findings with no symptoms to atrial fibrillation with recurrent syncope and sudden death
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Which one of the following is NOT a valid means of improving adherence to antipsychotic treatment? Select the single best answer.
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Adherence to antipsychotic therapy is often relatively poor, particularly in schizophrenia. For individuals who find tablets or capsules difficult to take, adherence may be improved by switching to formulations such as sublingual tablets or oral liquids.
Correct
Monitoring the concentration of an antipsychotic in the blood (‘therapeutic drug monitoring’) can be of value in case of antipsychotic toxicity (particularly with clozapine) is suspected; monitoring can also reveal complete absence of drug. However, concentration of the drug in blood says little about adherence other than how much medicine might have been taken shortly before the test. Also, unless reliable pharmacokinetic data are available for the individual, it is difficult to interpret one-off results.
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Adherence to antipsychotic therapy is often poor, particularly in schizophrenia. If a patient cannot reliably remember to take the dose, a pill organiser/reminder device can be used, particularly if several different medicines need to be taken throughout the day.
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Adherence to antipsychotic therapy is often poor, particularly in schizophrenia. When the antipsychotic treatment has been stabilised, a prolonged-release (‘depot’) antipsychotic can help with long-term adherence and reduce the risk of relapse.
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Adherence to antipsychotic therapy is often poor, particularly in schizophrenia. Although there may be a temptation to ‘play down’ the adverse effects of antipsychotics, it is good clinical practice to have an open dialogue with the patient about adverse effects—this can correct misconceptions, empower and involve the patient in treatment, and promote adherence.
A 24-year-old man with schizophrenia is treated with clozapine. At a routine appointment he reports improvement in his condition. He asks if you might prescribe something for his sore throat and fever because he feels he might have got the flu. Which of the following possible effects must you particularly consider? Select the single best answer.
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In patients taking an antipsychotic, leucocytosis typically occurs in association with neuroleptic malignant syndrome. While neuroleptic malignant syndrome cannot be completely ruled out, another clozapine-associated effect is more likely to fit the features mentioned.
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Myocarditis (with accompanying fever) can occur with clozapine use (most often in the first two months) and would need to be ruled out. However, chest pain or palpitations would usually be part of the presentation. Myocarditis would not seem to be the likely cause of the symptoms mentioned in the scenario.
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On starting clozapine, patients’ temperature may be raised, most often within 3 weeks. Generally the fever subsides without any intervention, but occasionally it may be associated with a serious adverse effect. In this case, neuroleptic malignant syndrome—which is characterised by high fever—would need to be ruled out. However, another clozapine-associated effect is more likely to fit the features mentioned.
Correct
A history of fever and sore throat suggests agranulocytosis as a possibility that must be ruled out immediately (by checking white cell count). The loss of neutrophils (neutropenia) in agranulocytosis leaves the patient vulnerable to overwhelming infection.
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Non-Hodgkin’s lymphoma is a cancer of the immune cells of the lymph nodes which is not associated with antipsychotic use.
All of the following medicines can increase the hypotensive effects of antipsychotics, EXCEPT (select the single best answer):
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Calcium-channel blockers (eg amlodipine, diltiazem, felodipine, lercanidipine, and nifedipine) lower blood pressure. Concomitant use of an antipsychotic and a calcium-channel blocker increases the risk of hypotensive effects including postural hypotension.
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ACE inhibitors (eg enalapril, lisinopril, perindopril, and ramipril) lower blood pressure. Concomitant use of an antipsychotic and an ACE inhibitor increases the risk of hypotensive effects including postural hypotension.
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Opioids (eg buprenorphine, dihydrocodeine, fentanyl, morphine and tramadol) can lower blood pressure. Concomitant use of an antipsychotic and an opioid increases the risk of hypotension.
Correct
Pseudoephedrine is associated with hypertensive effects.
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Beta-adrenoceptor blocking drugs (or beta-blockers eg atenolol, bisoprolol, metoprolol, and propranolol) can lower blood pressure. Concomitant use of an antipsychotic and a beta-blocker increases the risk of hypotension.
At a routine appointment, a 31-year-old lady on antipsychotic therapy for schizoaffective disorder says that she would like to start a family in the next year or so. All of the following may be useful to a discussion of risk and benefit, EXCEPT (select the single best answer):
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Antipsychotics, particularly those which increase prolactin secretion, are associated with reduced fertility but specialists may be able to overcome this effect by reducing the dose, discontinuing antipsychotic treatment or switching to an alternative medicine.
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Antipsychotics may cross the placenta and may be associated with adverse effects to the neonate, but these effects are not necessarily serious or enduring. Specialist advice should be sought; full discussion jointly by the woman and the clinician can identify the advantages and disadvantages of discontinuing therapy. In this case, the potential benefit to the embryo and fetus of discontinuing therapy should be weighed against the risks to mother (and fetus) of a relapse of symptoms.
Correct
While antipsychotics can cross the placenta, they are not all absolutely contraindicated in pregnancy. Specialist advice should be sought; full discussion jointly by the woman and the clinician can identify the advantages and disadvantages of discontinuing therapy. In this case, the potential benefit to the embryo and fetus of discontinuing therapy should be weighed against the risks to mother (and fetus) of a relapse of symptoms.
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Babies born to mothers who have been taking an antipsychotic in the last trimester may show adverse effects including lethargy, tremor, paradoxical hyperexcitability and extrapyramidal effects. The neonate may have a low Apgar score and manifest withdrawal effects such as agitation, tremor, somnolence and feeding problems.
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Specialist advice should be sought; full discussion jointly by the woman and the clinician can explore the advantages and disadvantages of continuing antipsychotic treatment and identify options for therapy during pregnancy.
You are asked to see a 19-year-old man admitted with a suspected first episode of psychosis and extreme agitation. The ward staff are having considerable difficulty managing his agitation and are concerned that he may become a threat to himself or others. Which of the following would NOT be appropriate for the patient’s initial management? Select the single best answer.
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Protocols for rapid tranquilisation may involve the use of medicines but non-pharmacological de-escalation such as transfer to a low-stimulus environment should be attempted first.
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If possible, a physical examination may be attempted to seek possible organic causes for agitation; however, the risk to safety of the patient and carers must be assessed before attempting examination.
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Lorazepam is licensed for unacceptable distress occurring in association with psychotic illness.
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Lorazepam is licensed for the treatment of acute excitement or acute mania, but the intramuscular route should be used only if lorazepam cannot be given by mouth or by slow intravenous injection. Absorption of lorazepam from the intramuscular injection site might be slower than absorption from an oral dose.
Correct
Although a number of antipsychotics are licensed for rapid tranquilisation, haloperidol at the relatively high dose of 10 mg by intramuscular injection would not be recommended, especially in the initial management of the patient (high risk of extrapyramidal side effects).
See also national guidelines on the treatment of acute episodes of psychosis
Question 18
Which of the following concerns has particularly led to the recommendation that antipsychotics (except in limited circumstances) are best avoided for the management of behavioural disorders in the elderly with dementia? Select the single best answer.
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Increased risk of antipsychotic-induced acute dystonia has not been raised as a special concern in the elderly with dementia. The risk of acute dystonia may be greater in younger patients than in the elderly.
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The risk of antipsychotic-induced parkinsonism is greater in the elderly than in younger patients. However, parkinsonism has not been raised as a special concern in the elderly with dementia.
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Elderly patients taking antipsychotics are more likely to suffer from an inability to regulate body temperature than younger patients. However, inability to regulate body temperature has not been raised as a special concern in the elderly with dementia.
Correct
There is a clear increased risk of stroke and a small increased risk of early death when antipsychotics (typical or atypical) are used in elderly people with dementia. For this reason antipsychotics are not licensed for the treatment of dementia-related behavioural disturbances (apart from the short-term use of risperidone in particular circumstances)
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The elderly are more prone to postural hypotension. However, postural hypotension has not been raised as a special concern in the elderly with dementia.
Which of the following is NOT thought to alter clozapine metabolism (select the single best answer):
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Beverages containing caffeine such as coffee can inhibit the metabolism of clozapine, thus increasing its concentration in plasma (but in most circumstances the effect may not large enough to require an adjustment to the clozapine dose).
Correct
Polycyclic aromatic hydrocarbons in tobacco smoke can induce the liver enzyme involved in metabolism of clozapine, leading to reduced concentration of clozapine. Nicotine itself does not induce the enzyme and therefore nicotine replacement gum will not alter clozapine metabolism (but giving up smoking may call for a change in clozapine dose).
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Beverages containing caffeine such as tea and coffee can inhibit the metabolism of clozapine, thus increasing its concentration in plasma (but in most circumstances the effect may not large enough to require an adjustment to the clozapine dose).
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Polycyclic aromatic hydrocarbons in tobacco smoke can induce the liver enzyme involved in metabolism of clozapine, leading to reduced concentration of clozapine. Smoking cessation may therefore call for possible reduction of the clozapine dose.
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Caffeine in tea and coffee as well as polycyclic aromatic hydrocarbons from cigarette smoking can alter the metabolism of clozapine. Although smoking cessation can affect the clozapine dose requirement, nicotine in cigarettes or in nicotine replacement patches does not affect clozapine metabolism.
Intramuscular injections of prolonged-release antipsychotics, also called ‘depot antipsychotics’, help promote adherence to treatment and reduce relapse risk. In which of the following situations should a prolonged-release antipsychotic NOT be used? Select the single best answer.
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It is possible to combine oral antipsychotic therapy with a depot antipsychotic, but the cumulative dose should remain within the licensed dose range. However, a prolonged-release antipsychotic must not be used concurrently with clozapine because persistence of the antipsychotic can hinder recovery from drug-induced blood disorders (eg neutropenia)
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Formal data on the use of depot antipsychotics in pregnancy are sparse, but in certain circumstances, especially for a woman who is stable on the current regimen, the woman and the physician might opt to continue use.
Correct
Depot antipsychotics are specifically not recommended for use in those aged under 18 years.
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A depot antipsychotic can be used for those aged over 65 years, but such use should take account of other significant morbidity (including renal function and the use of other medicines).
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Depot antipsychotics can also be used in the presence of cardiovascular, renal or liver disease, but a reduced dose may be required and attention must be paid to the severity of disease.