Central nervous system and psychiatry: Practice MCQs

100 practice questions with answers and explanations across 13 drug classes. All practice questions · Central nervous system and psychiatry study guides · Download as flashcards (CSV)

Antiepileptics

Revise the Antiepileptics guide

A patient stabilised on carbamazepine has a serum level checked one week after starting and again after six weeks, with no dose change. The later level is markedly lower. What best explains this?
1. Autoinduction of carbamazepine's own metabolism
2. Development of tolerance at the sodium channel
3. Reduced gastrointestinal absorption over time
4. Displacement from plasma protein binding
Show answer
Answer: A. Autoinduction of carbamazepine's own metabolism
Carbamazepine induces its own metabolism, and the label states that autoinduction is completed after three to five weeks of a fixed dosing regimen, so levels fall over that period without any dose change.
Which antiepileptic is described in its label as neither an inhibitor of nor a high-affinity substrate for human liver cytochrome P450 isoforms?
1. Levetiracetam
2. Carbamazepine
3. Phenobarbital
4. Phenytoin
Show answer
Answer: A. Levetiracetam
The levetiracetam label states that the drug and its major metabolite are neither inhibitors of nor high-affinity substrates for human liver cytochrome P450 isoforms, epoxide hydrolase or UDP-glucuronidation enzymes.
A patient of Han Chinese ancestry is being considered for carbamazepine. Which pre-treatment step does the label direct?
1. Screening for the HLA-B*1502 allele
2. Measuring serum bicarbonate
3. Formal visual field perimetry
4. Testing for POLG gene mutations
Show answer
Answer: A. Screening for the HLA-B*1502 allele
The boxed warning directs that patients with ancestry in genetically at-risk populations are screened for HLA-B*1502 before carbamazepine is started, and that those testing positive should not be treated unless the benefit clearly outweighs the risk.
Which adverse effect of topiramate follows directly from its inhibition of carbonic anhydrase?
1. Hyperchloraemic non-anion-gap metabolic acidosis
2. Gingival hyperplasia
3. Aplastic anaemia
4. Permanent visual field constriction
Show answer
Answer: A. Hyperchloraemic non-anion-gap metabolic acidosis
The topiramate label attributes a hyperchloraemic, non-anion-gap metabolic acidosis to renal bicarbonate loss caused by the drug's inhibitory effect on carbonic anhydrase.
Which statement about gabapentin's mechanism is correct?
1. It binds the alpha-2-delta subunit of voltage-activated calcium channels and has no effect on GABA binding
2. It is a direct agonist at the GABA-A receptor
3. It blocks voltage-gated sodium channels in the same way as phenytoin
4. It inhibits GABA transaminase irreversibly
Show answer
Answer: A. It binds the alpha-2-delta subunit of voltage-activated calcium channels and has no effect on GABA binding
The gabapentin label states that it binds with high affinity to the alpha-2-delta subunit of voltage-activated calcium channels, and that despite being structurally related to GABA it has no effect on GABA binding, uptake or degradation.
A patient develops a serum sodium of 122 mmol/L three weeks after starting a new antiepileptic. Which agent is most characteristically associated with this?
1. Oxcarbazepine
2. Gabapentin
3. Vigabatrin
4. Lamotrigine
Show answer
Answer: A. Oxcarbazepine
The oxcarbazepine label reports that 2.5% of treated patients in fourteen controlled epilepsy studies had a sodium below 125 mmol/L, generally within the first three months of treatment.
Which of these is listed in the lamotrigine label as a suggested factor that may increase the risk of serious rash?
1. Co-administration with valproate
2. Concurrent renal impairment
3. Co-administration with levetiracetam
4. A history of febrile convulsions
Show answer
Answer: A. Co-administration with valproate
The label lists coadministration with valproate, exceeding the recommended initial dose, and exceeding the recommended dose escalation as suggestions, yet to be proven, that the risk of rash may be increased.

Atypical antipsychotics

Revise the Atypical antipsychotics guide

Which single statement appears in the boxed warning of every atypical antipsychotic covered on this page?
1. Elderly patients with dementia-related psychosis have an increased risk of death when treated with antipsychotic drugs
2. Severe neutropenia requires an absolute neutrophil count before every dose
3. The drug prolongs the QT interval in all patients
4. Weight gain of at least 7% occurs in most treated patients
Show answer
Answer: A. Elderly patients with dementia-related psychosis have an increased risk of death when treated with antipsychotic drugs
The dementia mortality statement is the shared boxed warning across the class, quantified from seventeen placebo-controlled trials at 1.6 to 1.7 times the placebo risk of death. Neutropenia monitoring is specific to clozapine, and the QT and weight statements are agent-specific.
A patient with schizophrenia has failed two adequate trials of different antipsychotics. Which agent's label is written for exactly this situation?
1. Clozapine
2. Lurasidone
3. Pimavanserin
4. Paliperidone
Show answer
Answer: A. Clozapine
Clozapine is indicated for severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment, and its label states that because of the risks of severe neutropenia and of seizure it should be used only in such patients.
Which of these is NOT one of the headings in clozapine's boxed warning?
1. Permanent visual field constriction
2. Severe neutropenia
3. Myocarditis, pericarditis and cardiomyopathy
4. Orthostatic hypotension, bradycardia and syncope
Show answer
Answer: A. Permanent visual field constriction
Clozapine's boxed warning covers severe neutropenia, orthostatic hypotension with bradycardia and syncope, seizure, myocarditis with pericarditis and cardiomyopathy, and increased mortality in elderly patients with dementia-related psychosis. Visual field constriction belongs to a different drug entirely.
A patient develops galactorrhoea and amenorrhoea after starting an antipsychotic. Which agent is most characteristically implicated?
1. Risperidone
2. Aripiprazole
3. Pimavanserin
4. Quetiapine
Show answer
Answer: A. Risperidone
Its label states that risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents, and lists galactorrhoea, amenorrhoea, gynaecomastia and impotence among the reported consequences. Quetiapine shifted prolactin to a clinically significant value in only 3.6% of patients.
Which description of aripiprazole's mechanism matches its label?
1. Partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors with antagonist activity at 5-HT2A receptors
2. Irreversible blockade of dopamine D2 receptors in the striatum
3. Selective inverse agonism at serotonin 5-HT2A receptors with no dopamine affinity
4. Inhibition of dopamine reuptake at the presynaptic transporter
Show answer
Answer: A. Partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors with antagonist activity at 5-HT2A receptors
The label states that the efficacy of aripiprazole could be mediated through a combination of partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at 5-HT2A receptors. The third option describes pimavanserin instead.
Why can pimavanserin be used for psychosis in Parkinson's disease when most antipsychotics cannot?
1. It has no appreciable affinity for dopaminergic receptors including D2
2. It is a more potent D2 blocker and therefore acts at a lower receptor occupancy
3. It is cleared renally and so avoids central accumulation
4. It is given only for a short course, limiting motor harm
Show answer
Answer: A. It has no appreciable affinity for dopaminergic receptors including D2
Its label records no appreciable affinity, defined as a Ki value above 300 nanomolar, for dopaminergic receptors including D2, and attributes any effect to inverse agonist and antagonist activity at serotonin 5-HT2A receptors. Sparing dopaminergic transmission is precisely the point in a disease of dopamine loss.
Which pair of agents shares a prolactin-elevating effect because one is the active metabolite of the other?
1. Risperidone and paliperidone
2. Olanzapine and quetiapine
3. Clozapine and aripiprazole
4. Lurasidone and pimavanserin
Show answer
Answer: A. Risperidone and paliperidone
Paliperidone is the major active metabolite of risperidone, formed by CYP2D6 as 9-hydroxyrisperidone, and its label states that its prolactin-elevating effect is similar to that seen with risperidone.
A patient stabilised on clozapine misses several days of treatment and wants to restart at the previous dose. What does the label say about this situation?
1. Orthostatic hypotension, bradycardia and syncope can recur even after a brief interruption, so slow re-titration is required
2. Restarting at the previous dose is safe provided the neutrophil count is normal
3. The drug can be restarted at any dose because tolerance to hypotension is permanent
4. No neutrophil count is needed on restarting within one week
Show answer
Answer: A. Orthostatic hypotension, bradycardia and syncope can recur even after a brief interruption, so slow re-titration is required
The boxed warning states that these reactions can occur with the first dose, at very low doses, or when restarting patients who have had even a brief interruption in treatment, and directs slow titration with divided dosing. Any decision about restarting rests with the treating clinician.

Benzodiazepines

Revise the Benzodiazepines guide

How does a benzodiazepine differ from a barbiturate in its effect on the GABA-A chloride channel?
1. It increases the frequency of channel opening, while a barbiturate increases the time the channel stays open
2. It increases the time the channel stays open, while a barbiturate increases the frequency of opening
3. It blocks the channel pore, while a barbiturate opens it directly
4. Both increase the frequency of opening, but the benzodiazepine acts at the GABA site itself
Show answer
Answer: A. It increases the frequency of channel opening, while a barbiturate increases the time the channel stays open
A positive allosteric modulator raises the frequency with which the chloride channel opens when an agonist binds its own site, and this is the benzodiazepine action; barbiturates instead increase the time chloride channels remain open.
Which three of the agents below are cleared principally by conjugation to an inactive glucuronide rather than by oxidative metabolism to an active product?
1. Lorazepam, oxazepam and temazepam
2. Diazepam, alprazolam and midazolam
3. Clonazepam, flurazepam and diazepam
4. Midazolam, estazolam and clonazepam
Show answer
Answer: A. Lorazepam, oxazepam and temazepam
Lorazepam is rapidly conjugated at its 3-hydroxy group into a glucuronide with no demonstrable central nervous system activity, oxazepam has a single major inactive glucuronide metabolite, and temazepam is completely metabolised through conjugation with the O-conjugate predominating.
A patient on long-term benzodiazepine therapy for sedation in intensive care is unresponsive. Why is flumazenil not a routine first move?
1. Because its use has been associated with seizures, most frequently after long-term benzodiazepine sedation
2. Because it has no activity at the benzodiazepine recognition site
3. Because its effect lasts longer than that of any benzodiazepine
4. Because it worsens respiratory depression by an additive mechanism
Show answer
Answer: A. Because its use has been associated with seizures, most frequently after long-term benzodiazepine sedation
The flumazenil boxed warning states that its use has been associated with the occurrence of seizures, most frequent in patients on benzodiazepines for long-term sedation or in overdose with signs of serious cyclic antidepressant poisoning, and withdrawal seizures may follow even brief high-dose dependence.
Which single metabolite best explains why diazepam is classed as long acting?
1. N-desmethyldiazepam, with a terminal elimination half-life of up to 100 hours
2. Lorazepam glucuronide, which is renally excreted
3. 1-hydroxy-midazolam, formed by CYP3A4
4. The O-conjugate of temazepam
Show answer
Answer: A. N-desmethyldiazepam, with a terminal elimination half-life of up to 100 hours
Diazepam is N-demethylated by CYP3A4 and CYP2C19 to the active metabolite N-desmethyldiazepam, and its label puts the terminal elimination half-life of that metabolite at up to 100 hours.
Which statement about the modern benzodiazepine class boxed warning is correct?
1. It covers concomitant opioid use, abuse and addiction, and dependence with withdrawal reactions in one warning
2. It covers only the risk of respiratory depression during procedural sedation
3. It applies only to the long-acting members of the class
4. It warns solely about serious cutaneous reactions
Show answer
Answer: A. It covers concomitant opioid use, abuse and addiction, and dependence with withdrawal reactions in one warning
Current labels for diazepam, lorazepam, clonazepam, temazepam, oxazepam and estazolam all carry the same combined heading covering risks from concomitant use with opioids, abuse, misuse and addiction, and dependence and withdrawal reactions.
Which agent's label carries an explicit contraindication with strong CYP3A inhibitors such as the azole antifungals?
1. Alprazolam
2. Oxazepam
3. Temazepam
4. Lorazepam
Show answer
Answer: A. Alprazolam
Alprazolam is extensively metabolised primarily by CYP3A4, and its label contraindicates use in patients receiving strong inhibitors of CYP3A such as azole antifungal agents, with ritonavir the stated exception.
Roughly what proportion of patients who initially respond to clonazepam for seizures lose anticonvulsant activity, and over what period?
1. Up to 30%, often within three months
2. Up to 5%, usually after two years
3. Around 70%, within one week
4. Fewer than 1%, only after ten years
Show answer
Answer: A. Up to 30%, often within three months
The clonazepam label states that in some studies up to 30% of patients who initially responded have shown a loss of anticonvulsant activity, often within three months of administration.
Which agent is licensed for sedation, anxiolysis and amnesia before or during diagnostic, therapeutic or endoscopic procedures?
1. Midazolam
2. Oxazepam
3. Flurazepam
4. Estazolam
Show answer
Answer: A. Midazolam
Midazolam injection is indicated intravenously as an agent for sedation, anxiolysis and amnesia prior to or during diagnostic, therapeutic or endoscopic procedures, and its boxed warning requires trained personnel and airway equipment to be immediately available.

CNS stimulants and ADHD agents

Revise the CNS stimulants and ADHD agents guide

A methylphenidate label describes the drug's action on monoamine transporters. Which statement matches the label's own position on mechanism?
1. It blocks reuptake of noradrenaline and dopamine and increases their release, yet the mode of therapeutic action in ADHD is not known
2. It is a selective dopamine receptor agonist with a proven mechanism in ADHD
3. It irreversibly inhibits monoamine oxidase in the presynaptic terminal
4. It acts entirely through the alpha-2A adrenergic receptor
Show answer
Answer: A. It blocks reuptake of noradrenaline and dopamine and increases their release, yet the mode of therapeutic action in ADHD is not known
The label pairs a pharmacodynamic description of reuptake blockade and increased monoamine release in the extraneuronal space with an explicit statement that the mode of therapeutic action in ADHD and narcolepsy is not known.
Which ADHD medicine carries a boxed warning for suicidal ideation in paediatric patients rather than for abuse and addiction?
1. Atomoxetine
2. Lisdexamfetamine
3. Dexmethylphenidate
4. Dextroamphetamine
Show answer
Answer: A. Atomoxetine
Atomoxetine's boxed warning concerns suicidal thoughts and behaviours in paediatric patients aged six and over, with an incidence of 0.4% against 0% on placebo across twelve short-term studies. It is not a controlled substance.
How is lisdexamfetamine converted to its active moiety?
1. Hydrolysis primarily in blood by red blood cells, yielding dextroamphetamine and l-lysine
2. First-pass N-demethylation in the liver by CYP3A4
3. Hydrolysis by gastric acid before absorption
4. Renal tubular cleavage during excretion
Show answer
Answer: A. Hydrolysis primarily in blood by red blood cells, yielding dextroamphetamine and l-lysine
Its label states that lisdexamfetamine is converted to dextroamphetamine and l-lysine primarily in blood due to the hydrolytic activity of red blood cells, and that unconverted parent drug circulates only at low and transient concentrations.
A child treated with a stimulant every day for three years is likely to show which growth effect according to the labelling?
1. A temporary slowing of growth rate, on average about 2 cm less height and 2.7 kg less weight
2. Permanent loss of about 10 cm of final adult height
3. Accelerated growth with early epiphyseal closure
4. No measurable effect on height or weight at any point
Show answer
Answer: A. A temporary slowing of growth rate, on average about 2 cm less height and 2.7 kg less weight
Labelling reports that paediatric patients medicated on seven days a week throughout the year had a temporary slowing in growth rate averaging about 2 cm less growth in height and 2.7 kg less growth in weight over three years, with close monitoring advised.
Which agent's label specifically warns that abrupt discontinuation can cause rebound hypertension?
1. Clonidine
2. Atomoxetine
3. Modafinil
4. Dexmethylphenidate
Show answer
Answer: A. Clonidine
The extended-release clonidine ADHD label states that abrupt discontinuation can cause rebound hypertension and directs gradual reduction in small decrements over several days rather than stopping outright.
A patient stabilised on atomoxetine is started on fluoxetine for depression. What is the expected pharmacokinetic consequence?
1. A six- to eight-fold increase in plasma atomoxetine exposure through CYP2D6 inhibition
2. A halving of atomoxetine exposure through CYP3A4 induction
3. No interaction, because atomoxetine is renally cleared unchanged
4. Accelerated conversion of atomoxetine to an active metabolite
Show answer
Answer: A. A six- to eight-fold increase in plasma atomoxetine exposure through CYP2D6 inhibition
Atomoxetine is metabolised by CYP2D6, and its label records that concomitant paroxetine or fluoxetine produced six- to eight-fold increases in plasma atomoxetine exposure, effectively converting the patient into a poor metaboliser.
Which class of drug must be avoided for fourteen days before a stimulant is started, because of the risk of hypertensive crisis?
1. Monoamine oxidase inhibitors
2. Proton pump inhibitors
3. Beta-lactam antibiotics
4. Thiazide diuretics
Show answer
Answer: A. Monoamine oxidase inhibitors
Stimulant and non-stimulant labels alike exclude use during or within fourteen days of a monoamine oxidase inhibitor, because hypertensive crises with potentially fatal outcome may result.
Which statement about modafinil matches its labelling?
1. It is a Schedule IV controlled substance whose wakefulness mechanism is unknown
2. It is not a controlled substance and acts through proven histamine H3 antagonism
3. It is Schedule II and treats the underlying airway obstruction in sleep apnoea
4. It has no interaction with hormonal contraception
Show answer
Answer: A. It is a Schedule IV controlled substance whose wakefulness mechanism is unknown
Modafinil is a Schedule IV controlled substance, the mechanism through which it promotes wakefulness is unknown, and in obstructive sleep apnoea it is indicated for the excessive sleepiness and not as treatment for the underlying obstruction.

SSRI antidepressants

Revise the SSRI antidepressants guide

Which statement most accurately reflects the boxed warning carried by SSRI antidepressants?
1. Antidepressants increased the risk of suicidal thoughts and behaviour in paediatric and young adult patients in short-term studies
2. Antidepressants increase the risk of completed suicide in patients of every age
3. Antidepressants increase suicidal behaviour only in patients over 65
4. Antidepressants carry no warning about suicidal thoughts once the depression improves
Show answer
Answer: A. Antidepressants increased the risk of suicidal thoughts and behaviour in paediatric and young adult patients in short-term studies
The boxed warning is restricted by age. It states that antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies, and the supporting pooled analysis found fewer events than placebo in patients aged 25 to 64 and in those 65 and older.
A patient is being switched from fluoxetine to a monoamine oxidase inhibitor. What interval does the label require?
1. At least 5 weeks after stopping fluoxetine
2. At least 24 hours after stopping fluoxetine
3. At least 7 days after stopping fluoxetine
4. No interval is required in this direction
Show answer
Answer: A. At least 5 weeks after stopping fluoxetine
The fluoxetine label states that at least 14 days should elapse between stopping an MAOI and starting fluoxetine, and conversely that at least 5 weeks should be allowed after stopping fluoxetine before starting an MAOI, because of the long half-lives of fluoxetine and norfluoxetine.
Which SSRI is described in its label as causing dose-dependent QTc prolongation, with discontinuation directed at persistent QTc above 500 ms?
1. Citalopram
2. Sertraline
3. Fluvoxamine
4. Paroxetine
Show answer
Answer: A. Citalopram
The citalopram label states that the drug causes dose-dependent QTc prolongation, an ECG abnormality associated with Torsade de Pointes, and directs discontinuation in patients found to have persistent QTc measurements above 500 ms.
A woman taking tamoxifen after breast cancer needs an antidepressant. Which agent does its own label flag as a problem in this setting?
1. Paroxetine
2. Sertraline
3. Escitalopram
4. Fluvoxamine
Show answer
Answer: A. Paroxetine
The paroxetine label warns that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse and mortality, may be reduced with concomitant paroxetine as a result of paroxetine's irreversible inhibition of CYP2D6 and lower blood levels of tamoxifen, and suggests considering an antidepressant with little or no CYP2D6 inhibition.
An 82-year-old started on an SSRI four weeks ago presents with confusion, weakness and unsteadiness. Which investigation is most likely to explain the picture?
1. Serum sodium
2. Serum creatine kinase
3. Thyroid stimulating hormone
4. Serum calcium
Show answer
Answer: A. Serum sodium
SSRI-associated hyponatraemia commonly reflects the syndrome of inappropriate antidiuretic hormone secretion, and the labels list headache, difficulty concentrating, memory impairment, confusion, weakness and unsteadiness as its signs, with elderly patients at greater risk.
Which combination is explicitly contraindicated because of fluvoxamine's potency at CYP1A2?
1. Fluvoxamine with tizanidine
2. Fluvoxamine with paracetamol
3. Fluvoxamine with amoxicillin
4. Fluvoxamine with levothyroxine
Show answer
Answer: A. Fluvoxamine with tizanidine
Coadministration of tizanidine with fluvoxamine is contraindicated. In a study of healthy subjects, tizanidine peak concentration rose approximately twelve-fold and its area under the curve thirty-three-fold, with a mean maximal decrease of 35 mmHg in systolic blood pressure.
According to UK regulators, which antidepressants seem to be associated with a greater frequency of withdrawal reactions than other SSRIs?
1. Paroxetine and venlafaxine
2. Fluoxetine and sertraline
3. Citalopram and escitalopram
4. Fluvoxamine and mirtazapine
Show answer
Answer: A. Paroxetine and venlafaxine
The MHRA states that all SSRIs and SNRIs may be associated with withdrawal reactions on stopping or reducing treatment, and that paroxetine and venlafaxine seem to be associated with a greater frequency of withdrawal reactions than other SSRIs.
Which pair of drugs must be treated as monoamine oxidase inhibitors when an SSRI is prescribed?
1. Linezolid and intravenous methylene blue
2. Metronidazole and gentamicin
3. Rifampicin and isoniazid
4. Ciprofloxacin and clarithromycin
Show answer
Answer: A. Linezolid and intravenous methylene blue
The sertraline and paroxetine labels contraindicate use in patients taking, or within 14 days of stopping, MAOIs, and both name linezolid and intravenous methylene blue among them because of the increased risk of serotonin syndrome.

Triptans and migraine agents

Revise the Triptans and migraine agents guide

Through which receptors does sumatriptan act, according to its label?
1. 5-HT1B/1D receptors on intracranial vessels and trigeminal sensory nerves
2. 5-HT1F receptors on trigeminal ganglion neurons only
3. The calcitonin gene-related peptide receptor
4. Beta-1 adrenoceptors in cranial vessels
Show answer
Answer: A. 5-HT1B/1D receptors on intracranial vessels and trigeminal sensory nerves
The label states that sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors and acts at those receptors on intracranial vessels and trigeminal sensory nerves, causing cranial vasoconstriction and pro-inflammatory neuropeptide inhibition.
A patient with documented coronary artery vasospasm asks about an acute migraine treatment. Which agent is contraindicated by its label?
1. Sumatriptan
2. Ubrogepant
3. Rimegepant
4. Lasmiditan
Show answer
Answer: A. Sumatriptan
Coronary artery vasospasm, including Prinzmetal's angina, appears in the sumatriptan contraindications. Lasmiditan's label lists no contraindications, and the gepants are restricted by hypersensitivity and CYP3A4 interactions rather than by vascular disease.
What interval must separate an ergotamine-containing medication from sumatriptan?
1. Twenty-four hours
2. Four hours
3. Two weeks
4. Forty-eight hours
Show answer
Answer: A. Twenty-four hours
Recent use, defined as within twenty-four hours, of an ergotamine-containing or ergot-type medication is a contraindication to sumatriptan, because the vasospastic effects of the two may be additive.
The boxed warning on the ergotamine tartrate label concerns which combination?
1. Ergotamine with potent CYP3A4 inhibitors such as protease inhibitors and macrolides
2. Ergotamine with a non-steroidal anti-inflammatory drug
3. Ergotamine with an angiotensin receptor blocker
4. Ergotamine with a proton pump inhibitor
Show answer
Answer: A. Ergotamine with potent CYP3A4 inhibitors such as protease inhibitors and macrolides
The boxed warning states that serious or life-threatening peripheral ischaemia has been associated with the coadministration of ergotamine tartrate with potent CYP3A4 inhibitors, naming protease inhibitors and macrolide antibiotics.
Which agent on this page is licensed both for acute treatment and for preventive treatment of episodic migraine?
1. Rimegepant
2. Ubrogepant
3. Lasmiditan
4. Erenumab
Show answer
Answer: A. Rimegepant
Rimegepant carries both indications. Ubrogepant and lasmiditan are each stated not to be indicated for prevention, and erenumab is preventive only.
A patient taking lasmiditan asks about returning to work as a lorry driver. What does the label direct?
1. Hazardous activity requiring complete mental alertness is avoided for at least eight hours after each dose
2. There is no restriction, as lasmiditan is non-sedating
3. Driving is permitted once the headache has resolved
4. The restriction applies only to the first dose ever taken
Show answer
Answer: A. Hazardous activity requiring complete mental alertness is avoided for at least eight hours after each dose
A driving study showed that single doses significantly impaired the ability to drive, and the label advises against driving or operating machinery for at least eight hours after each dose, adding that those unable to follow the advice should not take the drug.
At what frequency of acute migraine drug use do the labels warn about exacerbation of headache?
1. Ten or more days per month
2. Two or more days per month
3. Twenty or more days per month
4. Any use on consecutive days
Show answer
Answer: A. Ten or more days per month
Both the sumatriptan and lasmiditan labels describe overuse of acute migraine drugs, including ergotamines, triptans and opioids or combinations of them, for ten or more days per month as leading to medication overuse headache.
Which adverse effect is specifically described in the erenumab label as sometimes requiring hospitalisation or surgery?
1. Severe constipation
2. Acute angle-closure glaucoma
3. Peripheral gangrene
4. Agranulocytosis
Show answer
Answer: A. Severe constipation
The label warns of constipation with serious complications, noting that severe constipation has developed, sometimes requiring hospitalisation or surgery, most often after the first dose.

Dementia agents

Revise the Dementia agents guide

Which statement most accurately reflects what the labels for donepezil, galantamine and memantine claim about disease course?
1. None of them claims to alter the underlying disease process
2. All three are stated to slow neurodegeneration
3. Only memantine is stated to slow neurodegeneration
4. Only the cholinesterase inhibitors are stated to slow neurodegeneration
Show answer
Answer: A. None of them claims to alter the underlying disease process
The donepezil and galantamine labels both state there is no evidence the drug alters the course of the underlying dementing process, and the memantine label states there is no evidence it prevents or slows neurodegeneration in patients with Alzheimer's disease.
An 82-year-old taking donepezil is started on tolterodine for urinary urgency. What is the pharmacological problem?
1. The antimuscarinic opposes the cholinergic action of the cholinesterase inhibitor
2. Tolterodine inhibits the renal excretion of donepezil
3. The combination causes additive serotonergic toxicity
4. Tolterodine induces the enzyme that metabolises donepezil
Show answer
Answer: A. The antimuscarinic opposes the cholinergic action of the cholinesterase inhibitor
Cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications, and tolterodine is named among those medicines. The two agents act in opposite directions on the same receptor system.
Which cardiac effect follows directly from the mechanism of a cholinesterase inhibitor?
1. Bradycardia and atrioventricular block from vagotonic effects on the conducting system
2. Sinus tachycardia from reflex sympathetic activation
3. Atrial fibrillation from direct atrial myocyte toxicity
4. Hypertensive crisis from noradrenaline release
Show answer
Answer: A. Bradycardia and atrioventricular block from vagotonic effects on the conducting system
Cholinesterase inhibitors have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block, and syncopal episodes have been reported. The galantamine label records a dose-related increase in the risk of syncope.
Which agent in this class is licensed for dementia associated with idiopathic Parkinson's disease?
1. Rivastigmine
2. Donepezil
3. Galantamine
4. Memantine
Show answer
Answer: A. Rivastigmine
European labelling for rivastigmine covers the symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson's disease, in addition to Alzheimer's dementia. Its label also warns that it may exacerbate extrapyramidal symptoms.
A patient on memantine is prescribed a carbonic anhydrase inhibitor. What is the expected consequence?
1. Reduced urinary elimination of memantine and higher plasma levels
2. Increased hepatic metabolism of memantine
3. Displacement of memantine from plasma protein binding
4. Loss of memantine efficacy through receptor competition
Show answer
Answer: A. Reduced urinary elimination of memantine and higher plasma levels
Memantine is excreted predominantly unchanged in urine, and conditions that raise urine pH decrease its urinary elimination, resulting in increased plasma levels. Carbonic anhydrase inhibitors and sodium bicarbonate are given as examples of drugs that alkalinise urine.
Which combination most clearly increases the risk of gastrointestinal bleeding in a patient on galantamine?
1. A concurrent non-steroidal anti-inflammatory drug
2. A concurrent proton pump inhibitor
3. A concurrent beta blocker
4. A concurrent carbonic anhydrase inhibitor
Show answer
Answer: A. A concurrent non-steroidal anti-inflammatory drug
The label directs close monitoring for active or occult gastrointestinal bleeding, especially in patients at increased risk of ulcers, such as those with a history of ulcer disease or those using concurrent non-steroidal anti-inflammatory drugs.

Mood stabilisers

Revise the Mood stabilisers guide

Which statement matches the boxed warning on the lithium carbonate label?
1. Lithium toxicity is closely related to serum lithium concentrations and can occur at doses close to therapeutic concentrations
2. Lithium toxicity occurs only after prolonged treatment at high concentrations
3. Lithium requires screening for a specific HLA allele before treatment begins
4. Lithium is contraindicated in all patients with any thyroid abnormality
Show answer
Answer: A. Lithium toxicity is closely related to serum lithium concentrations and can occur at doses close to therapeutic concentrations
The boxed warning ties toxicity directly to serum concentration and notes that it can occur near therapeutic levels, which is why the label also requires that assay facilities be available before treatment starts.
A patient stable on lithium is started on a thiazide diuretic for hypertension. What is the expected effect on the serum lithium concentration?
1. It rises, because diuretic-induced sodium loss reduces lithium clearance
2. It falls, because increased urine flow washes lithium out
3. It is unchanged, because lithium is cleared hepatically
4. It falls, because thiazides block proximal tubular reabsorption of lithium
Show answer
Answer: A. It rises, because diuretic-induced sodium loss reduces lithium clearance
The label states that diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations, so a diuretic pushes the level up rather than down.
How does the MHRA position on valproate in pregnancy differ between bipolar disorder and epilepsy?
1. For bipolar disorder there is an absolute contraindication in pregnancy, with no exception for absent alternatives
2. For bipolar disorder the restriction is looser, because manic relapse is less dangerous than a seizure
3. The two indications carry identical wording with no practical difference
4. The restriction applies only to epilepsy and not to psychiatric use at all
Show answer
Answer: A. For bipolar disorder there is an absolute contraindication in pregnancy, with no exception for absent alternatives
The MHRA sets an absolute contraindication to valproate in pregnancy for the bipolar indication, whereas in epilepsy use may still be considered where no suitable alternative exists.
Which co-prescription is listed in the lamotrigine label as a factor that may increase the risk of serious rash?
1. Valproate
2. Lithium carbonate
3. Quetiapine
4. Aripiprazole
Show answer
Answer: A. Valproate
Coadministration with valproate appears alongside exceeding the recommended initial dose and exceeding the recommended dose escalation among the factors that may raise rash risk, and valproate also more than doubles lamotrigine concentrations.
Which pre-treatment step does the carbamazepine boxed warning direct for patients with ancestry in genetically at-risk populations?
1. Screening for the HLA-B*1502 allele
2. Baseline visual field perimetry
3. Measuring serum lithium concentration
4. Testing for mitochondrial DNA polymerase gamma mutations
Show answer
Answer: A. Screening for the HLA-B*1502 allele
The boxed warning directs HLA-B*1502 screening before carbamazepine is started in those populations, because of serious and sometimes fatal reactions including toxic epidermal necrolysis and Stevens-Johnson syndrome.
Lamotrigine's licence in bipolar I disorder is best described as which of the following?
1. Maintenance treatment to delay the time to occurrence of mood episodes
2. First-line treatment of acute mania
3. Monotherapy for acute depressive episodes of bipolar disorder
4. Short-term adjunct to lithium for acute mixed episodes
Show answer
Answer: A. Maintenance treatment to delay the time to occurrence of mood episodes
The label gives maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in adults already treated for acute episodes, and states that effectiveness in acute treatment has not been established.
Which of these labels explicitly declines to state a definite mechanism for its mood effect?
1. Lithium carbonate, extended-release carbamazepine and olanzapine all do
2. Only lithium carbonate does
3. None of them do; each names a specific receptor
4. Only the antipsychotic labels do
Show answer
Answer: A. Lithium carbonate, extended-release carbamazepine and olanzapine all do
Lithium's mechanism as a mood stabilising agent is stated to be unknown, carbamazepine's mechanism in acute manic or mixed episodes is stated to be unclear, and the European regulator states that olanzapine's exact mechanism of action is unknown.
Which adverse outcome has been reported when lithium is given together with an antipsychotic?
1. An encephalopathic syndrome, in some cases followed by irreversible brain damage
2. Aplastic anaemia and agranulocytosis
3. Hyperchloraemic metabolic acidosis
4. Permanent bilateral visual field constriction
Show answer
Answer: A. An encephalopathic syndrome, in some cases followed by irreversible brain damage
The lithium label describes an encephalopathic syndrome occurring in patients treated with lithium and an antipsychotic, sometimes followed by irreversible brain damage, which matters because the combination is a licensed strategy in mania.

SNRIs and other antidepressants

Revise the SNRIs and other antidepressants guide

A patient started on an antidepressant for major depressive disorder is found at review to have a diastolic pressure 18 mmHg higher than at baseline, having risen after each increase in dose. Which agent best fits?
1. Venlafaxine
2. Mirtazapine
3. Trazodone
4. Moclobemide
Show answer
Answer: A. Venlafaxine
Controlled trials of venlafaxine showed dose-related increases in systolic and diastolic blood pressure and cases of sustained hypertension, which is the characteristic cardiovascular signature of the drug.
Which history is an absolute contraindication to bupropion according to its label?
1. A current or previous diagnosis of bulimia or anorexia nervosa
2. Treated hypothyroidism
3. A first-degree relative with epilepsy
4. Previous poor response to an SSRI
Show answer
Answer: A. A current or previous diagnosis of bulimia or anorexia nervosa
The label lists a current or prior diagnosis of bulimia or anorexia nervosa among the contraindications, alongside a seizure disorder and abrupt withdrawal of alcohol, benzodiazepines, barbiturates or antiepileptic drugs, because each raises seizure risk.
Why does an irreversible MAO inhibitor make aged cheese dangerous while moclobemide largely does not?
1. Reversible inhibitors are displaced from the enzyme as tyramine concentrations rise, restoring the capacity to break it down
2. Moclobemide destroys tyramine directly in the gut lumen
3. Moclobemide blocks the noradrenaline transporter so stored transmitter cannot be released
4. Irreversible inhibitors increase intestinal absorption of tyramine
Show answer
Answer: A. Reversible inhibitors are displaced from the enzyme as tyramine concentrations rise, restoring the capacity to break it down
Reversibility gives a built-in safety factor: if substrate rises, the inhibitor dissociates from its binding site and enzyme activity returns, which is why tyramine potentiation with the reversible agents is negligible.
Which antidepressant label warns of hepatic failure, sometimes fatal, and states that the drug should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease?
1. Duloxetine
2. Desvenlafaxine
3. Reboxetine
4. Vilazodone
Show answer
Answer: A. Duloxetine
Hepatotoxicity is the caution specific to duloxetine among the SNRIs, and its label also directs discontinuation if jaundice or other clinically significant liver dysfunction develops.
A man taking an antidepressant for depression attends with a painful erection lasting eight hours. Which drug is most likely to be responsible?
1. Trazodone
2. Bupropion
3. Milnacipran
4. Phenelzine
Show answer
Answer: A. Trazodone
The trazodone label records cases of priapism, defined as painful erection greater than six hours in duration, and warns that irreversible damage to erectile tissue can follow if treatment is delayed.
How many days must elapse after stopping venlafaxine before a monoamine oxidase inhibitor is started, according to the venlafaxine label?
1. At least seven days
2. At least fourteen days
3. At least five weeks
4. No interval is specified
Show answer
Answer: A. At least seven days
The label requires at least fourteen days between stopping an MAOI and starting venlafaxine, but at least seven days in the opposite direction, which is why the direction of the switch has to be read carefully.
Which combination of receptor actions is described on the mirtazapine label?
1. Antagonism at alpha-2 adrenergic, 5-HT2, 5-HT3 and histamine H1 receptors
2. Partial agonism at 5-HT1A with serotonin reuptake inhibition
3. Irreversible inhibition of monoamine oxidase A and B
4. Selective inhibition of the noradrenaline transporter
Show answer
Answer: A. Antagonism at alpha-2 adrenergic, 5-HT2, 5-HT3 and histamine H1 receptors
Mirtazapine is described as an antagonist at central presynaptic alpha-2 adrenergic autoreceptors and heteroreceptors and at 5-HT2, 5-HT3 and H1 receptors; the H1 action accounts for the drowsiness that dominates its profile.
Which statement about milnacipran matches its United States label?
1. It is indicated for the management of fibromyalgia and is not approved for major depressive disorder
2. It is indicated for major depressive disorder only
3. It is a selective serotonin reuptake inhibitor with no noradrenergic action
4. It requires no blood pressure monitoring
Show answer
Answer: A. It is indicated for the management of fibromyalgia and is not approved for major depressive disorder
Milnacipran is licensed there for fibromyalgia, its label states it is not approved for the treatment of major depressive disorder, and it inhibits noradrenaline uptake with about threefold higher in vitro potency than serotonin.

Typical antipsychotics

Revise the Typical antipsychotics guide

A patient started on a first-generation antipsychotic three days ago develops sustained painful neck twisting and an upward deviation of the eyes. Which syndrome is this?
1. Acute dystonia
2. Tardive dyskinesia
3. Akathisia
4. Neuroleptic malignant syndrome
Show answer
Answer: A. Acute dystonia
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment, and haloperidol's label lists opisthotonos and oculogyric crisis among the dystonic presentations.
Which statement best captures the relationship between potency and adverse effects among first-generation antipsychotics?
1. High-potency agents carry more extrapyramidal effects; low-potency agents carry more sedation and antimuscarinic effects
2. High-potency agents carry more sedation; low-potency agents carry more extrapyramidal effects
3. Potency predicts efficacy but has no bearing on the adverse-effect profile
4. Both groups carry an identical adverse-effect profile at equivalent doses
Show answer
Answer: A. High-potency agents carry more extrapyramidal effects; low-potency agents carry more sedation and antimuscarinic effects
High-potency agents have a high risk of extrapyramidal adverse effects including dystonia, bradykinesia, rigidity and tremor, whereas low-potency agents have high histaminic and muscarinic activity, a lower extrapyramidal risk and a heightened prevalence of dizziness, sedation and anticholinergic effects.
A patient on long-term haloperidol develops involuntary orofacial movements. What does the label say about the outlook?
1. The movements are potentially irreversible and there is no known treatment for established cases
2. The movements always resolve within days of stopping the drug
3. The movements respond reliably to an anticholinergic agent
4. The movements indicate that the dose is too low
Show answer
Answer: A. The movements are potentially irreversible and there is no known treatment for established cases
The warning describes a syndrome of potentially irreversible involuntary dyskinetic movements, states that no known treatment exists for established cases, and adds only that the syndrome may remit partially or completely if antipsychotic treatment is withdrawn.
Which combination of features should raise immediate concern for neuroleptic malignant syndrome?
1. Hyperpyrexia, muscle rigidity, altered mental status and autonomic instability
2. Bradycardia, hypothermia, flaccid paralysis and polyuria
3. Orofacial dyskinesia, galactorrhoea and photosensitive rash
4. Isolated restlessness of the lower limbs with no other findings
Show answer
Answer: A. Hyperpyrexia, muscle rigidity, altered mental status and autonomic instability
Haloperidol's label lists hyperpyrexia, muscle rigidity, altered mental status including catatonic signs, and autonomic instability such as irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias as the clinical manifestations of this potentially fatal complex.
Why does D2 blockade raise serum prolactin?
1. Antagonism at D2 receptors in the tuberoinfundibular pathway removes dopaminergic inhibition of prolactin release
2. Blockade of nigrostriatal D2 receptors stimulates the anterior pituitary directly
3. Histamine H1 blockade in the hypothalamus increases prolactin secretion
4. Muscarinic blockade in the vomiting centre increases prolactin secretion
Show answer
Answer: A. Antagonism at D2 receptors in the tuberoinfundibular pathway removes dopaminergic inhibition of prolactin release
Antagonism at the D2 receptors in the tuberoinfundibular pathway is believed to be responsible for the increase in the prolactin level, whereas blockade in the nigrostriatal pathway accounts for the extrapyramidal effects instead.
Which route of haloperidol injection is stated on its label to be unapproved, while also being associated with a higher risk of QTc prolongation and torsades de pointes?
1. Intravenous
2. Intramuscular
3. Subcutaneous
4. Sublingual
Show answer
Answer: A. Intravenous
The injection label states that haloperidol injection is not approved for intravenous administration, that higher than recommended doses and intravenous administration appear to carry a higher risk of QTc prolongation and torsades de pointes, and that the ECG should be monitored if the drug is given intravenously.
A patient given an antiemetic in the emergency department becomes intensely restless, unable to sit still, and paces the cubicle. Which drug and syndrome best fit?
1. Prochlorperazine causing akathisia
2. Prochlorperazine causing tardive dyskinesia
3. Loxapine causing a seizure
4. Chlorpromazine causing pigmentary retinopathy
Show answer
Answer: A. Prochlorperazine causing akathisia
Prochlorperazine is a first-generation antipsychotic indicated for control of severe nausea and vomiting, and akathisia presents as an inability to remain still with pacing and shifting position, typically soon after the drug is started.
Which finding is characteristic of the low-potency agents rather than the high-potency ones?
1. Dry mouth, urinary retention and constipation
2. Prominent bradykinesia and rigidity
3. Absence of any boxed warning
4. Failure to raise serum prolactin
Show answer
Answer: A. Dry mouth, urinary retention and constipation
Low-potency agents show high histaminic and muscarinic activity with a heightened prevalence of dizziness, sedation and anticholinergic effects, and chlorpromazine's own label lists dry mouth, constipation and urinary retention among its reactions.

Z-drugs and other hypnotics

Revise the Z-drugs and other hypnotics guide

A man taking a Z-drug for insomnia is found by his family to have driven to a shop overnight with no memory of it. What does the labelling direct?
1. Continue at the same dose and review in a month
2. Discontinue the medicine immediately and do not use it again in this patient
3. Halve the dose and add a melatonin agonist
4. Switch to the extended-release form of the same drug
Show answer
Answer: B. Discontinue the medicine immediately and do not use it again in this patient
The boxed warning covers exactly this event, and the labels both direct immediate discontinuation and contraindicate further use in a patient who has experienced a complex sleep behaviour.
Which statement most accurately reflects what the labels say about how the Z-drugs work?
1. All three labels state a proven selective action at alpha-1 subunit receptors
2. Zolpidem and zaleplon name a specific site, while the eszopiclone label calls its hypnotic mechanism unclear
3. They act as direct GABA-A channel openers independent of the benzodiazepine site
4. They inhibit orexin signalling in the hypothalamus
Show answer
Answer: B. Zolpidem and zaleplon name a specific site, while the eszopiclone label calls its hypnotic mechanism unclear
Zolpidem's label names the benzodiazepine site of alpha-1 subunit containing receptors and zaleplon's names the brain omega-1 receptor, but eszopiclone's states only that the effect could be related to interaction with GABA-receptor complexes near the benzodiazepine binding domains.
Which hypnotic on this page is stated by its label not to be a controlled substance?
1. Zolpidem
2. Eszopiclone
3. Ramelteon
4. Suvorexant
Show answer
Answer: C. Ramelteon
The ramelteon label states that it is not a controlled substance and that it does not appear to produce physical dependence, whereas zolpidem, eszopiclone and suvorexant are all Schedule IV.
A woman with narcolepsy asks about a newer insomnia medicine she has read about. Which class is contraindicated for her?
1. Melatonin-receptor agonists
2. Orexin-receptor antagonists
3. Benzodiazepine hypnotics
4. Antihistamine sedatives
Show answer
Answer: B. Orexin-receptor antagonists
Suvorexant, lemborexant and daridorexant are each contraindicated in narcolepsy, which follows from the loss of orexin signalling that characterises the disorder.
Why does the zolpidem label recommend a lower initial dose in women than in men?
1. Women report more taste disturbance
2. Zolpidem clearance is lower in women, giving roughly 45% higher peak and total exposure
3. Women absorb the drug more rapidly from the gut
4. The drug is more protein-bound in women
Show answer
Answer: B. Zolpidem clearance is lower in women, giving roughly 45% higher peak and total exposure
The label states that women clear zolpidem at a lower rate than men, that peak and total exposure are about 45% higher at the same dose, and that higher morning blood levels increase the risk of next-day impairment in some patients.
Which combination is explicitly barred by the ramelteon label?
1. Ramelteon with fluvoxamine
2. Ramelteon with rifampicin
3. Ramelteon with melatonin
4. Ramelteon with a proton pump inhibitor
Show answer
Answer: A. Ramelteon with fluvoxamine
CYP1A2 is the major isozyme metabolising ramelteon, and fluvoxamine raised its exposure roughly 190-fold, so the label states that the two should not be used together.
Which of these is the correct description of temazepam's place on this page?
1. A Z-drug with a long half-life
2. A melatonin-receptor agonist used in older adults
3. A benzodiazepine hypnotic included only as the comparator, with three boxed warnings
4. An orexin antagonist licensed for sleep maintenance
Show answer
Answer: C. A benzodiazepine hypnotic included only as the comparator, with three boxed warnings
Temazepam is a benzodiazepine indicated for short-term treatment of insomnia, generally seven to ten days, and its boxed warnings cover concomitant opioid use, abuse and addiction, and dependence with withdrawal reactions; the class itself is covered on the benzodiazepines page.

Antiparkinsonian agents

Revise the Antiparkinsonian agents guide

Why is levodopa given rather than dopamine itself in Parkinson's disease?
1. Dopamine does not cross the blood-brain barrier, whereas levodopa does
2. Dopamine is destroyed by gastric acid, whereas levodopa is not
3. Dopamine has no affinity for striatal dopamine receptors
4. Levodopa is a more potent agonist at the D3 receptor
Show answer
Answer: A. Dopamine does not cross the blood-brain barrier, whereas levodopa does
The label states that administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier, while levodopa, the metabolic precursor of dopamine, does cross it and is presumably converted to dopamine in the brain.
What is the pharmacological reason for combining levodopa with carbidopa?
1. Carbidopa inhibits decarboxylation of levodopa in the periphery and does not itself enter the brain
2. Carbidopa inhibits catechol-O-methyltransferase in the brain
3. Carbidopa is a dopamine agonist that supplements the levodopa effect
4. Carbidopa slows gastric emptying so that levodopa is absorbed more evenly
Show answer
Answer: A. Carbidopa inhibits decarboxylation of levodopa in the periphery and does not itself enter the brain
Carbidopa inhibits decarboxylation of peripheral levodopa, does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system, so more levodopa is available for transport to the brain and nausea and vomiting are less frequent than with levodopa alone.
A patient on a dopamine agonist for Parkinson's disease has begun gambling heavily and spending money uncontrollably. How should this be understood?
1. A recognised class effect of dopamine agonists that is generally reversible on dose reduction or withdrawal
2. An unrelated psychiatric illness with no bearing on the medicines
3. An early sign of levodopa-induced dyskinesia
4. A withdrawal phenomenon seen only when an agonist is being tapered
Show answer
Answer: A. A recognised class effect of dopamine agonists that is generally reversible on dose reduction or withdrawal
Pathological gambling, hypersexuality, compulsive eating and compulsive shopping have been reported with dopamine agonist therapy, and UK regulators describe pathological gambling and increased libido as rare class effects that are generally reversible upon reduction of the dose or discontinuation of treatment.
Which COMT inhibitor carries a boxed warning for potentially fatal acute fulminant liver failure?
1. Tolcapone
2. Entacapone
3. Opicapone
4. Carbidopa
Show answer
Answer: A. Tolcapone
The tolcapone label carries a boxed warning for potentially fatal acute fulminant liver failure and directs transaminase measurement at baseline and every two to four weeks for the first six months of therapy; entacapone and opicapone carry no equivalent warning.
Which statement about entacapone is correct?
1. It has no antiparkinsonian effect of its own and must be given with levodopa
2. It is effective as monotherapy in early Parkinson's disease
3. It requires transaminase monitoring every two weeks for six months
4. It acts by irreversibly inhibiting monoamine oxidase type B
Show answer
Answer: A. It has no antiparkinsonian effect of its own and must be given with levodopa
The label states that entacapone should always be administered in association with levodopa and carbidopa and that entacapone has no antiparkinsonian effect of its own; it is licensed for end-of-dose wearing-off rather than as a primary treatment.
A patient stabilised on rasagiline needs an antibiotic. Which agent most warrants caution because of an interaction with rasagiline?
1. Ciprofloxacin
2. Amoxicillin
3. Nitrofurantoin
4. Doxycycline
Show answer
Answer: A. Ciprofloxacin
CYP1A2 is the major isoenzyme involved in rasagiline metabolism, and the label reports that rasagiline plasma concentrations may increase up to twofold when ciprofloxacin is given with it.
An older patient on an antipsychotic develops rigidity and a resting tremor. Which agent is licensed for this drug-induced problem?
1. An antimuscarinic such as trihexyphenidyl
2. A COMT inhibitor such as opicapone
3. An MAO-B inhibitor such as rasagiline
4. A transdermal dopamine agonist such as rotigotine
Show answer
Answer: A. An antimuscarinic such as trihexyphenidyl
Trihexyphenidyl is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes and butyrophenones, although sensitivity to this class of drug increases after the age of sixty.
Which of these is the correct description of selegiline's licensed place in treatment?
1. An adjunct for patients on levodopa with carbidopa whose response has deteriorated, with no evidence of benefit without levodopa
2. First-line monotherapy for newly diagnosed Parkinson's disease
3. A treatment for tardive dyskinesia caused by antipsychotic drugs
4. A peripheral decarboxylase inhibitor given with levodopa
Show answer
Answer: A. An adjunct for patients on levodopa with carbidopa whose response has deteriorated, with no evidence of benefit without levodopa
Selegiline is indicated as an adjunct in the management of parkinsonian patients being treated with levodopa and carbidopa who exhibit deterioration in the quality of their response, and its label states there is no evidence from controlled studies of any beneficial effect without concurrent levodopa therapy.

Tricyclic antidepressants

Revise the Tricyclic antidepressants guide

A patient is brought to hospital after a large ingestion of a tricyclic antidepressant. The ECG shows a widened QRS complex. Which mechanism best explains this finding?
1. Blockade of fast sodium channels prolonging phase 0 of the myocardial action potential
2. Antagonism of cardiac muscarinic receptors
3. Blockade of alpha-1 adrenergic receptors in vascular smooth muscle
4. Inhibition of noradrenaline reuptake at cardiac sympathetic nerve endings
Show answer
Answer: A. Blockade of fast sodium channels prolonging phase 0 of the myocardial action potential
Blockade of fast sodium channels in myocardial cells slows the action potential and provides a membrane stabilising effect, and the characteristic QRS prolongation occurs secondary to prolongation of phase 0 of the myocardial action potential.
In tricyclic antidepressant poisoning, which QRS duration is described as predictive of arrhythmia?
1. Greater than 160 milliseconds
2. Greater than 60 milliseconds
3. Greater than 80 milliseconds
4. Greater than 200 milliseconds
Show answer
Answer: A. Greater than 160 milliseconds
Prolongation of the QRS beyond 100 milliseconds is described as predictive of seizures, while a QRS greater than 160 milliseconds is described as predictive of arrhythmia.
Which pairing of parent drug and its active metabolite is correct?
1. Amitriptyline to nortriptyline, and imipramine to desipramine
2. Nortriptyline to amitriptyline, and desipramine to imipramine
3. Clomipramine to nortriptyline, and doxepin to desipramine
4. Imipramine to nortriptyline, and amitriptyline to desipramine
Show answer
Answer: A. Amitriptyline to nortriptyline, and imipramine to desipramine
Amitriptyline is metabolised to nortriptyline, which is its active form, and imipramine is metabolised by CYP2C19 to desipramine, which is itself a tricyclic antidepressant.
Which group do desipramine, nortriptyline and protriptyline belong to, and what does that predict?
1. Secondary amines, with heightened inhibition of noradrenaline uptake
2. Tertiary amines, with heightened inhibition of noradrenaline uptake
3. Secondary amines, with greater serotonin reuptake inhibition
4. Tetracyclic agents, with no effect on monoamine transporters
Show answer
Answer: A. Secondary amines, with heightened inhibition of noradrenaline uptake
Desipramine, nortriptyline and protriptyline are categorised as secondary amines, and secondary amines display heightened inhibition of noradrenaline uptake, whereas tertiary amines show significant serotonin reuptake inhibition.
A tricyclic antidepressant is being considered three days after a monoamine oxidase inhibitor was stopped. What does the labelling require?
1. A minimum interval of fourteen days between the two agents
2. An interval of forty-eight hours is sufficient
3. No interval is required if the doses are low
4. A minimum interval of six months between the two agents
Show answer
Answer: A. A minimum interval of fourteen days between the two agents
The labels state that concomitant use is contraindicated and that a minimum of fourteen days should elapse when substituting one class for the other, because hyperpyretic crises or severe convulsive seizures may occur.
Which cardiac situation is a stated contraindication on tricyclic antidepressant labels?
1. The acute recovery period after a myocardial infarction
2. Well-controlled hypertension
3. A single episode of supraventricular tachycardia ten years ago
4. A resting heart rate at the lower end of normal
Show answer
Answer: A. The acute recovery period after a myocardial infarction
Tricyclic labels state that the drug is contraindicated during the acute recovery period after a myocardial infarction, and separately warn of conduction defects and arrhythmias in cardiovascular disease.
Which receptor effect of the tricyclics best explains sedation, increased appetite and weight gain?
1. Histamine H1 antagonism
2. Muscarinic receptor antagonism
3. Alpha-1 adrenergic antagonism
4. Serotonin transporter blockade
Show answer
Answer: A. Histamine H1 antagonism
Histamine blockade at H1 may lead to sedation, increased appetite, weight gain and confusion, and doxepin's very high H1 affinity is the basis of its separate licence in sleep-maintenance insomnia.
Which tricyclic antidepressant is licensed for the treatment of obsessions and compulsions in obsessive-compulsive disorder?
1. Clomipramine
2. Nortriptyline
3. Protriptyline
4. Trimipramine
Show answer
Answer: A. Clomipramine
Clomipramine is indicated for the treatment of obsessions and compulsions in patients with obsessive-compulsive disorder, and the label presumes the effect comes from its action on serotonergic neuronal transmission.