🧠 Central Nervous System, Psychiatry and Pain

1. What should a patient starting a selective serotonin reuptake inhibitor be told about the onset of benefit?

1. Mood improves within twenty-four hours, so a lack of benefit on day two means failure
2. Mood usually improves over several weeks, while adverse effects often appear at once
3. Mood takes at least a year to improve, so no assessment is made before that point
4. Mood improves only after the dose has been doubled at the end of the first week

The mismatch between early adverse effects and delayed therapeutic benefit is the leading cause of early discontinuation, so explaining the expected timeline and arranging early follow-up materially improves outcomes. The other timelines are inaccurate and would mislead the patient. Source: CPhA Therapeutic Choices, depression chapter.

2. Which antidepressant is most associated with a discontinuation syndrome if stopped abruptly?

1. Fluoxetine, because its long half-life and active metabolite make withdrawal abrupt
2. Paroxetine, because of its short half-life and lack of an active metabolite
3. Vortioxetine, because it is eliminated entirely unchanged within a few hours of dosing
4. Bupropion, because it is a potent serotonin reuptake inhibitor with a very short action

Discontinuation symptoms are most common with short half-life serotonergic agents such as paroxetine and venlafaxine, whereas fluoxetine self-tapers because of its long-lived active metabolite. Bupropion is not a serotonin reuptake inhibitor. Source: Health Canada product monograph for paroxetine.

3. Which combination most increases the risk of serotonin syndrome?

1. A selective serotonin reuptake inhibitor with an artificial tear preparation for dry eyes
2. A selective serotonin reuptake inhibitor with an inhaled corticosteroid used twice daily
3. A selective serotonin reuptake inhibitor with a topical emollient applied to dry skin
4. A selective serotonin reuptake inhibitor with tramadol and a triptan taken together

Serotonin syndrome arises from additive serotonergic activity, and tramadol, triptans, linezolid, monoamine oxidase inhibitors, lithium and St John's wort are the agents most often implicated alongside an antidepressant. Inhaled, topical and ophthalmic products carry no such risk. Source: CPhA Therapeutic Choices, depression chapter.

4. Which triad of findings suggests serotonin syndrome rather than an anticholinergic reaction?

1. Bradycardia with hypersalivation, wheeze and pinpoint pupils after an exposure
2. Dry skin with urinary retention, absent bowel sounds and dilated unreactive pupils
3. Neuromuscular hyperactivity with clonus, autonomic instability and altered mental state
4. Isolated fever with a widespread rash and no neurological findings whatsoever on examination of the patient

Clonus, hyperreflexia, tremor, agitation, diaphoresis and hyperthermia together define serotonin toxicity, whereas dry flushed skin with retention describes anticholinergic toxicity and bradycardia with secretions describes cholinergic excess. Source: CPhA Therapeutic Choices, drug toxicity chapter.

5. Which adverse effect of selective serotonin reuptake inhibitors is most relevant in an older adult?

1. Immediate irreversible hearing loss occurring after the very first oral dose
2. Marked weight gain of many kilograms in the first week of continuous therapy
3. Hyponatraemia, which may present as confusion, falls or increasing lethargy
4. Severe hyperkalaemia requiring urgent dialysis in the majority of older patients

Serotonergic antidepressants cause a syndrome of inappropriate antidiuresis, and older adults, particularly those also on diuretics, are at highest risk, so sodium is checked when confusion or falls develop. The other effects are not features of the class. Source: Health Canada product monographs for the serotonin reuptake inhibitors.

6. Which antidepressant is often chosen when sexual dysfunction on a previous agent was the problem?

1. Venlafaxine at high dose, which reliably reverses sexual dysfunction in most patients
2. Paroxetine, which has the lowest reported rate of sexual dysfunction in its class
3. Bupropion, which lacks the serotonergic effect responsible for that adverse effect
4. Citalopram, which is specifically indicated for the treatment of sexual dysfunction

Bupropion acts on noradrenaline and dopamine reuptake and is associated with a much lower rate of sexual adverse effects, which makes it a common alternative, though it lowers the seizure threshold. Paroxetine and venlafaxine are among the more likely to cause the problem. Source: CPhA Therapeutic Choices, depression chapter.

7. Which patient should not receive bupropion?

1. A patient with treated hypothyroidism whose thyroid function tests are all normal
2. A patient with well controlled hypertension taking a single antihypertensive agent
3. A patient with mild seasonal allergic rhinitis using an intranasal corticosteroid throughout the pollen season
4. A patient with a seizure disorder or an eating disorder that lowers the seizure threshold

Bupropion is contraindicated in seizure disorders and in current or previous bulimia or anorexia nervosa because of a dose-related reduction in the seizure threshold, and caution applies with other proconvulsant drugs. The other conditions are not contraindications. Source: Health Canada product monograph for bupropion.

8. Why are patients starting an antidepressant asked to report worsening agitation or suicidal thoughts?

1. Such symptoms are proof that the drug has already reached its full therapeutic effect
2. Such symptoms indicate that the diagnosis of depression was certainly incorrect and should be revisited
3. Such symptoms can emerge or worsen early in therapy, particularly in younger patients
4. Such symptoms occur only after several years of continuous antidepressant therapy

Regulators require a warning about emergent suicidal ideation and behaviour early in therapy and after dose changes, particularly in children, adolescents and young adults, so close monitoring in the first weeks is part of the plan. The other statements are incorrect. Source: Health Canada product monographs for the antidepressants.

9. Which parameters are monitored routinely in a patient on long-term lithium?

1. Bone mineral density measured twice a year throughout the treatment period
2. Serum amylase and lipase measured every month for the duration of the therapy
3. Serum lithium concentration, renal function, thyroid function and calcium
4. Pulmonary function tests repeated every three months from the day of initiation

Lithium has a narrow therapeutic index and affects the kidney, the thyroid and calcium homeostasis, so concentrations and those organ functions are monitored on a defined schedule, with sampling timed relative to the last dose. The other tests are not indicated. Source: CPhA Therapeutic Choices, bipolar disorder chapter.

10. Which combination is most likely to precipitate lithium toxicity?

1. Lithium with an inhaled bronchodilator used before exercise a few times each week
2. Lithium with an NSAID and a thiazide diuretic during an episode of dehydration
3. Lithium with a topical antifungal cream applied twice daily to a small skin area
4. Lithium with an artificial tear preparation instilled four times daily for dry eyes

Lithium is handled like sodium by the proximal tubule, so NSAIDs, thiazides, ACE inhibitors and any state of volume depletion reduce its clearance and can push a stable patient into toxicity. Inhaled, topical and ophthalmic products have no effect on lithium handling. Source: Health Canada product monograph for lithium carbonate.

11. What should a patient on lithium be told about fluid and salt intake?

1. Restrict all salt completely, since sodium competes with lithium for absorption from the intestinal tract
2. Maintain a steady intake of fluid and salt, and seek advice during vomiting or fever
3. Drink as little fluid as possible so that the lithium is not diluted in the blood
4. Add extra salt to every meal, which increases the therapeutic effect of the lithium

Because renal lithium handling follows sodium and water, a consistent intake keeps concentrations stable, and dehydration from illness, heat or exercise raises the level, so sick-day advice is essential. Salt restriction raises lithium and salt loading lowers it. Source: CPhA Therapeutic Choices, bipolar disorder chapter.

12. Why is valproate avoided in a woman of childbearing potential wherever possible?

1. It causes major congenital malformations and impaired neurodevelopment in exposed children
2. It is completely ineffective in women and is licensed only for use in male patients
3. It prevents absorption of every hormonal contraceptive taken at the same time during the treatment course
4. It causes irreversible hearing loss in the mother during the first month of therapy

Valproate exposure in pregnancy carries a high risk of neural tube and other major malformations and of neurodevelopmental impairment, so it is used in this group only when other options have failed, with a pregnancy prevention framework. It is effective in women and does not abolish contraception. Source: Health Canada safety review of valproate.

13. Why must lamotrigine be titrated slowly, especially with valproate?

1. Slow titration is required only so that the pharmacy can dispense smaller quantities
2. Rapid titration causes an immediate and permanent loss of the antiepileptic effect that cannot be regained later
3. Rapid titration increases the risk of a severe rash, and valproate raises its concentration
4. Valproate lowers lamotrigine concentrations, so a very slow increase avoids failure

The risk of serious cutaneous reaction rises with rapid dose escalation, and valproate inhibits lamotrigine glucuronidation so that concentrations roughly double, which is why a reduced and slower titration schedule is used with that combination. Source: Health Canada product monograph for lamotrigine.

14. Which extrapyramidal effect typically appears within hours to days of starting an antipsychotic?

1. Acute dystonia, with sustained muscle contraction such as torticollis or oculogyric crisis
2. Tardive dyskinesia, which characteristically appears within the first two days of therapy
3. Neuroleptic malignant syndrome, which occurs only after several years of stable therapy
4. Anticholinergic delirium, which appears exclusively in the third month of treatment of continuous antipsychotic use

Acute dystonia occurs early and responds to an anticholinergic, akathisia appears within days to weeks, parkinsonism within weeks and tardive dyskinesia only after prolonged exposure. Neuroleptic malignant syndrome can occur at any time but is not defined by years of therapy. Source: CPhA Therapeutic Choices, schizophrenia chapter.

15. A patient on an antipsychotic describes an inner restlessness and an inability to sit still. What is this?

1. Akathisia, which is frequently mistaken for worsening agitation of the illness itself
2. Tardive dyskinesia, which presents as an irresistible urge to move the whole body without any subjective distress
3. Acute dystonia, which presents as a sustained painful contraction of the neck muscles
4. Neuroleptic malignant syndrome, which presents as restlessness without any other sign apart from the motor agitation

Akathisia is a subjective inner restlessness with observable motor restlessness, and misreading it as psychotic agitation leads to an increased dose that makes it worse, so recognising it is clinically important. The other syndromes have different features. Source: CPhA Therapeutic Choices, schizophrenia chapter.

16. Which monitoring is mandatory for a patient taking clozapine?

1. A monthly measurement of the serum uric acid throughout the first two years
2. A weekly serum sodium measurement for the whole duration of the treatment course whatever the dose prescribed
3. An annual bone density scan of the lumbar spine and the femoral neck region performed in a hospital setting
4. Regular absolute neutrophil counts on a defined schedule through a registry programme

Clozapine can cause severe neutropenia, so haematological monitoring at defined intervals through a manufacturer registry is a condition of supply, alongside vigilance for myocarditis, seizures, severe constipation and metabolic effects. The other tests are not required. Source: Health Canada product monograph for clozapine.

17. Which gastrointestinal complication of clozapine can be fatal and is often overlooked?

1. Acute pancreatitis presenting within the first twenty-four hours of the first dose taken by the treated patient
2. Severe constipation progressing to ileus and bowel obstruction if not managed early
3. An immediate profuse watery diarrhoea that begins after the very first tablet swallowed by the treated patient
4. A sudden gastric perforation caused by direct erosion from the tablet coating

Clozapine has potent anticholinergic effects on the gut, and hypomotility progressing to ileus, obstruction and perforation is a recognised cause of death, so bowel habit is asked about routinely and prophylactic laxatives are often used. The other events are not typical. Source: Health Canada safety review of clozapine.

18. Which metabolic monitoring accompanies second-generation antipsychotic therapy?

1. Serum lithium concentration measured every three months regardless of the agent that has been prescribed
2. Weight or waist circumference, fasting glucose or glycated haemoglobin, and lipids
3. Thyroid stimulating hormone measured weekly during the first year of therapy of continuous antipsychotic use
4. Serum creatine kinase measured monthly for the whole duration of the therapy

Weight gain, dyslipidaemia and dysglycaemia are the principal long-term risks of this class, so anthropometric and metabolic parameters are measured at baseline and at defined intervals, with lifestyle support and agent switching considered. Source: CPhA Therapeutic Choices, schizophrenia chapter.

19. What is the first-line pharmacological therapy for generalised anxiety disorder?

1. A long-term benzodiazepine at a fixed dose continued indefinitely without review by the treating physician
2. A serotonergic antidepressant, alongside cognitive behavioural therapy where available
3. An antipsychotic at full dose as monotherapy from the first consultation onwards
4. A stimulant taken each morning to counteract the fatigue caused by the anxiety that the patient describes

Selective serotonin and serotonin-norepinephrine reuptake inhibitors are first-line, with psychological therapy of equal or greater importance, and benzodiazepines reserved for short-term use because of dependence and cognitive effects. Antipsychotics and stimulants are not first-line. Source: CPhA Therapeutic Choices, anxiety disorders chapter.

20. Why are benzodiazepines particularly hazardous in older adults?

1. They increase the risk of falls, fractures, confusion and motor vehicle collisions
2. They are eliminated so rapidly in older adults that they never reach an effective level
3. They cause an irreversible loss of hearing in the majority of patients over seventy
4. They are the only class that has never been associated with any cognitive effect

Age-related changes in distribution and clearance, together with pharmacodynamic sensitivity, increase sedation, cognitive impairment, falls and fracture risk, which is why the class appears on explicit criteria for potentially inappropriate medication in older adults. Source: Beers Criteria and CPhA Therapeutic Choices, insomnia chapter.

21. What is the recommended first-line treatment for chronic insomnia?

1. A sedative hypnotic taken every night indefinitely without any behavioural component
2. Cognitive behavioural therapy for insomnia, with medication used only as an adjunct
3. A daily antihistamine at high dose continued for as long as the insomnia persists
4. A nightly alcoholic drink, which shortens sleep latency and improves sleep quality

Behavioural therapy addressing sleep restriction, stimulus control and unhelpful beliefs produces durable benefit and is recommended ahead of medication, which is used for the shortest necessary period. Antihistamines and alcohol fragment sleep and are not appropriate treatments. Source: CPhA Therapeutic Choices, insomnia chapter.

22. Which advice accompanies a sedative hypnotic dispensed for short-term use?

1. Take it in the early evening so that the sedative effect has worn off before bedtime on the following working day
2. Take it immediately before bed with a full night available, and avoid alcohol entirely
3. Take it with alcohol so that the two act together and a smaller dose can be used
4. Take it whenever daytime drowsiness occurs so that a regular rhythm is established for the patient concerned

These agents are taken immediately before bed with sufficient time for sleep, because taking them too early or when a full night is not available produces next-day impairment, and alcohol markedly increases sedation and respiratory depression. Source: Health Canada product monographs for the sedative hypnotics.

23. Why can a small increase in the phenytoin dose produce a large rise in concentration?

1. Its renal clearance stops completely when the plasma concentration reaches the target
2. Its absorption increases sharply once the daily dose exceeds a critical amount
3. Its protein binding falls to zero at higher doses, releasing all bound drug at once
4. Its metabolism becomes saturated, so elimination follows zero-order kinetics

Phenytoin metabolism saturates within the therapeutic range, so once the enzyme system is saturated a further small dose increment produces a disproportionate rise in concentration and toxicity. This is the reason for small dose increments and concentration monitoring. Source: Health Canada product monograph for phenytoin.

24. Why must a phenytoin concentration be interpreted alongside the serum albumin?

1. Albumin determines the renal clearance of phenytoin through glomerular filtration
2. Phenytoin binds albumin only at very high concentrations that are never reached clinically during ordinary clinical use
3. Albumin is the enzyme responsible for metabolising phenytoin in the hepatic microsomes of the hepatocyte in the liver
4. Phenytoin is highly protein bound, so low albumin raises the free fraction at any total level

Total phenytoin concentration underestimates the pharmacologically active free fraction when albumin is low or when displacing drugs are present, so the result is corrected or free phenytoin is measured. Albumin is a binding protein rather than an enzyme. Source: Health Canada product monograph for phenytoin.

25. Which long-term adverse effect is characteristic of phenytoin?

1. Gingival hyperplasia, along with hirsutism, coarsening of facial features and neuropathy
2. Blue discolouration of the sclera developing within the first week of therapy of continuous oral treatment
3. A permanent loss of the sense of smell after the first month of continuous use of uninterrupted daily therapy
4. Severe hair loss that begins within forty-eight hours of the first dose taken

Gum overgrowth, hirsutism, acne, coarse facies, cerebellar signs and peripheral neuropathy are recognised long-term effects of phenytoin, and meticulous oral hygiene reduces the gingival changes. The other effects are not associated with the drug. Source: Health Canada product monograph for phenytoin.

26. Which genetic marker is associated with severe cutaneous reactions to carbamazepine?

1. A particular human leukocyte antigen allele more common in some Asian populations
2. A variant of the vitamin K epoxide reductase gene found in most European populations
3. An absence of the enzyme that metabolises alcohol in the liver of affected patients
4. A deficiency of glucose-6-phosphate dehydrogenase found mainly in male patients

Carriage of a specific human leukocyte antigen allele, more frequent in people of Han Chinese, Thai and some other Asian ancestries, markedly increases the risk of Stevens-Johnson syndrome with carbamazepine, so testing is recommended before starting in those groups. Source: Health Canada product monograph for carbamazepine.

27. Why does carbamazepine reduce the concentration of many other drugs?

1. It inhibits cytochrome enzymes, which paradoxically lowers the concentration of substrates
2. It binds other drugs irreversibly in the plasma and prevents them reaching the tissues
3. It blocks intestinal absorption of every other drug taken at the same time of day
4. It is a potent enzyme inducer and also induces its own metabolism over time

Carbamazepine induces several cytochrome isoenzymes, reducing exposure to hormonal contraceptives, warfarin, many antipsychotics and other substrates, and autoinduction means its own dose often needs increasing during the first weeks. It is an inducer, not an inhibitor. Source: Health Canada product monograph for carbamazepine.

28. What advice about driving is given to a person newly diagnosed with epilepsy?

1. Driving is unrestricted as long as the person avoids driving after taking a dose
2. Driving may continue immediately provided that medication has been prescribed by the treating neurologist
3. Driving is banned permanently after a single seizure of any type in any person at any stage of their life
4. Driving is restricted until seizure-free criteria set by the province have been met

Licensing authorities in each province set seizure-free intervals before driving may resume, and reporting obligations vary, so patients are directed to the applicable rules and to their physician. Neither immediate resumption nor a permanent lifetime ban is correct. Source: Canadian Council of Motor Transport Administrators medical standards.

29. Which principle applies to switching between manufacturers of an antiepileptic drug?

1. Switch to whichever product is cheapest without informing the patient at all about the change being made
2. Switch products at every refill so that the patient does not develop tolerance to the prescribed medicine
3. Maintain the same product where possible, because small changes may affect seizure control
4. Switching is prohibited by law for every antiepileptic drug in every province

For narrow therapeutic index antiepileptics, unplanned switches have been associated with loss of control and breakthrough seizures, so continuity of product is preferred and any change is discussed and monitored. Deliberate rotation and silent substitution are inappropriate. Source: CPhA Therapeutic Choices, epilepsy chapter.

30. Why is levodopa sometimes taken away from protein-rich meals?

1. Protein increases gastric acid so much that levodopa is converted to an inactive form
2. Protein destroys levodopa chemically in the stomach before it can be absorbed
3. Protein binds carbidopa and prevents it from protecting levodopa in the periphery
4. Large neutral amino acids compete with levodopa for the same intestinal transporter

Levodopa is absorbed by the large neutral amino acid transporter and crosses the blood-brain barrier by the same route, so a high-protein meal can blunt the response, and patients with motor fluctuations may benefit from timing doses away from protein. Source: CPhA Therapeutic Choices, Parkinson disease chapter.

31. Which class of antiemetic must be avoided in Parkinson disease?

1. Domperidone, which crosses the blood-brain barrier readily and blocks central receptors within the basal ganglia
2. Dopamine antagonists such as metoclopramide and prochlorperazine, which worsen symptoms
3. Ondansetron, which is a potent central dopamine antagonist in the basal ganglia of the treated patient
4. Dimenhydrinate, which acts by blocking dopamine receptors in the striatal region of the affected patient

Centrally acting dopamine antagonists worsen parkinsonian motor symptoms, so agents such as domperidone, which crosses the barrier poorly, or ondansetron, which acts on serotonin receptors, are preferred. Dimenhydrinate is an antihistamine rather than a dopamine blocker. Source: CPhA Therapeutic Choices, Parkinson disease chapter.

32. Which adverse effect of dopamine agonists must be raised with the patient and family?

1. Impulse control disorders such as pathological gambling, hypersexuality and compulsive buying
2. An irreversible loss of colour vision beginning in the first month of therapy of continuous dopaminergic use
3. A predictable and permanent fall in the platelet count requiring transfusion of platelets within a fortnight
4. Severe hyperkalaemia occurring in the majority of patients within two weeks of starting the medication

Impulse control disorders are a recognised and often concealed effect of dopamine agonists, so patients and families are told to watch for them and to report them, since they typically resolve when the drug is reduced or stopped. The other effects are not associated. Source: Health Canada safety review of the dopamine agonists.

33. What benefit can realistically be expected from a cholinesterase inhibitor in Alzheimer disease?

1. A complete reversal of the disease with restoration of premorbid cognitive function within a few months of starting
2. A modest symptomatic benefit in cognition and function, without altering the disease course
3. A guaranteed halt in progression for the whole remaining lifespan of the patient who continues to take the drug
4. A rapid improvement within twenty-four hours that is sustained without any decline over the following several years

Cholinesterase inhibitors provide a modest symptomatic effect in some patients and do not modify the underlying disease, so goals are set explicitly and therapy is reviewed for benefit and tolerability. Overstating the benefit undermines trust and later deprescribing. Source: CPhA Therapeutic Choices, dementia chapter.

34. Which class should be minimised in a patient with dementia because of anticholinergic burden?

1. Inhaled corticosteroids used with a spacer for the management of asthma in adults and in older children
2. Sedating antihistamines, bladder antimuscarinics and tricyclic antidepressants
3. Topical emollients applied twice daily to areas of chronically dry skin on the arms and on the legs
4. Ophthalmic lubricant drops used several times daily for symptomatic dry eye in a patient with dementia

Cumulative anticholinergic exposure worsens cognition, increases delirium and falls, and opposes the action of cholinesterase inhibitors, so these classes are reviewed and reduced where possible. Inhaled, topical and ophthalmic products contribute negligibly. Source: Beers Criteria and CPhA Therapeutic Choices, dementia chapter.

35. What is the usual maximum daily dose consideration for acetaminophen in a healthy adult?

1. There is no maximum, because acetaminophen has no dose-related hepatic toxicity
2. Only prescription products count towards the total, and non-prescription ones do not
3. The maximum applies to each individual product separately rather than to the total
4. Total intake from all sources must be counted, including combination products

Hepatotoxicity is dose related and unintentional overdose most often results from combining several acetaminophen-containing products, so counselling focuses on totalling all sources including cough and cold and opioid combination products. Source: Health Canada product monograph for acetaminophen.