1. A 19-year-old man is given intravenous metoclopramide in the emergency department for migraine-associated nausea. About 45 minutes later he develops sustained involuntary contraction of his neck muscles pulling his head to one side (torticollis) and an upward deviation of both eyes that he cannot voluntarily correct (oculogyric crisis). What is the most likely explanation for these findings?
A) An anaphylactic reaction to metoclopramide
B) A hypertensive emergency precipitated by metoclopramide
C) An acute dystonic reaction caused by dopamine D2 receptor blockade in the nigrostriatal pathway, a recognized early extrapyramidal effect of metoclopramide that is more common in young patients
D) A focal seizure unrelated to the medication
E) Tardive dyskinesia developing acutely after a single dose
ANSWER: C
Rationale:
The combination of torticollis and oculogyric crisis shortly after intravenous metoclopramide is a classic acute dystonic reaction, an extrapyramidal effect arising from dopamine D2 receptor blockade in the nigrostriatal pathway; acute dystonia is more common in young patients and after parenteral dosing.
Option A: Option A is incorrect because anaphylaxis presents with urticaria, angioedema, bronchospasm, and hypotension, not focal sustained muscle contractions.
Option B: Option B is incorrect because metoclopramide does not characteristically cause hypertensive emergency, and the described findings are dystonic rather than hypertensive.
Option D: Option D is incorrect because focal seizures would not produce this stereotyped dystonic posturing temporally linked to a D2 antagonist, and the presentation is characteristic of drug-induced dystonia.
Option E: Option E is incorrect because tardive dyskinesia develops after prolonged use and consists of repetitive choreoathetoid orofacial movements, not an acute single-dose dystonic reaction.
2. A 64-year-old woman recovering from elective surgery has nausea in the post-anesthesia care unit. Her preoperative ECG showed a borderline-prolonged QTc, and she takes a medication known to prolong the QTc. The anesthesiologist wants to treat the postoperative nausea while minimizing additional arrhythmia risk. Which approach is most appropriate?
A) Use dexamethasone as a low-arrhythmia-risk antiemetic and, if a second agent is needed, use the lowest effective dose of ondansetron with attention to her QTc, while avoiding droperidol given its black box warning for QTc prolongation and fatal arrhythmias
B) Use high-dose droperidol, since its black box warning applies only to children
C) Give a large single intravenous dose of ondansetron well above 32 mg to ensure rapid control
D) Withhold all antiemetics permanently because no agent is safe in this patient
E) Administer promethazine at high dose, as phenothiazines have no effect on the QTc
ANSWER: A
Rationale:
In a patient with a borderline-prolonged QTc on another QTc-prolonging drug, the safest approach is to favor a low-arrhythmia-risk antiemetic such as dexamethasone, and if a second agent is needed, to use the lowest effective ondansetron dose with QTc attention while avoiding droperidol, which carries a black box warning for QTc prolongation and fatal arrhythmias.
Option B: Option B is incorrect because the droperidol QTc black box warning applies to adults, and high-dose droperidol would be hazardous here.
Option C: Option C is incorrect because the FDA advises against single intravenous ondansetron doses greater than 32 mg precisely because of dose-dependent QTc prolongation.
Option D: Option D is incorrect because effective lower-risk options exist, so withholding all antiemetics is unjustified.
Option E: Option E is incorrect because phenothiazines such as promethazine do carry QTc prolongation risk, so high-dose use would add to the danger.
3. A 52-year-old woman received cisplatin-based chemotherapy and was given ondansetron on day 1. She did well on the day of treatment but developed substantial nausea and vomiting on days 2 and 3. What does this delayed pattern indicate, and what would have provided better coverage?
A) The day-1 ondansetron dose was simply too low, and a higher single dose would have prevented the delayed symptoms
B) This pattern indicates motion sickness, best prevented with a scopolamine patch
C) The delayed symptoms reflect gastroparesis and require a motilin receptor agonist
D) The pattern reflects an acute serotonin-mediated phase that a second 5-HT3 antagonist would have covered
E) The timing is characteristic of the delayed phase of chemotherapy-induced nausea and vomiting, mediated by substance P at NK1 receptors, so the regimen should have included an NK1 antagonist plus dexamethasone (and palonosetron is the preferred 5-HT3 antagonist for delayed coverage)
ANSWER: E
Rationale:
Nausea and vomiting peaking on days 2 to 3 after highly emetogenic chemotherapy is characteristic of the delayed phase, which is mediated by substance P acting at NK1 receptors. Guideline-concordant prophylaxis for such regimens therefore includes an NK1 antagonist plus dexamethasone, with palonosetron preferred among 5-HT3 antagonists for its superior delayed-phase coverage.
Option A: Option A is incorrect because the delayed phase is mechanistically distinct (NK1-mediated), so simply raising the day-1 ondansetron dose would not cover it and would risk QTc prolongation.
Option B: Option B is incorrect because the pattern is chemotherapy-induced delayed emesis, not motion sickness.
Option C: Option C is incorrect because the timing reflects delayed CINV, not gastroparesis, and motilin agonists are prokinetics rather than antiemetics for this purpose.
Option D: Option D is incorrect because the delayed phase is mediated by substance P at NK1 receptors rather than by serotonin, so a second 5-HT3 antagonist would not address it.
4. A 34-year-old woman with diabetic gastroparesis has been taking metoclopramide for several weeks. She now reports milky nipple discharge (galactorrhea) and has missed two menstrual periods (amenorrhea). A pregnancy test is negative. What is the most likely cause, and what is the appropriate response?
A) These symptoms indicate a prolactin-secreting pituitary adenoma unrelated to her medication, and metoclopramide should be continued unchanged
B) Metoclopramide-induced hyperprolactinemia from D2 blockade in the tuberoinfundibular pathway is the likely cause, and discontinuing or switching away from metoclopramide should be considered along with confirming the prolactin elevation
C) The findings are an expected benign effect of improved gastric emptying and require no change
D) These symptoms represent an acute dystonic reaction to metoclopramide
E) The galactorrhea reflects a hERG-mediated cardiac effect of metoclopramide
ANSWER: B
Rationale:
Metoclopramide blocks dopamine D2 receptors in the tuberoinfundibular pathway, removing dopamine's tonic inhibition of pituitary lactotrophs and raising prolactin; the resulting hyperprolactinemia causes galactorrhea, amenorrhea, and sexual dysfunction. The appropriate response is to consider discontinuing or switching away from metoclopramide and to confirm the prolactin elevation.
Option A: Option A is incorrect because the temporal association with metoclopramide makes drug-induced hyperprolactinemia far more likely than a coincidental adenoma, and continuing the drug unchanged ignores the probable cause.
Option C: Option C is incorrect because galactorrhea and amenorrhea are not benign expected effects of prokinesis and should not be dismissed.
Option D: Option D is incorrect because acute dystonia presents with sustained abnormal muscle contractions, not galactorrhea and amenorrhea.
Option E: Option E is incorrect because the symptoms arise from hyperprolactinemia due to D2 blockade, not from any cardiac hERG effect.
5. A 78-year-old man applies a scopolamine patch before a cruise to prevent seasickness. Two days later he becomes confused and disoriented, develops dry mouth and blurred vision, and is unable to urinate despite a full bladder. What is the most likely explanation and the appropriate first step?
A) An acute coronary syndrome precipitated by the patch, requiring cardiac catheterization
B) A serotonin syndrome from the scopolamine, requiring cyproheptadine
C) An extrapyramidal reaction from dopamine D2 blockade, requiring an anticholinergic agent
D) Anticholinergic toxicity from the scopolamine patch (its muscarinic blockade producing confusion, dry mouth, blurred vision, and urinary retention, with elderly patients especially susceptible), so the patch should be removed and supportive care provided
E) A normal and harmless response to the patch requiring no intervention
ANSWER: D
Rationale:
Scopolamine is a muscarinic antagonist, and its anticholinergic effects (confusion, dry mouth, blurred vision, urinary retention) are predictable and especially pronounced in elderly patients. The appropriate first step is to remove the patch and provide supportive care.
Option A: Option A is incorrect because the constellation of central confusion plus peripheral antimuscarinic signs points to anticholinergic toxicity, not acute coronary syndrome.
Option B: Option B is incorrect because scopolamine does not cause serotonin syndrome, which features autonomic instability, clonus, and hyperthermia rather than antimuscarinic dryness and retention.
Option C: Option C is incorrect because scopolamine causes anticholinergic toxicity rather than a dopamine-blockade extrapyramidal reaction, and giving more anticholinergic medication would worsen the picture.
Option E: Option E is incorrect because these symptoms represent genuine toxicity that warrants patch removal and monitoring, not a harmless response.
6. A 70-year-old man receiving palliative care for metastatic cancer has persistent nausea attributed to his opioid analgesics. The team wants an antiemetic that targets the chemoreceptor trigger zone effectively but avoids heavy sedation at antiemetic doses. Which choice best fits?
A) High-dose promethazine, accepting its deep sedation and anticholinergic burden
B) A scopolamine patch, since opioid-induced nausea is a vestibular phenomenon
C) Low-dose haloperidol (0.5 to 2 mg), a butyrophenone that blocks chemoreceptor trigger zone dopamine D2 receptors effectively with a lower sedation burden than phenothiazines at antiemetic doses
D) A motilin receptor agonist, since opioid-induced nausea is purely a gastric-emptying problem
E) An NK1 antagonist as monotherapy, which is the standard treatment for opioid-induced nausea
ANSWER: C
Rationale:
Low-dose haloperidol (0.5 to 2 mg) is a butyrophenone dopamine D2 antagonist widely used in palliative care for opioid-induced nausea; it acts effectively at chemoreceptor trigger zone D2 receptors with a lower sedation burden than phenothiazines at antiemetic doses.
Option A: Option A is incorrect because high-dose promethazine brings deep sedation and a heavy anticholinergic burden, which the team specifically wants to avoid.
Option B: Option B is incorrect because opioid-induced nausea is driven substantially by chemoreceptor trigger zone activation rather than a vestibular mechanism, so a muscarinic antagonist is not the best-targeted choice.
Option D: Option D is incorrect because opioid-induced nausea is not purely a gastric-emptying problem, and a motilin agonist does not target the chemoreceptor trigger zone.
Option E: Option E is incorrect because NK1 antagonist monotherapy is not the standard treatment for opioid-induced nausea, which is better addressed by low-dose dopamine antagonists.
7. A 61-year-old man on chronic warfarin with a previously stable INR begins chemotherapy with an aprepitant-containing antiemetic regimen. Over the following week his INR falls below his therapeutic range despite no change in his warfarin dose or diet. What is the most likely explanation and the appropriate response?
A) Aprepitant induces CYP2C9, accelerating warfarin metabolism and lowering the INR, so the INR should be monitored closely and the warfarin dose adjusted as needed
B) Aprepitant inhibits CYP2C9, which raises the INR, so the warfarin dose should be decreased
C) Aprepitant displaces warfarin from plasma proteins, raising the INR
D) Aprepitant has no interaction with warfarin, so the change must be a laboratory error
E) Aprepitant directly antagonizes vitamin K, raising the INR
ANSWER: A
Rationale:
Aprepitant induces CYP2C9, the enzyme largely responsible for metabolizing the active S-enantiomer of warfarin; this accelerates warfarin clearance and lowers the INR (international normalized ratio). The appropriate response is to monitor the INR closely during and after the aprepitant course and adjust the warfarin dose as needed.
Option B: Option B is incorrect because aprepitant induces rather than inhibits CYP2C9, so the INR falls rather than rises.
Option C: Option C is incorrect because the interaction is enzyme induction, not protein-binding displacement, and the observed change is a falling INR.
Option D: Option D is incorrect because a recognized CYP2C9-mediated interaction explains the falling INR, so it should not be dismissed as laboratory error.
Option E: Option E is incorrect because aprepitant does not antagonize vitamin K, and the observed effect is a decrease, not an increase, in the INR.
8. A 45-year-old woman with longstanding diabetic gastroparesis is admitted with a gastroparetic crisis: intractable vomiting, dehydration, and laboratory studies showing hypokalemia and hypomagnesemia. She cannot tolerate oral intake. What is the most appropriate initial inpatient management?
A) Immediate central venous parenteral nutrition as the first-line intervention
B) Oral metoclopramide tablets before meals, despite her inability to tolerate oral intake
C) A scopolamine patch as the primary therapy for the crisis
D) Discharge home with reassurance, since gastroparetic crises are self-limited
E) Intravenous hydration, correction of the hypokalemia and hypomagnesemia, intravenous metoclopramide, and antiemetic therapy, with nasojejunal tube feeding if oral intake remains inadequate after initial stabilization
ANSWER: E
Rationale:
An acute gastroparetic crisis is managed with intravenous hydration, correction of electrolyte abnormalities (hypokalemia and hypomagnesemia are common from vomiting), intravenous metoclopramide, and antiemetic therapy, with restoration of enteral nutrition by nasojejunal tube feeding when oral intake remains inadequate after initial stabilization.
Option A: Option A is incorrect because parenteral nutrition via central access is reserved as a last resort when jejunal feeding is not feasible, given its infection and line-complication risks.
Option B: Option B is incorrect because the patient cannot tolerate oral intake, so the intravenous route is required for the prokinetic.
Option C: Option C is incorrect because a scopolamine patch is a motion-sickness agent, not appropriate primary therapy for a gastroparetic crisis.
Option D: Option D is incorrect because an acute crisis with dehydration and electrolyte derangement requires active inpatient management rather than discharge.
9. A 72-year-old man with Parkinson disease is started on metoclopramide for nausea and delayed gastric emptying. Within days his tremor and rigidity noticeably worsen. What explains this deterioration, and what is the better antiemetic/prokinetic choice if one is needed?
A) The worsening is unrelated to metoclopramide, which should be continued at a higher dose
B) Metoclopramide crosses the blood-brain barrier and blocks central dopamine D2 receptors, worsening the already-deficient dopaminergic signaling of Parkinson disease; it should be stopped, and where a prokinetic is needed, domperidone (which is largely excluded from the CNS) is preferred because it spares central dopamine receptors
C) The deterioration is an allergic reaction to metoclopramide
D) Metoclopramide worsened the Parkinson disease through hERG channel blockade, and ondansetron should be substituted for the same prokinetic effect
E) The motor worsening is from hyperprolactinemia and will resolve if metoclopramide is continued
ANSWER: B
Rationale:
Metoclopramide crosses the blood-brain barrier and blocks central dopamine D2 receptors; in Parkinson disease, where dopaminergic signaling is already deficient, this additional blockade worsens motor symptoms, so it should be avoided. Where a prokinetic is needed, domperidone is preferred because it is a P-glycoprotein substrate largely excluded from the CNS and therefore spares central dopamine receptors.
Option A: Option A is incorrect because the worsening is a direct pharmacological consequence of central D2 blockade, and increasing the dose would worsen it.
Option C: Option C is incorrect because the deterioration reflects central dopamine blockade, not an allergic reaction.
Option D: Option D is incorrect because the motor worsening is from central D2 blockade rather than hERG effects, and ondansetron is an antiemetic without prokinetic activity, so it would not substitute for metoclopramide's prokinetic role.
Option E: Option E is incorrect because hyperprolactinemia does not cause worsening tremor and rigidity, and continuing metoclopramide would perpetuate the central D2 blockade.
10. A 16-month-old child is given promethazine for vomiting during a viral illness and subsequently develops dangerous respiratory depression. What is the relevant pharmacological principle?
A) Promethazine has no pediatric safety concerns and the event was unrelated to the drug
B) The respiratory depression resulted from a dystonic reaction obstructing the airway
C) Promethazine is the preferred antiemetic in infants because of its strong safety record
D) Promethazine carries an FDA black box warning against use in children under age 2 because it can cause fatal respiratory depression in this age group, so it should not have been administered
E) The respiratory depression was caused by promethazine-induced QTc prolongation
ANSWER: D
Rationale:
Promethazine carries an FDA black box warning for fatal respiratory depression in children under age 2; it should not be used in this age group, so it was inappropriate to administer to a 16-month-old.
Option A: Option A is incorrect because the warning specifically links promethazine to fatal respiratory depression in young children, making the event drug-related.
Option B: Option B is incorrect because the danger is direct central respiratory depression, not airway obstruction from dystonia.
Option C: Option C is incorrect because promethazine is contraindicated, not preferred, in this age group.
Option E: Option E is incorrect because the recognized lethal risk in young children is respiratory depression, not QTc prolongation.
11. A 58-year-old man with gastroparesis was started on oral erythromycin and had excellent symptom relief in the first week. By the third week of continuous use, the benefit has largely disappeared despite no change in dose. What explains the loss of effect, and what does it imply for how erythromycin should be used?
A) The erythromycin dose has accumulated to toxic levels, requiring discontinuation for safety
B) Tachyphylaxis has developed from motilin receptor downregulation, which occurs within days to weeks of continuous administration; erythromycin is therefore best reserved for acute exacerbations rather than chronic continuous management
C) The patient has developed antibiotic resistance, which abolished the prokinetic effect
D) The loss of effect reflects worsening tardive dyskinesia from the erythromycin
E) The benefit faded because erythromycin induced its own metabolism through CYP2C9
ANSWER: B
Rationale:
Erythromycin is a motilin receptor agonist, and its principal limitation is tachyphylaxis: motilin receptor downregulation develops within days to weeks of continuous administration, substantially reducing the prokinetic effect. This is why erythromycin is best reserved for acute gastroparetic exacerbations rather than chronic continuous outpatient management.
Option A: Option A is incorrect because the loss of effect is due to receptor downregulation, not toxic drug accumulation.
Option C: Option C is incorrect because the waning prokinetic effect reflects motilin receptor downregulation, a pharmacodynamic phenomenon unrelated to antimicrobial resistance.
Option D: Option D is incorrect because erythromycin does not cause tardive dyskinesia, which is a consequence of dopamine antagonists such as metoclopramide.
Option E: Option E is incorrect because erythromycin is a CYP3A4 inhibitor rather than a CYP2C9 autoinducer, and the loss of effect is explained by motilin receptor tachyphylaxis, not accelerated self-metabolism.
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