Opioids Practice Exam

OPIO-001 • Question 1

Activation of the μ-opioid receptor produces analgesia primarily through which intracellular signaling effect?

Gs activation → increased cAMP Gi activation → decreased cAMP and reduced presynaptic Ca2+ influx Gq activation → increased IP3/DAG Direct NMDA receptor blockade Opening of presynaptic Na+ channels

OPIO-002 • Question 2

Which triad is most consistent with acute opioid overdose?

Mydriasis, hyperreflexia, hypertension Miosis, respiratory depression, CNS depression Diarrhea, piloerection, tachycardia Hyperthermia, clonus, agitation Wheezing, urticaria, hypotension

OPIO-003 • Question 3

A patient with advanced CKD becomes progressively somnolent after receiving repeated doses of morphine. The best explanation is accumulation of:

Inactive morphine sulfate Active morphine-6-glucuronide Normeperidine Inactive fentanyl metabolites Hydromorphone-3-glucuronide only

OPIO-004 • Question 4

Which opioid is MOST likely to cause seizures due to an excitatory metabolite, especially in renal dysfunction?

Meperidine Fentanyl Methadone Buprenorphine Oxycodone

OPIO-005 • Question 5

A patient on transdermal fentanyl develops high fever. What is the biggest clinical concern?

Fever decreases fentanyl absorption leading to withdrawal Fever increases transdermal absorption increasing overdose risk Fever converts fentanyl to a toxic metabolite via CYP2E1 Fever blocks μ-receptor binding Fever increases renal clearance

OPIO-006 • Question 6

A patient given a single bolus of naloxone wakes briefly then becomes somnolent again 45 minutes later. Most likely explanation?

Naloxone is a partial agonist Naloxone duration is shorter than many opioids (renarcotization) Naloxone is converted to morphine Naloxone selectively blocks κ-receptors causing sedation Naloxone delays opioid absorption

OPIO-007 • Question 7

Rapid IV fentanyl in the OR causes sudden inability to ventilate with rigid chest wall (“wooden chest”). Best immediate step?

Flumazenil Naloxone with assisted ventilation Physostigmine Atropine Epinephrine

OPIO-008 • Question 8

Buprenorphine reduces the effect of heroin taken on top of it mainly because buprenorphine:

Is fully antagonized by naloxone when taken sublingually Has high μ-receptor affinity and partial agonist activity Irreversibly binds μ-receptors Induces heroin metabolism Is a selective κ-agonist only

OPIO-009 • Question 9

Starting buprenorphine too soon after a full μ-agonist can precipitate withdrawal because buprenorphine:

Is a full μ-antagonist Displaces full agonist but provides lower intrinsic activity Increases opioid metabolism abruptly Stimulates dopamine reuptake Fully blocks the BBB

OPIO-010 • Question 10

Which opioid has the most clinically significant QT prolongation and torsades risk?

Morphine Hydromorphone Methadone Remifentanil Codeine

OPIO-011 • Question 11

Which opioid has SNRI activity and increases risk of serotonin syndrome and seizures (especially with SSRIs)?

Oxycodone Tramadol Hydromorphone Fentanyl Morphine

OPIO-012 • Question 12

Which clinical finding is LEAST consistent with opioid intoxication?

Miosis Respiratory depression Bradycardia Diarrhea with hyperactive bowel sounds Hypothermia

OPIO-013 • Question 13

A patient on escalating opioid doses reports worsening diffuse pain and allodynia. Best diagnosis?

Tolerance Opioid-induced hyperalgesia Pseudoaddiction Serotonin syndrome Delirium tremens

OPIO-014 • Question 14

Which opioid commonly causes histamine release leading to pruritus and hypotension (non–IgE mediated), especially IV?

Morphine Fentanyl Methadone Buprenorphine Remifentanil

OPIO-015 • Question 15

Opioids can worsen biliary colic primarily because they:

Relax the sphincter of Oddi Increase sphincter of Oddi tone Increase gallbladder emptying Decrease bile viscosity Directly inflame the gallbladder

OPIO-016 • Question 16

Which medication is a peripherally acting μ-opioid receptor antagonist (PAMORA) used for opioid-induced constipation without reversing analgesia?

Methylnaltrexone Naloxone Naltrexone Buprenorphine Clonidine

OPIO-017 • Question 17

A patient on naltrexone (AUD) needs urgent surgery. Best implication for analgesia?

Opioid analgesia will be potentiated; halve opioid doses Opioid analgesia will be blunted; emphasize regional/non-opioid strategies and careful opioid escalation if needed Naltrexone prevents respiratory depression making opioids safer Naltrexone provides intrinsic analgesia Opioids are contraindicated due to malignant hyperthermia risk

OPIO-018 • Question 18

Which opioid is metabolized by nonspecific plasma/tissue esterases and is ultra–short acting (useful intraoperatively)?

Remifentanil Methadone Morphine Oxycodone Codeine

OPIO-019 • Question 19

A patient gets minimal analgesia from codeine. Most likely genotype?

CYP2D6 poor metabolizer CYP2D6 ultra-rapid metabolizer CYP3A4 ultra-rapid metabolizer UGT2B7 poor metabolizer CYP1A2 ultra-rapid metabolizer

OPIO-020 • Question 20

Which medication is best for reducing autonomic symptoms of opioid withdrawal (e.g., tachycardia, sweating, hypertension)?

Clonidine Naloxone Naltrexone Methylnaltrexone Flumazenil

OPIO-021 • Question 21

A key risk factor that most increases the chance of opioid-induced respiratory depression is:

Age < 30 Concomitant benzodiazepine use Hyperlipidemia Seasonal allergies Acne treated with topical retinoids

OPIO-022 • Question 22

Rifampin is started in a patient on chronic oxycodone. Most likely effect?

Increased opioid effect due to CYP inhibition Decreased opioid effect and possible withdrawal due to enzyme induction No change because opioids are not CYP-metabolized Seizures due to normeperidine accumulation Torsades due to rifampin

OPIO-023 • Question 23

Which opioid is generally preferred in severe renal failure due to lack of clinically important active renally cleared metabolites?

Fentanyl Morphine Meperidine Codeine Tramadol

OPIO-024 • Question 24

A patient becomes severely agitated and hypertensive after a large naloxone bolus for overdose. Best next approach?

Give repeated large boluses of naloxone until fully awake Titrate naloxone in small doses to adequate ventilation and consider infusion for long-acting opioids Administer morphine to reverse naloxone toxicity Stop oxygen to reduce agitation Give flumazenil

OPIO-025 • Question 25

Loperamide is best described as:

A centrally acting μ-agonist used for neuropathic pain A peripherally acting μ-agonist used for diarrhea with minimal CNS effects at therapeutic doses A μ-antagonist used for constipation An irreversible μ-receptor binder A κ-agonist sedative

OPIO-026 • Question 26

Which pairing has the HIGHEST risk of serotonin syndrome?

Morphine + bupropion Fentanyl + mirtazapine Tramadol + sertraline Hydromorphone + duloxetine Oxycodone + trazodone

OPIO-027 • Question 27

Which statement about opioid tolerance is most accurate?

Tolerance develops equally to all opioid effects Tolerance is mediated by increased μ-receptor numbers on the membrane Tolerance involves receptor desensitization and compensatory upregulation of the cAMP pathway Tolerance prevents withdrawal if opioids are stopped abruptly Tolerance is primarily due to irreversible receptor binding

OPIO-028 • Question 28

Which adverse effect is most directly mediated by opioid action on the Edinger–Westphal nucleus?

Miosis Diarrhea Hypertension Mydriasis Hyperreflexia

OPIO-029 • Question 29

A newborn exposed to opioids in utero develops high-pitched crying, tremor, diarrhea, and poor feeding 48 hours after birth. Diagnosis?

Neonatal opioid intoxication Neonatal abstinence syndrome Congenital hypothyroidism Sepsis Inborn error of metabolism

OPIO-030 • Question 30

A patient on chronic opioids starts gabapentin for neuropathic pain. What risk most increases?

Severe hepatotoxicity Additive CNS and respiratory depression Hypertensive crisis Serotonin syndrome Hemolytic anemia

OPIO-031 • Question 31

Which opioid should be avoided with MAOIs (or within 14 days) due to serotonin toxicity and seizure risk?

Tramadol Morphine Hydromorphone Oxycodone Buprenorphine

OPIO-032 • Question 32

Which opioid’s analgesic effect is most dependent on CYP2D6 activation to morphine?

Codeine Fentanyl Methadone Morphine Hydromorphone

OPIO-033 • Question 33

A patient develops syncope on methadone with QTc 520 ms. Which antibiotic most plausibly worsens risk via QT prolongation?

Azithromycin Amoxicillin Cephalexin Doxycycline Penicillin V

OPIO-034 • Question 34

Which opioid is a partial μ-agonist and κ-antagonist with a ceiling effect on respiratory depression?

Buprenorphine Methadone Morphine Hydromorphone Meperidine

OPIO-035 • Question 35

Which presentation most strongly indicates opioid WITHDRAWAL rather than overdose?

Miosis, bradycardia, hypothermia Somnolence and hypoventilation Mydriasis, piloerection, diarrhea, tachycardia Respiratory depression with pinpoint pupils Apnea and cyanosis

OPIO-036 • Question 36

A patient started on paroxetine reports reduced analgesia from codeine. Most likely mechanism?

CYP3A4 induction CYP2D6 inhibition reducing activation of codeine μ-receptor competitive antagonism Increased renal clearance of codeine Increased P-glycoprotein efflux decreasing absorption

OPIO-037 • Question 37

Which opioid is most associated with delayed respiratory depression due to long/variable half-life and accumulation during titration?

Methadone Remifentanil Fentanyl (IV bolus) Naloxone Loperamide

OPIO-038 • Question 38

A patient has opioid-induced constipation despite PEG and stimulant laxatives. Best mechanism-targeted add-on?

Methylnaltrexone Naloxone infusion Increase opioid dose Flumazenil Diphenhydramine

OPIO-039 • Question 39

Which opioid is most appropriate to avoid in renal impairment AND also has serotonergic activity increasing seizure risk?

Tramadol Fentanyl Methadone Buprenorphine Remifentanil

OPIO-040 • Question 40

Which opioid is the best choice to minimize histamine-related hypotension and pruritus (e.g., after morphine causes flushing)?

Fentanyl Morphine Meperidine Codeine Hydrocodone