Q1. To which opioid adverse effect does tolerance NOT develop? A. Nausea B. Drowsiness C. Constipation D. Respiratory depression ANSWER: C — constipation. Why: tolerance develops to nausea, sedation and respiratory depression over days, but not to the effect on gut motility. Constipation persists for as long as the opioid is taken. LEARNING POINT: co-prescribe a laxative from the start, not after the patient complains.

Q2. Codeine produces analgesia because it is: A. A direct full mu-receptor agonist B. A prodrug converted to morphine by CYP2D6 C. An NSAID D. A serotonin reuptake inhibitor only ANSWER: B — a prodrug requiring CYP2D6. Why: codeine itself has little analgesic activity; conversion to morphine is required. Genetic variation in CYP2D6 means poor metabolisers get little effect and ultra-rapid metabolisers can develop toxicity. LEARNING POINT: this explains both non-response and unexpected opioid toxicity, including in breastfed infants.

Q3. An elderly patient on ramipril and furosemide is given regular ibuprofen for back pain during an acute illness. Creatinine doubles. The mechanism is: A. Direct NSAID nephrotoxicity alone B. Combined loss of afferent dilation, efferent constriction and volume C. Obstruction D. Rhabdomyolysis ANSWER: B. Why: the NSAID blocks prostaglandin-mediated afferent dilatation, the ACE inhibitor blocks angiotensin-mediated efferent constriction, and diuretic plus illness deplete volume — removing every defence of glomerular filtration. LEARNING POINT: none of the three drugs is wrong alone; the combination during dehydration is.

Q4. A diabetic patient has burning, shooting foot pain with allodynia. Codeine has been escalated twice without benefit. The best next step is: A. Increase the codeine further B. Switch to morphine C. Start a drug for neuropathic pain such as a gabapentinoid, tricyclic or duloxetine D. Add an NSAID ANSWER: C — change class. Why: this is neuropathic pain, which responds poorly to opioids. Escalating delivers constipation and sedation without analgesia. D: an NSAID would be inappropriate given likely diabetic renal risk, and does not treat neuropathic pain. LEARNING POINT: failure to respond can mean the wrong class, not an inadequate dose.

Q5. A post-operative patient on morphine with renal impairment is rousable only to firm stimulation. Respiratory rate is 12. The correct interpretation is: A. Safe — the respiratory rate is normal B. Concerning — sedation precedes respiratory depression, and metabolites accumulate in renal impairment C. Expected pain relief D. Post-operative delirium requiring haloperidol ANSWER: B. Why: increasing sedation is the earlier and more sensitive warning of opioid toxicity. Renal impairment causes accumulation of active morphine metabolites, making this predictable. LEARNING POINT: monitor rousability, not just the respiratory rate.

Q6. A patient takes prescribed co-codamol, an over-the-counter cold remedy and paracetamol for headaches. She presents with deranged liver enzymes. The most likely explanation is: A. Viral hepatitis B. Cumulative paracetamol from combination products exceeding the maximum daily dose C. Codeine hepatotoxicity D. Alcohol ANSWER: B. Why: co-codamol contains paracetamol, as do most cold remedies. Taking all three can substantially exceed the maximum daily dose without the patient realising — a staggered supratherapeutic ingestion. LEARNING POINT: take a medication history that includes purchased products, and counsel about combination preparations.

Q7. Which analgesic property makes aspirin useful for cardiovascular prevention? A. Reversible COX inhibition B. IRREVERSIBLE inhibition of platelet COX C. Central action only D. Selective COX-2 inhibition ANSWER: B — irreversible platelet COX inhibition. Why: platelets have no nucleus and cannot synthesise new enzyme, so irreversible inhibition lasts the platelet's lifespan. That is why low-dose aspirin has a sustained antiplatelet effect. D: COX-2 selective agents lack this antiplatelet action and carry cardiovascular concerns. LEARNING POINT: the same enzyme, inhibited differently, produces an entirely different clinical use.