Page 30 of 32
PH3.1-9 | Central Nervous System Pharmacology — Graded Quiz
Click any question card to reveal the correct answer.
Minimum alveolar concentration (MAC) of an inhalational anaesthetic is defined as the alveolar concentration at which:
MAC is an ED50 for immobility in response to surgical incision. Low MAC = high potency (halothane 0.75%; isoflurane 1.15%; nitrous oxide 105%). Inversely correlates with the oil-gas partition coefficient (Meyer-Overton theory).
MAC measures immobility (ED50), not unconsciousness, analgesia, or safety. Key fact: N₂O has MAC >100% — cannot be used alone at atmospheric pressure to achieve anaesthesia.
Click to reveal answer
Flumazenil reverses benzodiazepine sedation by acting as a:
Flumazenil = competitive BZD site antagonist at GABA-A. Short half-life → resedation risk with long-acting BZDs. Contraindicated in BZD-dependent patients (precipitates withdrawal). Not effective for barbiturate, alcohol, or opioid sedation.
Reversal agents: BZD → flumazenil; opioid → naloxone; NMBs → neostigmine (for non-depolarising) or spontaneous recovery (succinylcholine). There is NO reversal for barbiturates.
Click to reveal answer
Which antiseizure drug is CONTRAINDICATED in absence epilepsy because it can paradoxically worsen seizure frequency?
Na⁺ channel blockers (carbamazepine, phenytoin, oxcarbazepine) are CONTRAINDICATED in absence and myoclonic epilepsy. Absence first-line: ethosuximide (pure absence), valproate (absence + other types), lamotrigine (alternative).
Key matrix: focal/tonic-clonic → carbamazepine (safe); absence/myoclonic → valproate, ethosuximide, lamotrigine (safe); carbamazepine/phenytoin in absence → DANGEROUS (worsens seizures).
Click to reveal answer
A 45-year-old man presents with morphine overdose and is given naloxone 0.4 mg IV with dramatic improvement. Thirty minutes later he becomes unresponsive again. The most likely explanation is:
Naloxone t½ ≈ 30-80 min vs morphine t½ ≈ 2-4 h. Single-bolus reversal is insufficient for most opioid overdoses. Monitor for at least 4-6 hours; use continuous infusion for long-acting opioids. This is why hospital discharge after naloxone reversal requires prolonged observation.
Key pharmacokinetic principle: the duration of effect of naloxone is shorter than most opioids. Re-narcotisation is a predictable outcome after single-dose reversal of long-acting opioid overdose.
Click to reveal answer
A patient has been on phenelzine (an irreversible MAOI) for depression. The psychiatrist wants to switch to sertraline. What is the minimum washout period required before starting sertraline?
MAOI → SSRI washout: 14 days (irreversible MAOIs). SSRI → MAOI washout: 14 days for most SSRIs, 5 weeks for fluoxetine. The danger: concurrent use = serotonin syndrome (potentially fatal). Also: tramadol, pethidine, and linezolid are serotonergic — same washout rules apply.
Memorise the washout asymmetry: irreversible MAOI-off → 14 days for enzyme regeneration; fluoxetine-off → 5 weeks for drug/metabolite clearance. The other SSRIs need only 14 days before starting MAOI.
Click to reveal answer
A patient with generalised anxiety disorder is switched from lorazepam to buspirone. She returns after 1 week reporting that buspirone 'does not work' and her anxiety is worse than before. The most appropriate response is:
Buspirone: 5-HT₁A partial agonist; delayed onset 2-4 weeks (receptor adaptation); no cross-tolerance with BZDs (cannot suppress BZD withdrawal); effective for GAD; safer long-term profile than BZDs (no dependence, no sedation, no cognitive impairment). Counsel patients explicitly about the delay.
Buspirone vs BZD: BZD = immediate effect (minutes to hours), dependence risk; Buspirone = delayed (2-4 weeks), no dependence, preferred long-term. The 2-4 week delay is the key clinical teaching point.
Click to reveal answer
Carbidopa is combined with levodopa in Parkinson's disease management. Which of the following best explains the rationale for this combination?
Levodopa/carbidopa combination logic: levodopa crosses BBB (dopamine cannot); carbidopa blocks peripheral DDC (does not cross BBB) → less peripheral dopamine (less nausea/vomiting/hypotension) + more levodopa available for CNS → better efficacy at lower doses. Standard ratio 4:1 (levodopa:carbidopa).
The carbidopa story: without it, only 1-3% of oral levodopa reaches the brain; with it, ~10% reaches the brain. Peripheral DDC inhibition also prevents the nausea and cardiovascular adverse effects that made early levodopa monotherapy poorly tolerated.
Click to reveal answer
A 50-year-old man with known chronic alcohol use is found unconscious. Blood glucose is 2.1 mmol/L. Before administering IV dextrose, which drug should be given first?
Rule: thiamine 100 mg IV before glucose in ANY confused/comatose patient with chronic alcohol use. Mechanism: glucose → glycolysis → pyruvate → thiamine-dependent step. Without thiamine, toxic metabolites accumulate → Wernicke's encephalopathy → if untreated → Korsakoff's syndrome (irreversible).
Wernicke's triad: confusion, ophthalmoplegia, ataxia. Any two of three suffice clinically. Precipitating thiamine deficiency with glucose is an iatrogenic disaster — always give thiamine first.
Click to reveal answer
Both cocaine and amphetamines increase synaptic dopamine in the nucleus accumbens, but their mechanisms differ. Which correctly distinguishes them?
Cocaine: DAT blockade (reuptake inhibition) → ↑synaptic DA. Amphetamines: DAT reversal + VMAT2 inhibition → active DA release + vesicular DA release → stronger, longer effect. Both: NET and SERT effects too. Clinically: amphetamine withdrawal more prolonged; cocaine binge-crash more characteristic.
The DAT blockade vs DAT reversal distinction is frequently tested. Cocaine is the 'plug' (blocks); amphetamine is the 'pump' (reverses and releases). Both increase dopamine in nucleus accumbens = reward.
Click to reveal answer
A first-year medical student asks why clozapine causes fewer extrapyramidal side effects (EPS) than haloperidol despite both being antipsychotics. The correct explanation is:
Atypical antipsychotic advantage over typicals: 5-HT₂A antagonism facilitates dopamine release in the nigrostriatal pathway, partially reversing D2 blockade there → fewer EPS. In the mesolimbic pathway (target for antipsychotic effect), 5-HT₂A blockade has less influence → therapeutic D2 blockade maintained. Clozapine additionally risks agranulocytosis (mandatory WBC monitoring) and metabolic syndrome.
EPS classification: acute dystonia, akathisia, drug-induced parkinsonism (all reversible), tardive dyskinesia (late, potentially irreversible). Atypicals cause less EPS but not zero. Clozapine: least EPS, most metabolic risk (agranulocytosis, weight gain, diabetes).
Click to reveal answer
A patient on phenelzine for depression is admitted for appendicectomy. The surgical team considers pethidine for post-operative analgesia. This combination is CONTRAINDICATED because it can cause:
Pethidine is the ONE opioid that inhibits SERT. MAOI prevents serotonin breakdown. Together → serotonin syndrome (not opioid toxidrome). Safe opioid alternatives in MAOI patients: morphine, fentanyl, oxycodone (no SERT inhibition). Tramadol also inhibits SERT — similarly contraindicated.
SERT-inhibiting opioids contraindicated with MAOIs: pethidine (meperidine), tramadol, methadone (weak SERT). Safe alternatives: morphine, fentanyl, hydromorphone. This is a high-stakes prescribing error — NMC explicitly tests it (PH3.4 'special instructions for opioids').
Click to reveal answer
Malignant hyperthermia is most likely to be triggered by which combination of agents?
MH triggers: halogenated volatile agents (halothane, isoflurane, sevoflurane, desflurane) + succinylcholine. Safe alternatives in MH-susceptible patients: propofol/thiopentone IV induction + nitrous oxide + non-depolarising NMBs + opioids. Dantrolene is the specific treatment — always available in any OR.
MH ≠ NMS ≠ serotonin syndrome. MH: OR setting, halogenated volatiles/succinylcholine, extreme rigidity, hyperCK. NMS: antipsychotics, days to develop, lead-pipe rigidity. Serotonin syndrome: serotonergic drugs, hours to develop, clonus/myoclonus.
Click to reveal answer