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PH3.1-9 | Central Nervous System Pharmacology — Practice Quiz
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Ethosuximide suppresses absence seizures by blocking which ion channel?
Ethosuximide selectively blocks T-type Ca²⁺ channels in thalamic neurons, suppressing the 3-Hz spike-and-wave discharges characteristic of absence seizures. It is narrow-spectrum — effective only for absence, not tonic-clonic.
Review the drug-seizure type matrix: Na⁺ channel blockers → focal/tonic-clonic; T-type Ca²⁺ blockers (ethosuximide) → absence only; GABA enhancers → broad-spectrum.
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A patient receiving long-term morphine for cancer pain develops miosis, constipation, and respiratory depression. All three effects are primarily mediated by which receptor?
The μ-receptor is the primary target of morphine, codeine, fentanyl, and pethidine. All three adverse effects — respiratory depression, constipation, and miosis — are μ-mediated. Naloxone (competitive μ-antagonist) rapidly reverses all three.
Memorise the μ (mu) mnemonic: Morphine binds μ → analgesia, euphoria, respiratory depression (↓respiratory centre response to CO₂), miosis, constipation, urinary retention. The others — κ and δ — are secondary targets.
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A 28-year-old woman is started on fluoxetine for major depressive disorder. The initial molecular event responsible for its antidepressant action is:
SSRIs block SERT → ↑synaptic 5-HT → downstream adaptations → antidepressant effect in 2-4 weeks. Selectivity for SERT avoids the α₁, H₁, and muscarinic blockade of TCAs, giving a cleaner adverse-effect profile.
Know the transporter targets: SSRIs → SERT; SNRIs → SERT + NET; TCAs → SERT + NET + multiple others; NDRIs → NET + DAT; MAOIs → MAO-A and/or MAO-B.
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A 35-year-old man on sertraline is given tramadol for post-operative pain. Six hours later he develops agitation, diaphoresis, whole-body tremor, clonus, and hyperthermia (39.2°C). Which diagnosis best fits and what is the most important next step?
Serotonin syndrome = SSRIs/SNRIs + any other serotonergic drug (tramadol, pethidine, linezolid, triptans, lithium). Hallmark signs: clonus, myoclonus, hyperreflexia, agitation, hyperthermia, diaphoresis. Onset is rapid (hours). Contrast with NMS (antipsychotics, slow onset, lead-pipe rigidity, bradyphrenia).
The four drug-induced hyperthermia syndromes to distinguish: (1) Serotonin syndrome — serotonergic excess, clonus, rapid onset; (2) NMS — DA blockade, lead-pipe rigidity, slow onset; (3) MH — volatile anaesthetics/succinylcholine, peri-operative; (4) Anticholinergic — dry skin, no diaphoresis.
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A 22-year-old woman has been seizing for 8 minutes. IV access is established. What is the correct first drug and dose?
Status epilepticus protocol: (1) Airway/IV/glucose. (2) First-line BZD (lorazepam IV or diazepam IV/rectal). (3) If fails: second-line — phenytoin, valproate, or levetiracetam. (4) Refractory: anaesthetic agents (propofol, midazolam infusion, thiopentone). Each step has a 5-10 minute window.
Remember the sequence: BZD first → second-line anticonvulsant → anaesthetic. First-line BZDs work fast (minutes). Second-line agents take longer. Never skip to phenytoin without trying a BZD.
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Both diazepam and phenobarbitone act on GABA-A receptors but differ in their mechanism. Which correctly distinguishes them?
BZDs = frequency ↑ (require GABA, have ceiling effect, reversible with flumazenil). Barbiturates = duration ↑ (can open channel without GABA at high doses, no ceiling, NO reversal agent). This explains why BZD overdose alone is rarely fatal but barbiturate overdose is.
The Cl⁻ channel mechanism mnemonic: 'BZDs are Frequent visitors; Barbiturates stay Longer (Duration).' Test yourself: which drug has NO ceiling effect? Which has a reversal agent?
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A 55-year-old woman with schizophrenia on haloperidol develops cogwheel rigidity, mask-like facies, and shuffling gait 4 weeks after starting treatment. The correct management is:
DIP management hierarchy: (1) reduce dose or switch antipsychotic to lower D2 affinity; (2) add trihexyphenidyl (anticholinergic) if symptoms persist. NMC OSCE standard prescription: Rx Tab Trihexyphenidyl 2 mg BD. Never add levodopa in an antipsychotic-maintained patient.
DIP = D2 receptor blockade → lost dopaminergic inhibition of indirect pathway → cholinergic excess → parkinsonism. Treatment restores balance: anticholinergics (not dopaminergics — which would worsen psychosis).
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A 40-year-old man is brought to the emergency department 10 hours after consuming illicit alcohol. He has severe metabolic acidosis (pH 7.1) and progressive visual blurring. Which antidote acts by the same mechanism as the toxin itself and is given IV?
Methanol → formaldehyde → formic acid (ADH-mediated). Formic acid inhibits cytochrome oxidase → optic neuropathy, metabolic acidosis. Treatment: fomepizole (direct ADH inhibitor, first choice) or ethanol IV (competitive ADH substrate); dialysis for severe acidosis/visual involvement; sodium bicarbonate adjunctively.
Methanol poisoning treatment sequence: (1) fomepizole/ethanol to block ADH; (2) sodium bicarbonate for acidosis; (3) folate (converts formate to CO₂); (4) haemodialysis for severe cases. Onset of visual toxicity after a latent period of 6-24 hours is the clinical hallmark.
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Which of the following adverse effects are correctly attributed to carbamazepine?
- Hyponatraemia due to SIADH
- Stevens-Johnson syndrome (SJS), particularly in HLA-B*1502-positive individuals
- Gingival hyperplasia
- Aplastic anaemia and agranulocytosis
- Dose-dependent hepatotoxicity similar to valproate
Carbamazepine unique ADR profile: (1) Hyponatraemia (SIADH — check Na⁺ in elderly). (2) SJS/TEN — screen HLA-B*1502 in South Asian patients (Indian, Chinese). (3) Haematological toxicity — aplastic anaemia, agranulocytosis (rare). (4) Also: autoinduction of metabolism, diplopia, ataxia. Contrast with phenytoin (gingival hyperplasia, hirsutism, nystagmus, zero-order kinetics).
Phenytoin-specific ADRs: gingival hyperplasia, hirsutism, coarsening of facies, megaloblastic anaemia (folate depletion), osteomalacia, nystagmus, cerebellar ataxia, SJS. Carbamazepine: SIADH, SJS, aplastic anaemia, diplopia.
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A 28-year-old man with heroin use disorder reports his last heroin use was 10 hours ago. He is now sweating, anxious, with dilated pupils and COWS score of 10. When should buprenorphine/naloxone (Suboxone) be initiated?
Buprenorphine induction rule: COWS ≥8 (moderate withdrawal) before first dose. This ensures adequate clearance of full agonist so buprenorphine doesn't precipitate withdrawal. Buprenorphine has high μ-affinity + ceiling effect → safer than full agonists for maintenance.
The precipitated withdrawal trap: buprenorphine is a PARTIAL agonist with HIGH affinity. If given when a full agonist is still on the receptor, it DISPLACES the full agonist and produces net antagonism — acute, severe withdrawal. Always confirm COWS ≥8 before induction.
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Statement 1 (Assertion):
Tricyclic antidepressant (TCA) overdose is treated with IV sodium bicarbonate even in the absence of acidosis.
BECAUSE
Statement 2 (Reason):
TCAs block fast voltage-gated Na⁺ channels in the myocardium, prolonging the QRS complex and predisposing to ventricular arrhythmias; alkalinisation reduces the un-ionised (membrane-permeable) fraction of TCA, decreasing channel blockade.
Select the correct relationship:
TCA overdose management: (1) Sodium bicarbonate for QRS >100 ms (or ventricular arrhythmia) — alkalinise to pH 7.50-7.55. (2) Avoid other QTc-prolonging drugs. (3) Physostigmine is CONTRAINDICATED (risk of seizures and cardiac arrest from cholinergic crisis). (4) ICU monitoring mandatory.
TCA toxidrome: sedation, dry mouth (antimuscarinic), hypotension (α₁ block), QRS widening and arrhythmia (Na⁺ channel block). The Na⁺ channel block mechanism is why TCA overdose is uniquely dangerous and why bicarbonate (not standard antiarrhythmics) is first-line.
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CLINICAL SCENARIO
Dr Meena, a general practitioner at a CHC in Vadodara, reviews Mrs Patel, a 58-year-old woman who has been prescribed diazepam 5 mg nightly for generalised anxiety disorder for the past 4 years. Mrs Patel reports she cannot sleep without the tablet and becomes severely anxious and experiences tremors if she misses a dose. She has tried stopping twice; on the second attempt she developed a seizure.
Answer the following questions based on the scenario above.
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What pharmacological phenomenon most explains Mrs Patel's inability to stop diazepam?
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Which of the following is the most appropriate management plan for Mrs Patel?
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