Show the model answerAttempt it first — that is what makes it stick
What earns the marks10 marks
| (a) Cellular mechanism, then the monitor | 2 marks. A thorough explanation of the depolarising action at the cellular level, then all the monitoring characteristics — not one or the other |
|---|---|
| (b) Both variant families | 5 marks. Dibucaine-resistant AND fluoride-resistant. Omitting the second is what capped most scores |
| (b) What the number actually reports | Genotype. Not the quantity of enzyme, and not its efficiency |
| (b) The bonus mark | Rare variants with increased enzyme activity, which cause resistance rather than prolongation |
| (b) Four things that scored zero | Malignant hyperthermia, acquired causes, and the management of suxamethonium apnoea |
| (c) Bradycardia, not arrhythmias | 3 marks. The word matters — the examination marked the two differently |
| (c) Hyperkalaemia needs its cause | Naming hyperkalaemia without undiagnosed muscular dystrophy did not earn the mark |
2 marks
The term phase 1 block
Two marks for two things, and most answers gave only the first. The examination wanted the cellular mechanism AND a full list of the monitoring characteristics.
The depolarising action at the cellular level
1 · What the drug is
Suxamethonium is two acetylcholine molecules joined back to back. It is therefore an agonist at the postjunctional nicotinic acetylcholine receptor, not an antagonist — the single fact from which everything else follows.
2 · What that receptor is
The receptor is the channel. Five subunits — two α1, one β1, one δ and one ε in the adult, with γ replacing ε in the immature and extrajunctional form — are arranged like the staves of a barrel around a central pore. Acetylcholine binds on the extracellular part of each α1 subunit, and both sites must be occupied: with only one bound the pore stays shut. That is also the basis of competitive antagonism.
3 · Which channel opens first
Occupying both sites opens the receptor’s own pore — a ligand-gated non-selective cation channel. Sodium and calcium flow inwards, potassium flows outwards, and anions such as chloride are excluded. The net inward current is depolarising and produces the end-plate potential. The muscle contracts, which is visible as fasciculation.
4 · Which channel carries the impulse
The end-plate potential itself does not travel. It depolarises the perijunctional zone just beyond the junction, which carries few acetylcholine receptors but a high density of voltage-gated sodium channels. Those open, and a propagated action potential sweeps along the muscle. Two different channels, in series — and it is the second one the block acts on.
5 · The two gates, and why acetylcholine gets away with it
A voltage-gated sodium channel has two gates. The voltage-dependent gate opens on depolarisation; shortly after, the time-dependent inactivation gate closes. Acetylcholine is destroyed by acetylcholinesterase in under a millisecond, so the end-plate repolarises and both gates reset, ready for the next impulse.
6 · Why suxamethonium does not
Suxamethonium is not hydrolysed by acetylcholinesterase — only by plasma cholinesterase, which is not present in the cleft — so it stays bound and the end-plate stays depolarised. The neighbouring sodium channels therefore keep their voltage gates open and their inactivation gates shut, and sodium cannot cross a channel whose inactivation gate is closed. The perijunctional membrane never depolarises, so it becomes a buffer shielding the rest of the muscle from the end-plate. That is a phase 1 block: not a blocked receptor, but a membrane that cannot be excited again.
What the stimulator shows in each kind of block
Three states, each given a train-of-four, then a five-second tetanic stimulus at 50 Hz, then a second train-of-four. Unblocked, every twitch is full and the tetanus is sustained. In a partial depolarising block the twitches are reduced but equal, the tetanus is sustained, and the second train-of-four is unchanged — there is no post-tetanic facilitation. In a partial non-depolarising block the twitches fade within the train, the tetanus fades, and the train that follows it is transiently larger, which is post-tetanic facilitation. Fade is presynaptic: the drug blocks the presynaptic acetylcholine receptors that mobilise transmitter during heavy demand. Heights are drawn to show these relationships, not traced from an axis; the source figure prints none.
| Feature | Phase 1 (depolarising) | Phase 2 or non-depolarising | Why they differ |
|---|---|---|---|
| Single twitch | Reduced | Reduced | The only feature the two share, and the only one that tells you nothing. A reduced twitch says the margin of safety has been exceeded and enough receptors are out of action to lose fibres. It does not say by what mechanism, which is why every other row exists |
| Train-of-four ratio (T4:T1) | Greater than 0.7 — all four equally reduced | Less than 0.7 — the fourth smaller than the first | The ratio measures fade, and fade is presynaptic. A non-depolariser blocks the presynaptic acetylcholine receptors that provide the positive feedback mobilising transmitter during repeated demand, so each successive response is smaller. Suxamethonium does not block those receptors, so mobilisation is intact and all four twitches are reduced by the same amount — small, but equal |
| Response to a 1 Hz or tetanic stimulus | Sustained — reduced but no fade | Fades with time | The same presynaptic mechanism under heavier load. Tetanic stimulation at 50 Hz makes the greatest possible demand on transmitter mobilisation, so a presynaptic block shows itself most clearly here. This is the most sensitive discriminator between the two |
| Post-tetanic potentiation | Absent | Present | After a tetanus, twitches are transiently larger — attributed to increased synthesis and mobilisation of acetylcholine, and to residual calcium in the nerve terminal. In a competitive block that surge of transmitter briefly out-competes the antagonist, so the twitch grows. In a depolarising block there is no competition to win: the end-plate is already depolarised and more acetylcholine cannot repolarise it |
| Effect of an anticholinesterase | Block augmented | Block antagonised | The same reasoning, applied deliberately. Raising junctional acetylcholine reverses a competitive block by mass action. Against a depolarising block it adds more agonist to a membrane whose problem is that it is already depolarised, so the block deepens. Neostigmine also inhibits plasma cholinesterase, so it prevents suxamethonium being destroyed and prolongs it twice over |
| Fasciculation before the block | Present | Absent | Not on the monitor, but free to observe. Suxamethonium is an agonist, so it depolarises and contracts the muscle before it paralyses it. An antagonist cannot excite anything, so a non-depolarising block is silent from the start. A phase 2 block is preceded by fasciculation only because it grew out of a phase 1 |
Commonly lost: Candidates were expected to list all the characteristics of phase 1 block on neuromuscular monitoring, and many answers were unsatisfactory. Five rows, thirty seconds. An answer that explains the mechanism beautifully and stops has taken one of the two marks.
5 marks
How genetic variation affects the metabolism of suxamethonium
Suxamethonium is destroyed in plasma before most of the dose arrives, so the enzyme that destroys it sets the duration. Vary the enzyme genetically and the duration varies with it.
| Phenotype | Genotype | Dibucaine number | Incidence | Response to suxamethonium |
|---|---|---|---|---|
| Homozygous typical | E1uE1u | 70–80 (quoted as 80) | Normal — about 96% of people | Normal |
| Heterozygous atypical | E1uE1a | 50–60 (quoted as 60) | 1 in 480, or 1 in 25 depending on the source | Block about 1.5 to 2 times longer than usual |
| Homozygous atypical | E1aE1a | 20–30 (quoted as 20) | About 1 in 3,200 | Block prolonged to 4 to 8 hours |
| Genotype | Incidence | Duration of block | Dibucaine number |
|---|---|---|---|
| Normal | |||
| Eu:Eu | 96% | Normal | 80 |
| Heterozygous — one abnormal allele | |||
| Eu:Ea | 1 in 25 | Prolonged | 60 |
| Eu:Es | 1 in 90 | Prolonged | 80 |
| Eu:Ef | 1 in 200 | Prolonged | 75 |
| Two abnormal alleles — the clinically serious ones | |||
| Ea:Ea | 1 in 2,800 | Very markedly prolonged | 20 |
| Ea:Ef | 1 in 20,000 | Moderately prolonged | 50 |
| Es:Ea | 1 in 29,000 | Very markedly prolonged | 20 |
| Es:Es | 1 in 100,000 | Very markedly prolonged | No value — see below |
| Ef:Es | 1 in 150,000 | Moderately prolonged | 60 |
| Ef:Ef | 1 in 154,000 | Moderately prolonged | 70 |
Read the question: Peck’s incidences are used above because it is the only source that tabulates the rare genotypes. Its figure for the common heterozygote, 1 in 25, is the one that differs twentyfold from the other texts. Quote the rare genotypes as orders of magnitude rather than exact fractions.
| Genotype | Fluoride number | Effect on the block |
|---|---|---|
| Usual, E1uE1u | 60 | Normal |
| Homozygous fluoride-resistant, E1fE1f | 36 | Mild to moderate prolongation |
| Heterozygous fluoride-resistant | Intermediate | Usually clinically insignificant — unless there is a second abnormal allele, or a coexisting acquired cause of enzyme deficiency |
Commonly lost: Most candidates described the dibucaine-resistant variants, but fluoride-resistant variants were less often mentioned, preventing higher marks. This is a five-mark part and one whole family of variants was routinely left out.
Commonly lost: Some candidates showed a lack of understanding that dibucaine and fluoride numbers only indicate genetic makeup, not the quality or concentration of enzyme. One sentence, and it distinguishes an answer that has understood the test from one that has memorised a table.
3 marks
Adverse effects that make it not a preferred relaxant in children
Three marks, and the examination was specific about both the wording it wanted and the answers it refused. Every effect must be tied to children rather than listed generally.
| Effect | Why it matters particularly in children | How to write it |
|---|---|---|
| Bradycardia | Muscarinic stimulation at the sinus node produces sinus or nodal bradycardia, and the effect is more pronounced in children. It is more severe after a second dose and can be prevented with atropine | Write bradycardia, not arrhythmias — the examination marked the two differently |
| Hyperkalaemia leading to cardiac arrest | In apparently healthy children, intractable cardiac arrest with hyperkalaemia, rhabdomyolysis and acidosis may follow suxamethonium, particularly with unsuspected Duchenne muscular dystrophy. A boy with an undiagnosed myopathy is the whole reason routine use in healthy children has been abandoned | Hyperkalaemia must be written WITH its predisposing factor. Naming it alone did not earn the mark |
| Malignant hyperthermia | Suxamethonium is a trigger, and a child may have had no previous anaesthetic to reveal susceptibility | Name masseter spasm alongside it — it may be the first sign, and it can make laryngoscopy impossible |
| Myalgia | From fasciculation | Less pronounced in small children than in young adults, which is worth saying rather than assuming |
| Anaphylaxis | About twice as likely as with a non-depolariser, at roughly 1 in 10,000 administrations | One line |
Commonly lost: Some candidates wrote arrhythmias where the answer wanted bradycardia, and many wrote hyperkalaemia without its predisposing factor, muscular dystrophy. Both are the same failure: the general fact written where the specific one was required.
Writing it in the time you actually have
Two, five and three
Part (b) is half the question. Part (a) is worth two marks and tempts a page, because the mechanism is satisfying to write.
| Minutes | Part | What to write |
|---|---|---|
| 0–4 | (a) · 2 marks | Four sentences of mechanism — agonist, depolarises, not hydrolysed at the junction, sodium channels stay inactivated — then the five-row monitoring table. Stop |
| 4–13 | (b) · 5 marks | Dibucaine table, then the fluoride table, then the sentence on what the number reports, then the increased-activity variants. Write nothing about malignant hyperthermia, acquired causes or management |
| 13–17 | (c) · 3 marks | Bradycardia, hyperkalaemia with muscular dystrophy named, malignant hyperthermia with masseter spasm. Each tied to children. No intracranial pressure, no vomiting |
| 17–18 | Check | Read part (b) back and delete anything that is not genetic. That deletion is worth more than another sentence |