Show the model answerAttempt it first — that is what makes it stick
What earns the marks10 marks
| Classify, do not list | The stem says classes. A flat list of fifteen drug names is one idea repeated fifteen times |
|---|---|
| One named example per class | The stem asks for it explicitly. A class with no example is an incomplete answer |
| State the direction | Prolongs or shortens. Half the classes are worth nothing until you say which |
| Give the mechanism | This is the mark. "Aminoglycosides prolong the block" earns far less than the reason |
| Include the shorteners | The stem says affect, not prolong — anticholinesterases, sugammadex and chronic anticonvulsants all belong |
| Relaxant on relaxant | A non-depolariser with another, and a non-depolariser with suxamethonium. Very few candidates write this |
| Nothing the stem did not ask | No NMBA classification, no pharmacokinetics, no physiological factors — these scored zero here |
Before you write a word
This question comes in two versions, and they are marked differently
The same material has been examined at six sittings, worded two ways. Getting the wording right is worth more than any single mechanism on this page.
| The stem says | Sittings | What earns marks | What earns nothing |
|---|---|---|---|
| Classes of drugs | 2014, 2019, 2025 | Drug classes only, each with an example, a direction and a mechanism | Physiological factors, organ failure, temperature, electrolytes, age |
| Factors | 2003, 2015, 2021 | Drugs and physiology together — temperature, pH, electrolytes, age, neuromuscular disease, hepatic and renal impairment all count | Repeating several electrolytes as separate points; they carry one mark between them |
Commonly lost: Most candidates listed drugs without explanation. The examination asked for the mechanism by which each class produces its effect, and the list on its own is the cheap half of the answer.
Commonly lost: Very few mentioned the interaction between one non-depolariser and another, or between a non-depolariser and a depolariser. Both were available for marks and both are in section 4.
The framework to write from
Four sites, two directions
Learn the sites rather than the list. A drug you have never seen can be placed correctly if you know where in the junction it acts, and the mechanism then writes itself.
Where a co-administered drug can change a neuromuscular block
Why any of this works
The junction holds a large surplus of receptors, so a block only becomes measurable once roughly 75% of postjunctional receptors are occupied. Any drug that shifts the balance between acetylcholine and antagonist moves the block in one direction or the other.
Four ways to deepen or prolong it
Presynaptic
Less acetylcholine released. Aminoglycosides, magnesium and calcium channel blockers all reduce calcium-dependent release from the nerve terminal.
Postjunctional receptor
Receptor made less responsive, or the antagonist made to bind harder. Volatile agents, tetracyclines and magnesium all act here.
Muscle membrane
Membrane stabilised and harder to depolarise. Local anaesthetics, lithium and quinidine, largely through sodium and potassium channel effects.
Clearance
Less relaxant removed. Either the eliminating organ is slowed, or the metabolising enzyme is inhibited — as when pancuronium inhibits butyrylcholinesterase and mivacurium cannot be broken down.
And two ways to shorten it
More transmitter
An anticholinesterase raises junctional acetylcholine so it out-competes the antagonist. The same drug augments a phase I depolarising block.
Antagonist removed or outnumbered
Sugammadex encapsulates an aminosteroid in plasma. Chronic anticonvulsants raise clearance and upregulate receptors, producing resistance.
The direction is decided by which side of the acetylcholine-versus-antagonist balance the drug moves. Say which side, and say why — that sentence is the mark.
Roughly 7 of the 10 marks
Classes that prolong the block
One row is one mark: the class, a named example, the direction, and the mechanism. Write the table, not paragraphs.
| Class | Example | Effect | Mechanism |
|---|---|---|---|
| Presynaptic — less acetylcholine released | |||
| Antibiotics | Gentamicin | Prolonged | Aminoglycosides, polymyxins, lincomycin and clindamycin inhibit prejunctional acetylcholine release by competing with calcium, and additionally depress postjunctional receptor sensitivity. Tetracyclines act postjunctionally only. Cephalosporins and penicillins have not been reported to potentiate blockade |
| Magnesium | Magnesium sulphate | Prolonged, markedly | Inhibits presynaptic calcium channels, so less transmitter is released, and separately depresses excitability of the muscle fibre membrane. After 40 mg/kg the ED₅₀ of vecuronium falls by 25%, onset nearly halves and recovery nearly doubles. Neostigmine-induced recovery is also attenuated |
| Calcium channel blockers | Verapamil | Prolonged | Reduced calcium influx into the nerve terminal and therefore reduced acetylcholine release. Verapamil and amlodipine impair transmission even in people without neuromuscular disease, though the clinical significance is probably minor |
| Postjunctional and membrane | |||
| Inhalational anaesthetics | Desflurane | Prolonged | A purely pharmacodynamic interaction: a central effect on α motoneurons and interneuronal synapses, inhibition of postsynaptic nicotinic receptors, and increased affinity of the antagonist for the receptor. Rank order desflurane > sevoflurane > isoflurane > halothane > nitrous oxide with an intravenous technique |
| Local anaesthetics | Lidocaine | Prolonged at small doses; large doses block transmission outright | Prejunctional depression of post-tetanic potentiation at small doses, and a stabilising effect on the postjunctional membrane at larger ones. Procaine additionally inhibits butyrylcholinesterase, so it prolongs suxamethonium and mivacurium as well |
| Antiarrhythmics | Quinidine | Prolonged | Sodium channel blockade and membrane stabilisation. Disopyramide has been reported to impair reversal of vecuronium |
| Psychotropics | Lithium carbonate | Prolonged, with both depolarising and non-depolarising agents | Lithium substitutes for sodium in cellular transport, entering cells through sodium channels and accumulating; it inhibits transmission presynaptically and muscular contraction postsynaptically. Doses should be reduced and titrated in a patient established on lithium |
| Clearance and enzyme effects | |||
| Diuretics | Frusemide | Variable, usually prolonged | Inhibition of cyclic AMP production and of ATP breakdown, reducing acetylcholine output; further indirect effects through serum potassium. Acetazolamide, by contrast, antagonises anticholinesterases experimentally |
| Anticholinesterases, on the depolarising side | Neostigmine | Prolongs suxamethonium and mivacurium | It inhibits plasma cholinesterase as well as acetylcholinesterase, so the ester-hydrolysed relaxants are not broken down. The same drug shortens a non-depolarising block — the direction depends entirely on which relaxant is in the patient |
| Corticosteroids with prolonged relaxant use | Hydrocortisone with vecuronium in critical illness | Markedly prolonged recovery | Critical illness myopathy, seen most often where corticosteroids and relaxants have been given together to a critically ill patient |
Roughly 2 of the 10 marks
Classes that shorten the block
The stem says affect, not prolong. An answer with no shortening class in it has declined a fifth of the question.
| Class | Example | Effect | Mechanism |
|---|---|---|---|
| Anticholinesterases | Neostigmine | Shortens a non-depolarising block | Acetylcholinesterase is inhibited by carbamylation, junctional acetylcholine rises, and the transmitter out-competes the antagonist at the receptor. Ceiling effect: once the enzyme is fully inhibited, more drug adds nothing |
| Selective relaxant binding agents | Sugammadex | Terminates an aminosteroid block at any depth | A γ-cyclodextrin encapsulates rocuronium or vecuronium in plasma, creating a concentration gradient that draws the relaxant away from the junction. No effect on the benzylisoquinoliniums |
| Chronic anticonvulsants | Carbamazepine, phenytoin | Resistance — accelerated recovery, larger doses needed | Vecuronium clearance is doubled by long-term carbamazepine; additional proposed mechanisms are increased binding to α₁-acid glycoprotein, reducing the free fraction, and upregulation of junctional receptors. Mivacurium, and probably atracurium, are exceptions. The same receptor upregulation explains hypersensitivity to suxamethonium and makes its hyperkalaemic response a genuine concern |
| Calcium salts | Calcium chloride | Shortens | Calcium triggers acetylcholine release and enhances excitation–contraction coupling; hypercalcaemia in hyperparathyroidism is associated with reduced sensitivity to atracurium and a shortened time course |
Roughly 1 of the 10 marks, and rarely written
One relaxant interacting with another
The examination has twice noted how few candidates mention this. It is a whole mark for two sentences, and it is the section that makes an answer look complete.
| Combination | Result | Why |
|---|---|---|
| Two non-depolarisers of the same chemical class | Additive | Atracurium with mivacurium, or two aminosteroids together. Antagonistic interactions have never been reported within this class |
| Two non-depolarisers of different chemical classes | Synergistic | An aminosteroid with a benzylisoquinolinium — rocuronium with cisatracurium, or rocuronium with mivacurium. Proposed explanations are the existence of multiple pre- and postsynaptic binding sites, and the unequal binding affinities of the two α subunits. A rocuronium–mivacurium pairing buys rapid onset and short duration together |
| Pancuronium then mivacurium | Marked potentiation | Pancuronium inhibits butyrylcholinesterase, so mivacurium's plasma clearance falls. A pharmacokinetic interaction on top of the pharmacodynamic one |
| Changing from one relaxant to another mid-case | The first drug's profile persists | About three half-lives are needed before 95% of the first drug has cleared and the block starts behaving like the second. Recovery from the first maintenance dose of the new drug is prolonged; by the third dose the effect is negligible |
| Non-depolariser before suxamethonium (defasciculating dose) | Antagonises the subsequent depolarising block | Receptors already occupied by a competitive antagonist cannot be depolarised, so the suxamethonium dose must be increased |
| Suxamethonium before a non-depolariser | Conflicting evidence | Potentiation of pancuronium, vecuronium and atracurium has been reported; other work found no significant effect on pancuronium, rocuronium or mivacurium. Say that the evidence conflicts rather than picking a side |
Not for the 2019 wording
If the stem says factors instead of drugs
Everything below scores zero on the 2019 paper and carries most of the 8 marks on the 2015 one. Check the wording, then use the right table.
| Factor | Effect | Mechanism |
|---|---|---|
| Hypothermia | Prolonged | Reduced clearance and altered distribution. Twitch force falls 10–16% per °C below a muscle temperature of 35.2 °C; vecuronium recovery to 10% twitch height rises from 28 minutes at 36.4 °C to 64 minutes at 34.4 °C, and atracurium's duration from 44 minutes at 37 °C to 68 at 34 °C, because Hofmann elimination is slowed by cold and by a fall in pH. Neostigmine's efficacy is not altered by mild hypothermia |
| Acidosis | Prolonged for most agents, metabolic more than respiratory | The protonated drug binds the receptor with greater affinity. Respiratory acidosis also opposes reversal |
| Hypokalaemia | Non-depolarising block potentiated; depolarising block antagonised | A more negative resting membrane potential makes the membrane harder to depolarise. Hyperkalaemia does the reverse |
| Hypocalcaemia and hypermagnesaemia | Prolonged | Reduced calcium-dependent transmitter release |
| Neuromuscular disease | Markedly prolonged and unpredictable | Myasthenia gravis reduces the receptor population, so the margin of safety is already spent before any drug is given |
| Hepatic or renal impairment | Prolonged for the organ-dependent agents | Reduced clearance. Atracurium and cisatracurium are the exceptions, being independent of both organs |
| Age | Prolonged at both extremes | Reduced clearance in the elderly; an immature junction and a larger volume of distribution in the neonate |
Commonly lost: On the 2021 version, repeated answers on different electrolytes carried a maximum of one mark between them. Hypokalaemia, hypocalcaemia and hypermagnesaemia written as three separate points is one point, and the writing time is better spent on a class you have not yet named.
Commonly lost: Also on the 2021 version, some candidates answered with factors that hasten the onset of blockade — precurarisation and the priming principle. Onset and duration are different questions.
Writing it in the time you actually have
A ten-mark plan
Ten marks in a paper of this length is roughly eighteen minutes. The plan below is built so that if you run out of time, what you have already written is the highest-scoring part.
| Minutes | What to write | Marks secured |
|---|---|---|
| 0–1 | Read the stem twice. Underline drugs or factors. Write the four site headings down the margin: presynaptic, postjunctional, membrane, clearance | None yet, and it is still the best-spent minute |
| 1–10 | The prolonging classes as a four-column table: class, example, direction, mechanism. Aim for eight rows, one line each | Around 7 |
| 10–14 | The shortening classes — anticholinesterase, sugammadex, chronic anticonvulsant | Around 2 |
| 14–16 | Relaxant on relaxant: same class additive, different class synergistic, and the defasciculating dose raising the suxamethonium requirement | Around 1 |
| 16–18 | Anything left over: the aminoglycoside reversal warning, the pancuronium–mivacurium enzyme interaction, the three-half-life changeover | Surplus, and it reads as depth |