14B07: Exam Report

Outline the mechanisms that potentiate the action of non-depolarising muscle relaxants and give examples.

15% of candidates passed this question.

A structured approach would work well for this question but was often lacking. Many answers were superficial providing short lists of factors affecting NDMRs without reference to mechanism. Candidates failed to differentiate factors which potentiate NDMRs from those which inhibit the action of the drugs. Some confusion also existed confusing speed of onset kinetics with potentiation kinetics. Candidates who structured their answer into pharmacokinetic and pharmacodynamic factors generally scored better marks. Candidates who used pre-post synaptic type structure tended to omit kinetics completely from their answers. Incorrect facts were common.

L2i / 14B07: Outline Mechanisms That Potentiate The Action Of Ndmr And Give Examples 15%


Competitive antagonism of nAChR → bind a subunit

Dynamic binding – repeated association & deassociation

Block causes gradual decline in EPP until it fails to reach threshold

To produce complete block requires 92% receptor occupancy

Some NDMR also block pre-junctional nAChR → these receptors act in +ve fdbk to increase ACh release during high frequency stimulation

Mechanisms of Potentiation

Potency = the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect

ie more potency means less drug dose required gives effect you want

PK Factors


↓Plasma proteins – mainly polar with low PPB so not affected

Vd – NDMR have small Vd bc are confined to plasma w minimal PPB

↓TBW = ↓Vd (shocked state)

Same dose will have greater effect


  • Monoquaternary have one quaternary cation + one tertiary amine
  • If pH becomes acidic, the tertiary amine can become protonated ∴ +vely charged

This ­potency of monoquaternary NDMR in acidic conditions


Liver – panc & vec undergo liver metabolism. ∴ liver impairment will↑ ­potency by ↑concentration of drug

Pseudocholineserase – deficiency/liver failure will ­↑potency by ↑ ­concentration of drug mivacurium

Hoffman – temp/pH dependant – shocked states of hypoxaemia/acidaemia will ↓metabolism and ­↑potency


Rocuronium has no metabolism

Excreted in urine and bile

Therefore shocked states = ↓RBF and biliary stasis= ↓elimination and ­↑potency

Presence of Other Drugs Which Affect ↑Potency

CNS Depression

  • Volatiles = depress somatic reflexes, ↓muscle tone

Prevention of Nerve Propagation

  • Local anaesthetics → block Action potential propagation

Pre Synaptic Modulation

  • ↓ATP synthesis = frusemide
  • Block pre-synaptic receptors = volatiles
  • Block Ca++ channels = CCB, Mg++, aminoglycosides
  • Deplete ACh stores = tetanus toxin
  • ­↑MEPP frequency which depletes ACh stores = Theophylline, digoxin, catecholamines

Post Synaptic Modulation

  • Block ACh receptors – volatiles, aminoglycosides, quinolones, >1 NMBD