Question 9

Discuss the factors that may potentially influence the speed of onset of neuromuscular blockade.

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College Answer

Speed of onset is related to how quickly an effective dose reaches the neuromuscular junction, the type of interaction with the receptor and the margin of safety of the receptors. Examples of  parameters that increase speed of onset include a high drug rate of delivery (high CO, high muscle  group blood flow, and fast injection rate), high drug concentration (higher dose, low potency, higher ED 95, lower protein binding) or  a depolarising block. A good answer would include a list of these factors, with a brief explanation. Mention of other factors such as electrolyte disturbances gained additional marks. It was expected that the direction of an effect would be clearly indicated  (e.g. “potency” would not score a mark unless the candidate wrote – “low potency increases  speed of onset”, etc.). These drugs are charged molecules which do not cross cell membranes and have a low volume of distribution. Absorption from GIT, Lipid solubility, pKa, metabolism and clearance have minimal relevance to speed of onset.


  • Factors that influence the rate of agent delivery to the muscles:
    • Route of administration (IV faster than IM)
    • Site of IV administration (CVC faster than PIVC)
    • Rate of administration (flushed bolus faster than infusion)
    • Cardiac output (faster in pregnancy, slower in cardiogenic shock)
    • Muscle position (those proximal to the heart affected faster)
  • Factors that influence plasma-effect site equilibration
    • Potency of the agent (less potent agents have faster onset)
      (this is the most important determinant and is mainly due to the larger molar concentration of the effective dose of the low potency agents)
    • Factors which influence diffusion to the site (minor influence),
      of which the only one that matters is:
      • Protein binding (less bound drugs have faster onset)
  • Factors that increase the required effective concentration (slowing the onset):
    • Factors that increase acetylcholine concentration
      • Acetylcholinesterase inhibitors
    • Factors that increase the number of receptors
      • Critical illness polyneuromyopathy
      • Burns
      • Tetanus
      • Spinal injury
      • Stroke
      • Antiepileptic agents
    • Factors that reduce the number of acetylcholine receptors, such as myasthenia gravis (for non-depolarising agents, this slows the onset)
    • Factors that hyperpolarise the motor endplate
      • Hyperkalemia (for nondepolarisng agents)
      • Hypercalcemia
      • Malignant hyperthermia
  • Factors that decrease the required effective concentration (hastening the onset):
    • Factors that reduce the synthesis or storage of acetylcholine
      • Hemicholinium
      • Vesamicol
    • Factors that decrease acetylcholine release
      • Foetal/neonatal motor endplates
      • General anaesthetic agents (volatiles)
      • Regional local anaesthesia
      • Frusemide
      • Calcium channel blockers
      • Aminoglycosides
    • Factors that partially depolarise the motor endplate
      • Hypermagnesemia
      • Hypocalcemia
      • Hyperkalemia (for depolarising agents)
    • Pre-curarisation or "priming" with a low dose of non-depolarising agent
    • Factors that reduce the number of acetylcholine receptors, such as myasthenia gravis (for depolarising agents, this slows the onset)


Kim, Yong Byum, Tae-Yun Sung, and Hong Seuk Yang. "Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents." Korean journal of anesthesiology 70.5 (2017): 500-510.