Neuromuscular Blockers

Understanding of the pharmacology of neuromuscular blocking drugs

The neuromuscular junction is a chemical communication between the motor neuron and the muscle cell. Vesicles containing ACh are released when activated by Ca2+, and influx of which occurs when the action potential reaches the nerve terminal.

Nictotinic ACh receptors sit on the shoulders of junctional folds of muscle cells, whilst acetylcholinesterase is buried in the clefts.

Factors Affecting Neuromuscular Blockade

Patient Factors

Factor Effect Mechanism
Hepatic Disease Prolonged duration of aminosteroids and suxamethonium Decreased metabolism, decreased production of succinylcholine in severe disease
Pseudocholinesterase deficiency Prolonged duration of suxamethonium Decreased metabolism
Age Increased sensitivity in neonates, particularly premature infants Incomplete maturation of NMJ
Hypokalaemia Potentiates non-depolarising blockade, reduces depolarising blockade Increases magnitude of stimulus required to depolarise cell
Hyperkalaemia Potentiate depolarising blockade, reduce non-depolarising blockade Decreases magnitude of stimulus required to depolarise cell
Hypermagnesaemia Potentiates blockade Decreases ACh release, decreases sensitivity of post-synaptic membrane
Hypocalcaemia Potentiates blockade Decreases presynaptic ACH release, decreases sensitivity of post-synaptic membrane
Respiratory acidosis Potentiates blockade Enhances effect of NMB agents
Hypothermia Potentiates blockade Reduces hepatic metabolism, renal elimination, Hoffman degradation
Hypovolaemia Slows rate of onset and enhances duration Prolonged circulation time
Myasthenia Gravis Increased sensitivity to non-depolarising agents Autoimmune blockade of receptors gives pre-existing level of block
Eaton-Lambert Syndrome Increased sensitivity to all NMBs Autoimmune destruction of voltage-gated Ca2+ channels prevent ACh vesicle exocytosis

Drug Factors

Drugs Effect Mechanism
Frusemide Potentiates blockade at low dose, reduces blockade at high dose Inhibits protein kinases (reducing AMP/ATP synthesis) at low dose, inhibits PDE at high doses which increases ACh release
Inhalational anaesthetics Potentiates blockade Stabilise post-junctional membrane, blockade of presynaptic ACh receptors
Antibiotics Potentiate blockade Variable. Aminoglycosides and tetracycles prolong blockade
Local anaesthetics Potentiate blockade Reduce ACh release and stabilise post-junctional membrane
Anticholinesterases Reduces blockade Increase ACH levels at the NMJ by decreasing breakdown
OCP Potentiates depolarising blockade Competes for binding sites on plasma cholinesterases
Ca2+-channel blockers Potentiate blockade Inhibit Ca2+ dependent ACh release
Lithium Potentiates blockade Augments action of NMBs

Additional Factors Affecting Onset of Neuromuscular Blockade

Most of these can be related to Fick's Law:

Factor Effect Mechanism
Potency Low potency decreases time to onset Bowman's principle: Less potent drugs must be administered in higher doses, and so have a greater concentration gradient driving diffusion to the effect site
Dose Increased dose decreases time to onset Greater concentration gradient
Cardiac Output High output decreases time to onset Increased drug delivery
Muscle group flow High muscular flow decreases time to onset Increased drug delivery
Priming Principle (May) decrease time to onset A 'priming' dose of non-depolarising blocker is to an awake patient given prior to induction. This occupies less than 70% of receptors, so does not cause significant neuromuscular blockade. After induction, a second dose is given to occupy the remaining receptors and complete blockade.

References

  1. Sterling E, Winstead PS, Fahy BG. Guide to Neuromuscular Blocking Agents. 2007. Anesthesiology News.
  2. ICU Adelaide. Neuromuscular Blockers.
  3. Pino RM. Revisiting the Priming Principle for Neuromuscular Blockers: Usefulness for Rapid Sequence Inductions. Austin J Anesthesia and Analgesia. 2014;2(5): 1030.
  4. ANZCA February/April 2011
Last updated 2017-09-21

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