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
|Hepatic Disease||Prolonged duration of aminosteroids and suxamethonium||Decreased metabolism, decreased production of pseudocholinesterase 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|
|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:
|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.|
- Sterling E, Winstead PS, Fahy BG. Guide to Neuromuscular Blocking Agents. 2007. Anesthesiology News.
- ICU Adelaide. Neuromuscular Blockers.
- Pino RM. Revisiting the Priming Principle for Neuromuscular Blockers: Usefulness for Rapid Sequence Inductions. Austin J Anesthesia and Analgesia. 2014;2(5): 1030.
- ANZCA February/April 2011