Neuromuscular blocking drugs Flashcards
Why are these drugs used?
To cause muscle paralysis with intubation (esp. suxamethonium b/c fast onset + short duration) + abdominal surgery (less anaesthetia used) and to assis ventilation in intensive care
Competitive blockers are also known as _____ and examples are ___
non-depolarising curares, e.g. tubocurarine, vecuronium, pancuronium + atracurium
Competitive blocker characteristics
High affinity for nAChR’s -> long residence in binding site so ACh release can’t effect synaptic potential -> too small to elicit a.p.
Features of competitive block:
- Relaxation without preliminary excitation of muscles
- Relaxant effect antagonised by anticholinesterases
- Tetanic “fade” more pronounced
- Myastenia gravis patients (autoimmune loss of ACh receptors) normally sensitive
Why may a cholinesterase blocker be used against a competitive blocker?
Reverse the administration of a competitive blocker as the duration of these blockers is quite long
Only example of a depolarising blocker
Suxamethonium = agonist of nAChr
How is suxamethonium different to ACh
Resistant to hydrolysis by local cholinesterase so can bind and rebind to receptor -> sustained depol of endplate muscle fibre
Why does mucle fibre membrane become inexcitable after initial a.p. with suxamethonium
Na channels around endplate inactive can’t generate ap
Features of depolarisation block:
- Initial fasciculation -> endplate depol. causes excitation of muscle fibres -: post-op muscle pain
- Block not relieved by anticholinesterases
- Myasthenia gravis patients insensitive to blocking action
- Action at endplate causes release of K+ from muscle cells -> hypokalaemia
Why can K+ release from suxamethonium be dangerous?
If plasma K+ already high (in severe burns or crush injuries) or if K+ release enhanced (disease/ injuries causing denervation)
Suxamethoniums relationship with cholinesterase
CHE from PLASMA. so action lasts only 5 mins
- If plasma CHE level low, action can be prolonged to several hours
Causes of low plasma CHE
Genetic abnormality due to mutation or liver disease, malnutrition or use of anticholinesterase drugs
What terrible side effect can be seen if suxamethnoium is used with GA’s in a susceptible patient and why are they susceptible
Malignant hyperthermia, someone with a mutation in calcium release channel on SR since calcium release produces persistent muscle spasm and hyperthermia
3 compounds that block cholinergic transmission
- Botulinum toxin
- hemincholinium
- streptomycin
Botulinum toxin origins
High molecular weight protein produced by an anaerobic bacillus (clostridium botulinum) which can grow in badly tined food -> rare but highly dangerous cause of food poisoning
Potency of botulinum toxin
Letal dose 70. ig and its effects are long lasting (weeks)
Botulinum toxin mech of action and uses
Blocks release of ACh at NMJ and ganglia without affecting postsynaptic mech’s -: prolonged relief of muscle spas min dystonia in severe localised excessive sudoration
Hemicholinium characteristics
- Structurally similar to choline
Hemicholinium mech of action and uses
- competitively inhibits uptake of choline by cholinergic nerve terminals
- > active, carrier-mediated transport
- > causes terminals to run short of choline, so ACh synthesis can’t keep up with release
- Action - slow -> mainly experimental
Streptomycin is a ____ antibiotic
aminoglycoside
Streptomycin means of action and side effect
Inhibit ACh by blocking Ca entry -> weakness as a side effect + potentiates action of neuromuscular blocking agents in anaesthetia
