Snake venom neurotoxins are a diverse group of toxins which clinically cause
paralytic effects mediated at the neuromuscular junction (in most cases). 100
years ago, snakebite paralysis usually condemned the victim to death due to
respiratory failure. In the current era of ICU care, intubation, ventilators
etc, such an outcome should be rare, but in many regions such high tech
facilities are unavailable, thus many snakebite victims still die annually of
neurotoxic paralysis.
Presynaptic neurotoxins generally are modified
phospholipase A2 toxins which specifically target the terminal axon of the neuromuscular
junction, causing first release of neurotransmitter, then extensive damage to
the axonal structure, completely disrupting transmitter synaptic vesicle production
and thus cessation of transmitter release. Clinically this causes a progressive
flaccid paralysis, with onset of first signs usually 1+ hours post bite, with
progressive paralysis thereafter. Full respiratory paralysis, including the
diaphragm, may take 3-24 hours, but once paralysed, recovery rate is determined
by axonal repair and is not influenced by antivenom therapy. It is therefore
critically important in this type of envenoming to recognise the early signs
of paralysis and institute effective antivenom therapy before more extensive
paralysis becomes irreversibly established. Complete paralysis may take days,
weeks or, rarely, months to resolve. During this period the victim is dependent
on external ventilatory support and at risk of a number of potentially severe
complications. Presynaptic neurotoxins are found in selected Elapid and Viperid
venoms.
Postsynaptic neurotoxins are polypeptides
of varying size, usually below 12 kD and also target the neuromuscular junction.
They act extracellularly, binding to the acetylcholine receptor on the muscle
end-plate, blocking neurotransmitter binding, thus causing paralysis. The cell
is not specifically damaged, therefore this type of flaccid paralysis is often
reversible with antivenom therapy, even if very extensive. The mode of action
also may allow more rapid onset and progression of paralysis, though major paralysis
is uncommon in under one hour post-bite. Postsynaptic neurotoxins are present
in many Elapid and a few Viperid venoms.
Dendrotoxins and Fasciculins are synergistic
neurotoxins found in some African mamba venoms. They both target the neuromuscular
junction, causing paralysis and muscle spasms or fasciculation. The dendrotoxins
target certain potassium channels in the terminal axon membrane, ultimately
resulting in over-release of neurotransmitter molecules, which swamp and overstimulate
the adjacent muscle end-plate receptors. The fasciculins inhibit or interfere
with the anticholinesterases in the junctional space, significantly reducing
the normal removal of synaptic acetylcholine. This enhances the effect of the
dendrotoxins, resulting in gross overstimulation of the muscle, causing spasm
or fasciculation, effectively paralysing the victim. Both toxins may exert their
effect rapidly, thus the clinical effects may manifest in less than an hour
post-bite.
There are other types of snake neurotoxins,
some targeting different areas, but they are either uncommon or have limited
or no significant clinical effects, particularly compared with the foregoing
toxins.
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