H is for Huey Ting (:: TYPES OF NEUROTOXINS + CLINICAL EFFECT OF NEUROTOXINS

Presynaptic neurotoxins (β-bungarotoxins)

Modified phospholipase A2 toxins
Found in selected Elapid and Viperid venoms.
slow onset
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
irreversible
only respond to antivenom if given early
recovery rate is determined by axonal repair and is not influenced by antivenom therapy

Postsynaptic neurotoxins
(α-bungarotoxins)

polypeptides of varying size
present in many Elapid and a few Viperid venoms
target the neuromuscular junction
Usually rapid onset
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
Respond to antivenom and anticholinesterases

Dendrotoxins and Fasciculins

synergistic neurotoxins
found in some African mamba venoms
target the neuromuscular junction
causing paralysis and muscle spasms or fasciculation
dendrotoxins
- target certain voltage-gated 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
fasciculins
- Inhibit or interfere with the cholinesterases in the junctional space, significantly reducing the normal removal of synaptic acetylcholine.
- enhances the effect of the dendrotoxins
resulting in gross overstimulation of the muscle, causing spasm or fasciculation, effectively paralysing the victim
In doing so they also stimulate many types of nerves, resulting in a diversity of effects, which can include pain, sweating, salivation, tearing, piloerection (body hair standing on end), muscle fasciculation, high blood pressure, tingling sensation, particularly around the lips, and flooding of the lungs with fluid (pulmonary oedema)
exert their effect rapidly, thus the clinical effects may manifest in less than an hour post-bite

Clinical effect: Paralysis

Flaccid paralysis caused by neurotoxins affects skeletal muscles and respiration
In most cases, clinically detectable paralysis will not be apparent until at least one hour post-bite and may be delayed up to 24 hours.
The cranial nerves are usually affected first, with ptosis often the first sign. Other common presenting signs are dysphonia, dysphagia, drooling and diplopia, the latter due to partial ophthalmoplegia. As paralysis progresses drooling may increase, ophthalmoplegia may become total, with fixed forward gaze, often associated with fixed dilated pupils. Limb weakness becomes apparent, the victim usually first noticing ataxic gait, then inability to walk, then stand or even sit up. The neck may become floppy ("broken neck" sign). Deep tendon reflexes will become reduced, then disappear. Respiratory distress develops and breathing may become shallow, rapid and cyanosis may be apparent. Complete respiratory failure will ensue, unless respiratory support is offered. Time from bite to respiratory failure is highly variable, from as little as 30 minutes (rare) to more than 24 hours, but commonly within 6-12 hours. Without antivenom therapy or anticholinesterases, the period of respiratory failure may vary from less than 24 hours, to several days, or even several weeks.

References

H is for Huey Ting (: