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Acetylcholinesterase inhibitors

Neurotoxic venom effects can appear within a very short time following bites of numerous elapid species, but also with several viper and Hydrophiidae species.

The currently available antivenoms are not very effective with regard to their neurotoxin-neutralising activity (see e.g. Bungarus candidus, Micrurus sp., Naja sp., Naja kaouthia, Naja philippinensis or Ophiophagus hannah).

For that reason alternative treatments that act in a timely and efficacious manner are required.

Endotracheal intubation and artificial respiration are reliable methods that are successful even if they need to be continued for days or even weeks.

Acetylcholinesterase inhibitors can be used in certain situations at least as adjunctive therapy. Their efficacy depends on the location of activity of the neurotoxins of a snake species and has been proven in clinical studies for some snake species, in particular for those species with postsynaptically active venoms (e.g. Naja philippinensis).

 

With presynaptically active neurotoxins it is assumed that they bind more or less irreversibly to acetylcholine-releasing nerve endings and thus cause a neuromuscular block. There are indications that 3,4-diaminopyridine may have a positive influence on the activity of these neurotoxins, which until now have been considered unresponsive to drugs (Watt 1992). Further developments must be awaited in order to be able to definitively assess the utility of this substance for this indication.

 


Table 5.4 Tensilon test and treatment with acetylcholinesterase inhibitors (Warrell 1991, Watt 1992)

 

Treatment step
Procedure Comments
Tensilon test atropine sulphate i.v.: 0.6 mg (adults),
50 µg/kg BW (children) followed by
Tensilon i.v.: 10 mg (adults),
0.25 mg/kg BW (children); caution is required in children below 12 years
Indication: all patients with neurological signs of envenoming following a bite from a snake whose venom contains neurotoxins
Long-acting anticholinesterase inhibitors neostigmine methylsulphate continuous i.v. infusion (Perfusor)
25(–50–100) µg/kg BW/h combined with
atropine sulphate s.c. 15 µg/kg BW 4-hourly

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neostigmine oral
initially 15 mg, 4 × daily or
pyridostigmine oral
initially 60 mg, 4 × daily
combined with
atropine oral
0.6 mg, 2 × daily or
propantheline hydrochloride oral
15 mg, 2 × daily
Indication: improvement of neurological signs of envenoming under the Tensilon test

Dose adjustment: titration according to the effect

Adverse reactions: among other reactions, acetylcholinesterase inhibitors may cause cramping abdominal pain, which can be controlled with atropine

An overdose of acetylcholinesterase inhibitors can lead to a cholinergic crisis with progressive muscle weakness and respiratory paralysis