Positive Response to Edrophonium in Patients with Neurotoxic Envenoming by Cobras (Naja naja philippinensis)

Abstract

To study the ability of anticholinesterase drugs to reverse the potentially fatal paralytic effects of cobra venom, we conducted a placebo-controlled, double-blind crossover trial of intravenous edrophonium (Tensilon) in 10 adults with neurotoxic envenoming caused by bites of the Philippine cobra (Naja naja philippinensis). There was significantly more improvement in ptosis and endurance of upward gaze after edrophonium than after placebo. Five minutes after injection, the mean difference (+/- SD) in the percentage of the iris that was uncovered was 39 +/- 5.47 (70 vs. 31 percent; P less than 0.01), and the mean difference in the number of seconds of upward gaze was 33.1 +/- 9.29 (39.7 vs. 6.6 seconds; P less than 0.01). The expiratory and inspiratory pressures, forced vital capacity, and ability to cough, speak, and swallow also improved after edrophonium. In both the patients who were studied electromyographically, pretreatment and postplacebo responses were typical of myasthenia gravis and became normal after edrophonium. We conclude that anticholinesterases are beneficial in the management of neurotoxic envenoming by Asian cobras (Naja naja), and we recommended a test of edrophonium in any patient with signs of neurotoxic envenoming after snakebite.

Envenomation by Micrurus coral snakes in the Brazilian Amazon region: report of two cases

“…Improvement in neurological signs was not seen until 24 hours after antivenom administration. Ancillary treatment has been recommended with anti-cholinesterase drugs; Edrophonium Chloride could benefit those patients bitten by a coral snake with postsynaptic neurotoxic venom 41 , and neostigmine had demonstrated the potential to reverse neuroparalysis 9,39 . Even when used in several occasions in clinical practice, no standard protocol has been followed.…”

Bites by coral snakes (Micrurus spp.) in Campinas, State of São Paulo, Southeastern Brazil

“…A clinical trial involving Naja naja philippinensis bites 34 has shown the effectiveness of anticholinesterase drugs in treating elapid envenoming with severe paralysis caused by a predominantly or exclusively postsynaptic action at the neuromuscular junction. A favorable response to neostigmine in three cases has also been observed in Brazil, two of which were attended a considerable time after being bitten 8,32 .…”

“…In one of our cases, which did not respond to anticholinesterase drugs, the offending species may have been M. corallinus, which venom acts presynaptically blocking the release of acetylcholine from nerve endings at the neuromuscular junction 17,31 . However, the effect of neostigmine is always temporary 8,32,34 , and complete reversal of postsynaptic neurotoxicity can be achieved only with antivenom.…”

Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite

“…sPLA2s are also some of the most pharmacologically active, multi-effect (neuro-myo-cyto-hemotoxic) venom components ( While sPLA2 inhibition might prove sufficient as a "bridge-to-survival" for many types of venoms when administered in a pre-referral setting and, at times, be sufficient for treatment, future SMTs might be mixtures of other SMT (Figure 3a). Some targets could also be inhibited indirectly by SMTs, such as three-finger toxins, whose effects might sometimes be mitigated by acetylcholinesterase inhibitors, though the use of these inhibitors remains controversial despite decades of use for this purpose [52,61,[64][65][66]. In addition, SMTs might be used to slow the spread of venom by paralyzing lymphatic smooth muscles (e.g., with lignocaine) [67].…”

“…In 1972, Banerjee et al presented an early example of repurposing an SMT for snakebite when neostigmine was used to treat the paralytic effects of an elapid bite [52]. Multiple groups have since investigated the use of this class of acetylcholinesterase inhibitors in the clinical setting with variable results [52,61,65,66]. Development of a hypothetical SMT using a repurposing pathway are shown in Figure 4.…”