Background: This study examines the use of topical pharmacological agents as a snakebite first aid where slowing venom
reaching the circulation prevents systemic toxicity. It is based on the fact that toxin molecules in most snake venoms are
large molecules and generally first enter and traverse the lymphatic system before accessing the circulation. It follows on
from a previous study where it was shown that topical application of a nitric oxide donor slowed lymph flow to a similar
extent in humans and rats as well as increased the time to respiratory arrest for subcutaneous injection of an elapid venom
(Pseudonaja textilis, Ptx; Eastern brown snake) into the hind feet of anaesthetized rats.

Methodology/Principal Findings: The effects of topical application of the L-type Ca2+ channel antagonist nifedipine and
the local anesthetic lignocaine in inhibiting lymph flow and protecting against envenomation was examined in an
anaesthetized rat model. The agents significantly increased dye-measured lymph transit times by 500% and 390%
compared to controls and increased the time to respiratory arrest to foot injection of a lethal dose of Ptx venom by 60% and
40% respectively. The study also examined the effect of Ptx venom dose over the lethal range of 0.4 to 1.5 mg/kg finding a
negative linear relationship between increase in venom dose and time to respiratory arrest.

Conclusions/Significance: The findings suggest that a range of agents that inhibit lymphatic flow could potentially be used
as an adjunct treatment to pressure bandaging with immobilization (PBI) in snakebite first aid. This is important given that
PBI (a snakebite first aid recommended by the Australian National Health and Medical research Council) is often incorrectly
applied. The use of a local anesthetic would have the added advantage of reducing pain.