title: Pharmacological approaches that slow lymphatic flow as a snakebite first aid.
abstract: 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.
  
  
  RESULTS
  The effects of topical application of the L-type Ca(2+) 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
  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.
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia ; Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
authors.forename: Dirk F
authors.initials: DF
authors.lastname: van Helden
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Queensland, Australia ; Department of Nuclear Medicine, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Thomas
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dosen
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Imtiaz
authors.affiliation: School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Derek R
authors.initials: DR
authors.lastname: Laver
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia ; Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Waratah, New South Wales, Australia.
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
mesh_terms: D000818:Animals; D004546:Elapid Venoms / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005260:Female; D005392:First Aid / Q000379:methods*; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology / Q000627:therapeutic use; D008208:Lymphatic System / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D012119:Respiration / Q000187:drug effects; D012909:Snake Bites / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D004546:Elapid Venoms; D008012:Lidocaine; D009543:Nifedipine